<SEC-DOCUMENT>0000874015-25-000123.txt : 20250430
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<ACCEPTANCE-DATETIME>20250430155617
ACCESSION NUMBER:		0000874015-25-000123
CONFORMED SUBMISSION TYPE:	10-Q
PUBLIC DOCUMENT COUNT:		67
CONFORMED PERIOD OF REPORT:	20250331
FILED AS OF DATE:		20250430
DATE AS OF CHANGE:		20250430

FILER:

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

	FILING VALUES:
		FORM TYPE:		10-Q
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		25894677

	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-Q
<SEQUENCE>1
<FILENAME>form10q.htm
<DESCRIPTION>IONIS PHARMACEUTICALS, INC. 10-Q 3-31-2025
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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;">For the transition period from _____ to _____</div>

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

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    <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>

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  <div style="text-align: justify; text-indent: 36pt; 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
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  <div style="text-align: justify; text-indent: 36pt; 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 and posted
    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_a46f7626cd4049ffb95a16fad34c023a" contextRef="c20250101to20250331">Yes</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9746;</span> No <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9744;</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; 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, 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><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: 50%; 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_ef6a68add663487faa734261655a6e22" contextRef="c20250101to20250331">Large Accelerated Filer</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9746;</span></div>
        </td>

    <td style="width: 50%; 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: 'Times New Roman', Times, serif;">&#9744;</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 50%; vertical-align: top;">&#160;</td>

    <td style="width: 50%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 50%; 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: 'Times New Roman', Times, serif;">&#9744;</span></div>
        </td>

    <td style="width: 50%; 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: 'Times New Roman', Times, serif;"><ix:nonNumeric name="dei:EntitySmallBusiness" id="Fact_cae682cfe2a84e65a19ea92ba1c09258" contextRef="c20250101to20250331" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 50%; vertical-align: top;">&#160;</td>

    <td style="width: 50%; 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: 'Times New Roman', Times, serif;"><ix:nonNumeric name="dei:EntityEmergingGrowthCompany" id="Fact_815558627e514d23964e229cbca37c25" contextRef="c20250101to20250331" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></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;">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 style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9744;</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant is a shell company (as defined in Rule 12(b)-2 of the Securities Exchange Act of 1934). Yes
    <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonNumeric name="dei:EntityShellCompany" id="Fact_6c1fbb606dd448f885c20a6dbcdaf37e" contextRef="c20250101to20250331" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric></span> No <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9746;</span></div>

  <div><br/>
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The number of shares of voting common stock outstanding as of April 24, 2025 was <ix:nonFraction name="dei:EntityCommonStockSharesOutstanding" id="Fact_9b648ee70e904b5db10e714854e3d8e3" contextRef="c20250424" unitRef="U001" decimals="INF" scale="0" format="ixt:num-dot-decimal">159,159,099</ix:nonFraction>.</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;"><a id="Index"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

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

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">INDEX</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: 9.24%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART I</div>
        </td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FINANCIAL INFORMATION</div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

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    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial Statements:</div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#BalanceSheet" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Balance
              Sheets</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> as of </span>March 31, 2025<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited) and </span>December 31, 2024</div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#IncomeStatementQ1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated
              Statements of Operations</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the </span>three months<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ended </span>March 31, 2025<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ComprehensiveIncomeQ1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated
              Statements of Comprehensive Loss</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the </span>three months<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ended </span>March 31, 2025<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#EquityQ1" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of
              Stockholders&#8217; Equity</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the </span>three months<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ended </span>March 31, 2025<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#CashFlows" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Condensed Consolidated Statements of
              Cash Flows</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the </span>three<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> months ended </span>March 31, 2025<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (unaudited)</span></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Notes" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Notes to Condensed Consolidated Financial
              Statements (unaudited)</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ITEM2MDAQ1" 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: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Overview" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Overview</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#CriticalAcctgEstimate" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Critical Accounting
              Estimates</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ResultsofOperations">Results of Operations</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 14.85pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Liquidity" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liquidity and Capital Resources</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 3:</div>
        </td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ITEM3MarketRisk">Quantitative and Qualitative Disclosures about Market Risk</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#Item4Controls" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Controls and Procedures</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART II</div>
        </td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#PARTII" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">OTHER INFORMATION</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; 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;">Legal Proceedings</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 1A:</div>
        </td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <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: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ITEM2" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unregistered Sales of Equity Securities and Use of Proceeds</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">51</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 3:</div>
        </td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <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;">Default upon Senior Securities</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">51</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; 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: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">51</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; 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: 82.75%; 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;">Other Information</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">51</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ITEM 6:</div>
        </td>

    <td style="width: 82.75%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="#ITEM6" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exhibits</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">51</div>
        </td>

  </tr>

  <tr>

    <td style="width: 9.24%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 82.75%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td colspan="2" style="width: 91.99%; vertical-align: top; background-color: #CCEEFF;">
          <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; font-weight: bold;">SIGNATURES</a></div>
        </td>

    <td style="width: 8.01%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; margin-right: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52</div>
        </td>

  </tr>


</table>
  <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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8220;</span>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="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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>

  <!--PROfilePageNumberReset%Num%3%%%-->
  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">PART I &#8212; FINANCIAL INFORMATION</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: 72pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ITEM 1.</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FINANCIAL STATEMENTS</div>
        </td>

  </tr>


</table>
  <div><br/>
  </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;">CONDENSED 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 data)</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="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;">March 31,</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2025</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; text-indent: 4.5pt;"><span style="text-indent: 0pt;">December 31</span>,</div>
          <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>

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

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: center; 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;">
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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: 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%;">
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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;">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;">
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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: 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>
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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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current assets</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;">&#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;">Property, plant and equipment, net</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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentNet" id="Fact_5ad23e93b4e4467b9feec47f0d291fee" contextRef="c20241231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">94,251</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;">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%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAsset" id="Fact_179ff6a866a84b438c8efa61e8abcbf5" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">159,269</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:OperatingLeaseRightOfUseAsset" id="Fact_c713ea7701c74914bb86349a6cb99f37" contextRef="c20241231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">161,856</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%; 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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAssetsNoncurrent" id="Fact_d40d8e0c343c4faa8c8a1998eaa5093e" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">131,822</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:OtherAssetsNoncurrent" id="Fact_20e82d483df24cd682d948f6abcde7a0" contextRef="c20241231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">127,278</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: 54pt; 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;">
          <div style="font-family: '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_e57f61237ed14bad8578d2b47564ba8a" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,812,948</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_bacec939ac84418cbf35df017212761d" contextRef="c20241231" unitRef="U002" 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>

  </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;">&#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: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">LIABILITIES AND 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;">
          <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%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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: 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%;">&#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:AccountsPayableCurrent" id="Fact_e36e66d0552f404099023f535d194dfe" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,456</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:AccountsPayableCurrent" id="Fact_0c0b6424e746450abd937b9f839aed88" contextRef="c20241231" unitRef="U002" 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%; 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 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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_552968f4f2a9496e83f175a2ee89b95c" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">26,575</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:EmployeeRelatedLiabilitiesCurrent" id="Fact_e06d0b21026d4d1db2ff5f69431f6629" contextRef="c20241231" unitRef="U002" 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%; 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 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:AccruedLiabilitiesCurrent" id="Fact_2fefcdea93734fcd9274bd7403d639f5" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">102,735</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:AccruedLiabilitiesCurrent" id="Fact_213f5a6701c24aa0979bad8e60ab97c3" contextRef="c20241231" unitRef="U002" 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%; 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;">Income taxes 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;">&#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%; 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: 36pt; 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%;">
          <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_d887201221a740aea76e93f31064660c" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_0a1872c9f2e3455e818bf2b640ac5593" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction></ix:nonFraction> percent</span>
            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_c0fc5fcce49c4087a352bddf06c66bc8" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">565,721</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_89a64b56e9b74eddbf0b8a08d35f85c8" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" 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>

  </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_8f936bdb27184eb5b8169603413c5f07" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7588d1dd3852474ba3856cb7b3f14161" contextRef="c20250331_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_a398a9b03d9944b0a160b5b317b0ca9e" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">629,326</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_6c57d7bc997a408eac5f0d23f91ceea6" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" 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>

  </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:LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" id="Fact_8f477c56c7cd4ff6ae1aa0b97c97c652" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">536,141</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:LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" id="Fact_6953eb07c33a44b891396237666db177" contextRef="c20241231" unitRef="U002" 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>

  </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 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_4596c688a41c42b78cc73859dc04d13e" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">159,392</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_d26d491783804ae585c5a8e472d53c44" contextRef="c20241231" unitRef="U002" 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>

  </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;">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:OtherLiabilitiesNoncurrent" id="Fact_833361e818bd4227a50326908a5d93bc" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">55,671</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:OtherLiabilitiesNoncurrent" id="Fact_900937686a98439d8db4be2ee360c60f" contextRef="c20241231" unitRef="U002" 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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 54pt; 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_b675286a500340028e4203fe4698ca8a" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,337,222</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_f7cd0990ec2c4e71bcb30f7b03262cba" contextRef="c20241231" unitRef="U002" 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>

  </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>

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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;">&#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>

    <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:AccumulatedOtherComprehensiveIncomeLossNetOfTax" id="Fact_ce487df6de7f42f7b8c77a08d145dc67" contextRef="c20241231" unitRef="U002" 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%; 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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RetainedEarningsAccumulatedDeficit" id="Fact_e5c1467d48e84e9db875c9a95c317d68" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,396,746</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:RetainedEarningsAccumulatedDeficit" id="Fact_49f9d5e423964e58bf47306bfe215fd4" contextRef="c20241231" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,249,808</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: 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;">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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_7233636d15704723b5b453128bcd0aa4" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">475,726</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:StockholdersEquity" id="Fact_72be79b3d961421696b3c821e00a1f9b" contextRef="c20241231" unitRef="U002" 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: 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: 54pt; 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_1ff304ed0ed84581b2d4f5f331ecaa3f" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,812,948</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_8ae3d57392c94bea981bfe93b9c946c0" contextRef="c20241231" unitRef="U002" 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>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">3</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="IncomeStatementQ1"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONDENSED 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 style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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;">
          <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;">Product sales, 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;">
          <div style="font-family: '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_8ccc59285b1c4fde8c989da3abc6e321" contextRef="c20250101to20250331_ProductOrServiceAxis_ProductMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,287</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_e6ae93e981cd404c8ec41482c0c61a6a" contextRef="c20240101to20240331_ProductOrServiceAxis_ProductMember" unitRef="U002" 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: 76%;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty revenue</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>

    <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: -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%; 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_cfa8337b5e334752ac7464c49aab7225" contextRef="c20240101to20240331_ProductOrServiceAxis_OtherCommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,208</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%;">
          <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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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_bd6472880fbb416b95f903f2621fca89" contextRef="c20250101to20250331_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">76,168</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: 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>

  </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;">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_867fe0ade3e74b7183b2588f9ee7e72b" contextRef="c20250101to20250331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">45,031</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_ed9b5b2f8b3047b282203f79707f4ee9" contextRef="c20240101to20240331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,345</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%; padding-bottom: 2px; background-color: #CCEEFF;">
          <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; 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_16724ac1f55547198e62e292ce92d841" contextRef="c20250101to20250331_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,413</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_baadb9fbcbb548dc9af9b6531ab3da71" contextRef="c20240101to20240331_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,559</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: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 45pt; 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_6818c90d3f4340a79eb48f6075623367" contextRef="c20250101to20250331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">55,444</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_9acb8deee3a34c1397a2b1443fc1e129" contextRef="c20240101to20240331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">59,904</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: 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_2bf4f3496f6849518a3c8f3f6a217401" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">131,612</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_f84a7b183364428784e980367c723478" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">119,497</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%;">&#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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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;">&#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: 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_4499b5b679ff47f7bed9ce8920aeae51" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,463</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_663654e8aea8473885024d02d30ebd7a" contextRef="c20240101to20240331" unitRef="U002" 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;">Research, development and patent</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:ResearchDevelopmentAndPatentExpense" id="Fact_f93c624eaa954c058d8154816214c2da" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">200,759</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:ResearchDevelopmentAndPatentExpense" id="Fact_fa6cd927397f439895ce14a0f18b74c3" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">214,215</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: -9pt; margin-left: 18pt; 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;">&#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:SellingGeneralAndAdministrativeExpense" id="Fact_f34df9e6f6d9403f9ae0fa92f72610c9" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">76,250</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 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: 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>

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  <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;">
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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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  </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;">
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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>

  </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;">Investment income</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:InvestmentIncomeNet" id="Fact_573e5c8299554c3792d055c9290d33bf" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">26,285</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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest 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:InterestExpense" id="Fact_16c967a0b5b54a6582b8afd87344a711" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,108</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <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:InterestExpense" id="Fact_f6c08235f881433697f9f2310d1d5428" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,151</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: 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_4167cad6c4ee4d299840d72f9664bd2d" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,822</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:InterestExpenseAndAmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_d5e504d20da849ca8679cbe842129c9b" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,959</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: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gain (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_4efb61f957e049fb91450158c453a603" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,164</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_49d1e6990aa9469bb836dc6b47671201" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,333</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other income</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:OtherNonoperatingIncomeExpense" id="Fact_80c233ede24b4e539f9c51f50efcbfb8" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">465</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:OtherNonoperatingIncomeExpense" id="Fact_2e62d867aa934eb4884f92c9931c0a4f" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">277</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;">&#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;">Loss before income tax 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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_17d54ee7ad4a4636abf6764960c4d9ba" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">146,822</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:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_017b25bf4b03468a8ac1b73de0c3d606" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">142,728</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;">&#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: 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;">Income tax 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;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_c5a69d2f02e24e19b6da5f9a18581cdf" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">116</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:IncomeTaxExpenseBenefit" id="Fact_2dab61c5ec204491bd1fc811b2bf4fbc" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">75</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;">&#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%; padding-bottom: 4px;">
          <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%; 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:NetIncomeLoss" id="Fact_93d0327ae14e442a8109ddf312da8fa3" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">146,938</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:NetIncomeLoss" id="Fact_dbd0dbd1d4234d58b258352ef6f9c468" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">142,803</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>

  <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;">&#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%; padding-bottom: 4px;">
          <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;">&#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:EarningsPerShareDiluted" id="Fact_1aabdd08223b4caebb285f5d916de379" contextRef="c20250101to20250331" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_d59214d8ae584a1e957e554c6b39c7eb" contextRef="c20250101to20250331" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.93</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;">
          <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:EarningsPerShareDiluted" id="Fact_8ed197c75da340a3a6411859d57c1e6b" contextRef="c20240101to20240331" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_14f9864fee9249b4a9c5c73faaa62d1b" contextRef="c20240101to20240331" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.98</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;">
          <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: left; text-indent: -9pt; margin-left: 9pt; 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; 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:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_9f417dae912e4189994eada2a8b2d4f7" contextRef="c20250101to20250331" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_cb5b708aa9d54d74894b78084744f61b" contextRef="c20250101to20250331" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">158,735</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;">&#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;">&#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:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_0bfcbfda806d43c4bf1a6393fe6973ab" contextRef="c20240101to20240331" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_f197f87c51c148d586ce6d486cb242e1" contextRef="c20240101to20240331" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">145,538</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;">&#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 style="width: 100%;" class="BRPFPageFooter"></div>

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">4</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="ComprehensiveIncomeQ1"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONDENSED 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 style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">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_915ab404992b41439ff8983bc3d53452" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">146,938</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_e2219f4b91ac4074bf0182268caca6fc" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">142,803</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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized gains (losses) on debt securities, 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_b5442f2d54144714936b29f9dc8919c3" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,630</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_9fdb4ea0ec7d4dc5b1e180547879efb8" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,205</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%; 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;">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_8c488c3b36034e08aa370c9ffb2c6875" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">232</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_3d7f7690411649a3a532188469a6cbe2" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">114</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: 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%; 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;">Comprehensive 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:ComprehensiveIncomeNetOfTax" id="Fact_49ad4947efda47a8b9b2ba8b913e17fd" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">145,076</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:ComprehensiveIncomeNetOfTax" id="Fact_2b15cd4eb3be402a951f50cf88199c7f" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">145,122</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>


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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">5</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="EquityQ1"><!--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;">CONDENSED 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 style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</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; 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;">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; 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;">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; 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;">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; 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;">Total</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; 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;">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; 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;">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; 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;">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; 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;">Equity</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: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at <span style="text-indent: 0pt;">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:SharesIssued" id="Fact_3a9555e88e8e4073b9ff1cc051b93040" contextRef="c20231231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" 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%; 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_f460bd0aff664980870ea8e5e75a1848" contextRef="c20231231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" 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%; 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_d4889378c8d9480b96b3dc528f1eba37" contextRef="c20231231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" 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%; 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_71ece9780b2d4b1d93e020fdbd319709" contextRef="c20231231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" 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>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; 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_e8e4cd7bbb904cd48d998a8bd1f6f2e2" contextRef="c20231231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" 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%; 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_3f376a9efe094721acc6c84a4a71de80" contextRef="c20231231" unitRef="U002" 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%; 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_2d62c0ec11c842a1ae5716602a4b6281" contextRef="c20240101to20240331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" 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_b6a7dd69f2a9463faae2144119abffd9" contextRef="c20240101to20240331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" 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_c64c542925414e8c83eea2321058db98" contextRef="c20240101to20240331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" 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_933de9acdba147e68bfe9bac7c541751" contextRef="c20240101to20240331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">142,803</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 valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;">
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        </td>

  </tr>

  <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>

    <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;">
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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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_45dd7d43b503464f9f0b0c364cd2be8a" contextRef="c20240101to20240331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" 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;">
          <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_d1aabbaae81446b0914967d0f2a70b44" contextRef="c20240101to20240331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" 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_a80b5f0672584087b5268c8be3599f13" contextRef="c20240101to20240331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" 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_3dad36a843ba40378664d3dccc6c0f86" contextRef="c20240101to20240331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">114</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_79cf286844754eb2849b8aa2a0d7b9d1" contextRef="c20240101to20240331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" 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_ad0279baba67468cabe84c403df03aec" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">114</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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_390f101888ea405bbe3d521b6bef7ec4" contextRef="c20240101to20240331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,504</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_f8cbb7d2b6794e98914b4f1d79fa628b" contextRef="c20240101to20240331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" 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%; 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_18e6b18461214b95a98ece00932a9e6d" contextRef="c20240101to20240331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">23,609</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_a4b0547c37454b19887e01e8f1ee7eee" contextRef="c20240101to20240331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" 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_87e0b376b11e4379bb1110dc1932f6bf" contextRef="c20240101to20240331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" 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_02f166611fb34440b8b62bdbb2913a8d" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">23,611</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_4c77ca1fbfed419c9eeb7d55e769dbc0" contextRef="c20240101to20240331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" 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_5f03b992ecab421d944ad01b791d4fbf" contextRef="c20240101to20240331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">31,340</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_11acf54b8adf49129c93405a9a9a35e2" contextRef="c20240101to20240331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" 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_ea1d443af1494feeb9c969facd4cd97a" contextRef="c20240101to20240331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" 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_6698c6866b274e68b2b91954263cd3ea" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">31,340</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 <span style="text-indent: 0pt;">March 31, 2024</span></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;">&#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_ba38bc2ac6c549c19380cdd7d23a7644" contextRef="c20240331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">145,845</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;">&#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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquity" id="Fact_44f1c20930ab40a4840b6a493c0c1c0d" contextRef="c20240331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">146</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;">&#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_8e3ae95fed3948e6aa338f7bcc06a024" contextRef="c20240331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,270,047</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_98d86fa0ae7f464e860e56b84513348e" contextRef="c20240331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">34,964</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_1609172481c04b6fae591dd8d4ed670c" contextRef="c20240331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,938,714</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_a23dd4b0f79747e6a869f76130e772d5" contextRef="c20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">296,515</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: 28%;">&#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>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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: 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 <span style="text-indent: 0pt;">December 31, 2024</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:SharesIssued" id="Fact_32f887af1f384adf8f9fd2b14798a9dc" contextRef="c20241231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" 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%; 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_90db06954a8d4d0ba6e8307a446925cd" contextRef="c20241231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" 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%; 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_d729ddf413884aada9a66c8ba510ae4d" contextRef="c20241231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" 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%; 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_e2545d09515d4485b16e0683e731851a" contextRef="c20241231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" 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%; 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_21ce6f0e307d4eb7ba78a66d3da6e84d" contextRef="c20241231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,249,808</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_7648bfdfbf0940a4bf96a7ce13cf1ad3" contextRef="c20241231" unitRef="U002" 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%; 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_c88d54dc726342e4972eaefd7a051920" contextRef="c20250101to20250331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" 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_9cf891be08ec4be38cb74bb1f2b5f043" contextRef="c20250101to20250331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" 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_cdc09fc9cea84c4bb56bf39a0b0f0bb2" contextRef="c20250101to20250331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" 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_35a1e22e0a16468e980e52ec905cdd6e" contextRef="c20250101to20250331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">146,938</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_f3fb7df78ee84b679a9455a24c8868ed" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">146,938</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 gains, 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_11314cebb76149f4a608afac24ac04b8" contextRef="c20250101to20250331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" 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>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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: 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>
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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;">&#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%;">
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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:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_e0d9b726e3a74e96bb34879db9ea1ac5" contextRef="c20250101to20250331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" 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_3ea72a4068e947c39ec89e6e3d5e6026" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">232</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;">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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_a0997c97f0564e8ebfa4ae2be270a0ee" contextRef="c20250101to20250331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,132</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_3bde1df7dd294f1f8495b7ecf8c23554" contextRef="c20250101to20250331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">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;">&#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_6681378e601142699475f5097b49f5b3" contextRef="c20250101to20250331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,241</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_fbd10a5446f64525ad97dbee65735ca9" contextRef="c20250101to20250331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" 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_dbb0d91398114cd388b84cf9228aaa69" contextRef="c20250101to20250331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" 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_a62772da70e144c280cbb85410455f37" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,242</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_68081df6527740dfa26ec4797ec27aa4" contextRef="c20250101to20250331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" 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_5314ac973db348bb85730f2174126923" contextRef="c20250101to20250331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">30,209</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_2b2724fdff53416ba79dd482f9ac014a" contextRef="c20250101to20250331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" 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_9b47baa9611d4ccbb269f9f88ab523c8" contextRef="c20250101to20250331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" 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_469cc0df4f854f08ad045ffae103da1d" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">30,209</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 <span style="text-indent: 0pt;">March 31, 2025</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_0f0be876932540309deb6071f37c6b70" contextRef="c20250331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">159,041</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_b71c12ae90734864a4463846ddf4a35f" contextRef="c20250331_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">159</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_f4b8bbee549b4d698629eeec3f6d69bc" contextRef="c20250331_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,901,262</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_b92a64b7192841d0ad0df25703888391" contextRef="c20250331_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">28,949</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_1599b9afeae3443694982451aff023a8" contextRef="c20250331_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,396,746</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_e457c14215284c388c791e447980f51c" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">475,726</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 style="width: 100%;" class="BRPFPageFooter"></div>

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">6</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </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;">CONDENSED 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 style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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>

  </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;">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_f7c36546ee144c2c86ebae7331367498" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">146,938</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_a21016941dc0429abc056d42872b32b2" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">142,803</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: 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>

  </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;">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_100d69cecae84cbdad6e81cc7ef52262" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,228</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_8c77ba4be59247e38c94131c141d0abf" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,547</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>

  </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;">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_9e6711269ac449af9f3ea5cf3d5eaa6a" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,587</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_5558af291e4642f9823614e737f072ce" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,465</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;">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_edc8ad178aa7466a8d83a15fca3ea881" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">582</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:AmortizationOfIntangibleAssets" id="Fact_f8039ed914974946804216d314447463" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">639</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;">Amortization of discount on investments, 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:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_246d1c45e9574034a56b56918f85ebb2" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,108</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:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_4aaed7ae1baf412b9dbc761309827e6d" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,257</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: 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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_0996ae3cb47d4deda2a70a7fe98905e0" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,642</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:AmortizationOfFinancingCosts" id="Fact_0c9f58357fb646578e9fa6d8e42f1be2" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,667</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;">Non-cash royalty revenue related to sale of 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:RoyaltyPayments" id="Fact_6292e26423504fc0bd79e28555a6db3c" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,891</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 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: 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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:InterestExpenseRelatedToSaleOfFutureRoyalties" id="Fact_086bf64fac6b4680b15353ddeab54f26" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,670</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: 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%; 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 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;">
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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: 76%;">
          <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 other 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%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ImpairmentOfIntangibleAssetsFinitelived" id="Fact_fe5c9b55fb8549bebb24e58da0204a34" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">133</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;">Changes in operating assets and 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: left; text-indent: -9pt; margin-left: 36pt; 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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:IncreaseDecreaseInContractWithCustomerAsset" id="Fact_16676ffc3ca64894b557287e56466f06" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">52,481</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%;">
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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: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Inventories</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:IncreaseDecreaseInInventories" id="Fact_6cc57db037e24224babb23341491fa27" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,010</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:IncreaseDecreaseInInventories" id="Fact_855e538885814931adc2c6ca522196ff" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">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: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; 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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:IncreaseDecreaseInOtherOperatingAssets" id="Fact_6beef6ad7156442b8b64be1683073767" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,366</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:IncreaseDecreaseInOtherOperatingAssets" id="Fact_6b1b789ac55944df81d7f4361d13837c" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">11,048</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: 36pt; 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;">&#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:IncreaseDecreaseInAccruedIncomeTaxesPayable" id="Fact_7d69cc8201f64afd824b1e83344b7747" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">25,968</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:IncreaseDecreaseInAccruedIncomeTaxesPayable" id="Fact_9dbc7ffee2dd4cec9138f42279355c3a" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">13,869</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <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; text-indent: -9pt; margin-left: 36pt; 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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:IncreaseDecreaseInAccountsPayable" id="Fact_34ff9906c57a488395e8e4d6dd87cd7c" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">92</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:IncreaseDecreaseInAccountsPayable" id="Fact_eece7264c05e421188bbeb013f920e4b" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">59</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: 36pt; 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%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_5f5c568dfefd46649d7f965b7bc2f695" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">43,039</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:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_e29dcd8047ff491884c92796c96013cb" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">46,190</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: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued liabilities and 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%;">
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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>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; 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;">
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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;">
          <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;">
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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;">
          <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: 54pt; 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;">&#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>

    <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;">
          <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;">&#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; font-weight: bold;">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>

  </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;">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_083200534ca3433a9d3c58296e5b5402" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">311,068</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:PaymentsToAcquireAvailableForSaleSecuritiesDebt" id="Fact_50e0b935822448d399c6da50df573ca5" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">519,001</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: left; text-indent: -9pt; margin-left: 36pt; 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_421423d1ea9a4d73aef63e7e59de4afb" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">494,755</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_6dc4fafd64864e3188177206b20e21e5" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">600,836</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: 36pt; 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_5c4c86b4988a4bcc93f568312cf27532" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,577</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_23746708bcf2482183689f1b17ed01be" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,493</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: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Acquisition of licenses and other assets, net</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:PaymentsToAcquireIntangibleAssets" id="Fact_bedfe0d50deb453aac9adee6a16b847b" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">651</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:PaymentsToAcquireIntangibleAssets" id="Fact_2503d109e9bf429abba6e180534abb50" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,237</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: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash provided by investing 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;">
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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:NetCashProvidedByUsedInInvestingActivities" id="Fact_98c358a7d9cc4f7dbda064764db082d3" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">76,105</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%;">&#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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from issuance of common stock through equity 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 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;">
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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 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>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; 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 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: 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;">&#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; 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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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;">
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        </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;">&#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;">Net increase (decrease) in cash and cash equivalents</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_381c34e8f196433d88bcc5a40e6d5ead" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">22,115</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_695ef20670484629abffb58a97885612" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">50,377</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%; 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;">Cash and cash equivalents at beginning of period</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_f005ffe7399e4372b86484b39e4de899" contextRef="c20241231" unitRef="U002" 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: 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_3210509ecac84ed4b36943c090a6ebe7" contextRef="c20231231" unitRef="U002" 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>

  </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;">Cash and cash equivalents at end of period</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_22fc70baf81348a4bed7f3a0cca2d925" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">264,192</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_26348b07f1404eb2b971660219ce0e2f" contextRef="c20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">348,889</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: 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;">&#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; font-weight: bold;">Supplemental disclosures of cash flow information:</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: 36pt; 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_1c0954c400a1482b8ec42df7704e2f57" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">92</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_99a9e46f9bbe4846a09670f406e934e7" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">95</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: 36pt; 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_e1a1dc9fdd464c8d8c36512a7e6251fb" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">400</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_85ce33dc7db749c6bac7ae7eadc1d4ee" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">13</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;">&#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>

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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; font-weight: bold;">Supplemental disclosures of non-cash investing and 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%;">&#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: 36pt; 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_e747862ab08345fcae14d5a69abc90c7" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">460</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_b758276d9ff04fe0a8e9a80dd38bfae6" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">924</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>
  <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>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">7</span></div>

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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

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  </div>

  <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 CONDENSED CONSOLIDATED FINANCIAL STATEMENTS</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2025</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Unaudited)</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;">1.&#160; Organization and Basis of Presentation</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;">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 initial public offering, we reorganized as a Delaware
    corporation in April 1991. We are a leader in the discovery and development of RNA-targeted therapeutics.</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;">Basis of Presentation</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepared the unaudited interim condensed consolidated financial statements for the three months ended&#160;March 31, 2025 and 2024 on the same basis as the audited financial statements for the year ended December 31, 2024. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at
    such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these
    financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2024
    included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</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 condensed 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; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We operate as a <span style="-sec-ix-hidden:Fact_716d7f6d27dd450bb3559e4e755739ee">single</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</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 <span style="-sec-ix-hidden:Fact_95a745ba91854ab0bbf27d495728685c">single</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>operating segment. Refer to Note 14, <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: justify; text-indent: 36pt; 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We prepare our condensed consolidated financial statements in
      conformity with accounting principles generally accepted in the United States, or </span>U.S., that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying
    notes. Actual results could differ from our estimates.</div>
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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;">2.&#160; 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;">Below, we have included our accounting policies for revenue recognition related to product sales, net and cost of sales as a result of our
    launch of TRYNGOLZA in the U.S. Our other significant accounting policies have not changed substantially from those included in our Annual Report on Form 10-K for the year ended December 31, 2024.</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;">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; font-style: italic;">Product Sales, Net</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 revenue from product sales when the customer obtains control of our product in the amount of the transaction price, which is
    the amount that reflects the consideration which we expect to receive. We estimate reserves for variable consideration related to applicable discounts, rebates, chargebacks and other allowances included in our agreements with customers, payors and
    other third parties. We include the amount of variable consideration in the transaction price to the extent that it is probable that a significant reversal in the amount of the cumulative revenue recognized will not occur in a future period. If actual
    results vary significantly from our estimates, we adjust our estimates in the period that we become aware of such variances.</div>
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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">8</span></div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
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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;">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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales for a newly launched product, such as TRYNGOLZA, does not include the full cost of manufacturing until we manufacture and
    sell additional inventory after exhausting pre-launch inventory, which we previously recorded as research and development, or R&amp;D, expense.</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;">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 Accounting Standards Codification, or ASC, Topic 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. We adopted the reporting requirements in our 2024 Annual Report on Form 10-K and in this Quarterly Report on Form 10-Q for the first quarter of 2025. Refer to Note 14, <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: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any recently issued accounting standards other than those included in our Annual Report on Form 10-K for the year ended December 31, 2024 to have a material impact to our financial results.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3. Supplemental Financial Data</div>
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<div style="text-align: justify; margin-left: 36pt; 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 inventories consisted of the following (in thousands):</div>
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    <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;">March 31, 2025</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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        </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" 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;">
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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; 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>
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    <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 valign="bottom" style="vertical-align: bottom; width: 76%; white-space: nowrap;">
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        </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;">
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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%; 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;">
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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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    <td valign="bottom" style="vertical-align: bottom; width: 76%; 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; 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;">
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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; 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;">
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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>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; white-space: nowrap;">
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        </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;">
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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>

    <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>
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    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;">
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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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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our accrued liabilities consisted of the following (in thousands):</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; 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;">March 31, 2025</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;">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: 76%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: justify; 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; 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="ions:AccruedClinicalExpenses" id="Fact_9fa65e9eb4874e529d2b5a8558dbeefc" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">67,614</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; 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="ions:AccruedClinicalExpenses" id="Fact_e1554d35bd0e4c82aabac0d765ba6ddc" contextRef="c20241231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">77,436</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%; white-space: nowrap;">
          <div style="text-align: justify; 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%; 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="ions:AccruedInLicensingFeesCurrent" id="Fact_c222f622055145968e8cd08ff3a569bd" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,374</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="ions:AccruedInLicensingFeesCurrent" id="Fact_7076c86dd1604e5a826b9716b8c0ca6e" contextRef="c20241231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,951</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; white-space: nowrap;">
          <div style="text-align: justify; 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; 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="ions:AccruedCommercialExpensesCurrent" id="Fact_74d1a19cf230440593ea60ac85e2acd3" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,257</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="ions:AccruedCommercialExpensesCurrent" id="Fact_0c409149156e4e1bb3090f026e0406df" contextRef="c20241231" unitRef="U002" 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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; white-space: nowrap;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; 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; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAccruedLiabilitiesCurrent" id="Fact_9ed0b35c739e48bbb51027c4ea2073ae" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,490</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; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAccruedLiabilitiesCurrent" id="Fact_b95beacb8e88464e9674b3d0a46cdaf4" contextRef="c20241231" unitRef="U002" 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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: justify; margin-left: 28.45pt; 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; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 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; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_eda2e67f42534d11b5f9b63e05969ad1" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">102,735</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; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 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; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_e41fd559b7f64fab9ce5f7f42569b6db" contextRef="c20241231" unitRef="U002" 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>

  </tr>


</table>
</ix:continuation></ix:continuation></div>

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

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">9</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>
<div><ix:nonNumeric name="us-gaap:RevenueFromContractWithCustomerTextBlock" id="Text_6b1d63434c574c6a8112cdba1e5b15e3" contextRef="c20250101to20250331" escape="true" continuedAt="Text_e4cec36646b54e48956b38d7a1624ccd1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4. Revenues</div>
</ix:nonNumeric>

  <ix:continuation id="Text_e4cec36646b54e48956b38d7a1624ccd1" continuedAt="Text_e4cec36646b54e48956b38d7a1624ccd2">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_e4cec36646b54e48956b38d7a1624ccd2" continuedAt="Text_e4cec36646b54e48956b38d7a1624ccd3"><ix:nonNumeric name="us-gaap:DisaggregationOfRevenueTableTextBlock" id="Text_f2e15c2700584bae9782b0e80d3a26fc" contextRef="c20250101to20250331" escape="true" continuedAt="Text_efaf28603d57447899140b7d705c9be81">
<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 three months ended March 31, 2025 and 2024, our revenues were comprised of the
    following (in thousands):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_e4cec36646b54e48956b38d7a1624ccd3" continuedAt="Text_e4cec36646b54e48956b38d7a1624ccd4"><ix:continuation id="Text_efaf28603d57447899140b7d705c9be81" continuedAt="Text_efaf28603d57447899140b7d705c9be82">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_e4cec36646b54e48956b38d7a1624ccd4" continuedAt="Text_e4cec36646b54e48956b38d7a1624ccd5"><ix:continuation id="Text_efaf28603d57447899140b7d705c9be82">
<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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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;">
          <div style="text-align: left; 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;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net:</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%; 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;">TRYNGOLZA sales, net</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b9351c771646484f8cb63156d51b63e6" contextRef="c20250101to20250331_ProductOrServiceAxis_TryngolzaMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,287</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_f3370003dfee465c8e3078cbdd9f84bb" contextRef="c20240101to20240331_ProductOrServiceAxis_TryngolzaMember" unitRef="U002" 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: 76%;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total product sales, 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_bde0da5f45ea483b98a3a261adf52a2b" contextRef="c20250101to20250331_ProductOrServiceAxis_ProductMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,287</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_d421bd393d1a43ab90a50dfac8c0c58d" contextRef="c20240101to20240331_ProductOrServiceAxis_ProductMember" unitRef="U002" 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: 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;">Royalty 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: -9pt; 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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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_760152c1d68145f7b3c9e9065b377e3e" contextRef="c20250101to20250331_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">48,010</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_7c522503a2114fd88228be49c21d4681" contextRef="c20240101to20240331_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">38,455</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: 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%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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_74b296ccf3564739966276d34274679c" contextRef="c20250101to20250331_ProductOrServiceAxis_WainusRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,372</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_3eaa1ec789ed4ed4bcdfb728c7348a74" contextRef="c20240101to20240331_ProductOrServiceAxis_WainusRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,125</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: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other royalties</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_ff7a496cc61f4d608b19affee2de913c" contextRef="c20250101to20250331_ProductOrServiceAxis_OtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,784</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_328f8b46c22146a8abafd77fdc79961a" contextRef="c20240101to20240331_ProductOrServiceAxis_OtherRoyaltiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,805</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; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total royalty 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_f90f645b7153432fb5c56bdfa6922893" contextRef="c20250101to20250331_ProductOrServiceAxis_RoyaltyMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">64,166</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_35aabd37fde34dafbf6fa7b8a4fa61ca" contextRef="c20240101to20240331_ProductOrServiceAxis_RoyaltyMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,385</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: -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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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: 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%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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_1ae98644c2cf4e8c9555955cd21da71d" contextRef="c20250101to20250331_ProductOrServiceAxis_TegsediAndWaylivraMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,715</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_c76fa406a67f4f26a5425e463085552d" contextRef="c20240101to20240331_ProductOrServiceAxis_TegsediAndWaylivraMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,628</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#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;">Other 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_d66d5751b4974402ae17bf5fb24a9d16" contextRef="c20250101to20250331_ProductOrServiceAxis_OtherMember" unitRef="U002" 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_abdf2838a31048fa87ef2cc948b78a78" contextRef="c20240101to20240331_ProductOrServiceAxis_OtherMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,580</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: 2px; background-color: #CCEEFF;">
          <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; 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_213340fa359148a4bf0f05e01b08ab45" contextRef="c20250101to20250331_ProductOrServiceAxis_OtherCommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,715</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_c0124bdd3a6744868a4c4a1681fdc0ca" contextRef="c20240101to20240331_ProductOrServiceAxis_OtherCommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,208</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%;">
          <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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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_0b2734c53e014b07a919ab78916cc9dc" contextRef="c20250101to20250331_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">76,168</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_a5b9ecb6664346608f528122253efd24" contextRef="c20240101to20240331_ProductOrServiceAxis_CommercialMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">59,593</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;">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>

  </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;">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_c9c2044706e443229a4d1710320d2cab" contextRef="c20250101to20250331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">45,031</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_29313697fc374437aad276febede3fb5" contextRef="c20240101to20240331_ProductOrServiceAxis_CollaborativeAgreementRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,345</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%; padding-bottom: 2px; background-color: #CCEEFF;">
          <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; 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_9f171df7f70c48bdb2f8eefd093963e5" contextRef="c20250101to20250331_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,413</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_17bdbaaed9b948c5a92a548ffe151612" contextRef="c20240101to20240331_ProductOrServiceAxis_WainuaJointDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,559</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: 2px;">
          <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;">&#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_130654354eff4c6eb5fe4539fe1d3a9e" contextRef="c20250101to20250331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">55,444</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_2d5c1f893e844b1fa3430a1f32fbb5cf" contextRef="c20240101to20240331_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">59,904</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: 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: 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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5b1cf3ec1cb84c15887154107b2bc1fe" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">131,612</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:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_b41ed6d4cfdf4a78b725e5bf556da9ba" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">119,497</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>


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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;">Revenue Sources</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 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; font-style: italic;">Commercial Revenue</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2024, the U.S. Food and Drug Administration, or FDA, approved TRYNGOLZA (olezarsen) for the treatment of familial
    chylomicronemia syndrome, or FCS. Following the approval, we launched TRYNGOLZA and began earning revenue from TRYNGOLZA sales. We recognize product sales, net of variable considerations related to applicable discounts and allowances, when the customer
    obtains control of our product.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn royalty payments primarily on net sales of SPINRAZA, WAINUA and QALSODY.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn commercial revenue from TEGSEDI and WAYLIVRA sales under our distribution agreements with Swedish Orphan Biovitrum AB, or Sobi. In
    addition, we receive royalties from PTC Therapeutics International Limited, or PTC, for TEGSEDI and WAYLIVRA sales. 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>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 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; 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><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
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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 that may involve 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></span> 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.</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></span> We
    consider milestone payments to be variable consideration and include them 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.</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.</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></span> 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.</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_183ad00f1c244f45887d306ae2c90532" contextRef="c20210101to20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment in 2021.</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 Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808, and identified <ix:nonFraction name="ions:NumberOfMaterialComponents" id="Fact_784abf7441294980aecea5f51a0b2271" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U006" 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 Topic 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>, or ASC 606, for the license we granted to AstraZeneca and as a result we had <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_e6fe35aa87e44a3b876a21faaa5a2140" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U007" 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_213c3fa8f5f94eada5849b6952e3bf1d" contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember" unitRef="U002" 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_2a080dd76c62479d99491c48185ab4bd" contextRef="c20250101to20250331_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 selling, general and administrative, or SG&amp;A, expense and R&amp;D expense, respectively.</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;">Swedish Orphan Biovitrum AB (Sobi)</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;">Under our distribution agreements with 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>
</ix:continuation></div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:CollaborativeArrangementDisclosureTextBlock" id="Text_80736ca15cff42788a97f47831eeb088" contextRef="c20250101to20250331" escape="true" continuedAt="Text_4bbcfd51c22e4f4897c3067ad261d6ed1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; Collaborative Arrangements and Licensing Agreements</div>
</ix:nonNumeric>

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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;">Below, we have included our Ono collaboration, which is the
      only collaboration that had either substantive changes or was new from those included in Part IV, Item 15, Note 4, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and
      Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024.</span></div>
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<div><br/>
  </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;">Ono</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 March 2025, we entered into an agreement with Ono Pharmaceutical, Ltd, or Ono, to develop and commercialize sapablursen, an
    investigational RNA-targeted medicine for the potential treatment of polycythemia vera, or PV, a rare and potentially life-threatening hematologic disease. We are responsible for completing the ongoing Phase 2 IMPRSSION study, while Ono will be solely
    responsible for subsequent development, regulatory filings and commercialization of sapablursen.</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;">Over the term of our sapablursen collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_aede8b9ef220439980fe3002bfb04d1c" contextRef="c20250331_TypeOfArrangementAxis_OnoCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">940</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" id="Fact_cf4f7782dc2e4bd1bbf88508bc23dd48" contextRef="c20250331_TypeOfArrangementAxis_OnoCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">280</ix:nonFraction> million upfront payment and up
    to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_68281c2f896147ed83de58ec367ded6b" contextRef="c20250331_TypeOfArrangementAxis_OnoCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">660</ix:nonFraction> million in development, regulatory and sales milestone payments. In addition, we are eligible to receive royalties in the mid-teen
    percentage range on net sales.</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 April 2025, we achieved a $<ix:nonFraction name="ions:UpfrontPaymentAchieved" id="Fact_c07cd0091879446c949a49812609acb6" contextRef="c20250401to20250430_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_OnoCollaborationMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">280</ix:nonFraction>
    million upfront payment when this transaction received clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, or HSR Act.</div>
</ix:continuation></div>

  <div><br/>
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<div><ix:nonNumeric name="us-gaap:EarningsPerShareTextBlock" id="Text_e075129cfb9942b3964291d17e5f7c43" contextRef="c20250101to20250331" escape="true" continuedAt="Text_570c6b73c5eb412ba96e2bac796a1e431">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6. Basic and Diluted Net Loss Per Share</div>
</ix:nonNumeric>

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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; font-weight: bold;">Basic net loss per share</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 calculated our basic net loss per share for the three months ended&#160;March 31, 2025 and 2024 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_570c6b73c5eb412ba96e2bac796a1e435" continuedAt="Text_570c6b73c5eb412ba96e2bac796a1e436"><ix:continuation id="Text_3052dac0f9094361bab3f48a12eda4763" continuedAt="Text_3052dac0f9094361bab3f48a12eda4764">
<div><br/>
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  <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div style="width: 100%;" class="BRPFPageFooter"></div>

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">12</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>
<div><ix:continuation id="Text_570c6b73c5eb412ba96e2bac796a1e436" continuedAt="Text_570c6b73c5eb412ba96e2bac796a1e437"><ix:continuation id="Text_3052dac0f9094361bab3f48a12eda4764" continuedAt="Text_3052dac0f9094361bab3f48a12eda4765">
<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;">Diluted net loss per share</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;">For the three months ended&#160;March 31, 2025 and 2024, 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>
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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">


  <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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c986c01cbb444066a7e824267b553c63" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_3a2083716ddd4730819016cdb82da19b" contextRef="c20240331_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_c00629b9d05c48cb8f16fd43debe6951" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_571c26f266cf4c0e951650343e51e1c9" contextRef="c20240331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction></ix:nonFraction>% Notes;</div>
        </td>

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</table>
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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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8b907fce034b4f1badde44a8fb62a0b6" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2b7cd2d9d34345fc9c896a1aa0b9ffed" contextRef="c20240331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction> percent convertible senior notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_44599631b354431d83fbafd427b84a2e" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_0ea297d0210a42d9a665d5dda26140b2" contextRef="c20240331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction>% Notes;</div>
        </td>

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</table>
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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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_cbe2bcc4c3d14b47bcbdeabac6ac057d" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b7898ddbacfc4ae1946b18f1568fd7cf" contextRef="c20240331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction>% Notes;</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;">Dilutive stock options;</div>
        </td>

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  <ix:continuation id="Text_570c6b73c5eb412ba96e2bac796a1e4314" continuedAt="Text_570c6b73c5eb412ba96e2bac796a1e4315"><ix:continuation id="Text_3052dac0f9094361bab3f48a12eda47612" continuedAt="Text_3052dac0f9094361bab3f48a12eda47613">
<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;">Unvested restricted stock units, or RSUs;</div>
        </td>

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</table>
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  <ix:continuation id="Text_570c6b73c5eb412ba96e2bac796a1e4315" continuedAt="Text_570c6b73c5eb412ba96e2bac796a1e4316"><ix:continuation id="Text_3052dac0f9094361bab3f48a12eda47613" continuedAt="Text_3052dac0f9094361bab3f48a12eda47614">
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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;">Unvested performance restricted stock units, or PRSUs; and</div>
        </td>

  </tr>


</table>
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  <ix:continuation id="Text_570c6b73c5eb412ba96e2bac796a1e4316" continuedAt="Text_570c6b73c5eb412ba96e2bac796a1e4317"><ix:continuation id="Text_3052dac0f9094361bab3f48a12eda47614" continuedAt="Text_3052dac0f9094361bab3f48a12eda47615">
<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;">Employee Stock Purchase Plan, or ESPP.</div>
        </td>

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</table>
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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;">For the three months ended&#160;March 31, 2024, common stock underlying the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_965e7ceb15d04eb491c6aca5bc86c0da" contextRef="c20240331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</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_5af03faa08274640af951818052bae98" contextRef="c20240331_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</span>, and n<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ote hedges related to the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4ff5b7e64da94403bac303957becd85b" contextRef="c20240331_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 </span>would also have had an anti-dilutive effect on net loss per share.</div>
</ix:continuation></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;">Additionally, as of March 31, 2025
    and 2024, we had warrants related to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9677a118662748d9a1a4c288ec8df0bd" contextRef="c20240331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_79673f01eb3f4d0f8cc2a2ee82ba16a8" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction>%
    and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1e03cef7d5634d66bd83b2797fbacdda" contextRef="c20240331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8b9684e867694bc788bcce48cf27b9cb" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction>% Notes outstanding. 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.</div>
</ix:continuation></ix:continuation></div>

  <div><br/>
  </div>
<div><ix:nonNumeric name="us-gaap:InvestmentTextBlock" id="Text_9c14342eb23f428ab65b1e5fc1fe2953" contextRef="c20250101to20250331" escape="true" continuedAt="Text_2b9b411c5a6b443bb4e39eb008ff8ecb1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7.&#160; Investments</div>
</ix:nonNumeric>

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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;">The following table summarizes the contract maturity of the available-for-sale securities we held as of March 31, 2025:</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_2b9b411c5a6b443bb4e39eb008ff8ecb3" continuedAt="Text_2b9b411c5a6b443bb4e39eb008ff8ecb4"><ix:continuation id="Text_22ef57927bd9419185054bc5124b80a31" continuedAt="Text_22ef57927bd9419185054bc5124b80a32">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_2b9b411c5a6b443bb4e39eb008ff8ecb4" continuedAt="Text_2b9b411c5a6b443bb4e39eb008ff8ecb5"><ix:continuation id="Text_22ef57927bd9419185054bc5124b80a32">
<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: left; 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_4b3282e6abbf4694b90d56a12cb3a78d" contextRef="c20250101to20250331" 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_26a36804df4340729bec0b2f463acda4" contextRef="c20250331" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">67</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%;">
          <div style="text-align: left; 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_3bd993e525784a5398b297b7856fe228" contextRef="c20250101to20250331" format="ixt-sec:durwordsen">one year</ix:nonNumeric></span>
            but within <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_beb1ea76eb4a4045aff26b90fc4a4ee3" contextRef="c20250101to20250331" format="ixt-sec:durwordsen">two years</ix:nonNumeric></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="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" id="Fact_b3c2ee50dd694d208197df43360458a9" contextRef="c20250331" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">27</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; 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_812c571149d64b329fe4410606d76c7a" contextRef="c20250101to20250331" format="ixt-sec:durwordsen">two years</ix:nonNumeric></span>
            but within <span style="text-indent: 0pt;"><span style="-sec-ix-hidden:Fact_f12cc57cfa544d218ac6c26f9aae5797">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_8cd01e7f5688446294ec6f1b2d7e38df" contextRef="c20250331" 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%; border-bottom: #000000 solid 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; 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;">&#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="ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" id="Fact_6217a171f5784696968b178278e97ffa" contextRef="c20250331" 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%; border-bottom: #000000 double 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_2b9b411c5a6b443bb4e39eb008ff8ecb5" continuedAt="Text_2b9b411c5a6b443bb4e39eb008ff8ecb6">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_2b9b411c5a6b443bb4e39eb008ff8ecb6" continuedAt="Text_2b9b411c5a6b443bb4e39eb008ff8ecb7">
<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 March 31, 2025,
    <ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="Fact_ecfa1cb8a4484b48a192e8436b1431fe" contextRef="c20250331" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">94</ix:nonFraction> percent of our available-for-sale securities had a maturity of less than <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_34c87d75876e42c988ffebc06f56b6a3" contextRef="c20250101to20250331" format="ixt-sec:durwordsen">two years</ix:nonNumeric>.</div>
</ix:continuation>
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<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;">All of our available-for-sale debt 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>
</ix:continuation>
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<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;">We invest in debt securities</span> 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>
</ix:continuation>
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<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;">At March 31, 2025, we had an
    equity ownership interest of less than 20 percent in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_b7edbc55e46842cb916a4ced56279788" contextRef="c20250331" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">seven</ix:nonFraction> private companies and <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_8144a98eb4174391a5f3065f3f804da4" contextRef="c20250331" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> public companies with which we conduct business.</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation></div>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">13</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>
<div><ix:continuation id="Text_2b9b411c5a6b443bb4e39eb008ff8ecb14" continuedAt="Text_2b9b411c5a6b443bb4e39eb008ff8ecb15"><ix:nonNumeric name="us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock" id="Text_6d9fa3e82c0142dbb746fb5a3a6dc3c0" contextRef="c20250101to20250331" escape="true" continuedAt="Text_c2023e456ccb4bc891feb4b8c7d977eb1">
<div style="display:none;"><br/></div>
<div style="text-align: left; 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>

  <ix:continuation id="Text_2b9b411c5a6b443bb4e39eb008ff8ecb15" continuedAt="Text_2b9b411c5a6b443bb4e39eb008ff8ecb16"><ix:continuation id="Text_c2023e456ccb4bc891feb4b8c7d977eb1" continuedAt="Text_c2023e456ccb4bc891feb4b8c7d977eb2">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_2b9b411c5a6b443bb4e39eb008ff8ecb16" continuedAt="Text_2b9b411c5a6b443bb4e39eb008ff8ecb17"><ix:continuation id="Text_c2023e456ccb4bc891feb4b8c7d977eb2" continuedAt="Text_c2023e456ccb4bc891feb4b8c7d977eb3">
<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; text-indent: 6.5pt;">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; padding-bottom: 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;"><span style="text-indent: 0pt;">March 31, 2025</span></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;"><span style="text-decoration: underline;">Available-for-sale debt securities:</span></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_7842515e18104a5cafcff84ddb01d951" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">516,458</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_c7e1b54bc6f94cda93f41712a4a9675c" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">299</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_6987932b0c734a95908cba3dde93f730" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">247</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_35d357c29e5b420daf82588703d78d8d" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">516,510</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%;">
          <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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_80e0d5c6be1c4870adc06685000bf257" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">120,961</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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_18ba7ad7166c418da8278eb1c1894a6f" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">156</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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_e9cc451da55c4d1c9aa3ad82c7ca9aae" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">32</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:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_9e8a5c54173d453cb9fb728033354336" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">121,085</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: 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_17f5c15fd8fe452b890ee866cfaa6b85" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">592,770</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_45e8bcb24cc241f2bf8f293a9b67a6a6" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">393</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_36dcce36e9b446bcb8f2877352fd5851" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">270</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_cf007fb70961423eb9a3dd191872008b" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">592,893</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;">
          <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;">&#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:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_7c05793868aa4afb94fcfb88fcffcb2b" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,072</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="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_6c641805a540462f9d84d76f2727c1e9" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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; 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="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_3e3856bd21754e01ab011686088d0aa5" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_893fcba0e0004d12b5940266add3822a" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,074</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: 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;">Total debt 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_3e165eb36915445a94e7bca3626be047" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,233,261</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_3c026731cf6c4d2c9f3bb6487eb52874" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">850</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_cbaf34a8cf1344ed8d1c9bd3764052c6" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">549</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_401ef7ec0ee84b33b734c6646f73945d" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,233,562</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%;">
          <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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_e739ce406a594fdab205b3f709378b35" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">471,479</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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_1465e0f748cd4bfaa10d9f2bc25757c3" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,086</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%;">
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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: 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_4069992e62e44ec39ab5806e1ac879fa" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,184</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_13b8b3118986468c94cef784db3d7d85" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">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="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_8c034ba7ebd94e519637bf63e04e1b9f" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">116</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_907c5df34a09413bb109221fad1ea266" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,256</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%;">
          <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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_e43e28c5271b42a889a3b5a4967cc28d" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">145,922</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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_4a47ab58cf674aa491198b0931ea7362" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">373</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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_54bac431fed2433b9abbb4c98f4e8737" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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%; 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:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_df46987f0ff442a68229243874a3a796" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">146,243</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: 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 states of the U.S. and political subdivisions of the 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;">&#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_88a5ddd88e4d45979b29d5e42040f8ce" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,595</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_fffdb004d982451bbdc6a1254b8b201a" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">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;">&#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_d27fe9b01df44e7d9bcca3a7840176d2" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_8bb4f05a1a2544ecab43d40e22579301" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,596</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt</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:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_cb13a0fbf7da419aa2956a471586d40f" contextRef="c20250331_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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; 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="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_3cf7a3b606b84892b6f3a24b1eba24ad" contextRef="c20250331_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_9b71aeb61a58417fae78f0d86286fca1" contextRef="c20250331_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_4a6c1956934848aea2e997bb1f305eef" contextRef="c20250331_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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; 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;">Total debt 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: #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_2b2ee63d727e423482b317c18a37ce81" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">680,878</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_22456af2bd1a42a5aaa84149b3a6373e" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,648</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_3f93907b739e4f8a80f71070bbbc98e2" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,177</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_33930b14001f46ccb9bf26b44f06a253" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">681,349</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;">
          <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 debt securities</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;">
          <div style="font-family: '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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_c63efe923e13426992c34154ca0ceb66" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,914,139</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;">
          <div style="font-family: '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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_4d9475d7048b443985ccf0e54c482dde" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,498</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;">
          <div style="font-family: '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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_abe680e773e045d898d7e780327a8001" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,726</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;">
          <div style="font-family: '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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_ed64a9779a3842959199d38607dc68f6" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,914,911</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: 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;"><span style="text-decoration: underline;">Equity securities:</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;">&#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>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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: 52%;">
          <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%;">&#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:EquitySecuritiesFvNiCost" id="Fact_795298199a7149089987fd608d910788" contextRef="c20250331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" 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%; 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="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_95a1e63d6d4c49f48092f55cc7344a6f" contextRef="c20250331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">41</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="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_720e14f204184668ac412128829c1d4c" contextRef="c20250331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,856</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:EquitySecuritiesFvNi" id="Fact_c9668cdfca24444facba84f5586a8b21" contextRef="c20250331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,082</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: 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;">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: #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:EquitySecuritiesFvNiCost" id="Fact_642c9681829a411280b706605512aec4" contextRef="c20250331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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: #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:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_5465f26f407f4c8cbf1a7f4bc78d58bb" contextRef="c20250331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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: #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:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_8f26e7f4482346919fb9fd971a0e1bd2" contextRef="c20250331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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: #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:EquitySecuritiesFvNi" id="Fact_c86ece7c238c409db75f4e86d57eaa03" contextRef="c20250331_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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: #CCEEFF; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 9pt; 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;">&#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:EquitySecuritiesFvNiCost" id="Fact_74700e6175be499286aad7c1da529560" contextRef="c20250331" unitRef="U002" 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; 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="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_023010caa8f343509b0246de63732628" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,042</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="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_b4350186c9724e47b1cac8c01c4216b9" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,949</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:EquitySecuritiesFvNi" id="Fact_10dc545d20404abda7146b5a706c0e00" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">44,105</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: 52%; padding-bottom: 4px; 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 debt and equity securities</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:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_6c45e37635ae4e82a8fe9a524ce7bc4f" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,949,151</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:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_5ab4e59a3fb946b2bfa63a42fd6cc9c5" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,540</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:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_571cea17cf8743fbb59b7749cbf08cd2" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,675</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="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_29d056dd0bc546a5b95f13a73db1588f" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,959,016</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>
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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">14</span></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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    <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>

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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; 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>
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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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          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">December 31, 2024</span></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; 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>
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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; 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>
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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; 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>

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  <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;"><span style="text-decoration: underline;">Available-for-sale debt securities:</span></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_b358568c049541b1856e64106205b629" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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_870aab605dd4403c879855738490612a" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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_e219351c2ba44027b99a7eb94f4fb4bd" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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_baf860337cb14231b2612b277c5a61c8" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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%;">
          <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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_68fdb285d5a54bedba4551932330f29f" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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%; 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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_90dbffe642224d96bbf19226414d77d9" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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%; 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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_1777d6b10a6444f78df8d692409a590a" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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%; 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:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_2130cf6d51914dc0afd1eccb0e4dfdad" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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%; 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_d8fc413c165c4a2c8aa4472257c08e29" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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_c7bb5d4884cd42d0a8a8ff87cdcd691a" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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_32a3a41f82bb44c799d99e85af07437d" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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;">
          <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_4ed162913c2d4a49b2bae214aa82a90e" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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;">
          <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;">&#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:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_e6152f86899e46e196de685960cf0520" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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; 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="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_976e0d2fac214a4a8ce8d68be3812eda" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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; 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="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_e332742abab244fa8bc1de590d821dcc" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_072984a5e1e94320b84fd889d20ca860" contextRef="c20241231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; 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:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_5d62eb1de663460d8a9d559d81878a58" contextRef="c20241231" unitRef="U002" 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_32d0c20dd09a4965be6545f5ef1e1d0e" contextRef="c20241231" unitRef="U002" 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_a65f661f76de418c8ded0d80f7684b50" contextRef="c20241231" 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; 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_5269f1e3ba9b4b5f9397e201edccca32" contextRef="c20241231" unitRef="U002" 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%;">
          <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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_a2fd30f9900b415194cd94d357af784b" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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%; 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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_34ab02ad304f441abe8a81962651c7ce" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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%; 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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_3d4b4abb3a29485786b07cbc63b828cb" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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%; 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:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_e00dab3b4cb04062a2e6a17f853d0e52" contextRef="c20241231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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%; 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_d714f0d4eecc4d92b9b830449bba7fd1" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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_270ced43418a4c2faa9a7f0a3bd756eb" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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_cc8c6fd4825a4a8ca13fdce32ea0a599" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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_11b446490081470aa73bc2871b0b1042" contextRef="c20241231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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%;">
          <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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_e8d68ba6fad84cecafc9cdd32dea1e2f" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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%; 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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_28fa2a9aa6c3425bb5c7af4315f2d4c3" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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%; 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:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_feb5ebb376f64b648a49adafb20944f7" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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%; 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:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_5a7c49cad6044951b9d764adb62179ca" contextRef="c20241231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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%; 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_6c8de04190604570ba67ddf11625d813" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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_8855a6653fd54ca4bb41a1592144ebb7" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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_b2ac226289334d138e0788d2a825f1cf" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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_c641136d180141e99a3d139db97e3f98" contextRef="c20241231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt 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;">&#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:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_d8f9bd55d10c46e8a7923b828bf66f7b" contextRef="c20241231" unitRef="U002" 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; 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="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_9edb30f88d124e4f98e5fc6733baa317" contextRef="c20241231" unitRef="U002" 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; 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="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_35b1772ea2884933bfa48eab5441097a" contextRef="c20241231" unitRef="U002" 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; 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:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_bd78e79378ff4eecb24ada86ee7d4685" contextRef="c20241231" unitRef="U002" 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; 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 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;">
          <div style="font-family: '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_d8842e093daf4aa8a441e191da86ea99" contextRef="c20241231" unitRef="U002" 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_4a16a27e0c4144fea9d33948c111d40b" contextRef="c20241231" unitRef="U002" 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_5d60bf6074c241728013af9aebe4f553" contextRef="c20241231" unitRef="U002" 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_282a1da5440143508a579978a45d2601" contextRef="c20241231" unitRef="U002" 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%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</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%;">&#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>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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: 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_b8a712e5f4af42cdb9018ff5937f5e79" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" 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_8b35758c336d4c378e03fdeaeaa046d7" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" 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_d23a46f787e04e259237398f99054fea" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" 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_8651c4c7cf0b40ec9603b79cfd50d43b" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" 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;">
          <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;">&#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:EquitySecuritiesFvNiCost" id="Fact_2faff3973c0f4ab0bd4fcffd3307bce8" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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; 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="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_e3dee8ea479d4e8fbda5e68ba7814a7e" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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; 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="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_53a829bbd230481e83c9e355f575a8b7" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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; 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:EquitySecuritiesFvNi" id="Fact_90b3f028c4c64df180eb902de39038aa" contextRef="c20241231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U002" 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; 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;">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;">&#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:EquitySecuritiesFvNiCost" id="Fact_cfbea931b88e4baf9112a7e54d02cbfc" contextRef="c20241231" unitRef="U002" 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;">&#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:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_5e7e8a83411f4b40bf00d16a3e60d487" contextRef="c20241231" unitRef="U002" 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;">&#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:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_d45ad7a12cac403ea2d5a2edb37a0eed" contextRef="c20241231" unitRef="U002" 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;">&#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_8bd47c89fd1645cfa78adda562a9364e" contextRef="c20241231" unitRef="U002" 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;">
          <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 debt and equity securities</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:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_6808aa03681547cca1d6c98d32aab031" contextRef="c20241231" unitRef="U002" 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; 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="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_f7a5c21d883b40c784a842b4eab86b9d" contextRef="c20241231" unitRef="U002" 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; 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="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_bf106be9d5824af3aa9e4c635557fb8a" contextRef="c20241231" unitRef="U002" 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; 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="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_ecad1868d9ae4c4cb68ebd3c78a85d30" contextRef="c20241231" unitRef="U002" 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; white-space: nowrap;">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>

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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%; 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_2ec4116852e041e3a2a38cb16ff4ea22" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Includes investments classified as cash equivalents in our condensed
            consolidated balance sheets.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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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%; 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_20cf8a92586d4d88bc45b040cb662025" 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 three months ended&#160;March 31, 2025, we recorded a $<ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_3313864190a543a6b47d32b6b504a1c9" contextRef="c20250101to20250331_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.2</ix:nonFraction> million net unrealized loss
            in our condensed consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies.</ix:footnote></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;">(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_55aad856d839435daad2d772a2ea1bc5" 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<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></ix:footnote></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;">The following is a summary of our investments we consider to be temporarily impaired at March 31, 2025 (in thousands, except for number of investments):</div>
</ix:nonNumeric></ix:continuation>
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<div><br/>
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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;">&#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>
        </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;">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 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;">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 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; 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>
        </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;">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; 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;">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; 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;">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; 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;">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; 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;">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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; 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</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_333cdd7221c74a659058428cb96f027e" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U009" decimals="0" scale="0" format="ixt:num-dot-decimal">244</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_2e0cac4f3e6445e4af1d421cd8ba2264" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">466,130</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_903a58d3bf3c421b9166ac1d0a37f22d" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,236</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_183b7171ce6948fe93c1afb5708dc040" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,945</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_2bc4f2d4d6bd455e9474ce6348458023" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">20</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:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_39ca68f5ced34e02a3fb7f209ed77346" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">476,075</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:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_6a521c4aea4b4d6186a40cc4ac11ef16" contextRef="c20250331_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,256</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%;">
          <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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_f82ef35b85bc4b76a2ca3ea408acca74" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U009" decimals="0" scale="0" 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;">&#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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_0a9f0760b76943a0bb457df5aa11d275" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">45,578</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_a606df5dbef24526ade176d96aa0c07b" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">148</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_2d0505e6d78b437083a13a36af9d0e35" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_be6630f1d422413eb69c31e0abbb4c84" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_9e4b0d43d3f14d11b3cdc492ef07dd02" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">45,578</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:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_eba3f72c498e466687adcba61f086b48" contextRef="c20250331_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">148</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;">
          <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;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_2e46b5062fb3478c908336d6d2d994c6" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U009" decimals="0" scale="0" format="ixt:num-dot-decimal">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>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_392a47ad8b314b019fde0f086884f91a" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">271,642</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_b473b5a2bf6f472895d5dbf195a86994" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">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;">
          <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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_631f14e2221f4205b5b6af1f14754c3c" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,931</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_366adc85dd3e4261abd0ad4c81e9ed06" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">56</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:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_8fe8a8c8d9ba4dbe9a0815a2dd6c7215" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">284,573</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:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_039c758638b24f77831d5dfe6f4ab76e" contextRef="c20250331_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">322</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%; padding-bottom: 2px;">
          <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;">&#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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_2cef1dcb51a449edb7fe76af4b2c0e0c" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U009" decimals="0" scale="0" 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; 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_2b2f7503adc14be999f6518218accc8a" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">471</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_f999f2e853164a178503a3147b33ac68" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_1ee53f584ab24cb6b581f7eae1eba196" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_98453b0c0b144bba86ec994206fdc1cb" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_4d01726992bb4d94b31e50877ad828f0" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">471</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:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_401d55f983434e8d9399ad8c2fc7758d" contextRef="c20250331_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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: 16%; 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 temporarily impaired securities</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_7e1f0b8e65b4437a89df6913266edd37" contextRef="c20250331" unitRef="U009" decimals="0" scale="0" format="ixt:num-dot-decimal">312</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_a321ec73c6744478ab33de1911123ebf" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">783,821</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_32652639154d4153a0f3bf2d89e86160" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,650</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_c18b9c577f3c4038843a9b7ee496d0d4" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">22,876</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:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_b3760c7e65ef40e2ab47903dd7c9443a" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">76</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:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_08acbc6cc04049ed9b3d48be01027292" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">806,697</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:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_cf642061255f4432b68bd3618eb2a416" contextRef="c20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,726</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>


</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;">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>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">15</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>
<div><ix:nonNumeric name="us-gaap:FairValueDisclosuresTextBlock" id="Text_2a6de6f9bc2e421d838e9ff6c089fad5" contextRef="c20250101to20250331" escape="true" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8.&#160; Fair Value Measurements</div>
</ix:nonNumeric>

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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;">The following tables present the major security types we held at March 31, 2025 and December 31, 2024 that we regularly measure and
    carry at fair value. 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 security&#8217;s fair value (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; 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;">March 31, 2025</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: left; 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_ab8b93d31763462f825afbb8d94ca1c5" contextRef="c20250331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">176,876</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_435272b4ab6d4fb0a17848af08d9ea64" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">176,876</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_b9e898ee93984d899874de0b216f6350" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" 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: 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_1b769ef466ea447fba9ad51918866940" contextRef="c20250331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">988,066</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_1a622d10285342d4ab574fbc330e9b6a" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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_2a11d5be65ff43b2bc3316d459599b2f" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">988,066</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: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</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_4ce9866198094ab9bb0fba527e9f7a46" contextRef="c20250331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">182,341</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_cc73c7dd4336416d8872098ddc72f3db" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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_418e9f44ebbb42dd9a510d3d5c448b72" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">182,341</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;">Debt securities issued by the U.S. Treasury (3)</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_144b8361be90457089523a487891e260" contextRef="c20250331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">739,136</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_80cb88c905824e2f9a4af8d421a3ae6c" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">739,136</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_2e48b747b93e49a19ff9c8c29a110e0c" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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 (3)</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_c11eb07ea3324e24902d31be146e2aba" contextRef="c20250331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,670</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_5239338c06b14e6a85429a23967f6b00" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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_d3641150e44941fa942aa4dc4b80dcba" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,670</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 (3)</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_3f41577848d94505a87188bb79c7a341" contextRef="c20250331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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%; 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_923d9a1ea29d404f84bd863cc83c4565" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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_1341ad8fa64a48b79c9b2c6e34f2a053" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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%; 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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</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_345ac2114958402e8c0526123b413533" contextRef="c20250331_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,082</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_49579a46ef144e9db6adc23b832e2254" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,082</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_714e6b6bc417487db0580f5a9df0b246" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" 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_9623b6fc811d446d8de6fe8c0a84d07a" contextRef="c20250331_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,094,869</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_5e3adc88dc374a21be5199cc974a06ca" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">919,094</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_fb2ce086644c437499ac32ea8b2ab24d" contextRef="c20250331_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,175,775</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_ce4986e081b44939bfdcbecdc1de2b6d5" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d6"><ix:continuation id="Text_892a9b262d044425b8e23434e69031813" continuedAt="Text_892a9b262d044425b8e23434e69031814">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d6" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d7"><ix:continuation id="Text_892a9b262d044425b8e23434e69031814" continuedAt="Text_892a9b262d044425b8e23434e69031815">
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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; 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: left; 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_3abef904d1ac4dac9365cd6a89ce306b" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" 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_d7eb290d8c5b4341953ea8ce19b70167" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" 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_9d277c8fc4ff4a19a7ee29dcea9663b9" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" 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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (3)</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_6d98cfd31fed4be1bc5dd4e5765ff970" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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_880b4c0e0d2d48df987d8eb4b3893eda" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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_641d49c2d0c64af9adad977b14b03585" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" 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: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</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_a02ee28d048e4f4a86d13e676be48142" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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_2c0dd2ce365841a7940c2b161ab7aa5b" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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_276eb2ce23b74c76b7109fee3b729859" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U002" 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: 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 (3)</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_92f2c745baa2467ebc8da9f308582732" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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_4f65ddc8bb1f41b18f4a4fafb05aa5bf" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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_cad6d847f28b41d1ba345ee379c53c3a" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U002" 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 (3)</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_8ac6126992144e2d902abafe0f05aaf1" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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_c4b11390dafb4d68ab357a12be102e2b" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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_984ae9d0003e4112b370b64ac08e73fa" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U002" 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 (3)</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_5b8327917d664895a6742c992d7886e3" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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_10e46d8365b3409d8153541239814cc4" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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_45000a765e64436f97a25905ff15825b" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U002" 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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</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_2d42bf872f544c81919721ce64a97544" contextRef="c20241231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" 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_e4b5ecb96353409f8174273ca47cf4bd" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" 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_a7b2fd7148674fabb6e271a364c858e7" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U002" 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_d3bd323a8b614ca5970873ceac15876b" contextRef="c20241231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" 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_309c74f6dec14486a89fc6b78983b26a" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" 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_11ff54c661534a3abddbec83ad68c19a" contextRef="c20241231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" 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_ce4986e081b44939bfdcbecdc1de2b6d7" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d8"><ix:continuation id="Text_892a9b262d044425b8e23434e69031815" continuedAt="Text_892a9b262d044425b8e23434e69031816">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d8" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d9"><ix:continuation id="Text_892a9b262d044425b8e23434e69031816" continuedAt="Text_892a9b262d044425b8e23434e69031817">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following footnotes reference lines in our condensed consolidated balance sheets:</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d9" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d10"><ix:continuation id="Text_892a9b262d044425b8e23434e69031817" continuedAt="Text_892a9b262d044425b8e23434e69031818">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d10" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d11"><ix:continuation id="Text_892a9b262d044425b8e23434e69031818" continuedAt="Text_892a9b262d044425b8e23434e69031819">
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  <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_a07f61350d6c43dcbc95f9a5735b974a" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in cash and cash equivalents.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d11" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d12"><ix:continuation id="Text_892a9b262d044425b8e23434e69031819" continuedAt="Text_892a9b262d044425b8e23434e690318110">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d12" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d13"><ix:continuation id="Text_892a9b262d044425b8e23434e690318110" continuedAt="Text_892a9b262d044425b8e23434e690318111">
<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_2009e9e101cd4940acd892bb1ca9a15f" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_0a80d2918e1d4d1989dc35c373fb07fb" contextRef="c20250331_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">34.0</ix:nonFraction> million was included in cash and cash equivalents, with the difference included in short-term investments.</ix:footnote></div>
        </td>

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</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d13" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d14"><ix:continuation id="Text_892a9b262d044425b8e23434e690318111" continuedAt="Text_892a9b262d044425b8e23434e690318112">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d14" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d15"><ix:continuation id="Text_892a9b262d044425b8e23434e690318112" continuedAt="Text_892a9b262d044425b8e23434e690318113">
<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_67f6ff09f4d443248a7bd7fe03ce1bd9" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in short-term investments.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d15" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d16"><ix:continuation id="Text_892a9b262d044425b8e23434e690318113" continuedAt="Text_892a9b262d044425b8e23434e690318114">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d16" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d17"><ix:continuation id="Text_892a9b262d044425b8e23434e690318114">
<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_c75f21d8ce054e70804aa6d61db09222" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in other current assets.</ix:footnote></div>
        </td>

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</table>
</ix:continuation></ix:continuation>

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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d18" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d19">
<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>
</ix:continuation>
  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d19" continuedAt="Text_ce4986e081b44939bfdcbecdc1de2b6d20">
<div><br/>
  </div>
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  <ix:continuation id="Text_ce4986e081b44939bfdcbecdc1de2b6d20">
<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_7200e147053b45f7a2764da0990ef981" contextRef="c20250331_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_b833626f3a78482499357f6dc9795346" contextRef="c20250331_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_6ec6de3fdf56419ca13cab79c9519015" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">559.0</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_e2d5869342504cbea6cdb10162937afd" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">623.0</ix:nonFraction> million at March 31, 2025, respectively.
    Our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_259bcd44607a4109b2fe67e9ec9124e7" 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_66b5226223dc4f51b84fc7abeb96c856" 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_d42f5c070228490ba1f1f750e7d421f6" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">569.3</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_572d2a1ef8f740a6958da9503d2f0642" contextRef="c20241231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">612.8</ix:nonFraction>
    million at December 31, 2024, 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 style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
    <div style="width: 100%;" class="BRPFPageFooter"></div>

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">16</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>
<div><ix:nonNumeric name="us-gaap:DisclosureOfCompensationRelatedCostsShareBasedPaymentsTextBlock" id="Text_68a9d92d88dc4032a19e261806b63702" contextRef="c20250101to20250331" escape="true" continuedAt="Text_954aa3f78b724ea7b834a9a55eb9521f1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">9. Stock-based Compensation Expense</div>
</ix:nonNumeric>

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<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_954aa3f78b724ea7b834a9a55eb9521f2" continuedAt="Text_954aa3f78b724ea7b834a9a55eb9521f3"><ix:nonNumeric name="us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" id="Text_41bb03e5346543ff85da32e114653473" contextRef="c20250101to20250331" escape="true" continuedAt="Text_fa002056cf5f4c68823985097f7046101">
<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 three months ended&#160;March 31, 2025 and 2024 (in thousands):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_954aa3f78b724ea7b834a9a55eb9521f3" continuedAt="Text_954aa3f78b724ea7b834a9a55eb9521f4"><ix:continuation id="Text_fa002056cf5f4c68823985097f7046101" continuedAt="Text_fa002056cf5f4c68823985097f7046102">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_954aa3f78b724ea7b834a9a55eb9521f4" continuedAt="Text_954aa3f78b724ea7b834a9a55eb9521f5"><ix:continuation id="Text_fa002056cf5f4c68823985097f7046102">
<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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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</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:AllocatedShareBasedCompensationExpense" id="Fact_99e0a32e2d2345afb5dae8769531813a" contextRef="c20250101to20250331_IncomeStatementLocationAxis_CostOfSalesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">100</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:AllocatedShareBasedCompensationExpense" id="Fact_40be1fccef3b4d09a3e3fd20a32e9617" contextRef="c20240101to20240331_IncomeStatementLocationAxis_CostOfSalesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">204</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;">Research, development and patent 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:AllocatedShareBasedCompensationExpense" id="Fact_d17f71a28c014450810cc3b1536b5b8b" contextRef="c20250101to20250331_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,298</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:AllocatedShareBasedCompensationExpense" id="Fact_3c2e5d8e247446ac9584c5c2161ac0d5" contextRef="c20240101to20240331_IncomeStatementLocationAxis_ResearchDevelopmentAndPatentExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">22,225</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: 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;">Selling, general and administrative 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:AllocatedShareBasedCompensationExpense" id="Fact_10a81038cb0946ad979fbbbc68e8f89e" contextRef="c20250101to20250331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,320</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_763195b2b34c488bb094472395ab650d" contextRef="c20240101to20240331_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,911</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: 2px;">
          <div style="text-align: left; 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%; 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:AllocatedShareBasedCompensationExpense" id="Fact_37c70987df5942dca080bc3b42561140" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">29,718</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:AllocatedShareBasedCompensationExpense" id="Fact_86de138e6be541fb84e1e7a4408d2c3f" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">31,340</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: 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;">
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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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: left; 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;">
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        </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;">
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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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</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_954aa3f78b724ea7b834a9a55eb9521f6" continuedAt="Text_954aa3f78b724ea7b834a9a55eb9521f7">
<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 March 31, 2025, total
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    Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures, including any PRSUs that do not vest. We expect to recognize the cost of stock-based compensation
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</ix:continuation>
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<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;">Refer to Part IV, Item 15, Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization







      and Significant Accounting Policies</span>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 for further details on how we determine the fair value of stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP.</div>
</ix:continuation>
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<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;">For the three months ended&#160;March 31, 2025 and 2024, we used the
    following weighted-average assumptions in our Black-Scholes calculations:</div>
</ix:continuation>
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<div><br/>
  </div>
</ix:continuation>
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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;">Employee Stock Options:</div>
</ix:nonNumeric></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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">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;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" id="Fact_ffb253cdaa2c497d9f158f41530bd3b8" contextRef="c20250101to20250331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U003" decimals="3" 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%; 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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" id="Fact_e90f6a95b57e4e9785b5740f296f22cb" contextRef="c20240101to20240331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U003" decimals="3" scale="-2" 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%; 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; 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%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_7dae66b76386466dbd8280f7df578286" contextRef="c20250101to20250331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" 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_6fd1d504e21a42f18d1513595b6d94a7" contextRef="c20240101to20240331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" 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: 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;">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_6c30560991c34955ac78828b469d91f7" contextRef="c20250101to20250331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">41.9</ix:nonFraction></div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">
          <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_470fb7c2bc154d46b527889f6bc045b5" contextRef="c20240101to20240331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">44.0</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;">
          <div style="text-align: left; 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_e3f0b01c2b014194af0169f71cb6cace" contextRef="c20250101to20250331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" 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_c25f6066e793481b89742397fce1babb" contextRef="c20240101to20240331_AwardTypeAxis_EmployeeStockOptionMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" 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 style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_954aa3f78b724ea7b834a9a55eb9521f15" continuedAt="Text_954aa3f78b724ea7b834a9a55eb9521f16"><ix:nonNumeric name="us-gaap:ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" id="Text_b29fc346515045afbfa448496c73e46c" contextRef="c20250101to20250331" escape="true" continuedAt="Text_20baa6de8d49496c8d20f018f3a7c7db1">
<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;">ESPP:</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_954aa3f78b724ea7b834a9a55eb9521f16" continuedAt="Text_954aa3f78b724ea7b834a9a55eb9521f17"><ix:continuation id="Text_20baa6de8d49496c8d20f018f3a7c7db1">
<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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">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>

    <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:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" id="Fact_4d0a456ae4dc4871b24fbb25908cd45b" contextRef="c20240101to20240331_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">5.3</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: bottom; width: 76%;">
          <div style="text-align: left; 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%;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" id="Fact_6ca23795eddd40b2a9ffe6e5b60ab59e" contextRef="c20250101to20250331_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>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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_c44f5d5a2f164df58a55c39c846c87a6" contextRef="c20240101to20240331_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>

  </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;">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_bd9236668f60473db27e250b8060dc0d" contextRef="c20250101to20250331_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">41.3</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>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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_b5d4da261dad4007b283535f0efbd4b2" contextRef="c20240101to20240331_AwardTypeAxis_EmployeeStockMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">38.4</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>

  </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;">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_4cc29778c0e447968d90cd4b1be3691e" contextRef="c20250101to20250331_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durmonth">6</ix:nonNumeric> months</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_6e6a732476bd479cad0b8af2fbcf4659" contextRef="c20240101to20240331_AwardTypeAxis_EmployeeStockMember" format="ixt-sec:durmonth">6</ix:nonNumeric> months</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: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">17</span></div>

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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
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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;">RSUs:</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The weighted-average grant date fair value of RSUs granted to employees for the three months ended&#160;March 31, 2025 and 2024 was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_7654fd0b1d374d55b0c76914d3cd1ad7" contextRef="c20250101to20250331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">33.21</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_84da630fe5f54cd0a41a1019638d365c" contextRef="c20240101to20240331_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">53.54</ix:nonFraction> per share, 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;">PRSUs:</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;">Under the terms of the PRSUs we granted in 2025 and 2024, <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_ee2c4be053bf4d4fa0f118c56e90ebdf" contextRef="c20250101to20250331_AwardDateAxis_GrantedIn2025Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_cbf3053ca8e544a2845e072c5fa5a23b" contextRef="c20250101to20250331_AwardDateAxis_GrantedIn2024Member_AwardTypeAxis_PerformanceSharesMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction></ix:nonFraction> percent of the PRSUs may vest at the end of the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_9b5887d1a570488aacfe20f1184224d2" contextRef="c20250101to20250331_AwardDateAxis_GrantedIn2025Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" format="ixt-sec:durwordsen"><ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_ae9ec08f58e1428b8e5cb44dcf0f4b8f" contextRef="c20250101to20250331_AwardDateAxis_GrantedIn2024Member_AwardTypeAxis_PerformanceSharesMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric></ix:nonNumeric> performance period based on our relative
    total shareholder return, or 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_9adf31a81b37424ba5ceceeb2b680336" contextRef="c20250101to20250331_AwardDateAxis_GrantedIn2024Member_AwardTypeAxis_PerformanceSharesMember" unitRef="U001" decimals="INF" scale="0" format="ixt-sec:numwordsen"><ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" id="Fact_29b835c3ddfd4dc5ab1566473b632e77" contextRef="c20250101to20250331_AwardDateAxis_GrantedIn2025Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U001" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction></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_ff7ab7a487cb4ba0a0e92defee6b71c3" contextRef="c20250101to20250331_AwardDateAxis_GrantedIn2024Member_AwardTypeAxis_PerformanceSharesMember_RangeAxis_MinimumMember" unitRef="U003" decimals="INF" scale="0" format="ixt-sec:numwordsen"><ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_211159fa772f42fe85db7b075cbfbbec" contextRef="c20250101to20250331_AwardDateAxis_GrantedIn2025Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MinimumMember" unitRef="U003" decimals="INF" scale="0" format="ixt-sec:numwordsen">zero</ix:nonFraction></ix:nonFraction> to <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_0e7b60fe29aa482d8859dbb9cc4cfdf9" contextRef="c20250101to20250331_AwardDateAxis_GrantedIn2024Member_AwardTypeAxis_PerformanceSharesMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_0d3c47a0216c47e79e969763111e120c" contextRef="c20250101to20250331_AwardDateAxis_GrantedIn2025Member_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">200</ix:nonFraction></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;">The weighted-average grant date fair value of PRSUs we granted to our executive officers for the three months ended&#160;March 31, 2025 and 2024 was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_ef4bc03bc66841889f6c887d0636e91f" contextRef="c20250101to20250331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">48.81</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_f37b71af46f844b7971b1a2b89993315" contextRef="c20240101to20240331_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">78.41</ix:nonFraction> per share, respectively.</div>
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  <div><br/>
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<div><ix:nonNumeric name="us-gaap:IncomeTaxDisclosureTextBlock" id="Text_d3ef5f132e9f4b459c8640b25e10b2da" contextRef="c20250101to20250331" escape="true" continuedAt="Text_8e495558a4c649e48d2c071e97a4bd161">
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<div style="text-align: left; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">10.&#160; 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 recorded income tax expense of $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_4e27a16ccc0a4a9a935e661064462787" contextRef="c20250101to20250331" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction>
    million for the three months ended March 31, 2025 compared to $<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_c4cfd6c6ade44e8abc410de2d704e0d9" contextRef="c20240101to20240331" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction> million for the same period in 2024.</div>
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<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 of our net deferred tax assets.</div>
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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;">11. 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 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. As a result, we received an upfront payment of $<ix:nonFraction name="ions:UpfrontRoyaltyPaymentReceived" id="Fact_378c023c31584e55b0617bdf49309947" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" 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_45c4a4d71b5f46aa8fc6a9fd8e84328e" contextRef="c20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" 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_01f145be530749a2b5f41c92469f3150" contextRef="c20250331_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" 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_4defe32cd3804cbb97e4c7a2e3a297be" contextRef="c20250331_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" 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_4af0123d3f9a49d28566cdb7b703162e" contextRef="c20250331_ProductOrServiceAxis_SpinrazaMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" 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_5ab159c91cd6498eabdc7aec74f5b116" contextRef="c20250331_ProductOrServiceAxis_PelacarsenMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of any future royalty payments on pelacarsen, our medicine in
    development to treat patients with elevated lipoprotein(a)-driven cardiovascular disease. 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_8efbfdbd4aec4c57ba48a38ed1338a40" contextRef="c20250331_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">475</ix:nonFraction> million or $<ix:nonFraction name="ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" id="Fact_d8115145c7914c85b8aa1e8af6fd697a" contextRef="c20250331_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" 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>
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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 recorded the upfront payment of $<ix:nonFraction name="ions:UpfrontRoyaltyPaymentReceived" id="Fact_9289646b66ea4d879d32f2749df14834" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" 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_8a6642fa98914052a22927c1568c95ba" contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-5" scale="6">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>
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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 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 March 31, 2025 and 2024, the estimated effective interest rate under the agreement was <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_c5aa7e1147f648338034fbac9b150014" contextRef="c20240331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_b086ad26f3df4c96a5fb5a381fd3f7e6" contextRef="c20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">13.5</ix:nonFraction></ix:nonFraction> percent.</div>
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    <div style="width: 100%;" class="BRPFPageFooter"></div>

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">18</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </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 sets forth information on our liability related to sale of future royalties (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: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties, net as of December 31, 2024</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:LiabilityRelatedToSaleOfFutureRoyaltiesNet" id="Fact_3b7b9d43c6f54a7cacb07fc1a05bb2bc" contextRef="c20241231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" 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>

  </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;">Royalty payments to Royalty Pharma</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_e9a3ca9fe5b04711b74d0c6a76dde538" contextRef="c20250101to20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,891</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;">Interest expense 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_002685b59715478a910f724de61959f1" contextRef="c20250101to20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,670</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%; padding-bottom: 2px;">
          <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;">&#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:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties" id="Fact_619a93a9c8f0480e8113fad674ced5d5" contextRef="c20250101to20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" 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%; 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;">Liability related to sale of future royalties, net as of March 31, 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="ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet" id="Fact_10d08d4e6c8642349705c72c81e29f3f" contextRef="c20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">548,143</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%; padding-bottom: 2px;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion (1)</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:LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent" id="Fact_b01b2bb503094ea89f3b958f84f5facb" contextRef="c20250331_BalanceSheetLocationAxis_OtherCurrentLiabilitiesMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,002</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: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties, net as of March 31, 2025 &#8211; Non-current</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:LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" id="Fact_a207a7fc31024c369b958802e4a63152" contextRef="c20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">536,141</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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<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;">Included in other current liabilities in our condensed consolidated balance sheet.</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: 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><br/>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">12. Convertible Debt</div>
</ix:nonNumeric>

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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;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8fd7985775c44bfcace9d8ce7112cfeb" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction> Percent
    Convertible Senior Notes</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 2023, we completed a $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_9ac73a0c76054664989ce3b276636b04" contextRef="c20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" 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_f21341e2866a47aeb2b342e8def388f6" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes. We used $<ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_fa4be4826d1d4393908c609847f7c435" contextRef="c20230101to20231231_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">532.7</ix:nonFraction>
    million of the net proceeds from the issuance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_406d1a1bdf0b4ba1876e7c87768507dd" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">1.75</ix:nonFraction>% Notes to repurchase and settle our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_aa260fe8f27f4107b319ed5903eeeac9" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes, which matured in December 2024.</div>
</ix:continuation>
  <ix:continuation id="Text_7345d5f6516247619132364799b1e2575" continuedAt="Text_7345d5f6516247619132364799b1e2576">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_7345d5f6516247619132364799b1e2576" continuedAt="Text_7345d5f6516247619132364799b1e2577"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_a6052bc8837240ebaade9f70205e7cda" contextRef="c20250101to20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" escape="true" continuedAt="Text_4af58889c2554d91b1046f7901548e8a1">
<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 March 31, 2025, we had the following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1d9824693ca647f4b8493a97101ddfc4" contextRef="c20250331_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_7345d5f6516247619132364799b1e2577" continuedAt="Text_7345d5f6516247619132364799b1e2578"><ix:continuation id="Text_4af58889c2554d91b1046f7901548e8a1" continuedAt="Text_4af58889c2554d91b1046f7901548e8a2">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_7345d5f6516247619132364799b1e2578" continuedAt="Text_7345d5f6516247619132364799b1e2579"><ix:continuation id="Text_4af58889c2554d91b1046f7901548e8a2">
<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_493083a106b640dfb30fc2df3363ada0" contextRef="c20250331_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_16f4cefcf3bb4178bd27236563ff3ff8" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" 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_cc60571356a14f7986c00ab61560a9dc" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U002" decimals="-5" scale="6">9.3</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_ac460e99cb6b43a8b64e987880ed0dd5">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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:DebtInstrumentInterestRateStatedPercentage" id="Fact_427672d827e5468ca1aa478fe963dfd0" contextRef="c20250331_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;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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:DebtInstrumentInterestRateEffectivePercentage" id="Fact_9a8e690230834f42858d17acc18433f0" contextRef="c20250331_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_2508d5a342a249ecbe2d658f907d3a63" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U004" decimals="2">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_bfa13a09b4f34edabb1b3a7da10b5d07" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U001" 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>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_7345d5f6516247619132364799b1e2579" continuedAt="Text_7345d5f6516247619132364799b1e25710">
<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>
</ix:continuation>
  <ix:continuation id="Text_7345d5f6516247619132364799b1e25710" continuedAt="Text_7345d5f6516247619132364799b1e25711">
<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_0e3676949d7c473e97d1d20974f8f44c" contextRef="c20250331_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_7345d5f6516247619132364799b1e25711" continuedAt="Text_7345d5f6516247619132364799b1e25712">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_7345d5f6516247619132364799b1e25712" continuedAt="Text_7345d5f6516247619132364799b1e25713">
<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_a0fd38d74d5c4c09be72aabda7cb2eb5" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" 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_730f32942afb4ec58a0cc90a7aa04c99" contextRef="c20250331_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_670c4c4c9cce4c0a8be8b9ce9abe0221" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" 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_3466ffd4d4504e1188d0a2b60f294e3c" contextRef="c20250331_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_a2f8d0d7959a490286f7e79b2d806d9a" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U002" 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_0e2006b11da549a3947b9eee3f6cd658" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction> percent convertible senior
    notes, or <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8d9d2a025a2344138bcff5fbcf9b7cfd" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes, in 2021.</div>
</ix:continuation>
  <ix:continuation id="Text_7345d5f6516247619132364799b1e25713" continuedAt="Text_7345d5f6516247619132364799b1e25714">
<div><br/>
  </div>
</ix:continuation>
  <ix:continuation id="Text_7345d5f6516247619132364799b1e25714" continuedAt="Text_7345d5f6516247619132364799b1e25715"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_74f2863953cd4c8a92fbe46c683ba95f" contextRef="c20250101to20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" escape="true" continuedAt="Text_be107b12d1f34dd3a566109f68bb7fc81">
<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 March 31, 2025, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_16e7fa8c1a5840b1ac5c8aa87a6ecf14" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes outstanding (in millions except interest rate and price
    per share data):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_7345d5f6516247619132364799b1e25715" continuedAt="Text_7345d5f6516247619132364799b1e25716"><ix:continuation id="Text_be107b12d1f34dd3a566109f68bb7fc81" continuedAt="Text_be107b12d1f34dd3a566109f68bb7fc82">
<div><br/>
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_7345d5f6516247619132364799b1e25716" continuedAt="Text_7345d5f6516247619132364799b1e25717"><ix:continuation id="Text_be107b12d1f34dd3a566109f68bb7fc82">
<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_72099b84515a4987a6ed39e66479bffc" contextRef="c20250331_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_a67ad95abe2d4dd9908f49e9f2b5ff38" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" 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_5ec7acd6c2514e8cabe31debb2a3b6a9" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.2</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_edbb9fb31e834f86ad026d22e567df04">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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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:DebtInstrumentInterestRateStatedPercentage" id="Fact_eb33a4a1dda248649a730b726ee6e4ab" contextRef="c20250331_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;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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:DebtInstrumentInterestRateEffectivePercentage" id="Fact_63a78b08d33541519708442f3d1e2957" contextRef="c20250331_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_95d4f72d952f49fb80b34fdc489ad77a" contextRef="c20250331_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_81a2de43ec8947979830016c7ae89c30" contextRef="c20250331_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_88ccdeff6aeb43b2b0d735cbf3651c87" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" 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>
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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
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<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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8d1a4d03d8144e47b63f8e4fe5edea5e" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes by increasing the effective conversion price on our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f647ae8c9e9d49c78dd3b8a8f601fbe6" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes. We increased our effective conversion price to $<ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_8f89399b6ebc43edbd9bf57eae0f6a00" contextRef="c20250331_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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e1f0bf581c4e4cd09ceef3c4a8c66d8b" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%&#160;</span>Notes.
    The call spread cost us $<ix:nonFraction name="ions:CallSpread" id="Fact_adc134900f3e4b2a8095bb94c51ff448" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">46.9</ix:nonFraction> million, of which $<ix:nonFraction name="us-gaap:PaymentsForHedgeFinancingActivities" id="Fact_27fba3d5bc6e4961a0ec541d9ce880e5" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" 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_fae589c1422f409bab0ef5a3d362a9d2" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">89.8</ix:nonFraction> million we received for selling the warrants. Similar to our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f275e8ed60f84ce58a3fb217a7effde2" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes, our note hedges are subject to adjustment. Additionally, our note hedges
    are exercisable upon conversion of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9a0025dc07b948759f15259d7f5c6fdb" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes. The note
    hedges will expire upon maturity of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_26151b0f7f634b91a20e7b74ac5f57d7" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes, or April
    2026. The warrants will expire in July 2026. The note hedges and warrants are separate transactions and are not part of the terms of our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7bd39b60327b4b2a961691b5ae863d0a" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> Notes. The holders of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c3580cc62da242428fa842ae2cebc7fc" contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%</span> 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
    condensed consolidated balance sheets. Refer to Part IV, Item 15, Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span>, of our audited
    financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 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_ab48834238d94f4fa9c36835a1893833" contextRef="c20250331_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_5d91082f2f294fef8074e8c471432051" contextRef="c20250331_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_c3f426789f134fd0af153508f94192fc" contextRef="c20250101to20250331_DebtInstrumentAxis_ConvertibleSeniorNotes175PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_c1b493c9732d4c10b7a9b007c17934ab" contextRef="c20250101to20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" 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.</div>
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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;">13. 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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">14. 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_92f78800150c4bacb3c7033e970a29cb">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="display:none;"><br/></div>
<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 4, <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="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">20</span></div>

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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
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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 sets forth information on segment profit or loss, including significant segment expenses (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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  <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 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;">
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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%;">&#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;">
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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%;">
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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;">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_49db61d2ca2f4333a5a6e5130d3afebc" contextRef="c20250101to20250331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">26,989</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_a140d9618b2c4864a682db6886b7f6d9" contextRef="c20240101to20240331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,171</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;">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_73f7abbf00434006bc7acfaf52d92bc5" contextRef="c20250101to20250331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">112,946</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: 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_2c6404283d1f49b9a9fd43433ea16144" contextRef="c20250101to20250331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,642</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_83afb262154e4426bfa1e411fe38e7c3" contextRef="c20240101to20240331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,676</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;">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_5f4b4c96ad9548aea4e7dda8797616a5" contextRef="c20250101to20250331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,281</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_5314072f551f49d1b1bf881c55fc12a0" contextRef="c20240101to20240331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,441</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: 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;">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_bd18ea6efe534a64899d1282a6d26c74" contextRef="c20250101to20250331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,553</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:ResearchAndDevelopmentSupportExpenses" id="Fact_a41ecc174b8e4b48827606f6ff945f04" contextRef="c20240101to20240331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">21,946</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;">Selling, general and administrative</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:SellingGeneralAndAdministrativeExpense" id="Fact_25876e75f84b44d6a0f7dc4d4338c93e" contextRef="c20250101to20250331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">66,980</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%; 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 segment items (1)</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:SegmentReportingOtherItemAmount" id="Fact_616d002476dc4632b2bcf2f5fbbf9a2c" contextRef="c20250101to20250331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">29,796</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:SegmentReportingOtherItemAmount" id="Fact_01a883e8e3a940a2936967598eca4b1e" contextRef="c20240101to20240331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">24,630</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%;">&#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%; 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>
        </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_a085697f97814cfb8bab4a59ce8fd144" contextRef="c20250101to20250331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_87a78315b4b94b71b08237750833c05c" contextRef="c20250101to20250331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">146,938</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:NetIncomeLoss" id="Fact_a5747b8a822c424fbcd08a623962e9c4" contextRef="c20240101to20240331" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_fa0c7ce78fe84888b1c4d69c298071d3" contextRef="c20240101to20240331_StatementBusinessSegmentsAxis_IonisOperationsMember" unitRef="U002" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">142,803</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>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_435877b6be5343299603b9db52c861259" continuedAt="Text_435877b6be5343299603b9db52c8612510"><ix:continuation id="Text_4797f89ed7754f878ada563f7bc3ba0f3" continuedAt="Text_4797f89ed7754f878ada563f7bc3ba0f4">
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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:nonNumeric name="us-gaap:SegmentReportingOtherItemCompositionDescription" id="Fact_00c99f1e28f9432097c3b709fe9c71aa" contextRef="c20250101to20250331_StatementBusinessSegmentsAxis_IonisOperationsMember">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.</ix:nonNumeric></div>
        </td>

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</ix:continuation></ix:continuation></div>


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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">21</span></div>

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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

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  <div><a id="ITEM2MDAQ1"><!--Anchor--></a></div>
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    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 2.</span></td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">MANAGEMENT&#8217;S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS</div>
        </td>

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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; font-style: italic;">In this Report on Form 10-Q, unless the context requires otherwise, &#8220;Ionis,&#8221; the &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us,&#8221;
    means Ionis Pharmaceuticals, Inc. and its subsidiaries.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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; font-weight: bold;">In addition to historical information contained in this Report on Form 10-Q, the Report 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 and
    described in additional detail in our annual report on Form 10-K for the year ended December 31, 2024, which is on file with the U.S.
    Securities and Exchange Commission and is available from us, and those identified within Part II Item 1A. Risk Factors of this Report. 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; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Overview"><!--Anchor--></a>Overview</div>

  <div><br/>
  </div>

  <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>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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). In addition, we are also positioned to independently launch multiple medicines in the next two years, including donidalorsen for the treatment of hereditary angioedema, or HAE. Donidalorsen is currently
    under regulatory review in the U.S., positioning us for our second independent commercial launch in the second half of this year. We are also on track for Phase 3 readouts later this year, which include olezarsen for severe hypertriglyceridemia, or
    sHTG, and zilganersen for Alexander disease, or AxD. We also have a rich innovative pipeline across our focus areas of neurology, cardiology and select areas of high patient need. We currently have three wholly owned medicines and six partnered
    medicines in Phase 3 development and additional medicines in early and mid-stage development, including ION528 for Angelman syndrome, or AS, which we plan to advance into a Phase 3 study in the second quarter of 2025.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our multiple sources of revenue and capital structure enable 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 to deliver increasing product and royalty 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;">Our Marketed Medicines</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">
    <div style="text-align: justify; font-family: 'Times New Roman',Times,serif; font-size: 10pt;">TRYNGOLZA is a once monthly, self-administered LIgand-Conjugated Antisense, or LICA, medicine 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 and only FDA-approved treatment that significantly and substantially reduces triglyceride levels in adults with FCS and provides a clinically meaningful
      reduction in acute pancreatitis, or AP, events. TRYNGOLZA is the first medicine we are commercializing independently in the U.S. TRYNGOLZA is currently under regulatory review in the European Union, or EU. Sobi has exclusive rights to commercialize
      TRYNGOLZA in most countries outside of the U.S., Canada and China.</div>

  </div>

  <div><br/>
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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">22</span></div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
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    <div style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAINUA (WAINZUA in Europe) is a once monthly, self-administered subcutaneous LICA medicine that is approved in the U.S., EU and other
      countries for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis, or ATTRv-PN, a debilitating, progressive, and fatal disease. WAINUA is the only approved medicine for the treatment of ATTRv-PN that can be
      self-administered via an auto-injector. The launch of WAINUA is underway in numerous countries, including the EU, following the approval by the European Commission, or EC, in March 2025. AstraZeneca has exclusive rights to commercialize WAINUA
      outside of the U.S. From inception through March 31, 2025, we have earned more than $545 million in revenues from our WAINUA collaboration, including approximately $30 million in royalties on sales of WAINUA.</div>

  </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;">SPINRAZA is an antisense medicine for the treatment of
      patients with spinal muscular atrophy, or SMA, a progressive, debilitating and often fatal genetic disease. Our partner, Biogen, is responsible for commercializing SPINRAZA worldwide</span>. From inception through March 31, 2025, we have earned more than $2.3
    billion in revenues from our SPINRAZA collaboration, including more than $1.9 billion in royalties on 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">QALSODY is an antisense 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, a rare, neurodegenerative disorder that causes progressive loss of motor neurons leading to death. QALSODY was the first treatment approved to target a genetic cause of ALS. Our partner, Biogen, is responsible for commercializing QALSODY
      worldwide. </span>Biogen is also evaluating QALSODY as a potential treatment for presymptomatic SOD1-ALS patients in the ongoing ATLAS study. QALSODY was granted Orphan Drug designation by the FDA and EMA.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI is a once weekly, self-administered subcutaneous medicine approved in Europe and Brazil for the treatment of patients with
    ATTRv-PN. We currently sell TEGSEDI in Europe through our distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. 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>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAYLIVRA is a once weekly, self-administered, subcutaneous medicine approved in Europe and Brazil as an adjunct to diet in adult
      patients with genetically confirmed FCS and at high risk for pancreatitis. 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>

  </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 Innovative Late-Stage Pipeline of Ionis-Owned Investigational Medicines</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olezarsen is our medicine in development for sHTG, a second potential indication which has a more prevalent patient population. We are
    currently conducting a broad Phase 3 development program for olezarsen for the treatment of sHTG including three Phase 3 studies supporting development (CORE, CORE2 and ESSENCE), which achieved full enrollment in 2024. In March 2025, we published the
    Phase 3 study design and baseline characteristics for the CORE, CORE2 and ESSENCE studies in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">American Heart Journal</span>. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We licensed commercialization rights for olezarsen to Sobi in most countries outside of the U.S., Canada and China, and Theratechnologies in Canada.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Donidalorsen is our medicine in development for the prophylactic treatment of HAE. Donidalorsen is currently under regulatory review in
      the U.S. with a Prescription Drug User Fee Act, or PDUFA, action date of August 21, 2025. Donidalorsen is also under regulatory review in the EU. Our regulatory submissions are based on the positive results from our comprehensive Phase 2 and Phase 3
      development program for donidalorsen. This included the Phase 3 OASIS-HAE study in patients treated every four weeks and every eight weeks that were published in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">NEJM</span>, and positive results from OASISplus, our trial that includes an open-label, or OLE, cohort for patients rolling over from the Phase 3 study and a separate cohort for patients who have transitioned to donidalorsen from other
      prophylactic HAE medications that we refer to as the &#8220;switch study.&#8221; We licensed commercialization rights for donidalorsen to Otsuka Pharmaceutical Co., Ltd., or Otsuka, in Europe and the Asia-Pacific region. In addition, we licensed
      commercialization rights for donidalorsen to Theratechnologies in Canada. The FDA and EMA granted Orphan Drug designation to donidalorsen.</div>

  </div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Zilganersen is our medicine in development for AxD. We completed enrollment in the Phase 3 portion of the ongoing study for patients with
    AxD in July 2024. Zilganersen was granted Fast Track designation for the treatment of AxD and Rare Pediatric designation by the FDA. Additionally, zilganersen was granted Orphan Drug designation by the FDA and EMA.</div>

  <div><br/>
  </div>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">23</span></div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ION582 is our medicine in development for AS. 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. 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 second quarter of 2025. The FDA and EMA granted Orphan Drug designation to ION582. Additionally, the FDA
    granted Fast Track and Rare Pediatric designations to ION582.</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 Innovative Late-Stage Pipeline of Partnered Investigational Medicines</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen is our medicine in development to treat patients with transthyretin amyloidosis cardiomyopathy, or ATTR-CM. We completed
    enrollment in the Phase 3 CARDIO-TTRansform study in July 2023. The FDA granted Fast Track designation to eplontersen for the treatment of patients with ATTR-CM. Additionally, the FDA and EMA granted Orphan Drug designation to eplontersen for the
    treatment of ATTR.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pelacarsen is our medicine in development to treat patients with elevated lipoprotein(a)-driven cardiovascular disease, or Lp(a)-driven
    CVD. Novartis is developing pelacarsen, including conducting the ongoing Phase 3 Lp(a) HORIZON cardiovascular outcome study in patients with elevated Lp(a)-driven CVD, which achieved full enrollment in July 2022 with more than 8,000 patients. The study
    design and baseline characteristics of the Phase 3 Lp(a) HORIZON study were published in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">American Heart Journal</span> in April 2025. The FDA granted
    Fast Track designation and the Center for Drug Evaluation of China National Medical Products Administration granted Breakthrough Therapy designation to pelacarsen for the treatment of patients with elevated Lp(a) and established CVD.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Bepirovirsen is our medicine in development for chronic hepatitis B virus, or HBV. GSK is developing bepirovirsen, including conducting
    the ongoing B-Well Phase 3 program in patients with HBV, which achieved full enrollment in June 2024. The FDA granted Fast Track designation and the Japanese Ministry of Health, Labour and Welfare granted SENKU designation to bepirovirsen for the
    treatment of patients with HBV.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sefaxersen is our medicine in development for immunoglobulin A, or IgA, nephropathy, or IgAN. In the second quarter of 2023, Roche
    advanced sefaxersen into Phase 3 development in patients with IgAN based on interim Phase 2 data.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ulefnersen is our medicine in development for amyotrophic lateral sclerosis, or ALS, with mutations in the fused in sarcoma gene, or FUS.
    We are currently conducting a Phase 3 study of ulefnersen in juvenile and adult patients with FUS-ALS. We licensed global commercialization rights for ulefnersen to Otsuka. The FDA and EMA granted Orphan Drug designation to ulefnersen.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="CriticalAcctgEstimate"><!--Anchor--></a>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 condensed 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. 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/>
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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;">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;">There have been no material changes to our critical accounting estimates from the information provided in 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>, included in our Annual Report on Form 10-K for the year ended December 31, 2024.</div>

  <div><br/>
  </div>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">24</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="ResultsofOperations"><!--Anchor--></a>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;">The following is a summary of our financial results (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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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;">&#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: justify; 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;">131.6</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;">
          <div style="font-family: '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;">119.5</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;">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;">278.5</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%;">
          <div style="font-family: '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;">269.0</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%; 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 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;">(146.9</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;">(149.5</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; 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;">(146.9</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;">(142.8</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>
  <div><br/>
  </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 the three months ended&#160;March 31, 2025 was $131.6 million compared to $119.5 million for the same period in 2024 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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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;">
          <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;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product sales, net:</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%; 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;">TRYNGOLZA sales, net</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;">6.3</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;">
          <div style="font-family: '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;">&#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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total product sales, 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;">6.3</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;">&#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;">Royalty 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: -9pt; 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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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;">48.0</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;">38.5</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; text-indent: -9pt; 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%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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;">9.4</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;">1.1</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: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other royalties</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;">6.8</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;">9.8</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%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total royalty 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;">64.2</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;">&#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;">49.4</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;">Other 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%;">&#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: 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%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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;">5.7</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;">&#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;">8.6</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: 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;">&#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;">1.6</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: 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; 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;">5.7</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;">10.2</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; margin-left: 72pt; 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;">76.2</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;">59.6</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;">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>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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;">45.0</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;">49.3</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%; 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;">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;">10.4</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;">10.6</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: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: 27pt; margin-left: 45pt; 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;">55.4</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;">59.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 36pt; margin-left: 81pt; 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; 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;">131.6</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>

    <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;">119.5</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>

  </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 for the three months ended March 31, 2025 increased 28% compared to the same period in 2024, driven in part by revenue
    from U.S. product sales from the launch of TRYNGOLZA. Higher royalty revenues from SPINRAZA, WAINUA and QALSODY also contributed to the year over year increase.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The remainder of our revenue came from programs under our research and development, or R&amp;D, collaborations, reflecting the value that
    our pipeline and technology continue to generate.</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 (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 three months ended March 31, 2025 and 2024 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's development expenses, in the
    same period we incur the related development expenses.</div>

  <div><br/>
  </div>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">25</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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 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 for ATTR-CM 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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">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;">10.6</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: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development expenses related to Phase 3 development of 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;">21.5</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;">22.7</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;">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;">1.6</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;">1.3</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;">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;">7.7</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;">6.0</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="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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">248.8</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;">&#160;</td>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; 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;">237.7</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;">29.7</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;">31.3</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%; 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;">278.5</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;">269.0</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, for the three months ended&#160;March 31, 2025 increased slightly compared to the
    same period in 2024. SG&amp;A expenses increased year over year primarily due to the launches of WAINUA and TRYNGOLZA, and advancing launch
    preparation activities for donidalorsen. R&amp;D expenses decreased year over year as several late-stage studies ended. We expect our operating expenses, excluding non-cash compensation expense related to equity awards, to continue to increase during
    the remainder of 2025 as we advance our commercialization activities.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To analyze and compare our results of operations to other similar companies, we believe it is important to exclude non-cash compensation
    expense related to equity awards from our operating expenses. We believe non-cash compensation expense related to equity awards is not indicative of our operating results or cash flows from our operations. Further, we internally evaluate the
    performance of our operations excluding it.</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 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;">Cost of sales for a newly launched product, such as TRYNGOLZA, does not include the full cost of manufacturing until we manufacture and
    sell additional inventory after exhausting pre-launch inventory, which we previously recorded as R&amp;D 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 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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">1.4</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;">2.0</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;">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;">0.1</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;">0.2</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 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;">1.5</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;">2.2</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>

  </tr>


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

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">26</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><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;">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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">180.4</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;">192.0</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;">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;">20.4</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;">22.2</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 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;">200.8</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;">214.2</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>

  </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="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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">27.0</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;">28.2</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%; 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;">4.1</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;">4.3</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%; 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;">31.1</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;">32.5</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>

  </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;">Drug discovery expenses</span>, excluding non-cash
    compensation expense related to equity awards,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> were essentially flat in the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>March 31, 2025<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</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;">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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen</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;">21.1</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;">21.7</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%;">
          <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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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>

    <td valign="bottom" colspan="1" style="vertical-align: bottom; width: 1%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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;">39.5</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; 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%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; 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;">5.1</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;">4.8</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;">Zilganersen</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;">5.2</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;">2.1</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;">Ulefnersen</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;">3.0</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;">&#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;">3.5</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;">Other development projects</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;">22.2</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;">25.1</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%; 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;">Development overhead 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;">
          <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%; 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;">29.1</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>

  </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 drug development 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;">112.9</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;">125.8</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%; 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;">9.5</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;">10.4</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 drug development 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;">122.4</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;">136.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </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;">Our development expenses</span>, excluding non-cash
    compensation expense related to equity awards,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> decreased for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>March 31, 2025<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>as several late-stage studies ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>We expect our development expenses will continue to stabilize as
    several late-stage studies end and we reallocate resources toward earlier stage programs.</div>

  <div><br/>
  </div>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">27</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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: justify; 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="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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">5.6</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;">
          <div style="font-family: '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;">4.7</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;">0.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <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;">0.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </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;">5.9</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;">5.6</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Medical affairs expenses</span>, excluding non-cash
    compensation expense related to equity awards, increased in the three months ended&#160;March 31, 2025 compared to the same period in 2024 as we continued
    advancing our late-stage pipeline.</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;">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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">14.3</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;">11.4</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%; 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;">2.1</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;">2.3</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%; 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;">16.4</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>

    <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;">13.7</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, increased in </span>the three months ended&#160;March 31, 2025 compared to the same period in 2024 due to the timing
    of manufacturing performed by our contract manufacturing organizations for drug product related to several late-stage programs.</div>

  <div><br/>
  </div>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">28</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>

  <div style="text-align: left; 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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">Occupancy</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;">7.3</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;">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>

  </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;">Personnel 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%;">&#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;">6.8</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;">7.8</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;">Computer software and licenses</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;">3.2</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;">&#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;">1.6</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: 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%;">&#160;</td>

    <td valign="bottom" colspan="1" style="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;">1.0</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;">0.9</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;">Patent 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;">0.6</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;">0.7</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%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consulting 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;">0.1</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;">0.6</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;">1.6</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;">3.2</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;">20.6</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;">21.9</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: -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;">4.4</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;">4.3</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: 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;">25.0</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;">26.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </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;">R&amp;D support expenses</span>, excluding non-cash
    compensation expense related to equity awards,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> were essentially flat in the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>March 31, 2025<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</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;">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, information technology systems and outside costs associated with the commercialization and
    pre-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 and cost
    sharing payments associated with co-commercialization activities under our WAINUA collaboration with AstraZeneca.</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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 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;">67.0</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;">43.7</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;">9.3</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <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;">8.9</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

  </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;">76.3</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;">52.6</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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SG&amp;A expenses</span>, excluding non-cash compensation
    expense related to equity awards,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> increased in the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>March 31, 2025<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> compared to the same period in </span>2024 due to the launches of WAINUA and TRYNGOLZA and advancing
    launch preparation activities for donidalorsen. We expect SG&amp;A expenses to increase as we continue to invest in our independent commercial launches.</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 the three months ended&#160;March 31, 2025 was $24.7
    million compared to $26.3 million for the same period in 2024. Our investment income decreased primarily due to a decrease in interest rates associated with our investments during the three months ended&#160;March 31, 2025 compared to the same period in 2024.</div>

  <div><br/>
  </div>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">29</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </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;">Interest Expense</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 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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible 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;">1.5</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;">1.6</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: 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;">2.5</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;">2.5</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%; 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 manufacturing facility</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;">0.1</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;">0.1</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>

  </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;">4.1</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;">4.2</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </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;">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>18.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>18.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of interest expense related to the sale of future royalties in the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>March 31, 2025<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and 2024. 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 I, Item 1,
    Note 11, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Liability Related to Sale of Future Royalties</span>, in the Notes to Condensed Consolidated Financial Statements for further details.</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;">Gain (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 net loss on investments of $2.2
    million for the three months ended&#160;March 31, 2025 compared to a net gain on investments of $2.3 million for the same period in 2024 primarily due to changes in the fair value of our investments in 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;">Income Tax Expense</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded income tax expense of $0.1
    million for the three months ended March 31, 2025 compared to $0.1 million for the same period in 2024.</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 of our net deferred tax assets.</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;">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 had a net loss of $146.9
    million for the three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>March 31, 2025 compared to a net loss of $142.8
    million for the same period in 2024, which reflects the fluctuations discussed above. Our b<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">asic and diluted net loss per share for the </span>three months ended<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>March 31, 2025<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> was $</span>0.93<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and $</span>0.98<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, respectively.</span></div>

  <div><br/>
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Liquidity"><!--Anchor--></a>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;">We have financed our operations primarily from research and development collaborative agreements. We also financed our operations from
    commercial revenue from SPINRAZA, WAINUA and QALSODY royalties and TEGSEDI and WAYLIVRA commercial revenue. In addition, we began earning commercial revenue from TRYNGOLZA product sales in late December 2024. From our inception through March 31, 2025, we have earned approximately $8.0
    billion in revenue. We have also financed our operations through the sale of our equity securities, the issuance of long-term debt and the sale of future royalties. From the time we were founded through March 31, 2025, we have raised net proceeds of approximately $2.6
    billion from the sale of our equity securities. Additionally, from our inception through March 31, 2025, we have borrowed approximately $2.7 billion under long-term debt arrangements and received proceeds of $0.5 billion from the sale of future royalties to finance a portion of our
    operations.</div>

  <div><br/>
  </div>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">30</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </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;">From </span>December 31, 2024<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span>March 31, 2025, our working capital decreased as our cash, cash equivalents and short-term investments decreased, while our long-term obligations did not change significantly.</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 summarizes our contractual obligations, excluding our liability related to the sale of future royalties, as of March 31, 2025. The table provides a breakdown of when obligations become due. We provide a more detailed description of the major components of our debt
    in the paragraphs following the table:</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;">
          <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 (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; border-bottom: #000000 solid 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</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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;">&#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</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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) (1)</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;">255.0</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;">&#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;">234.1</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: 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;">9.5</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;">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;">9.0</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: 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;">1,508.0</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;">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;">1,476.4</div>
        </td>

    <td valign="bottom" colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;">&#160;</td>

  </tr>


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

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1) Our 0% Notes become due in April 2026.</div>

  <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: justify; 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;">Refer to Part I, Item 1, Note 12, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Convertible







      Debt</span>, in the Notes to Condensed Consolidated Financial Statements for the significant terms of each convertible debt instrument.</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 Part IV, Item 15, Note 7 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 for further details on our operating facilities.</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;">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 Part IV, Item 15, Note 7 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 for further details on our operating leases.</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;">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;">Refer to Part I, Item 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 11, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Liability Related to Sale of Future Royalties, </span>in the Notes to Condensed Consolidated Financial Statements for further details on our royalty purchase
    agreement with Royalty Pharma.</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 March 31, 2025 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>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">31</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>

  <div><a id="ITEM3MarketRisk"><!--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">


  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 3.</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-weight: bold;">QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK</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 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 are 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.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also exposed to changes in foreign currency exchange rates as we have foreign subsidiaries with functional currencies other than
    the U.S. dollar. We translate our subsidiaries&#8217; functional currencies into our reporting currency, the U.S. dollar. As a result, our financial position, results of operations and cash flows can be affected by market fluctuations in the foreign
    currencies to U.S. dollar exchange rate, which are difficult to predict. A hypothetical 10 percent change in foreign exchange rates during any of the periods presented would not have had a material impact on our condensed consolidated financial
    statements.</div>

  <div><br/>
  </div>

  <div><a id="Item4Controls"><!--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">


  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 4.</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-weight: bold;">CONTROLS AND PROCEDURES</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 maintain disclosure controls and procedures 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 design and evaluate 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 our most recently completed fiscal year and as of the end of the period covered by this Quarterly Report on Form 10-Q, we carried
    out an evaluation of the effectiveness of the design and operation of our disclosure controls and procedures, as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended, under the supervision 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 March 31, 2025. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">There have been no significant changes in our
      internal controls or in other factors that could significantly affect internal controls subsequent to</span>&#160;March 31, 2025.</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also performed an evaluation of any changes in our internal controls over financial reporting that occurred during our last fiscal
    quarter and that have materially affected, or are reasonably likely to materially affect, our internal controls over financial reporting. We conducted this evaluation under the supervision of and with the participation of our management, including our
    Chief Executive Officer and Chief Financial Officer. That evaluation did not identify any changes in our internal controls over financial reporting that occurred during our latest fiscal quarter and that have materially affected, or are reasonably
    likely to materially affect, our internal controls over financial reporting.</div>

  <div><br/>
  </div>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">32</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="PARTII"><!--Anchor--></a>PART II &#8212; OTHER INFORMATION</div>

  <div><br/>
  </div>

  <div><a id="ITEM1"><!--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">


  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 1.</span></td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">LEGAL PROCEEDINGS</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 details of legal proceedings, refer to Part I, Item 1, Note 13, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Legal Proceedings</span>, in the Notes to Condensed Consolidated Financial Statements<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

  <div><br/>
  </div>

  <div><a id="ITEM1A"><!--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">


  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 1A.</span></td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">RISK FACTORS</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;">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. We have marked with an asterisk those risk
    factors that reflect substantive changes from the risk factors included in our Annual Report on Form 10-K for the year ended December 31, 2024.</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. Some of the principal risks related to our business include the
    following:</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;">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: 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;">&#932;</span>he 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: justify;">
          <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: justify;">
          <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: justify;">
          <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: justify;">
          <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: justify;">
          <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>
  <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 ability to protect our intellectual property;</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 ability to maintain the effectiveness of our personnel;</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 impacts of health epidemics, climate change, war and other events;</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 dependence upon our own and third-party information technology systems; and</div>
        </td>

  </tr>


</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;">The other factors set forth below.</div>
        </td>

  </tr>


</table>
  <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 or maintain an effective commercialization infrastructure, 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;">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. If 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.</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>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">33</span></div>

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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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 the risks set forth above will occur.</div>

  <div><br/>
  </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
    several factors, including the:</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;">receipt and scope of marketing authorizations;</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;">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>

  </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;">cost and effectiveness of our medicines compared to other available therapies;</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;">patient convenience of the dosing regimen 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;">reimbursement policies of government and third-party payers.</div>
        </td>

  </tr>


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

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

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">34</span></div>

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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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>

  <div><br/>
  </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>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">35</span></div>

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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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/>
  </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;">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">


  <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;">reimbursed more favorably by government and other third-party payers 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">


  <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>

  </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;">more effective than our medicines; 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;">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>

  <div><br/>
  </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 that our own 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/>
  </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;">Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;</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;">Acoramidis, patisiran, tafamidis, tafamidis meglumine and vutrisiran compete with 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;">Nexiguran ziclumeran, ALXN2220 and NNC6019-0001 could compete with WAINUA;</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;">Plozasiran, pegozafermin and NST-1024 could compete with TRYNGOLZA and WAYLIVRA;</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;"><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;"> NTLA-2002 and STAR-0215 could compete with donidalorsen;</span></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;"><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>

  </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;">NI-005/AP-101 could compete with 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;"><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, REP 2139-Mg and VTP-300 could complete with bepirovirsen;</span></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;">Budesonide, sparsentan, atrasentan, iptacopan, zigakibart, sibeprenlimab, atacicept, ravulizumab, vemircopan, felzartamab, telitacicept and povetacicept could compete
            with sefaxersen; 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;">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>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">36</span></div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
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    <div style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </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;">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. The FDA and foreign regulatory bodies have the authority to impose significant restrictions on an approved medicine through the product label.&#160; 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;">Promotional communications regarding prescription medicines must be consistent with the information in the product&#8217;s approved labeling.
    Additionally, 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>

  <div><br/>
  </div>

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

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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;">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>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">37</span></div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
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    <div style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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 are co-developing and co-commercializing WAINUA in the U.S. and AstraZeneca has 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>

  <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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">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,
      tariffs on the raw materials, components, or equipment we use to manufacture our products, or on our drug substance or finished products, will increase our manufacturing costs. There have also 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</span>.</div>

  <div><br/>
  </div>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">38</span></div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
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    <div style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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>

  <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 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/>
  </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. 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. As a result, such
    data should be viewed with caution until the final data are available.</div>

  <div><br/>
  </div>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">39</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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>

  <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 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>

  <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>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">40</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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 some 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 those 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>

  <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;">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>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">41</span></div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
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    <div style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">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>

  <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 March 31, 2025, we had cash, cash equivalents and short-term investments equal to $2.1
    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>

  <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;">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>

  </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;">continued scientific progress in our research, drug discovery and development programs;</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 size of our programs and progress with preclinical and 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;">the time and costs involved in obtaining marketing authorizations;</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;">competing technological and market developments, including the introduction by others of new therapies that address our markets; 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;">our manufacturing requirements and capacity to fulfill such requirements.</div>
        </td>

  </tr>


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

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">42</span></div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
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    <div style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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 March 31, 2025, we had an accumulated deficit of approximately $2.4 billion and stockholders&#8217; equity of approximately $0.5
    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>

  <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>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">43</span></div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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>

  <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 disruptions of the U.S. government.*</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>

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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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.</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 development and commercialization activities could be harmed or delayed by staffing shortages or a shutdown or other
    significant disruption of the U.S. government, including the FDA or the U.S. PTO.</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 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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    <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;">harm our reputation;</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;">delay progress on the development of 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">


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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;">compel us to comply with applicable security or data breach notification obligations (including laws);</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;">result in the diversion of monetary funds and other company resources;</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;">subject us to financial or other penalties, regulatory investigations or actions, including mandatory and costly corrective actions; and</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;">require us to verify the correctness of database contents and otherwise subject us to litigation or other liabilities.</div>
        </td>

  </tr>


</table>
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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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/>
  </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, 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;">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 March 31, 2025, the closing market price of our common stock ranged from $51.86 to $30.17 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.</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 recent tariffs announcements and 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/>
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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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 tariffs
    announcements and 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>

  <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;">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/>
  </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;">compliance with differing or unexpected regulatory requirements for our medicines and foreign employees;</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;">complexities associated with managing multiple payer reimbursement regimes, government payers or patient self-pay systems;</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;">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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  <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;">foreign government taxes, regulations and permit requirements;</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;">U.S. and foreign government tariffs, trade and export restrictions, price and exchange controls and other regulatory requirements;</div>
        </td>

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</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;">anti-corruption laws, including the Foreign Corrupt Practices Act, or the FCPA, and its equivalent in foreign jurisdictions;</div>
        </td>

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</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;">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">


  <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;">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>

  </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 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>

  </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;">compliance with tax, employment, privacy, immigration and labor laws, regulations and restrictions for employees living or traveling abroad;</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;">workforce uncertainty in countries where labor unrest is more common than in the U.S.; 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;">changes in diplomatic and trade relationships.</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 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>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">47</span></div>

    <div style="page-break-after: always;" class="BRPFPageBreak">
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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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>

  <div><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 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 2024, we used $44.5 million of the net proceeds to settle the remaining principal balance of our 0.125% Notes upon maturity. 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 began expiring 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>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">48</span></div>

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      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><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;">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/>
  </div>

  <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>

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

  <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>

  <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;">interruption of our research, development and manufacturing efforts;</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;">injury to our employees and others;</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;">environmental damage resulting in costly clean up; 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;">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>
        </td>

  </tr>


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

  <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;">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>

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    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">49</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </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>

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

  <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, 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>

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">50</span></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 style="width: 100%;" class="BRPFPageHeader">
      <div><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </div>

    </div>

  </div>

  <div><a id="ITEM2"><!--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">


  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 2.</span></td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS</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;">Not applicable.</div>

  <div><br/>
  </div>

  <div><a id="ITEM3"><!--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">


  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 3.</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-weight: bold;">DEFAULT UPON SENIOR SECURITIES</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;">Not applicable.</div>

  <div><br/>
  </div>

  <div><a id="ITEM4"><!--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">


  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 4.</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-weight: bold;">MINE SAFETY DISCLOSURES</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;">Not applicable.</div>

  <div><br/>
  </div>

  <div><a id="ITEM5"><!--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: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 5.</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-weight: bold;">OTHER INFORMATION</div>
        </td>

  </tr>


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

  <div style="text-align: left; text-indent: -72pt; margin-left: 72pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Trading Plans</div>

  <div><br/>
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the quarter ended March 31, 2025,
    our directors and officers (as defined in Rule 16a-1(f) under the Exchange Act), or Section 16 officers and directors, did not <ix:nonNumeric name="ecd:NonRule10b51ArrAdoptedFlag" id="Fact_60e96e5600574cd598df27fc2cb18976" contextRef="c20250101to20250331" format="ixt:fixed-false"><ix:nonNumeric name="ecd:Rule10b51ArrAdoptedFlag" id="Fact_5a13e415c4c74f36860d24b6e9b22bb3" contextRef="c20250101to20250331" format="ixt:fixed-false">adopt</ix:nonNumeric></ix:nonNumeric> or <ix:nonNumeric name="ecd:NonRule10b51ArrTrmntdFlag" id="Fact_b54b8bdd508940c9835c08a0179bd8b7" contextRef="c20250101to20250331" format="ixt:fixed-false"><ix:nonNumeric name="ecd:Rule10b51ArrTrmntdFlag" id="Fact_8c6d9d33eda54893bb5295c96cda5916" contextRef="c20250101to20250331" format="ixt:fixed-false">terminate</ix:nonNumeric></ix:nonNumeric> contracts, instructions or written plans for the purchase or sale of our securities.</div>

  <div><br/>
  </div>

  <div><a id="ITEM6"><!--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">


  <tr>

    <td style="width: 72pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ITEM 6.</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-weight: bold;">EXHIBITS</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: 36pt;"/>

    <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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exhibits</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%; border-collapse: collapse; text-align: left; color: #000000; border-spacing: 0;">


  <tr>

    <td style="width: 8.46%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit Number</div>
        </td>

    <td style="width: 1.5%; vertical-align: top;">&#160;</td>

    <td style="width: 90.04%; 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;">Description of Document</div>
        </td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="ex10-1.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.1</a></div>
        </td>

    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Third Amended Non-Employee Director Compensation Policy.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="ex10-2.htm" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.2</a></div>
        </td>

    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">License Agreement between Ionis Pharmaceuticals, Inc. and Ono Pharmaceutical Co., Ltd., dated March 10, 2025. 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.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="ex31-1.htm">31.1</a></div>
        </td>

    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;">
          <div>Certification by Chief Executive Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended. <br/>
          </div>
        </td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="ex31-2.htm">31.2</a></div>
        </td>

    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification by Chief Financial Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="ex32-1.htm">32.1</a>*</div>
        </td>

    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.04%; 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: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101</div>
        </td>

    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.04%; 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. Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, formatted in Inline Extensible Business Reporting Language (iXBRL): (i) condensed consolidated balance sheets, (ii) condensed
            consolidated statements of operations, (iii) condensed consolidated statements of comprehensive income (loss), (iv) condensed consolidated statements of stockholders&#8217; equity, (v) condensed consolidated statements of cash flows and (vi) notes to
            condensed consolidated financial statements (detail tagged).</div>
        </td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 1.5%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.04%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 8.46%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 4.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104</div>
        </td>

    <td style="width: 1.5%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.04%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; 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">


  <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 1933, as amended, or the Securities Exchange Act of 1934, as amended.</div>
        </td>

  </tr>


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

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

    <div style="text-align: center;" class="BRPFPageNumberArea"><span style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: normal; font-style: normal;">51</span></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><a href="#Index"><span style="font-weight: normal; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt; font-style: italic; font-variant: normal; text-transform: none;">Index</span></a><br/>
      </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><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><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: 27.57%; 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;">Signatures</div>
        </td>

    <td style="width: 2.19%; vertical-align: bottom;">&#160;</td>

    <td style="width: 50.36%; 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;">Title</div>
        </td>

    <td style="width: 2.15%; vertical-align: bottom;">&#160;</td>

    <td style="width: 17.72%; 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>

  </tr>

  <tr>

    <td style="width: 27.57%; vertical-align: top;">&#160;</td>

    <td style="width: 2.19%; vertical-align: bottom;">&#160;</td>

    <td style="width: 50.36%; vertical-align: top;">&#160;</td>

    <td style="width: 2.15%; vertical-align: bottom;">&#160;</td>

    <td style="width: 17.72%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 27.57%; 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 rowspan="2" style="width: 2.19%; vertical-align: bottom;">&#160;</td>

    <td style="width: 50.36%; 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 rowspan="2" style="width: 2.15%; vertical-align: bottom;">&#160;</td>

    <td style="width: 17.72%; vertical-align: bottom;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 27.57%; 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: 50.36%; 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: 17.72%; vertical-align: bottom;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">April 30, 2025</div>
        </td>

  </tr>

  <tr>

    <td style="width: 27.57%; vertical-align: top;">&#160;</td>

    <td style="width: 2.19%; vertical-align: bottom;">&#160;</td>

    <td style="width: 50.36%; vertical-align: top;">&#160;</td>

    <td style="width: 2.15%; vertical-align: bottom;">&#160;</td>

    <td style="width: 17.72%; vertical-align: bottom;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 27.57%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ELIZABETH L. HOUGEN</div>
        </td>

    <td rowspan="2" style="width: 2.19%; vertical-align: bottom;">&#160;</td>

    <td style="width: 50.36%; 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 rowspan="2" style="width: 2.15%; vertical-align: bottom;">&#160;</td>

    <td style="width: 17.72%; vertical-align: bottom;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 27.57%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elizabeth L. Hougen</div>
        </td>

    <td style="width: 50.36%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Principal financial and accounting officer)</div>
        </td>

    <td style="width: 17.72%; vertical-align: bottom;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">April 30, 2025</div>
        </td>

  </tr>


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  <div>
    <div style="text-align: right; color: rgb(0, 0, 0); font-weight: bold;">Exhibit 10.1</div>
    <div><br>
    </div>
    <div style="text-align: center; color: #000000; font-weight: bold;">Third Amended Non-Employee Director Compensation Policy</div>
    <div style="text-align: center; color: #000000; font-weight: bold;">As of March 6, 2025</div>
    <div><font style="font-size: 12pt; color: #000000;"> </font><br>
    </div>
    <div style="color: #000000;">Ionis Pharmaceuticals, Inc. (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;) values the contributions made by its Board of Directors.&#160; In recognition of these valuable contributions, Ionis will provide
      each non-employee Director with the compensation described in this policy.</div>
    <div><font style="font-size: 12pt; color: #000000;"> </font><br>
    </div>
    <div style="color: #000000; font-weight: bold;"><u>Cash Compensation</u></div>
    <div>&#160;</div>
    <div style="color: #000000;">Each non-employee Director will receive cash compensation based on his or her role on the Board and Board committees as follows:</div>
    <div style="color: #000000;"> <br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; text-align: left; color: #000000; width: 100%;" id="z4d89b115989941b49a564985902d0a9b" class="cfttable">

        <tr>
          <td valign="bottom" style="vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-left: 2px solid rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Role</div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" colspan="2">
            <div style="text-align: center; font-weight: bold;">Cash Compensation</div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);">
            <div>Board Member (base retainer)</div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftcurrcell">
            <div>$</div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftnumcell">
            <div>60,000</div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
            <div>Non-Executive Chairman of the Board (additional)</div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftcurrcell">
            <div>$</div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftnumcell">
            <div>40,000</div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);">
            <div>Independent Lead Director (additional)</div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftcurrcell">
            <div>$</div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftnumcell">
            <div>40,000</div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0);">
            <div>Committee Chair (additional):</div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; border-left: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1" class="cftcurrcell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1" class="cftnumcell">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
            <div style="margin-left: 9pt">-Audit</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftcurrcell">$</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftnumcell">25,000</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0);" rowspan="1">
            <div style="margin-left: 9pt">-Compliance</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: #000000 solid 2px;" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%;" rowspan="1" colspan="1" class="cftcurrcell">$</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" rowspan="1" colspan="1" class="cftnumcell">20,000</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: #000000 solid 2px;" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
            <div style="margin-left: 9pt">-Compensation</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftcurrcell">$</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftnumcell">20,000</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0);" rowspan="1">
            <div style="margin-left: 9pt">-Finance</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: #000000 solid 2px;" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%;" rowspan="1" colspan="1" class="cftcurrcell">$</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" rowspan="1" colspan="1" class="cftnumcell">20,000</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: #000000 solid 2px;" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
            <div style="margin-left: 9pt">-Nominating, Governance and Review</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftcurrcell">$</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftnumcell">20,000</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">
            <div style="margin-left: 9pt">-Science/Medical</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1" colspan="1" class="cftcurrcell">$</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1" colspan="1" class="cftnumcell">20,000</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
            <div>Committee Member (additional):</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftcurrcell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftnumcell">&#160;</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0);" rowspan="1">
            <div style="margin-left: 9pt">-Audit</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: #000000 solid 2px;" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%;" rowspan="1" colspan="1" class="cftcurrcell">$</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" rowspan="1" colspan="1" class="cftnumcell">12,500</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: #000000 solid 2px;" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
            <div style="margin-left: 9pt">-Compliance</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftcurrcell">$</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftnumcell">10,000</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0);" rowspan="1">
            <div style="margin-left: 9pt">-Compensation</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: #000000 solid 2px;" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%;" rowspan="1" colspan="1" class="cftcurrcell">$</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" rowspan="1" colspan="1" class="cftnumcell">10,000</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: #000000 solid 2px;" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" rowspan="1">
            <div style="margin-left: 9pt">-Finance</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftcurrcell">$</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftnumcell">10,000</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: #000000 solid 2px; background-color: #CCEEFF;" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0);" rowspan="1">
            <div style="margin-left: 9pt">-Nominating, Governance and Review</div>
          </td>
          <td valign="bottom" style="text-align: center; vertical-align: bottom; width: 1%; border-left: #000000 solid 2px;" rowspan="1" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%;" rowspan="1" colspan="1" class="cftcurrcell">$</td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" rowspan="1" colspan="1" class="cftnumcell">10,000</td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: #000000 solid 2px;" rowspan="1" colspan="1" class="cftfncell">&#160;</td>
        </tr>
        <tr>
          <td valign="bottom" style="vertical-align: top; width: 88%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);">
            <div style="margin-left: 9pt;">-Science/Medical</div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; border-left: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
          <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftcurrcell">
            <div>$</div>
          </td>
          <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftnumcell">
            <div>10,000</div>
          </td>
          <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-right: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
        </tr>

    </table>
    <div><font style="font-size: 12pt; color: #000000;"> </font><br>
    </div>
    <div style="color: #000000; font-weight: bold;"><u>Equity Compensation</u></div>
    <div>&#160;</div>
    <div style="color: #000000;">Each non-employee Director will receive an initial stock option award and restricted stock unit award upon joining the Board and an annual stock option award and restricted stock unit award for each year of continued
      service as follows (subject to the aggregate grant date value limit described below):</div>
    <div><font style="font-size: 12pt; color: #000000;"> </font><br>
    </div>
    <table cellspacing="0" cellpadding="0" id="z24477d7943b54080a672c99b27b23c4a" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

        <tr>
          <td style="width: 62.48%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Type of Grant</div>
          </td>
          <td style="width: 37.52%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Number of Shares*</div>
          </td>
        </tr>
        <tr>
          <td style="width: 62.48%; 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>Initial Stock Option Grant</div>
          </td>
          <td style="width: 37.52%; 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;">24,000</div>
          </td>
        </tr>
        <tr>
          <td style="width: 62.48%; 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>Initial Restricted Stock Unit Grant</div>
          </td>
          <td style="width: 37.52%; 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;">10,667</div>
          </td>
        </tr>
        <tr>
          <td style="width: 62.48%; 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>Annual Stock Option Grant</div>
          </td>
          <td style="width: 37.52%; 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;">12,000</div>
          </td>
        </tr>
        <tr>
          <td style="width: 62.48%; 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>Annual Restricted Stock Unit Grant</div>
          </td>
          <td style="width: 37.52%; 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;">5,333</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">1</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="color: #000000;">*These equity awards are to be automatically granted pursuant to the terms of the Ionis Pharmaceuticals, Inc.&#160;Amended and Restated 2002 Non-Employee Directors Stock Option Plan as approved by our stockholders on June 4,
      2020 (the <font style="font-weight: bold; font-style: italic;">&#8220;NED Plan&#8221;</font>).&#160; Notwithstanding the terms of the NED Plan, the following annual equity compensation limits will apply to all non-employee Directors through May 24, 2026: (1)
      incumbent non-employee Directors will receive no more than $450,000 in annual equity compensation per year based on the aggregate grant date fair value (as determined in accordance with FASB Topic ASC 718 or its successor), and (2) newly appointed
      non-employee Directors will receive no more than $675,000 in initial equity compensation based on the aggregate grant date fair value (as determined in accordance with FASB Topic ASC 718 or its successor).</div>
    <div><br>
    </div>
    <div style="color: #000000;">The exercise price of each stock option will be the Fair Market Value (as defined in the NED Plan) of Ionis&#8217; common stock on the date of grant.</div>
    <div><br>
    </div>
    <div>As set forth in the NED Plan, one-third of the shares subject to stock options or restricted stock units for initial grants to new non-employee Directors vest on each annual anniversary of the date of grant and annual grants <font style="color: #000000;">vest on either (1) the annual anniversary of the date of grant, or (2) the next regularly scheduled annual meeting of stockholders, whichever occurs earlier.</font></div>
    <div><font style="font-size: 12pt; color: #000000;"> </font><br>
    </div>
    <div style="text-align: justify;">While serving on the Board, each non-employee Director may not sell Ionis shares obtained pursuant to vesting of restricted stock unit awards if selling such shares would reduce the shares owned by such non-employee
      Director (not including stock options or unvested restricted stock units) below an amount that is equal to five times his or her annual base cash retainer.</div>
    <div>&#160;</div>
    <div style="color: #000000; font-weight: bold;"><u>Review of Non-Employee Director Compensation Policy</u></div>
    <div><br>
    </div>
    <div style="color: #000000;">This policy will be reviewed annually by Ionis&#8217; Compensation Committee and Board of Directors.</div>
    <div><br>
    </div>
    <div style="color: #000000;">On at least an annual basis, Ionis will retain an independent consultant to (1) advise the Compensation Committee on recent developments and best practices concerning director compensation, and (2) compare Ionis&#8217; director
      compensation levels, policies, practices, and procedures to a set of peer companies selected by the Compensation Committee with input from the independent consultant.</div>
    <div><br>
    </div>
    <div style="color: #000000;">Ionis reserves the right to amend this compensation policy at any time so long as the issuance of the equity awards comply with the terms of the NED Plan or any successor thereto.</div>
    <div><br>
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    <div><br>
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<DOCUMENT>
<TYPE>EX-10.2
<SEQUENCE>3
<FILENAME>ex10-2.htm
<DESCRIPTION>EXHIBIT 10.2
<TEXT>
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    <div style="text-align: right; font-weight: bold;">
      <div style="font-style: italic; font-weight: bold;">Execution Version</div>
      <br>
    </div>
    <div style="text-align: right; font-weight: bold;">Exhibit 10.2</div>
    <div>&#160;</div>
    <div style="text-align: justify; margin-right: 52pt; margin-left: 40.5pt; color: rgb(0, 0, 0);">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;">LICENSE AGREEMENT</div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">BETWEEN</div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">AND</div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">ONO PHARMACEUTICAL CO., LTD.</div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Dated March 10, 2025</div>
    <div>&#160;</div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
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    <div style="text-align: center; font-weight: bold;">TABLE OF CONTENTS</div>
    <div>&#160;</div>
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          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 1 OVERVIEW</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">1</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>1.1</div>
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          <td style="width: 82%; vertical-align: top;">
            <div>Development and Commercialization</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">1</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>1.2</div>
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          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Governance</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">1</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>1.3</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Purpose</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">1</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 2 LICENSES</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">2</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>2.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>License Grant to Ono</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">2</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>2.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Sublicensing Terms</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">2</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>2.3</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Subcontracting Terms</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">3</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>2.4</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Responsibility for Sublicensees and Subcontractors</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">3</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>2.5</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>[***]</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">3</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>2.6</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>No Other Rights and Retained Rights</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">3</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>2.7</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Existing Third-Party IP Agreements</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">4</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>2.8</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Future Third-Party IP Agreements</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">4</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>2.9</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>[***]</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">5</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 3 EXCLUSIVITY</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">5</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>3.1</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Exclusivity Covenants of the Parties</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">5</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>3.2</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Limitations and Exceptions to Exclusivity Covenants</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">6</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>3.3</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Effect of Exclusivity on Indications</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">6</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="1" rowspan="1">&#160;</td>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="2" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 4 GOVERNANCE</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">6</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>4.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Joint Steering Committee</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">6</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>4.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Additional Participants</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">8</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>4.3</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Decision-Making</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">8</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>4.4</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Resolution of Committee Disputes</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">8</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>4.5</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Day-to-Day Responsibilities</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">9</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>4.6</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Liaisons</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">9</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 5 CLOSING</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">9</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>5.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Closing</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">9</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>5.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Antitrust Filings</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">10</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 6 TECHNOLOGY TRANSFER</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">11</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>6.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Initial Know-How Transfer</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">11</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>6.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Additional Know<font style="font-style: italic;">-</font>How Transfer</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">11</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>6.3</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Manufacturing Technology Transfer</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">11</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>6.4</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Technology Transfer Costs and Support</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">12</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;">i</font></div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</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;">

        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 7 DEVELOPMENT</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">12</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>7.1</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Ongoing Clinical Trial</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">12</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>7.2</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Extension of Ongoing Clinical Trial</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">12</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>7.3</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Performance by Ionis</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">12</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>7.4</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Development Activities Prior to Effective Date</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">12</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>7.5</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Development Diligence</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">13</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>7.6</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Development Costs</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">13</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>7.7</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Pivotal Clinical Trial Design and Regulatory Strategy</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">13</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>7.8</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Development Reports</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">13</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>7.9</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Development Records</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">13</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 8 REGULATORY AFFAIRS</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">14</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>8.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Regulatory Responsibility</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">14</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>8.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Correspondence with Regulatory Authorities</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">14</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>8.3</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Regulatory Meetings</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">14</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>8.4</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Regulatory Submissions</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">14</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>8.5</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Investigator&#8217;s Brochure</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">14</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>8.6</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Cooperation and Support</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">14</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>8.7</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Cost of Regulatory Activities</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">14</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>8.8</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>No Harmful Actions</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">14</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>8.9</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Adverse Event Reporting; Global Safety Database</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">15</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>8.10</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Ionis Internal Oligonucleotide Safety Database</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">15</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 9 COMMERCIALIZATION</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">16</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>9.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Commercialization Responsibilities for Licensed Product</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">16</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>9.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Commercialization Reporting</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">16</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>9.3</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Commercialization Diligence Obligations</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">16</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>9.4</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Standards of Conduct; Compliance</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">16</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 10 MANUFACTURING</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">17</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>10.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Ionis Manufacturing and Supply</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">17</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>10.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Related Drug Substance Supply</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">17</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>10.3</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Ono Manufacturing</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">17</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>10.4</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Third Party CMOs</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">17</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 11 PAYMENTS</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">17</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>11.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Upfront Payment</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">17</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>11.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Milestone Payments</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">17</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>11.3</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Royalties</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">19</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;">ii</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</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;">

        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>11.4</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Other Amounts Payable</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">21</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>11.5</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Financial Records and Audits</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">21</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>11.6</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>No Refunds</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">21</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>11.7</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Accounting Standards</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">21</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>11.8</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Method of Payment; Exchange Rate</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">21</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>11.9</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Blocked Payments</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">22</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>11.10</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Taxes</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">22</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>11.11</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Late Payments; Disputed Payments</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">23</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 12 INTELLECTUAL PROPERTY</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">23</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>12.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Inventions</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">23</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>12.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Patent Prosecution</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">25</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>12.3</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Enforcement Against Third Party Infringement or Misappropriation</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">26</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>12.4</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Defense of Third Party Challenges</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">27</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>12.5</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Third Party Infringement Claims</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">29</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>12.6</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Patent Challenges of Third Party Patent Rights</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">29</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>12.7</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Orange Book Listing</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">30</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>12.8</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Patent Term Extensions</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">30</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>12.9</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Unified Patent Court</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">30</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>12.10</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Common Interest</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">31</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 13 REPRESENTATIONS, WARRANTIES, AND COVENANTS</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">31</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>13.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Mutual Representations and Warranties</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">31</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>13.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Additional Ionis Warranties and Covenants</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">31</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>13.3</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Additional Ono Warranties</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">33</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>13.4</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Additional Covenants</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">33</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>13.5</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Disclaimer</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">34</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>13.6</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Limitation of Liability</div>
          </td>
          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">34</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 14 CONFIDENTIALITY</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">34</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>14.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Duty of Confidence</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">34<br>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>14.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Confidential Information</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">35</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>14.3</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exemptions</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">35</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>14.4</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Authorized Disclosures</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">36</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>14.5</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Publications</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">37</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>14.6</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Publication and Listing of Clinical Trials</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">38</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>14.7</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Publicity; Use of Names</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">39</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>14.8</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Acknowledgement</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">39</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;">iii</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
      <div class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</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;">

        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 15 INDEMNIFICATION</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">39</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>15.1</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Indemnification by Ionis</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">39</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>15.2</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Indemnification by Ono</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">40</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>15.3</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Indemnification Procedure</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">40</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>15.4</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Insurance</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">41</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 16 TERM AND TERMINATION</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">41</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>16.1</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Term</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">41</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>16.2</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Termination for Material Breach</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">41</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>16.3</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Termination by Ono for Convenience</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">42</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>16.4</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>[***]</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">42</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>16.5</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Termination for Patent Challenge</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">42</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>16.6</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Termination for Insolvency</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">42</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>16.7</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Full Force and Effect During Notice Period</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">43</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>16.8</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Effects of Termination</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">43</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>16.9</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Survival; Accrued Rights</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">47</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 17 DISPUTE RESOLUTION; GOVERNING LAW</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">47</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>17.1</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Executive Officers; Disputes</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">47</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>17.2</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Arbitration</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">48</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>17.3</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Intellectual Property Disputes</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">48</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>17.4</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Equitable Remedies</div>
          </td>
          <td style="width: 5%; vertical-align: top; text-align: right;">48</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>17.5</div>
          </td>
          <td style="width: 82%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Governing Law; English Language</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">48</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%;" colspan="3" rowspan="1">&#160;</td>
          <td style="width: 5%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; width: 6%; background-color: rgb(204, 238, 255);" colspan="3" rowspan="1">
            <div style="margin-right: 36pt;">ARTICLE 18 MISCELLANEOUS</div>
          </td>
          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">49</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
          <td style="width: 7%; vertical-align: top;">
            <div>18.1</div>
          </td>
          <td style="width: 82%; vertical-align: top;">
            <div>Assignment</div>
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          <td style="width: 5%; vertical-align: top;">
            <div style="text-align: right;">49</div>
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          <td style="width: 5%; vertical-align: top; text-align: right;">50</td>
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            <div>Severability</div>
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          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">50</td>
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          <td style="width: 5%; vertical-align: top; text-align: right;">50</td>
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          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
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            <div>Notices</div>
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          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">51</td>
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          <td style="width: 5%; vertical-align: top; text-align: right;">51</td>
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          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">51<br>
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          <td style="width: 5%; vertical-align: top; text-align: right;">51</td>
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            <div>Cumulative Remedies</div>
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          <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">52</td>
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          <td style="width: 6%; vertical-align: top;" colspan="1">&#160;</td>
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    <div style="text-align: center; font-weight: bold;">LICENSE AGREEMENT</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">This <font style="font-weight: bold; font-variant: small-caps;">License Agreement</font><font style="font-weight: bold;">&#160;</font>(this &#8220;<font style="font-weight: bold; font-style: italic;">Agreement</font>&#8221;)

      is signed as of March 10, 2025 (the &#8220;<font style="font-weight: bold; font-style: italic;">Execution Date</font>&#8221;) between <font style="font-weight: bold; font-variant: small-caps;">Ionis Pharmaceuticals, Inc.</font>, a Delaware corporation, having
      its principal place of business at 2855 Gazelle Court, Carlsbad, CA 92010, USA (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis</font>&#8221;), and <font style="font-weight: bold; font-variant: small-caps;">Ono Pharmaceutical Co., Ltd.</font><font style="font-variant: small-caps;">, </font>a company organized and existing under the laws of Japan, having its principal place of business at 8-2 Kyutaromachi 1-chome, Chuo-ku, Osaka-shi, Osaka 541-8564, Japan (&#8220;<font style="font-weight: bold; font-style: italic;">Ono</font>&#8221;).&#160; Ionis and Ono may be referred to in this Agreement individually as a &#8220;<font style="font-weight: bold; font-style: italic;">Party</font>&#8221; and collectively as the &#8220;<font style="font-weight: bold; font-style: italic;">Parties</font>.&#8221; Capitalized terms used in this Agreement, whether used in the singular or the plural, have the meaning set forth in <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 1</u>.&#160; All attached appendices and
      schedules are part of this Agreement.</div>
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    <div style="text-align: center; font-weight: bold;">RECITALS</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">WHEREAS</font>, Ionis possesses certain Patent Rights, Know-How, technology and expertise with respect to research, development, and manufacturing of RNA-targeted
      antisense drugs, and is currently developing the Licensed Product;</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">WHEREAS</font>, Ono (itself and through its Affiliates) has expertise in the development of biopharmaceutical products and has regulatory, development, and commercial
      capabilities to bring the Licensed Products to patients in the Territory; and</div>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">WHEREAS</font>, Ono wishes to receive from Ionis, and Ionis desires to grant to Ono a worldwide license to develop, manufacture, and commercialize the Licensed
      Products as set forth in, and subject to the terms of, this Agreement.</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">NOW THEREFORE</font>, the Parties agree as follows:</div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 1</div>
    <div style="text-align: center; font-weight: bold;">OVERVIEW</div>
    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Development and Commercialization</font>.&#160; As of the Execution Date, Ionis is Developing the Licensed Product in an ongoing Clinical Trial in the Territory (such study is further described and defined in <u>Section

                7.1</u> (Ongoing Clinical Trial)).&#160; Under this Agreement, the Parties intend that, as between the Parties: (a) Ionis will continue to conduct the Ongoing Clinical Trial, at [***] cost and expense, in accordance with the Ongoing Clinical
              Trial Development Plan, (b) if requested by Ono, Ionis will conduct an extension of the Ongoing Clinical Trial at [***] cost and expense, (c) other than the Ongoing Clinical Trial, including any extension of such study, Ono will conduct all
              further Development of the Licensed Product in the Territory, which Development will be at [***] cost and expense, and (d) Ono will seek Regulatory Approval for the Licensed Product in the Territory and, following Regulatory Approval,
              Commercialize the Licensed Product in the Territory.</div>
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    <div><br>
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            <div><font style="font-weight: bold;">Governance</font>.&#160; The Parties have agreed to form a joint steering committee to oversee and coordinate the Development activities with respect to the Licensed Products under this Agreement through the
              [***] Regulatory Approval of the [***] Licensed Product [***].</div>
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    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Purpose</font>.&#160; The purpose of this <u>Article 1</u> (Overview) is to provide a high-level overview of the roles, responsibilities, rights, and obligations of each Party under this Agreement, and
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    <div>&#160;</div>
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    <div style="text-align: center; font-weight: bold;">ARTICLE 2</div>
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            <div><font style="font-weight: bold;">License Grant to Ono</font>. Subject to the terms of this Agreement (including Ionis&#8217; retained rights set forth in <u>Section 2.6</u> (No Other Rights and Retained Rights)), and effective as of the
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    <div>&#160;</div>
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            <div>an exclusive (even as to Ionis and its Affiliates), royalty-bearing license, with the right to grant sublicenses (through multiple tiers, solely in accordance with <u>Section 2.2.1(a)</u> (Rights of Ono to Grant Sublicenses)), under the
              Ionis Product-Specific Technology and Ionis Core Technology, in each case to Develop, Manufacture, Commercialize and otherwise Exploit the Licensed Compounds and the Licensed Products in the Field in the Territory; and</div>
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    <div>&#160;</div>
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            <div>a non-exclusive, royalty-bearing license, with the right to grant sublicenses (solely in accordance with <u>Section 2.2.1(b)</u> (Rights of Ono to Grant Sublicenses)), under the Ionis Manufacturing and Analytical Technology to Manufacture
              the Licensed Compounds and the Licensed Products in the Field in the Territory, solely for the Development and Commercialization of the Licensed Products in the Field in the Territory.</div>
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    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Sublicensing Terms</font>.</div>
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    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Rights of Ono to Grant Sublicenses</font>.</div>
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    <div>&#160;</div>
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            <div>Subject to the terms of this Agreement, Ono may grant sublicenses of the rights granted under <u>Section 2.1.1</u> to its Affiliates and to Third Parties[***].</div>
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    <div>&#160;</div>
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            <div>Subject to the terms of this Agreement, Ono may grant sublicenses of the rights granted under <u>Section 2.1.2</u> (i) to its Affiliates to [***], (ii) to [***]; and (iii) to [***] (A) to [***], and (B) to [***].</div>
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    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Requests to Grant Sublicenses to CMOs</font>.&#160; If Ono provides Ionis with a written request for Ionis to grant a license under the Ionis Manufacturing and Analytical Technology to a Third Party designated
              by Ono solely for such Third Party to Manufacture the Licensed Compounds in the Territory for Ono, its Affiliate or Sublicensee in a manufacturing facility owned or operated by such Third Party, and such Third Party does not have a valid
              license granted by Ionis under the Ionis Manufacturing and Analytical Technology, then Ionis will [***].&#160; Before Ionis grants such a license to such Third Party, Ionis will require such Third Party to complete a CMO qualification process,
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              which will govern quality matters pertaining to the Manufacturing and supply of the Licensed Compounds for Development, Commercialization, and Exploitation purposes in the Territory.</div>
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    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Sublicense Agreements</font>.&#160; Each sublicense granted by Ono pursuant to this <u>Section 2.2</u> (Sublicensing Terms) will (a) be subject and subordinate to this Agreement, (b) be consistent with the
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              include terms that are consistent with the intellectual property provisions set forth in this Agreement.&#160; Without limiting the generality of the foregoing, Ono&#8217;s right to sublicense to Third Parties, including through multiple tiers, is
              conditioned on every sublicense agreement with a Third Party entered into after the Effective Date [***].&#160; At Ionis&#8217; request, Ono will provide Ionis with a copy of any executed sublicense agreement with a Third Party that will perform [***],
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    <div>&#160;</div>
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    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Right to Subcontract</font>. Each Party may engage one or more Third Party subcontractors to perform services in furtherance of the performance of its obligations or exercise of its rights under this
              Agreement; <font style="font-style: italic;">provided </font>that (a) neither Party will engage any such Third Party that has been Debarred/Excluded, (b) no engagement of any such Third Party subcontractors will relieve the engaging Party
              of its obligations under this Agreement or any liability hereunder, and (c) the engagement of such Third Party subcontractors is consistent with the engaging Party&#8217;s standard business practices.</div>
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    <div>&#160;</div>
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            <div><font style="font-weight: bold;">Subcontract Agreements</font>.&#160; Each agreement pursuant to which a Party engages any Third Party subcontractor to perform its obligations or exercise its rights under this Agreement will (a) be subject and
              subordinate to this Agreement, (b) be consistent with the terms of this Agreement, (c) include obligations of confidentiality and non-use applicable to the Confidential Information of the other Party that are at least as stringent as those
              set forth in <u>Article 14</u> (Confidentiality), and (d) include terms that are consistent with the intellectual property provisions set forth in this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z295f8cee736e49deb64dee3eb30af1fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Responsibility for Sublicensees and Subcontractors</font>.<font style="font-weight: bold;">&#160; </font>Notwithstanding any sublicense or subcontract granted in accordance with <u>Section 2.2</u>
              (Sublicensing Terms), <u>Section 2.3</u> (Subcontracting Terms), or <u>Section 2.5</u> (Improvement Enabling License), the sublicensing or subcontracting Party will remain primarily liable to the other Party for the performance of all of
              its obligations under, and such Party&#8217;s compliance with all provisions of, this Agreement.&#160; Each Party agrees that it will be fully responsible and liable for any breach of the terms of this Agreement by any of its Sublicensees or
              subcontractors to the same extent as if such Party itself had committed any such breach.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7b55fd4397454bc4932a52a8e329ed5d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc49f4248707b453a89ad91752cb6cad1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Other Rights and Retained Rights</font>.&#160; Nothing in this Agreement will be interpreted to grant a Party any rights under any intellectual property rights owned or Controlled by the other Party,
              including Ionis Technology or Ono Technology, in each case, that are not expressly granted herein, whether by implication, estoppel, or otherwise.&#160; Ono will not practice the Ionis Technology other than as expressly licensed and permitted
              under this Agreement [***].&#160; Any rights not expressly granted to Ono by Ionis under this Agreement are hereby retained by Ionis, [***].&#160; Without limiting the foregoing, Ionis hereby expressly retains the right to perform (a) Development
              activities for the Licensed Products worldwide in accordance with the Ongoing Clinical Trial Development Plan, (b) Manufacturing activities worldwide to support Ionis&#8217; Development activities under the Ongoing Clinical Trial Development Plan,
              and (c) Ionis&#8217; other obligations under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">3</font></div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z2e5b46a23c964c188b303eb4917044cd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-weight: bold;">Existing Third-Party IP Agreements.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z34ab286c4a734bbc8b465722f89e253e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">2.7.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Compliance</font>.&#160; Ono acknowledges and agrees that (a) the rights and licenses granted to Ono under this Agreement are subject to the applicable terms of all Existing Third-Party IP Agreements with
              respect to the Ionis Technology that is being sublicensed thereunder, (b) Ionis&#8217; ability to comply with its obligations, and grant rights and licenses to Ono, under this Agreement are limited by any and all requirements and restrictions
              imposed on Ionis under the Existing Third-Party IP Agreements with respect to the Ionis Technology that is being sublicensed by Ionis under such Existing Third-Party IP Agreements, and (c) Ionis will not be required to take any action or
              inaction pursuant to this Agreement that would cause Ionis to be in breach of any Existing Third-Party IP Agreement or to grant any rights to Ono hereunder that are in violation of, or inconsistent with, any Existing Third-Party IP Agreement,
              [***].&#160; Ono will, and will cause its Affiliates, licensees, and Sublicensees to, abide by the applicable terms of the Existing Third-Party IP Agreements (to the extent such Existing Third-Party IP Agreements were disclosed to Ono), and,
              subject to Ionis&#8217; compliance with <u>Section </u><u>2.7.2</u> (Existing Third Party IP Amendments), any amendments thereto, to the extent disclosed in the copies of the Existing Third-Party IP Agreements.&#160; If [***], which [***], then [***]
              shall promptly, but in no event less than [***] thereafter, provide written notice thereof to [***].&#160; Subject to [***].&#160; If [***] within [***] of [***], then [***].&#160; Notwithstanding any provision to the contrary in this Agreement, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf1870bded03144edb9085ee047289c12" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">2.7.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Existing Third-Party IP Amendments</font>.&#160; During the Term, Ionis will not[***] terminate any Existing Third-Party IP Agreement or amend any Existing Third-Party IP Agreement, in each case, to the extent
              that doing so would conflict with, or materially and adversely affect, Ono&#8217;s rights under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z79267a42a4514ed3a12855a555438571" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Future Third-Party IP Agreements</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zcb5f5ec4dc4445a7bb307fb1c855d43e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Identification of Future Third Party Patent Rights</font>.&#160; If either Party identifies additional Third Party Patent Rights that would be considered Ionis Product-Specific Technology or Ionis Core
              Technology if Ionis Controlled such Third Party Patent Rights (&#8220;<font style="font-weight: bold; font-style: italic;">Future Third Party IP</font>&#8221;), then such Party will provide the other Party with written notice of such Future Third Party
              IP.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3b6eebaf9b244e1baf25ed886c571c64" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Future Third Party </font>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z8496e9b83d0e40469154aec82c2e7bd0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ono First Right</font>.&#160; If such Party believes that such Future Third Party IP is [***] and would be considered Ionis Product-Specific Patents or Ionis Product-Specific Know-How if Ionis Controlled such
              Patent Rights or Know-How (such Patent Rights and Know-How, &#8220;<font style="font-weight: bold; font-style: italic;">Future Third Party </font>[***]&#8221;), then Ono will have the first right, but not the obligation, to negotiate, and enter into an
              agreement, with a Third Party to acquire or obtain a license, covenant not to sue, or other similar right to such Future Third Party [***].&#160; If Ono enters into an agreement with such Third Party for rights to such Future Third Party [***],
              then Ono will pay the financial obligations due under such agreement that are attributable to the Development or Commercialization of any Licensed Product, and, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 72pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Step-In Right</font>.&#160; If Ono elects not to obtain rights to such Future Third Party [***], then Ono will so notify Ionis, and Ionis may obtain rights to such Future Third Party [***].&#160; If Ionis
              obtains such rights, then, upon Ono&#8217;s request, Ionis will include such Future Third Party [***] in the license granted to Ono under <u>Section 2.1</u> (License Grant to Ono), <font style="font-style: italic;">so long as </font>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">4</font></div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z9eb44863d531408ea297aabb897fef92" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">2.8.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Future Third Party </font>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z35139548fb194cc4b9057e1127f8723c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ono First Right</font>.&#160; If such Party believes that such Future Third Party IP is [***] and would be considered Ionis Product-Specific Patents or Ionis Product-Specific Know-How if Ionis Controlled such
              Patent Rights or Know-How (such Patent Rights and Know-How, &#8220;<font style="font-weight: bold; font-style: italic;">Future Third Party </font>[***]&#8221;), then Ono will have the first right, but not the obligation, to negotiate, and enter into an
              agreement, with a Third Party to acquire or obtain a license, covenant not to sue, or other similar right to such Future Third Party [***].&#160; If Ono enters into an agreement with such Third Party for rights to such Future Third Party [***],
              then [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7a05009757b34989987c3b88204e947d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Step-In Right</font>.&#160; If Ono elects not to obtain rights to such Future Third Party [***], then Ono will so notify Ionis, and Ionis may obtain rights to such Future Third Party [***].&#160; If Ionis
              obtains such rights, then, upon Ono&#8217;s request, Ionis will include such Future Third Party [***] in the license granted to Ono under <u>Section 2.1</u> (License Grant to Ono), <font style="font-style: italic;">so long as </font>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd12f1310b1d84eafb928df30c2d70992" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">2.8.4</td>
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            <div><font style="font-weight: bold;">Future Third Party Core IP</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd8ea31cc8fd244f68abe7d5a24648595" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis First Right</font>. <font style="font-weight: bold;">&#160;</font>If such Future Third Party IP would be considered Ionis Core Patents or Ionis Core Know-How if Ionis Controlled such Patent Rights or
              Know-How (such Patent Rights and Know-How, &#8220;<font style="font-weight: bold; font-style: italic;">Future Third Party Core IP</font>&#8221;), then Ionis will have the first right, but not the obligation, to negotiate, and enter into an agreement,
              with a Third Party to acquire or obtain a license, covenant not to sue, or other similar right to such Future Third Party Core IP.&#160; If Ionis enters into an agreement with such Third Party for rights to such Future Third Party Core IP, then
              Ionis will include such Future Third Party Core IP in the license granted to Ono under <u>Section 2.1</u> (License Grant to Ono), and, subject to <u>Section 11.3.3(d)</u> (Royalty Floor), [***] will pay the financial obligations due under
              such agreement with respect to such Future Third Party Core IP.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z15549dbe3d3a45d0b6cc7797ff335cad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ono Step-In Right</font>.&#160; If Ionis elects not to obtain rights to such Future Third Party Core IP, then Ionis will so notify Ono, and Ono may obtain rights to such Future Third Party Core IP.&#160; [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z93415db19fda48248956c6210bf3108d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">2.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3337d6f2311446f78f25494ce6a06619" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z291a1511d86e40e38f44819b50dcfe82" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">2.9.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 3</div>
    <div style="text-align: center; font-weight: bold;">EXCLUSIVITY</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z018acc2e5ea2437290474aa1f98f4c23" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">3.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Exclusivity Covenants of the Parties</font>.&#160; Except in the performance of its obligations or exercise of its rights under this Agreement, and except as set forth in <u>Section 3.2</u> (Limitations and
              Exceptions to Exclusivity Covenants):</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z81dae928af254a119392191cfafe94af" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">3.1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>from the Effective Date until the earliest to occur of (a) [***], (b) [***], and (c) the termination of this Agreement, neither Party nor its Affiliates will [***], itself or through a Third Party, [***]; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zcfe1fb4e077741828909d57dc733562c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>from the Effective Date until the earliest to occur of (a) [***] and (b) the termination of this Agreement, neither Party nor its Affiliates will [***], itself or through a Third Party, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0534fe1d08a74cae864bde71a47b52ba" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Limitations and Exceptions to Exclusivity Covenants</font>.&#160; Notwithstanding anything to the contrary in this Agreement, a Party&#8217;s practice of the following will not violate <u>Section 3.1</u> (Exclusivity
              Covenants of the Parties):</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc293a081361f41cc883d218048c2e594" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">3.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>performance of the activities designated to such Party under the Ongoing Clinical Trial Development Plan;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze13c4ad7d93e4a34910679f8b4521edd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">3.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>performance of any activities or fulfillment of any obligations under any Prior Agreement;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7d4941ea81d444e1b9f090716fad658d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">3.2.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the granting of, or performance of obligations under, Permitted Licenses;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z956666b58e4d4f19ae34e09557a4af7b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">3.2.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the performance of non-clinical Development activities; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zac02b7c66d7e45e2b5480a64092bb225" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">3.2.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the granting of, or performance of obligations or exercise of rights under, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd01fd6ef8e1f43a3b233fdbde5878d5e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">3.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Effect of Exclusivity on Indications</font>.&#160; Ionis and Ono are subject to certain exclusivity covenants under <u>Section 3.1</u> (Exclusivity Covenants of the Parties); <font style="font-style: italic;">however</font>,
              the Parties acknowledge and agree that each Party (on its own or with or through a Third Party or an Affiliate) may develop and commercialize products for the same indication as a Licensed Product so long as such product is [***].&#160; Unless
              otherwise agreed in a separate agreement between the Parties, after the expiration of the exclusivity covenants set forth in <u>Section 3.1</u> (Exclusivity Covenants of the Parties), neither Party will be prohibited from pursuing (on its
              own or with or through a Third Party or an Affiliate) any products for any target or therapeutic area.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 4</div>
    <div style="text-align: center; font-weight: bold;">GOVERNANCE</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9ab8108e773a4b9d8013ef6595bdb855" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Joint Steering Committee</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z54ff216d46a840cc87175a2f78be88e7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">4.1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Formation and Purpose of the JSC</font>.&#160; Within [***] after the Effective Date, Ionis and Ono will establish a joint steering committee (&#8220;<font style="font-weight: bold; font-style: italic;">JSC</font>&#8221;)
              to oversee, review, monitor, coordinate, and, where specified in this <u>Section 4.1</u> (Joint Steering Committee), [***] the Parties&#8217; [***] activities under this Agreement for the Licensed Products in the Territory and updates to the
              Ongoing Clinical Trial Development Plan in accordance with this <u>Section 4.1</u> (Joint Steering Committee).&#160; The JSC will dissolve upon [***].&#160; From time to time, the JSC may establish working groups to oversee particular activities, as
              it deems necessary or advisable (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Working Group</font>&#8221;).&#160; Each Working Group shall consist of such number of representatives of each Party as the JSC determines is appropriate from
              time to time.&#160; Such representatives shall be individuals with expertise relevant to the particular Working Group.&#160; Each Working Group shall meet with such frequency as the Working Group, once formed, deems to be advisable.&#160; If the Working
              Group cannot reach unanimity on any topic, the matter shall be immediately referred to the JSC, which shall resolve such matter in accordance with <u>Section 4.3</u> (Decision-Making) and <u>Section 4.4</u> (Resolution of Committee
              Disputes).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">6</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zb574a0f5537b49dbb830642266e1db19" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">4.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Membership</font>.&#160; The JSC will be composed of an equal number of representatives from each Party who have the appropriate and direct knowledge and expertise and requisite decision-making authority.&#160; Each
              Party may replace any of its representatives on the JSC and appoint a person to fill the vacancy arising from each such replacement.&#160; A Party that replaces a representative will notify the other Party at least [***] prior to the next
              scheduled meeting of the JSC.&#160; Ionis will designate one of its JSC members as one of the co-chairpersons of the JSC and Ono will designate one of its members as the other co-chairperson of the JSC (each, a &#8220;<font style="font-weight: bold; font-style: italic;">JSC</font><font style="font-style: italic;">&#160;</font><font style="font-weight: bold; font-style: italic;">Co-Chairperson</font>&#8221;).&#160; The JSC Co-Chairpersons or their designees, in collaboration with the Liaisons, will be
              responsible for calling meetings, preparing and circulating an agenda in advance of each meeting, and preparing and issuing minutes of each meeting promptly thereafter.&#160; Such minutes will not be finalized until all JSC members have had [***]
              to review and confirm the accuracy of such minutes.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf3d9f1a71a7345de82bda79b0cd88090" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">4.1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Meetings</font>.&#160; The JSC will hold meetings at such times as it elects to do so, but, (a) until [***], will meet no less frequently than [***], and (b) commencing with the [***], will meet no less
              frequently than every [***], in each case ((a) and (b)), unless otherwise agreed by the Parties.&#160; The JSC may meet in person or by means of audio or video conference as determined by the JSC.&#160; Each Party will be responsible for all its own
              costs and expenses of participating in any JSC meeting.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zdf02040d3ac743b6b78aa2b19bba4dfd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">4.1.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Meeting Agendas</font>.&#160; Each Party will disclose to the other Party the proposed agenda items along with appropriate information at least [***] in advance of each meeting of the JSC; <font style="font-style: italic;">provided</font> that under exigent circumstances requiring JSC input, a Party may provide its agenda items to the other Party within a shorter period of time in advance of a meeting, or may propose that there not
              be a specific agenda for a particular meeting, so long as such other Party consents to such later addition of such agenda items or the absence of a specific agenda for such JSC meeting.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za2269dcd431d445b8ad8deb2b703fc7f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">4.1.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Specific Responsibilities of the JSC</font>.&#160; The responsibilities of the JSC will be to:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3f0cb8552aba4b8db2a7e8a6b51b6e51" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>manage the overall strategic alignment between the Parties under this Agreement and maintain the relationship between the Parties;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zebbf615018d749fda794131ebc4b6b31" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review, discuss, and manage the activities related to the Technology Transfers;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6bd1c9eeeeac439da5327d8adda1058a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zabd5fe24835c47428374eb6b594ad678" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>share information related to, and review and discuss activities and progress under, the Ongoing Clinical Trial Development Plan;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z1ae5b0ee14ed41c297853c36dbb7b06c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(e)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z4b44102493eb48ac977a721c6c88d8fc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(f)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review and discuss&#160;the study design, high-level plan, and timeline for [***] Pivotal Clinical Trial for [***] Licensed Product, as described in <u>Section 7.7</u> (Pivotal Clinical Trial Design and Regulatory Strategy);</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5e14cf17942e4690940b73ed3fc8b1b5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(g)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review and discuss the regulatory strategy for [***] Regulatory Approval of [***] Licensed Product [***], as described in <u>Section 7.7</u> (Pivotal Clinical Trial Design and Regulatory Strategy);</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z567c6cb5bef243fc8cd10a7fe78b42db" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(h)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review and discuss any matters related to the Development of the Licensed Products referred to the JSC by either Party&#8217;s representatives;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">7</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z0702f7ab474047b4978a67ce03ba7cde" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(i)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>review and discuss, either at meetings of the JSC or through any manufacturing Working Group of the JSC, any matters related to Manufacturing and supply chain plans for the Licensed Compounds and Licensed Products, the performance of CMOs
              that Manufacture the Licensed Compounds and Licensed Products, and any other issues pertaining to the Manufacturing of the Licensed Compounds and Licensed Products; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7a3c40a6f6024910b3995a75318ef174" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(j)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>perform such other functions as appropriate to further the purposes of this Agreement as determined by the Parties.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0a69ca6df4a54ef3916fcefe83a1c343" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Additional Participants</font>.&#160; Employees of a Party or any of its Affiliates involved in the Exploitation of the Licensed Products may attend meetings of the JSC as non-voting participants with the prior
              notice of the other Party.&#160; In addition, with the prior notice of each Party, consultants, representatives, or advisors involved in the same activities and under written obligations of confidentiality and non-use applicable to the
              Confidential Information of each Party that are at least as stringent as those set forth in <u>Article 14</u> (Confidentiality) may attend meetings of the JSC as non-voting observers.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z65fa095618cd41429f31ebcacc827315" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Decision-Making</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc170a8fee295426bb3e6ad027dab5d50" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">4.3.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">General Decision-Making Process</font>.&#160; Each Party&#8217;s representatives on the JSC will, collectively, have [***].&#160; The JSC will [***], which will be reflected in the minutes of the committee meeting or
              [***].&#160; Except as otherwise expressly set forth in this Agreement, the phrase [***] the JSC and similar phrases used in this Agreement will mean [***] in accordance with this <u>Section 4.3</u> (DecisionMaking&#8209;), [***].&#160; [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z4f8a0ca8f5c741a797e00074b49189ee" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">4.3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Decisions of the JSC</font>.&#160; The JSC will use good faith efforts, in compliance with this <u>Section 4.3.2</u> (Decisions of the JSC), to promptly resolve any such matter for which it has authority.&#160; If
              the JSC does not resolve any such matter within [***], then the Parties may refer such matter to their respective Executive Officers for resolution in accordance with <u>Section 4.4.1</u> (Referral to Executive Officers).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0d9b418e44a14e61908baa88824e752e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">4.3.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Except as otherwise expressly stated in this Agreement, the JSC will have no decision-making authority and will act as a forum for sharing information about the activities conducted by the Parties hereunder and as an advisory body, in each
              case only on the matters described in, and to the extent set forth in, this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7a00950eb82d4110bfa929fc6d343bc2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Resolution of Committee Disputes</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0dbcd02acd6e41d5bb426958588f2c39" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">4.4.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Referral to Executive Officers</font>.&#160; If a Party refers a matter to the Executive Officers under <u>Section 4.3.2</u> (Decisions of the JSC), then the Executive Officers will use good faith efforts to
              resolve any such matter so referred to them as soon as practicable but, in any event, within [***] after such matter is referred to them, and any final decision that the Executive Officers agree to in writing will be conclusive and binding on
              the Parties.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6c38a5de26084cf0b0f23d634c6d0eaf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">4.4.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Final Decision-Making Authority</font>.&#160; If the Executive Officers do not reach agreement on any matter referred to them in accordance with <u>Section 4.4.1</u> (Referral to Executive Officers) within
              [***] after such matter is referred to them (or such longer period as the Executive Officers may agree upon), then, subject to <u>Section 4.4.3</u> (Limitations on Decision Making):</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">8</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="za7e03a787f0b462cb2a7e2b82d39b23a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Final Decision-Making Authority</font>.&#160; Ionis will have final decision-making authority over [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc294ea7cde094aefbdb217b55f88e930" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ono Final Decision-Making Authority</font>.&#160; Ono will have final decision-making authority over [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z07e361d3e7d243f78b4a371de14a7c12" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Change; Status Quo</font>.&#160; Neither Party will have final decision-making authority with respect to the final resolution of any disagreement related to (a) [***], or (b) [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9dd71c524a464a1f918125129b572687" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">4.4.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Limitations on Decision Making</font>.&#160; Notwithstanding anything to the contrary set forth in this Agreement, no decision of the JSC, or a Party&#8217;s Executive Officer (in the exercise of a Party&#8217;s
              decisionmaking authority on any such matters), in each case may, without the other Party&#8217;s prior written consent, (a) [***], (b) [***], (c) [***], or (d) [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbb78285c46184a0dbf19a21f1fa3a780" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Day-to-Day Responsibilities</font>.&#160; Each Party will: (a) be responsible for day-to-day implementation and conduct of the activities hereunder for which it has or is otherwise assigned responsibility under
              this Agreement, <font style="font-style: italic;">provided</font> that [***]; and (b) provide the other Party with [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc3beafa157694a3b8089c605f4a9da1b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">4.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Liaisons</font>.&#160; Each Party will appoint a representative of such Party to act as its liaison under this Agreement no later than [***] after the Effective Date (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Liaison</font>&#8221;).&#160; The role of the Liaison is to act as a single point of contact between the Parties to ensure a successful relationship under this Agreement.&#160; The Liaisons will attend all JSC meetings and will support
              the JSC Co-Chairpersons in the discharge of their responsibilities.&#160; Liaisons will be non-voting participants in all JSC meetings, but a Liaison may bring any matter to the attention of the JSC if such Liaison reasonably believes that such
              matter warrants such attention.&#160; Each Party may change its designated Liaison at any time upon written notice to the other Party.&#160; Any Liaison may designate a substitute to temporarily perform the functions of that Liaison by written notice
              to the other Party.&#160; Each Liaison will also: (a) be the point of first referral in all matters of conflict resolution; (b) provide a single point of communication for seeking consensus between the Parties regarding key strategy and plan
              issues; (c) identify and bring disputes to the attention of the JSC in a timely manner; (d) plan and coordinate cooperative efforts and internal and external communications; and (e) take responsibility for ensuring that governance activities,
              such as the conduct of required committee meetings and production of meeting minutes, occur as set forth in this Agreement, and that the relevant action items resulting from such meetings are appropriately carried out or otherwise addressed.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 5</div>
    <div style="text-align: center; font-weight: bold;">CLOSING</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z30a881ee02d445fb8e392044e1f676e7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Closing</font>.&#160; Subject to the last sentence of <u>Section 16.1</u> (Term), the closing of the transaction contemplated by this Agreement will be deemed to have taken place on the date that all necessary
              authorizations, consents, orders or approval of, or declarations or filings with, or expirations of waiting periods under the HSR Act, as applicable to the consummation of the transactions contemplated by this Agreement (&#8220;<font style="font-weight: bold; font-style: italic;">HSR Clearance</font>&#8221;) have been received, authorized, permitted, or expired (the &#8220;<font style="font-weight: bold; font-style: italic;">Effective Date</font>&#8221;).&#160; Ono shall immediately provide
              written notice to Ionis of such Effective Date.&#160; Except for the Parties&#8217; rights and obligations under <u>Section 7.4</u> (Development Activities Prior to Effective Date), <u>Article 13</u> (Representations, Warranties, and Covenants), <u>Article

                14</u> (Confidentiality), <u>Article 17</u> (Dispute Resolution; Governing Law), and this <u>Article 5</u> (Closing), which will be effective as of the Execution Date, this Agreement will not become effective until the Effective Date.&#160;
              Upon the occurrence of the Effective Date, all other provisions of this Agreement will become effective automatically without the need for further action by the Parties.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">9</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zcf2bd37327184c7790ed464b750b0e3e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">5.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Antitrust Filings</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9c33ee212e6744828458d991211a6d8e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">5.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The Parties shall, as promptly as practicable (but no later than [***] after the Execution Date, or as otherwise mutually agreed by the Parties and their respective antitrust counsel), and before the expiration of any relevant legal
              deadline, prepare and file with the United States Federal Trade Commission and the Antitrust Division of the United States Department of Justice (collectively, the &#8220;<font style="font-weight: bold; font-style: italic;">Antitrust Authorities</font>&#8221;),

              the Notification and Report Form for Certain Mergers and Acquisitions (as that term is defined in the HSR Act) required for the transactions contemplated hereby, together with all required documentary attachments thereto and any supplement
              information requested in connection therewith pursuant to the HSR Act (the &#8220;<font style="font-weight: bold; font-style: italic;">Antitrust Filings</font>&#8221;).&#160; Notwithstanding the foregoing, the Parties may, upon mutual agreement, delay the
              filing of any of the Antitrust Filings if they reasonably believe that such delay would result in obtaining any clearance required under the HSR Act for the consummation of this Agreement and the transactions contemplated hereby more
              expeditiously.&#160; The Parties shall cooperate in the antitrust clearance process, including by furnishing to each other&#8217;s counsel such necessary information and reasonable assistance as the other may request in connection with its preparation
              of any filing or submission that is necessary under the HSR Act and to furnish promptly with the Antitrust Authorities any information reasonably requested by them in connection with such filings.&#160; Each Party shall be responsible for its own
              fees, costs, and expenses associated with any Antitrust Filings or in connection with its obligations pursuant to this <u>Section 5.2</u> (Antitrust Filings).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5a22c203918f485aa0c23c515ac02164" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">5.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The Parties shall use their commercially reasonable efforts to promptly obtain HSR Clearance and shall keep each other apprised of the status of any communications with, and any inquiries or requests for additional information from, any
              Antitrust Authority and shall use commercially reasonable efforts to comply promptly with any such inquiry or request.&#160; Commercially reasonable efforts as used in this <u>Section 5.2.2</u> will not include proposing, negotiating, committing
              to or effecting, by consent decree, hold separate order, or otherwise, (a) the sale, divestiture, disposition, licensing or sublicensing of any of a Party&#8217;s or its Affiliates&#8217; assets, properties, or business, (b) behavior limitations, conduct
              restrictions, or commitments with respect to such assets, properties, or business, or of any of the rights or obligations of a Party under this Agreement, or (c) defending through litigation any claim asserted in court by any Third Party that
              would restrain, prevent, or delay the Effective Date.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z32ca481a49b0484ebbf21a894c6f0c1f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">5.2.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Subject to <u>Section 5.2.2</u>, the Parties shall instruct their respective counsel to cooperate with each other and use commercially reasonable efforts to facilitate and expedite the identification and resolution of any issues arising
              under the HSR Act at the earliest practicable dates.&#160; Such commercially reasonable efforts and cooperation include counsel&#8217;s undertaking to (a) keep each other informed of communications, inquiries, and requests from and to personnel of the
              reviewing Antitrust Authorities, including by providing copies thereof to the other Party (subject to reasonable redactions for privilege or confidentiality concerns), and (b) confer with each other regarding appropriate contacts with and
              response to personnel of such Antitrust Authorities and the content of any such contacts or presentations.&#160; Each Party shall consult with the other Party, to the extent practicable in advance of participating in any substantive meeting or
              discussion with any Antitrust Authority with respect to any such filings, applications, investigation, or other inquiry and, to the extent permitted by the relevant Antitrust Authority, give the other Party the opportunity to attend and
              participate in such meeting or discussion.&#160; Each Party shall give the other Party the opportunity to review in advance, and shall consider in good faith the other Party&#8217;s reasonable comments in connection with, the content of any
              presentations, white papers, or other written materials to be submitted to any Antitrust Authority.&#160; Neither Party shall withdraw its filing under the HSR Act or agree to delay the Effective Date without the prior written consent of the other
              Party.&#160; The Parties&#8217; rights and obligations hereunder apply only in so far as they relate to this Agreement and to the transactions contemplated under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">10</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 6</div>
    <div style="text-align: center; font-weight: bold;">TECHNOLOGY TRANSFER</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z1f96095e307a40ad9fdc3b30cd98e859" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Initial Know-How Transfer</font>.&#160; Subject to <u>Section 6.4</u> (Technology Transfer Costs and Support), at a time period to be agreed upon by the Parties after the Effective Date, Ionis will provide and
              transfer to Ono copies of the Ionis Know-How (other than Ionis Manufacturing and Analytical Know-How, the transfer of which will be conducted pursuant to <u>Section 6.3</u> (Manufacturing Technology Transfer)) that (a) exists on the
              Effective Date, (b) was not previously provided to Ono, (c) is [***] for Ono to Develop, Manufacture, Commercialize, and otherwise Exploit the Licensed Compounds and the Licensed Products in the Territory, and (d) is [***], in each case
              ((a)-(d)), in the form in which Ionis maintains such Know-How (such transfer, the &#8220;<font style="font-weight: bold; font-style: italic;">Initial Know-How Transfer</font>&#8221;) [***]. Upon Ono&#8217;s request, Ionis will [***].&#160; Such Initial Know-How
              Transfer shall include: (i) [***]; (ii) [***]; (iii) [***]; (iv) [***], in each case ((i)-(iv)), [***] for Ono to obtain Regulatory Approvals for the Licensed Products in the Field in the Territory.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zeee6157a267d469e9ecbbe91c5c62603" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Additional Know</font><font style="font-weight: bold; font-style: italic;">-</font><font style="font-weight: bold;">How Transfer</font><font style="font-style: italic;">.</font><font style="font-weight: bold; font-style: italic;">&#160; </font>Subject to <u>Section 6.4</u> (Technology Transfer Costs and Support), following the Initial Know-How Transfer, Ionis will make available to Ono all such Ionis Know-How, other than Ionis Manufacturing
              and Analytical Know-How, in Ionis&#8217; possession that (a) is [***], or, (b) [***], in each case ((a) and (b)), that is [***] for the Development, Manufacture, Commercialization, or other Exploitation of the Licensed Compounds and the Licensed
              Products in the Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Additional Know-How Transfer</font>,&#8221; and together with the Initial Know-How Transfer, the &#8220;<font style="font-weight: bold; font-style: italic;">Non-Manufacturing


                Technology Transfer</font>&#8221;).&#160; Ono may only use the Ionis Know-How to perform its obligations or exercise its rights under this Agreement (including, for the avoidance of doubt, the licenses granted under <u>Section 2.1</u> (License Grant
              to Ono)) and in accordance with the terms hereof and will not use such Know-How for any other purpose.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6325c88b45c44782b82eaf161be15a19" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Manufacturing Technology Transfer</font>.&#160; Subject to <u>Section 6.4</u> (Technology Transfer Costs and Support), upon Ono&#8217;s request after the Effective Date at a time mutually agreed by the Parties, Ionis
              will make available to Ono all Ionis Manufacturing and Analytical Know-How and materials that are [***], for Ono to Manufacture the Licensed Product and Licensed Compound in the Territory, in the form in which Ionis maintains such Know-How
              and materials (the &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology Transfer</font>&#8221;).&#160; Upon Ono&#8217;s request, Ionis will [***].&#160; Any materials provided by Ionis to Ono in connection with the transfer of the Ionis
              Manufacturing and Analytical Know-How will remain the sole property of Ionis, and Ono will (a) use such materials only in the fulfillment of obligations or exercise of rights under this Agreement (including, for the avoidance of doubt, the
              licenses granted under <u>Section 2.1</u> (License Grant to Ono)), and (b) not provide such Ionis Manufacturing and Analytical Know-How or materials to any Third Party, without Ionis&#8217; prior written consent, except to its Sublicensees in
              accordance with <u>Section 2.2.1</u> (Rights of Ono to Grant Sublicenses).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">11</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zf5de399b9ee94ec38e11d9ca6858140a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">6.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Technology Transfer Costs and Support</font>.&#160; Ionis will perform the Non-Manufacturing Technology Transfer and the Manufacturing Technology Transfer (collectively, the &#8220;<font style="font-weight: bold; font-style: italic;">Technology Transfers</font>&#8221;) including [***] until the earlier of (a) [***], and (b) [***].&#160; Thereafter, if Ono requests, and Ionis agrees to provide, additional support for the Technology Transfers, Ionis will provide
              [***], and Ono will [***].&#160; In addition, [***], <font style="font-style: italic;">provided </font>that any such [***].&#160; [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 7</div>
    <div style="text-align: center; font-weight: bold;">DEVELOPMENT</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z640d43d8f2be4661befede5c34731fe3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold; color: #000000;">Ongoing Clinical Trial</font><font style="color: #000000;">.</font><font style="font-weight: bold; color: #000000;">&#160; </font>As of the Execution Date, Ionis is conducting a Clinical Trial
              with respect to the Licensed Product under a protocol entitled, &#8220;A Phase 2a, Randomized, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 702843 Administered to Patients with
              Phlebotomy Dependent Polycythemia Vera (PD-PV)&#8221; (the &#8220;<font style="font-weight: bold; font-style: italic;">Ongoing Clinical Trial</font>&#8221;).&#160; The development plan for the Ongoing Clinical Trial mutually approved by the Parties is set forth on
              <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 7.1</u> (such development plan as it may be modified in accordance with the terms and conditions of this Agreement, the &#8220;<font style="font-weight: bold; font-style: italic;">Ongoing

                Clinical Trial Development Plan</font>&#8221;). From time to time during the Term, either Party may submit to the JSC any proposed update to the Ongoing Clinical Trial Development Plan. The JSC will [***] Ongoing Clinical Trial Development Plan.
              [***], each update to the Ongoing Clinical Trial Development Plan will become effective and supersede the previous Ongoing Clinical Trial Development Plan, as of the date of [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9b6568543ed44a478dae5897de8b46ee" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold; color: #000000;">Extension of Ongoing Clinical Trial.&#160; </font>After the Effective Date, if Ono wishes Ionis to extend the treatment period in the Ongoing Clinical Trial to a treatment period of [***] (the &#8220;<font style="font-weight: bold; font-style: italic;">Ongoing Clinical Trial Extension</font>&#8221;), then Ono will notify Ionis in writing as soon as possible after the Effective Date, but in any event no later than [***] after the Effective Date, and
              the Parties, through the JSC, will meet as soon as possible after Ono has notified Ionis of its desire to extend the Ongoing Clinical Trial [***].&#160; Ionis&#8217; estimate of such updated development plan and budget are set forth in <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 7.2</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7e39159e391f4d2f88aa4c087d8873e3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold; color: #000000;">Performance by Ionis</font>.&#160; With respect to the Ongoing Clinical Trial, including any Ongoing Clinical Trial Extension, Ionis shall update Ono at least [***] every [***] at the meetings of
              the JSC regarding the progress of the Ongoing Clinical Trial, including any Ongoing Clinical Trial Extension.&#160; Such update may be in the form in which Ionis presented such information to its senior management in the regular course of its
              business.&#160; Ionis will use Commercially Reasonable Efforts to complete the Ongoing Clinical Trial, including any Ongoing Clinical Trial Extension, in accordance with the Ongoing Clinical Trial Development Plan.&#160; Ionis will conduct all
              Development activities with respect to the Licensed Compound and the Licensed Product in a good scientific manner, in accordance with GLP and GCP, as applicable, and in compliance with Professional Requirements and Applicable Law.&#160; Ionis
              [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z43ce76a53ca24be188a2fc493a290596" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold; color: #000000;">Development Activities Prior to Effective Date</font>.&#160; After the Execution Date and prior to the Effective Date, Ionis will [***] in accordance with the Ongoing Clinical Trial Development
              Plan.&#160; Ionis will promptly notify Ono if Ionis is required to make any material changes to such performance (a) to comply with any changes in Applicable Law, (b) to comply with specific requirements imposed by Regulatory Authorities, or (c)
              as Ionis reasonably determines in good faith are necessary for safety reasons.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">12</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z55620292327742cca3d6a81f33eae6ce" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold; color: #000000;">Development Diligence</font><font style="color: #000000;">.&#160; </font>From and after the Effective Date, Ionis will be responsible for conducting, and will use Commercially Reasonable Efforts
              to conduct, the Ongoing Clinical Trial until [***], in accordance with the Ongoing Clinical Trial Development Plan, and, subject to <u>Section 7.6</u> (Development Costs), any extension of such Ongoing Clinical Trial approved in accordance
              with <u>Section 7.2</u> (Extension of Ongoing Clinical Trial).&#160; Other than the Ongoing Clinical Trial, Ono will be responsible for Developing, and will use Commercially Reasonable Efforts to [***].&#160; Subject to <u>Section 4.4.3</u>
              (Limitations on Decision-Making) and <u>Section 8.8</u> (No Harmful Actions), [***].&#160; Each Party will conduct all Development activities for which it is responsible under this Agreement in a good scientific manner, in accordance with GLP and
              GCP, as applicable, and in compliance with Professional Requirements and Applicable Law.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z34b8c5eb773440308cf76c29a2fcc2a2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold; color: #000000;">Development Costs</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbff008c20ac44901911c752a7d21e0cb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">7.6.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Costs</font>.&#160; Ionis will be solely responsible for (a) [***]<font style="color: #000000;">, and (b) </font>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zfbfc111e8382477a9df384714b8929b7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">7.6.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ono Costs</font>.&#160; After the Effective Date, Ono will be solely responsible for [***].&#160; On a Calendar Quarter-by-Calendar Quarter basis, Ionis will issue an invoice for the [***] incurred in each Calendar
              Quarter no later than [***] after the end of such Calendar Quarter, and Ono will pay the invoiced amounts within [***] after receipt of such invoice.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd4357e1f4aa3436692644edd5fd576b5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">7.6.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cost Overruns</font>.&#160; Ionis will use Commercially Reasonable Efforts to [***].&#160; Ionis will notify the JSC without undue delay if it anticipates that [***] (a &#8220;<font style="font-weight: bold; font-style: italic;">Cost Overrun</font>&#8221;).&#160; Ionis will [***].&#160; Thereafter, the JSC will promptly meet to evaluate whether [***], and if not, the JSC will discuss what steps to take to [***].&#160; If the JSC [***], then [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd757d86cf71b4d9180905199ff46cc5a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold; color: #000000;">Pivotal Clinical Trial Design and Regulatory Strategy</font>.&#160; Within [***], or a longer period agreed by the Parties, after the Effective Date, Ono will provide to the JSC for review and
              discussion the proposed design and an initial draft of the high-level development plan, including a timeline, for [***] Pivotal Clinical Trial for [***] Licensed Product, as well as the regulatory strategy for [***] Regulatory Approval of
              [***] Licensed Product [***].&#160; After submission of the initial draft plan, Ono [***].&#160; The JSC will meet promptly thereafter to discuss the proposed design, plan, and timeline for such study and the proposed regulatory strategy.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze4653493ba5b47aba3d02a941579d419" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold; color: #000000;">Development Reports</font>.&#160; At each JSC meeting, (a) Ionis will [***], and (b) Ono will [***].&#160; For [***] after dissolution of the JSC, on a Calendar Year-by-Calendar Year basis, Ono will
              [***].&#160; Each Party will also promptly provide written notice to the other Party of any significant Development events with respect to the Licensed Products that [***] the other Party under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z1bafab330ebe42d3b0203c2c3bf9a4ad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">7.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold; color: #000000;">Development Records</font>.&#160; Each Party and its Affiliates will maintain written or electronic records, in sufficient detail, in a good scientific manner (in accordance with GLP, GCP, GMP,
              and Applicable Laws, as applicable), and appropriate for regulatory and patent purposes, and that are complete and accurate in all material respects and reflect all Development work performed and results achieved, in each case, by or on
              behalf of such Party and its Affiliates for the Licensed Products.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">13</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 8</div>
      <div style="text-align: center; font-weight: bold;">REGULATORY AFFAIRS</div>
    </div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" id="z63ae8577654b4e26a53ae78d729021f5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Regulatory Responsibility</font>.&#160; Subject to the obligations in this <u>Article 8</u> (Regulatory Affairs), after the Effective Date, Ono will be responsible for[***] all Regulatory Submissions,
              communications, and other dealings with Regulatory Authorities related to the Licensed Products in the Territory and the regulatory strategy for the Licensed Products; <font style="font-style: italic;">provided </font>that, (a) Ionis shall
              have the right to [***], (b) Ionis will [***], and (c) Ionis shall have the right to [***].&#160; At a time period to be agreed upon by the Parties after the Effective Date, Ionis will transfer and assign to Ono the Regulatory Submissions, and all
              related documentation, as applicable, related to the Licensed Products, except, with respect to regulatory filings for Development activities for the Licensed Products for which Ionis is responsible under this Agreement.&#160; Without limiting <u>Section

                8.4</u> (Regulatory Submissions) and <u>Section 8.8</u> (No Harmful Actions), Ono will not be required to delay any submission, correspondence, or communication with any Regulatory Authorities in a manner that affects Ono&#8217;s ability to
              comply with any Regulatory Authority requirement or deadline or Applicable Law in such jurisdiction.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7794a83a9abe4248af26fd81d1db5427" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Correspondence with Regulatory Authorities</font>.&#160; Each Party will provide the other Party with (a) copies of any material written correspondence submitted to or received from any Regulatory Authority, and
              (b) summaries of any material oral communications with any Regulatory Authority, in each case ((a) and (b)), relating to Regulatory Submissions for the Licensed Products, reasonably promptly after receipt or delivery by such Party of such
              correspondence or communication with any Regulatory Authority [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbe899b8d401d452ca7582ea1a814cc4c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Regulatory Meetings</font>.&#160; At any time after the Effective Date, at Ono&#8217;s reasonable request, Ionis will use Commercially Reasonable Efforts to [***].&#160; Ionis will [***].&#160; Ionis will strictly follow Ono&#8217;s
              instructions with respect to any such meeting that it attends and will not [***] except as required by Applicable Law or authorized by Ono in writing.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zebe4e428acdd4604aa0efaf9c5000469" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Regulatory Submissions</font>.&#160; Ono will provide Ionis with a copy of all proposed material Regulatory Submissions (including any Regulatory Submissions related to the Approved Labeling) that it intends to
              file with or submit to any Regulatory Authority [***] for Ionis&#8217; review and comment reasonably in advance of Ono&#8217;s filing or submission thereof, [***].&#160; Ono will [***] any comments received from Ionis into such Regulatory Submissions.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z1234e827ec454f2db88a206ae886e7dd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Investigator&#8217;s Brochure</font>.&#160; Once prepared for any Clinical Trial of the Licensed Products, Ono will share a copy of the investigator&#8217;s brochure with Ionis.&#160; Thereafter, Ono will provide updated
              versions of such investigator&#8217;s brochure to Ionis annually and upon any substantive change to the safety or risk of the Licensed Products.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z1c06225459674dd8ae4fce7630291864" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cooperation and Support</font>.&#160; The Parties will cooperate with each other to achieve the regulatory objectives contemplated herein in a timely, accurate, and responsive manner. Upon Ono&#8217;s reasonable
              request, Ionis will [***], <font style="font-style: italic;">provided </font>that [***].&#160; Ono will reimburse Ionis for [***].&#160; Ionis may invoice Ono for [***] incurred each Calendar Quarter no later than [***] after the end of such Calendar
              Quarter in connection with [***] under this <u>Section 8.6</u> (Cooperation and Support), and Ono will pay the invoiced amounts within [***] after receipt of such invoice.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd9d0aa28229b4e9e931133704ff0a3ea" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cost of Regulatory Activities</font>.&#160; Ionis will be responsible for the costs it incurs in conducting its regulatory activities [***].&#160; Ono will be responsible for [***] in connection with all other
              activities under this <u>Article 8</u> (Regulatory Affairs), including the preparation of Regulatory Submissions and the maintenance of Regulatory Approvals with respect to the Licensed Products and any associated filing and transfer fees.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc26e989f4bdd4172afbb4a30e85d942e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Harmful Actions</font>.&#160; Notwithstanding any provision to the contrary in this Agreement, Ono will not (a) [***], or (b) [***], in each case ((a) and (b)), [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">14</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z7ccdfc30ac034e43abe341b022d534f5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Adverse Event Reporting; Global Safety Database</font>.&#160; The Parties will cooperate with regard to the reporting and handling of safety information involving the Licensed Products in accordance with
              Applicable Law, regulatory requirements, and regulations on pharmacovigilance and clinical safety.&#160; Ionis will transfer the global safety database to Ono on a mutually agreed and appropriate timeline before [***].&#160; After the transfer of such
              database is complete, Ono will be responsible for all processing of information related to any adverse events for the Licensed Products in the Territory, including any information regarding such adverse events that is received from a Third
              Party.&#160; Each Party will promptly provide to the other Party in a timely manner the relevant safety information it receives (either directly or indirectly) related to the Licensed Products.&#160; Within [***] following the Effective Date (or such
              longer time as agreed upon by the Parties), the Parties will negotiate in good faith and enter into a Pharmacovigilance Agreement related to the Licensed Products, which will define the pharmacovigilance responsibilities of the Parties and
              include safety data exchange procedures governing the exchange of information affecting the class and products (<font style="font-style: italic;">e</font>.<font style="font-style: italic;">g</font>., serious adverse events, emerging safety
              issues) to enable each Party to comply with all of its legal and regulatory obligations related to such Licensed Product.&#160; Ono will own and maintain the global safety database for the Licensed Products in accordance with its internal policies
              and procedures, consistently applied.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5f272692a84d4e6f9e675b26b52af07b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">8.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Internal Oligonucleotide Safety Database</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z961f3e22a63e406e99486b07abeacb12" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">8.10.1</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 non-clinical and clinical Development (the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Internal Oligonucleotide Safety Database</font>&#8221;).&#160; To maximize understanding of the safety profile and pharmacokinetics of Ionis compounds, Ionis will have the right to use any
              safety-related information provided by Ono pursuant to the Pharmacovigilance Agreement or this <u>Section 8.10</u>&#160; (Ionis Internal Oligonucleotide Safety Database) solely for the purposes of maintaining the Ionis Internal Oligonucleotide
              Safety Database or with the prior approval of Ono.&#160; In addition, with respect to Clinical Trials of the Licensed Products conducted by or on behalf of Ono, Ono will provide Ionis with copies of annual safety updates filed with each IND and
              the safety sections of any final Clinical Trial reports within [***] following the date such information is filed, as applicable.&#160; Furthermore, Ono will promptly provide Ionis with supporting data and answer any follow-up questions reasonably
              requested by Ionis or its Affiliates to the extent such data and answers are reasonably available to Ono, subject to any confidentiality obligations that are imposed on Ono by Third Parties or Applicable Law.&#160; With respect to any
              confidentiality obligations that are imposed on Ono after the Effective Date by any Third Party in connection with any Clinical Trial of a Licensed Product, Ono will use Commercially Reasonable Efforts [***].&#160; All such information disclosed
              by Ono to Ionis will be Ono&#8217;s Confidential Information; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that so long as Ionis does not disclose the identity of a Licensed Product or Ono&#8217;s
              identity, and such information is included in the Ionis Internal Oligonucleotide Safety Database, Ionis may disclose any such Confidential Information of Ono to (i) Ionis&#8217; other partners if such information is regarding class generic
              properties of oligonucleotides, (ii) any Third Party that contributes to the populating of the Ionis Internal Oligonucleotide Safety Database, or (iii) any Regulatory Authority.&#160; Ono will deliver all such information to Ionis at [***] (or to
              such other address/contact designated in writing by Ionis).&#160; Ono will also cause its Affiliates and Sublicensees to comply with this <u>Section 8.10</u> (Ionis Internal Oligonucleotide Safety Database).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbbb8dd9af22a4b739f7d30c6905d876d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">8.10.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>From time to time, Ionis utilizes the information in the Ionis Internal Oligonucleotide Safety Database to conduct analyses to keep Ionis and its partners informed regarding class generic properties of oligonucleotides, including with
              respect to safety.&#160; As such, if and when Ionis identifies safety or other related issues that may be relevant to a Licensed Product (including any potential class-related toxicity), Ionis will promptly inform Ono of such issues and provide
              the data supporting Ionis&#8217; conclusions.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">15</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z6a0c2090d9b24e768cd68c3c45170507" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">8.10.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>During the Term, Ono may submit written requests to Ionis for Ionis to have queries run of the Ionis Internal Oligonucleotide Safety Database relevant to the Licensed Products, and Ionis will cause such queries to be run and will use
              Commercially Reasonable Efforts to promptly deliver to Ono the results of such queries.&#160; Any information disclosed between the Parties under this <u>Section 8.10.3</u> will be treated as Confidential Information of Ionis in accordance with <u>Article

                14</u> (Confidentiality), to the extent such information would not constitute Confidential Information of Ono.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 9</div>
    <div style="text-align: center; font-weight: bold;">COMMERCIALIZATION</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z78024c33b21d4a298a9554136f121e3f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Commercialization Responsibilities for Licensed Product</font>.&#160; Subject to the terms and conditions of this Agreement, including but not limited to <u>Section 9.3</u> (Commercialization Diligence
              Obligations), Ono and its Affiliates will have [***] with respect to the Commercialization of the Licensed Products in the Territory [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z8493f58aa5fe4f99acc5333a45592fad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Commercialization Reporting</font>.&#160; For each Fiscal Year following the [***] Regulatory Approval for a Licensed Product in the Territory, Ono will provide to Ionis a [***] of the [***] Commercialization
              activities conducted by Ono or its Affiliates, licensees, or Sublicensees for such Licensed Product [***] during such Fiscal Year and the [***] Commercialization activities expected to be conducted by Ono or its Affiliates, licensees, or
              Sublicensees for such Licensed Product [***] during the upcoming Fiscal Year.&#160; Each such report will contain sufficient detail [***] and may be in the form in which Ono presented such information to its senior management in the regular course
              of its business.&#160; In addition, Ono will provide to Ionis a report of the forecasted Net Sales of Licensed Products anticipated to be generated by Ono or its Affiliates, licensees, or Sublicensees during the upcoming Fiscal Year, which
              forecast will be broken down [***] by Calendar Quarter[***].&#160; Ono will provide the first preliminary report of forecasted Net Sales for the Fiscal Year in which a Licensed Product is expected to be launched no later than [***] before the
              expected [***] Regulatory Approval for such Licensed Product and will revise the preliminary report as necessary after such Regulatory Approval, if applicable.&#160; Ono will provide subsequent reports of forecasted Net Sales for each subsequent
              Fiscal Year no later than [***] after the end of each Fiscal Year.&#160; As both Parties&#8217; mutual understanding of the foregoing, it will not constitute a breach of this Agreement if the forecasted Net Sales for any Fiscal Year as set forth in such
              reports differs from actual Net Sales for such Fiscal Year.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z788f72f5381a4d9e89ff71b59dce5bde" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Commercialization </font>[***].&#160; On a Licensed Product-by-Licensed Product basis, following receipt of Regulatory Approval for a Licensed Product [***], Ono will use [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z2b70ec0086794d938dee20fe1ca8f378" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">9.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Standards of Conduct; Compliance</font>.&#160; Ono will perform, or will require that its Affiliates, Sublicensees, and subcontractors perform, all Commercialization activities in a professional and ethical
              business manner and in compliance with Applicable Law and applicable Professional Requirements.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">16</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div>
      <div style="text-align: center; font-weight: bold;">ARTICLE 10</div>
      <div style="text-align: center; font-weight: bold;">MANUFACTURING</div>
    </div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" id="z19d150fd917042548efaacbcabf5d937" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis Manufacturing and Supply</font>.&#160; Ionis will have sole responsibility [***], the Manufacture of all supplies of the Licensed Compounds and Licensed Products required for its Development activities
              under the Ongoing Clinical Trial Development Plan (other than the costs of [***].&#160; In addition, Ono will purchase from Ionis, and Ionis will sell to Ono, the Licensed Compounds and the Licensed Products as set forth in <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 10.1(A)</u> at [***].&#160; Ionis may dispose of any such inventory and drug products that Ono has not taken possession of by [***].&#160; Notwithstanding the foregoing, [***].&#160; [***].&#160; The
              Parties will enter into a definitive supply agreement and quality agreement, which will include provisions stipulating the quality standards agreed upon by the Parties, and Manufacturing for [***] will be carried out under such supply
              agreement and quality agreement.&#160; </div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z784e1f1a4e4b40dcab07be526f3120f5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Related Drug Substance Supply</font>.<font style="font-weight: bold;">&#160; </font>Upon Ono&#8217;s request after the Effective Date, at a time mutually agreed by the Parties, Ionis will supply to Ono [***].&#160; Ionis
              may dispose of such substances that Ono has not taken possession of by [***].&#160; Ionis shall provide the foregoing in this <u>Section 10.2</u> (Related Drug Substance Supply) [***].&#160; Ono will be responsible for [***] pursuant to this <u>Section

                10.2</u> (Related Drug Substance Supply) that is [***] under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze12e584e8ce0482683499f5ee47751d9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ono Manufacturing</font>.&#160; Subject to <u>Section 8.8</u> (No Harmful Actions), during the Term, except as set forth in <u>Section 10.1</u> (Ionis Manufacturing and Supply), Ono will have sole
              responsibility for and sole decision-making authority over all Manufacturing activities and [***] for the Development and Commercialization of the Licensed Compounds and Licensed Products in the Field in the Territory.&#160; Ionis shall provide
              Ono with assistance as set forth in <u>Section 6.3</u> (Manufacturing Technology Transfer), and the Parties, through the JSC or a Working Group of the JSC, will discuss manufacturing and supply issues to the extent they arise, as set forth
              in <u>Section 4.1.5(i)</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbb4549cdcada468db76031211a73db21" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">10.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Third Party CMOs</font>.&#160; Upon Ono&#8217;s written request after the Effective Date, Ionis will provide Ono with an introduction to a Licensed CMO and a CMO Ionis has used to manufacture finished drug product and
              will reasonably cooperate to authorize such parties to manufacture the Licensed Compounds and Licensed Products for Ono to Exploit in accordance with this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; margin-left: 4.5pt; font-weight: bold;">ARTICLE 11</div>
    <div style="text-align: center; margin-left: 4.5pt; font-weight: bold;">PAYMENTS</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc7025c6dc6ba4d5a9cf627a99f9b49cd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Upfront Payment</font>.&#160; In partial consideration of the licenses and rights granted to Ono hereunder, Ono will pay to Ionis, by wire transfer of immediately available funds, a non-refundable,
              non-creditable upfront payment of $280,000,000 on or after the Effective Date and within [***] (the &#8220;<font style="font-weight: bold; font-style: italic;">Upfront Payment</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zedcb0e12fe804e08a6f401de316649f7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Milestone Payments</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7390bb10ef1f4bedb6197b2a281b7c31" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">11.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Development Milestone Payments</font>.&#160; In further consideration of the licenses and rights granted to Ono hereunder, Ono will pay to Ionis the corresponding milestone payment, as set forth below (each
              milestone event set forth in <u>Table 11.2.1</u>, a &#8220;<font style="font-weight: bold; font-style: italic;">Development Milestone Event</font>,&#8221; and each milestone payment set forth in <u>Table 11.2.1</u>, a &#8220;<font style="font-weight: bold; font-style: italic;">Development Milestone Payment</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">17</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="margin-left: 72pt;">
      <table cellspacing="0" cellpadding="0" border="0" id="zc76ff7de501e455083dc9c0225f195d4" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

          <tr>
            <td style="background-color: #7DB3E2; border-bottom: 2px solid #000000; border-left: 2px solid; border-top: 2px solid #000000; vertical-align: top; width: 1%;" colspan="1">&#160;</td>
            <td style="background-color: #7DB3E2; border-bottom: 2px solid #000000; border-right: 2px solid; border-top: 2px solid #000000; vertical-align: top;" colspan="2">
              <div style="text-align: center; font-weight: bold;">Table 11.2.1 &#8211; Development Milestones</div>
            </td>
          </tr>
          <tr>
            <td style="background-color: #C6D9F1; border-bottom: 2px solid #000000; border-left: 2px solid; vertical-align: middle; width: 1%;" colspan="1">&#160;</td>
            <td style="background-color: #C6D9F1; border-bottom: 2px solid #000000; border-right: 2px solid; vertical-align: middle; width: 75%;">
              <div style="text-align: center; font-style: italic; font-weight: bold;">Development Milestone Event</div>
            </td>
            <td style="background-color: #C6D9F1; border-bottom: 2px solid #000000; border-left: 2px solid; border-right: 2px solid; vertical-align: middle; width: 23.86%;">
              <div style="text-align: center; font-style: italic; font-weight: bold;">Development</div>
              <div style="text-align: center; font-style: italic; font-weight: bold;">Milestone</div>
              <div style="text-align: center; font-style: italic; font-weight: bold;">Payment</div>
              <div style="text-align: center;"><font style="font-weight: bold; font-style: italic;">(in </font>[***]<font style="font-weight: bold; font-style: italic;">)</font></div>
            </td>
          </tr>
          <tr>
            <td 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);" colspan="1">&#160;</td>
            <td style="width: 75%; 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;">[***]</div>
            </td>
            <td style="width: 23.86%; 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>
          </tr>
          <tr>
            <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 75%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify;">[***]</div>
            </td>
            <td style="width: 23.86%; 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>
          </tr>
          <tr>
            <td 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);" colspan="1">&#160;</td>
            <td style="width: 75%; 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;">[***]</div>
            </td>
            <td style="width: 23.86%; 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>
          </tr>
          <tr>
            <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 75%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify;">[***]</div>
            </td>
            <td style="width: 23.86%; 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>
          </tr>
          <tr>
            <td 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);" colspan="1">&#160;</td>
            <td style="width: 75%; 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;">[***]</div>
            </td>
            <td style="width: 23.86%; 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>
          </tr>

      </table>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; margin-left: 72pt;">If Ono or its Affiliates or Sublicensees achieve all the Development Milestone Events, then the Development Milestone Payments payable by Ono under this <u>Section 11.2.1</u> (Development Milestone
      Payments) will not exceed [***].</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf506f433ca374cb3a074de07f1bf74f0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">11.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Sales Milestone Payments</font>.&#160; In further consideration of the licenses and rights granted to Ono hereunder, Ono will pay to Ionis the corresponding milestone payment, as set forth below (each milestone
              event set forth in <u>Table 11.2.2</u>, a &#8220;<font style="font-weight: bold; font-style: italic;">Sales</font>&#160;<font style="font-weight: bold; font-style: italic;">Milestone Event</font>&#8221; and each milestone payment set forth in <u>Table
                11.2.2</u>, a &#8220;<font style="font-weight: bold; font-style: italic;">Sales</font>&#160;<font style="font-weight: bold; font-style: italic;">Milestone Payment</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="margin-left: 72pt;">
      <table cellspacing="0" cellpadding="0" border="0" id="zb6d6b1ecff1148ccbc293ebc2af2a4d5" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

          <tr>
            <td style="background-color: #7DB3E2; border-bottom: 2px solid #000000; border-left: 2px solid; border-top: 2px solid #000000; vertical-align: top; width: 1%;" colspan="1">&#160;</td>
            <td style="background-color: #7DB3E2; border-bottom: 2px solid #000000; border-right: 2px solid; border-top: 2px solid #000000; vertical-align: top;" colspan="2">
              <div style="text-align: center; font-weight: bold;">Table 11.2.2 &#8211;Sales Milestones</div>
            </td>
          </tr>
          <tr>
            <td style="background-color: #C6D9F1; border-bottom: 2px solid #000000; border-left: 2px solid; vertical-align: middle; width: 1%;" colspan="1">&#160;</td>
            <td style="background-color: #C6D9F1; border-bottom: 2px solid #000000; border-right: 2px solid; vertical-align: middle; width: 75%;">
              <div style="text-align: center; font-style: italic; font-weight: bold;">Sales Milestone Event</div>
            </td>
            <td style="background-color: #C6D9F1; border-bottom: 2px solid #000000; border-left: 2px solid; border-right: 2px solid; vertical-align: middle; width: 23.86%;">
              <div style="text-align: center; font-style: italic; font-weight: bold;">Sales Milestone</div>
              <div style="text-align: center; font-style: italic; font-weight: bold;">Payment</div>
              <div style="text-align: center;"><font style="font-weight: bold; font-style: italic;">(in </font>[***]<font style="font-weight: bold; font-style: italic;">)</font></div>
            </td>
          </tr>
          <tr>
            <td 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);" colspan="1">&#160;</td>
            <td style="width: 75%; 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;">&#160;[***]</div>
            </td>
            <td style="width: 23.86%; 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>
          </tr>
          <tr>
            <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 75%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify;">&#160;[***]</div>
            </td>
            <td style="width: 23.86%; 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>
          </tr>
          <tr>
            <td 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);" colspan="1">&#160;</td>
            <td style="width: 75%; 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;">&#160;[***]</div>
            </td>
            <td style="width: 23.86%; 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>
          </tr>
          <tr>
            <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
            <td style="width: 75%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify;">&#160;[***]</div>
            </td>
            <td style="width: 23.86%; 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>
          </tr>

      </table>
    </div>
    <div style="text-align: justify; margin-left: 79.9pt;"><br>
    </div>
    <div style="text-align: justify; margin-left: 72pt;">If Ono or its Affiliates or Sublicensees achieve all the Sales Milestone Events, then the Sales Milestone Payments payable by Ono under this <u>Section 11.2.2</u> (Sales Milestone Payments) will not
      exceed [***].</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z84ac08d7b08f477596e872f8e36265c7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">11.2.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Notice and Payment.</font>&#160; Ono will notify Ionis in writing of the achievement of each Development Milestone Event within [***] after achievement of such Development Milestone Event by Ono, its Affiliates
              or Sublicensees, and the corresponding Development Milestone Payment will be due within [***] after receipt of the corresponding invoice and Taxation Forms from Ionis.&#160; Ono will notify Ionis in writing of the achievement of each Sales
              Milestone Event no later than [***] after the end of the Calendar Quarter in which the Sales Milestone Event is achieved, and the corresponding Sales Milestone Payment will be due within [***] after receipt of the corresponding invoice and
              Taxation Forms from Ionis.&#160; If more than one of the Sales Milestone Events is achieved for the first time in a given Calendar Quarter during the Term, then Ono will pay to Ionis a separate Sales Milestone Payment with respect to each such
              Sales Milestone Event.&#160; A failure or delay by Ono to deliver such notice of achievement of any Milestone Event will not relieve Ono of its obligation to pay Ionis the corresponding Milestone Payment for achievement of such Milestone Event.&#160;
              For the avoidance of doubt, each Milestone Payment is payable only on the first occurrence of the achievement of the corresponding Milestone Event, regardless of how many Licensed Products achieve such Milestone Event or the number of times a
              Milestone Event is achieved by the same Licensed Product (i.e., no Milestone Payment would be due for subsequent or repeated achievements of the same Milestone Event, whether by the same Licensed Product or a different Licensed Product).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">18</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z38b0ba1b071040fc886782986f461366" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalties</font><font style="color: #000000;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb5f1df201bcb4e028b7977746f97fd6c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">11.3.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Rate</font>.&#160; In further consideration of the licenses and rights granted to Ono hereunder, subject to the provisions of <u>Section 11.3</u> (Royalties), on a Licensed Product-by-Licensed Product
              and country-by-country basis, Ono will pay to Ionis royalties on the Annual Net Sales of the applicable Licensed Product sold by Ono, its Affiliates and Sublicensees in the Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Royalties</font>&#8221;)


              at a rate of [***] (the &#8220;<font style="font-weight: bold; font-style: italic;">Full Royalty Rate</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5b1703134b604638a810eb65f811f450" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">11.3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Term</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z885d5d3107124bcd993d5f3e8d85e8da" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Ono&#8217;s obligation to pay Royalties to Ionis under this Agreement will commence, on a Licensed Product-by-Licensed Product and country-by-country basis, on the date of the First Commercial Sale of the applicable Licensed Product in the
              applicable country in the Territory and, subject to <u>Section 11.3.2(b)</u>, will end on the latest to occur of (a) [***] after First Commercial Sale of such Licensed Product in such country, (b) [***] of such Licensed Product in such
              country, and (c) [***] and that Cover such Licensed Product in such country (the &#8220;<font style="font-weight: bold; font-style: italic;">Royalty Term</font>&#8221;). &#160; </div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z73103dd19b364d809b1e2d48e8c973f3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Notwithstanding anything to the contrary in <u>Section 11.3.2(a)</u>, on a country-by-country and Licensed Product-by-Licensed Product basis, if at any time during the applicable Royalty Term [***], then the Royalty Term will end at 11:59
              p.m. Pacific Time on the last day of the Calendar Quarter in which [***] occurred.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0621e0b1bc0d43f4a3bcfa32fd112dc1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">11.3.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Adjustments</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf5f4dd8c578e43a5abc7cd4e8ebc979f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Generic Entry</font>.&#160; On a country-by-country and Licensed Product-by-Licensed Product basis, if at any time during the Royalty Term a Generic Product obtains Regulatory Approval in such country and the
              aggregate unit equivalent volume of such Licensed Product in such country in any Calendar Quarter thereafter decreases by at least [***]% as compared to [***], the Full Royalty Rate will be reduced by [***]% for such Licensed Product in such
              country commencing with such Calendar Quarter and for all Calendar Quarters thereafter during the applicable Royalty Term.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze2188bc2544d47859b593c079b1a9776" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Offset for Third Party Payments</font>.&#160; Subject to <u>Section 11.3.3(d)</u> (Royalty Floor), Ono may offset [***]% of any Third Party Payments made for a Licensed Product in a country in the Territory in
              a Calendar Quarter during the Royalty Term against the Royalties due and payable by Ono to Ionis on the Net Sales for such Licensed Product in such country in such Calendar Quarter; <font style="font-style: italic;">provided </font>that<font style="font-style: italic;">&#160;</font>the terms of this <u>Section </u><u>11.3.3(b)</u> (Offset for Third Party Payments) will not apply to any license agreement entered into in violation of the terms of <u>Section 12.5.3</u> (Settlement).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">19</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z86f96d82156a4ea9bd370275fb04b643" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].&#160; Subject to <u>Section 11.3.3(d)</u> (Royalty Floor), on a country-by-country and Licensed Product-by-Licensed Product basis, if during any Calendar Quarter during the Royalty Term for such Licensed Product in such country, (i)
              [***], and (ii) [***] (the &#8220;<font style="font-weight: bold; font-style: italic;">Reduction Circumstances</font>&#8221;), then, commencing the first Calendar Quarter when the Reduction Circumstances first exist and for all Calendar Quarters
              thereafter during which the Reduction Circumstances exist, the Full Royalty Rate due on Net Sales of such Licensed Product in such country for such Calendar Quarter will be reduced by [***]%; <font style="font-style: italic;">provided </font>that,


              [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze57b861e68144e8a9d2ef06d993bc16b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Floor</font>.&#160; In no event will the Full Royalty Rate due to Ionis for a Licensed Product in a country in the Territory in any given Calendar Quarter during the Royalty Term for such Licensed
              Product in such country be reduced to an amount that is less than the greater of (i) [***], and (ii) [***].&#160; Notwithstanding the foregoing, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z08d31303e7d94aebb489aa12f94fabc0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">11.3.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Payments and Reports</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc8b44463521544afa0399ed84fa86062" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Flash Reports</font>.&#160; Commencing with the Calendar Quarter during which the First Commercial Sale of a Licensed Product is made anywhere in the Territory, within [***] after the end of each Calendar
              Quarter, Ono will provide to Ionis flash reports containing [***]: (i) the total aggregate Net Sales of the Licensed Products sold by Ono or its Affiliates or Sublicensees in the Territory in such Calendar Quarter; (ii) the expected Royalties
              to be paid to Ionis on the Net Sales of the Licensed Products sold by Ono or its Affiliates or Sublicensees in the Territory in such Calendar Quarter, including any reduction pursuant to <u>Section 11.3.3</u> (Royalty Adjustments) (if
              applicable); and (iii) the exchange rates used to calculate the Royalties payable in U.S. Dollars (the &#8220;<font style="font-weight: bold; font-style: italic;">Flash Report</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zada76f765af14eb69eea3539ead7975b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Report</font>.&#160; In addition to the Flash Reports to be provided in accordance with <u>Section 11.3.4(a)</u> (Flash Reports), commencing with the Calendar Quarter during which the First Commercial
              Sale of a Licensed Product is made anywhere in the Territory, within [***] after the end of each Calendar Quarter, Ono will provide to Ionis a written report (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Royalty Report</font>&#8221;)

              setting forth in reasonable detail: (i) the aggregate Net Sales of the Licensed Products sold by Ono or its Affiliates or Sublicensees in the Territory in such Calendar Quarter; (ii) all deductions used to determine the Net Sales of the
              Licensed Products for such Calendar Quarter and the Royalties payable with respect to the Licensed Products for such Calendar Quarter, including any reduction pursuant to <u>Section 11.3.3</u> (Royalty Adjustments) (if applicable); (iii) the
              exchange rates used to calculate the Royalties payable in [***]; (iv) any withholding taxes required to be made from such Royalties; and (v) the quantity and description of the Licensed Products sold by Ono or its Affiliate or Sublicensee in
              the Territory during such Calendar Quarter comprising such Net Sales.&#160; The Parties will seek to resolve any questions or issues related to a Royalty Report within [***] following receipt by Ionis of each Royalty Report.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z015d19b22999482b994ee4e96a71d319" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Royalty Payments</font>.&#160; The information contained in each Flash Report and Royalty Report will be considered the Confidential Information of Ono.&#160; Following receipt of each Royalty Report, [***], Ono will
              pay the Royalties due hereunder for the Calendar Quarter covered by the applicable Royalty Report.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">20</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zbeb0b528a8c44f988a7e2966050a0303" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Other Amounts Payable</font>.&#160; With respect to any amounts owed under this Agreement by one Party to the other for which no other invoicing and payment procedure is specified hereunder, within [***] after
              the end of each Calendar Quarter, each Party will provide an invoice, together with reasonable supporting documentation, to the other Party for such amounts owed in respect of such Calendar Quarter.&#160; The owing Party will pay any undisputed
              invoiced amounts within [***] after the date of the invoice, and any disputed amounts owed by a Party will be paid within [***] following resolution of the dispute.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z06728725e0c742978d152c7310541fb9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Financial Records and Audits</font>. Each Party will, and will require its Affiliates, Sublicensees and subcontractors to, maintain complete and accurate records in accordance with such Party&#8217;s Accounting
              Standards in sufficient detail to permit the other Party to confirm the accuracy of any amounts payable under this Agreement for at least the preceding [***], including (as applicable) any [***], Royalties, Sales Milestone Payments, and sales
              of the Licensed Products (including all calculations of Net Sales).&#160; Upon reasonable prior notice, each Party will permit such records to be open during regular business hours for examination by an independent and internationally recognized
              certified public accountant selected by the auditing Party and reasonably acceptable to the audited Party for the sole purpose of verifying the accuracy of the financial reports furnished by the audited Party pursuant to this Agreement or of
              any payments made, or required to be made, by the audited Party pursuant to this Agreement; <font style="font-style: italic;">provided </font>that<font style="font-style: italic;">&#160;</font>such independent accounting firm is subject to
              written obligations of confidentiality and non-use applicable to each Party&#8217;s Confidential Information that are at least as stringent as those set forth in <u>Article 14</u> (Confidential Information).&#160; Such audit will not be (a) performed
              more frequently than once per [***] period, or (b) repeated for any [***] or with respect to the same set of records (in each case, unless a prior audit indicated a discrepancy, in which case the auditing Party may conduct an additional audit
              with respect to such period or records).&#160; Such auditor will disclose only whether such reports or payments made by the audited Party are correct or not, and, if not, any discrepancies and the specific details concerning any such discrepancies
              to the auditing Party.&#160; The auditor will not share any other information with the auditing Party, and the results of the audit will be subject to <u>Article 14</u> (Confidentiality).&#160; The [***] will pay any amounts shown to be owed to the
              auditing Party but unpaid within [***] after the accountant&#8217;s report, <font style="font-style: italic;">plus</font> interest (as set forth in <u>Section 11.11</u> (Late Payments; Disputed Payments)) from the original due date solely if the
              [***] is responsible for the discrepancy.&#160; If such examination of records reveals any overpayment by Ionis, then Ono will reimburse Ionis for the amount overpaid within [***] after the accountant&#8217;s report, <font style="font-style: italic;">plus</font>
              interest (as set forth in <u>Section 11.11</u> (Late Payments; Disputed Payments)) from the original due date [***].&#160; If such examination of records reveals any overpayment by Ono, then Ionis will [***].&#160; The [***] will bear the full cost of
              such audit unless such audit reveals an underpayment by the [***] of more than [***]% of the amount actually due for the time period being audited, in which case Ono will reimburse Ionis for the reasonable audit fees for such examination.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb68a36c110044871bdc5ac8e50423d0e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Refunds</font>.&#160; Except as expressly provided herein, all payments under this Agreement will be irrevocable, non-refundable, and non-creditable.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf11f5d8b2be94b32bb5dc10dd3d192d1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Accounting Standards</font>.&#160; If a Party changes its general accounting principles from its then-current Accounting Standard (<font style="font-style: italic;">e.g.</font>, from GAAP to IFRS) at any time
              during the Term, then at least [***] prior to adopting such change in principles, such Party will provide written notice to the other Party of such change.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z23c63248e12d4cca8bdccec722566152" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Method of Payment; Exchange Rate</font>.&#160; All amounts to be paid pursuant to this Agreement will [***] and will be paid by wire transfer in immediately available funds to a bank account designated by the
              receiving Party.&#160; The rate of exchange to be used in computing the amount of currency equivalent in [***] owed to a Party under this Agreement will be the Selling Party&#8217;s then-current standard exchange rate methodology employed for the
              translation of foreign currency sales into [***] in accordance with its Accounting Standards and consistently applied during the period.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">21</font></div>
      <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>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zc7a01cf166f342fab25745f77e9d7a17" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Blocked Payments</font>.&#160; If by reason of Applicable Law in any country or jurisdiction, it becomes impossible or illegal for a Party to transfer, or have transferred on its behalf, payments owed the other
              Party hereunder, then such Party will promptly notify the other Party of the conditions preventing such transfer and use reasonable efforts to deposit such payments in [***] or [***], as applicable.&#160; If, after using reasonable efforts, such
              Party is not able to deposit such payments in [***] or [***], as applicable, then such payments will be deposited in [***] in the relevant country to the credit of the other Party in a recognized banking institution designated by the other
              Party or, if none is designated by the other Party within a period of [***], in a recognized banking institution selected by the transferring Party, as the case may be, and identified in a written notice given to the other Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb605fcab333049fda8abf6bf524086cc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Taxes</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z31a59a0dcbd94ce2991ad803036e043d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">11.10.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Taxes on Income</font>.&#160; Each Party will be solely responsible for the payment of any and all income Taxes levied on account of all payments it receives under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb300d3f77a544f8d95716a385eca477a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">11.10.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Withholding Tax</font>. Any and all payments made pursuant to this Agreement will be paid without deduction or withholding for any Taxes, except as required by Applicable Law. To the extent a Party is
              required by Applicable Law to deduct or withhold Taxes on any payment to the other Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Withheld Amount</font>&#8221;), such Party will remit such Withheld Amount to the proper
              Governmental Authority in a timely manner and promptly transmit to the other Party an official Tax certificate or other reasonable evidence of any withholding sufficient to enable the other Party to claim available credits for such Withheld
              Amount.&#160; The withholding Party will have the right to deduct such Withheld Amount from payment due to the other Party.&#160; For the avoidance of doubt, to the extent such Withheld Amount is so withheld and remitted in accordance with this <u>Section

                11.10.2</u> (Withholding Tax), such Withheld Amount will be treated for all purposes of this Agreement as having been paid to the other Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za5e6eb02f819495a9a0e886d33d02058" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">11.10.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Tax Cooperation</font>.&#160; The Parties agree to cooperate with one another in accordance with Applicable Law and use reasonable efforts to [***] Tax withholding or similar obligations in respect of payments
              made by each Party to the other Party under this Agreement.&#160; Without limiting the generality of the foregoing, each Party will provide the other with any Tax forms and other information that may be reasonably necessary to [***] withholding
              based on an applicable treaty or otherwise, including a properly completed Internal Revenue Service (&#8220;<font style="font-weight: bold; font-style: italic;">IRS</font>&#8221;) Form W-9 or appropriate IRS Form W-8, as applicable, before a payment is
              made.&#160; If any Tax form or other information a Party previously delivered expires or becomes obsolete or inaccurate in any respect, then such Party will provide the other Party with an updated version of such form or certification or promptly
              notify the other Party in writing of its legal inability to do so.&#160; Each Party will provide the other Party with reasonable assistance to enable the recovery, as permitted by Applicable Law, of withholding Taxes or similar obligations
              resulting from payments made under this Agreement, such recovery to be for the benefit of the Party bearing such withholding Tax.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd0dc3eba9dfe40d69df667d6015089c4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">11.10.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Changes in Domicile</font>.&#160; Notwithstanding any provision to the contrary in this Agreement, including <u>Section 11.10.2</u> (Withholding Tax), if as a result of a Party assigning, transferring, or
              conveying rights under this Agreement to an Affiliate or changing its domicile, additional Taxes become due that would not otherwise have been due hereunder with respect to payments under this Agreement, then such Party will be responsible
              for all such additional withholding Taxes.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">22</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z05477042fb294d578245622105cc15bb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">11.11</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Late Payments; Disputed Payments</font>.&#160; Any undisputed payments or portions thereof due hereunder that are not paid on or before the date such payments are due under this Agreement will bear interest from
              the due date until the date of payment at a per-annum rate equal to the lesser of: (a) [***]; or (b) the maximum rate permitted by Applicable Law. If a Party disputes an invoice or other payment obligation under this Agreement, then such
              Party will timely pay the undisputed amount of the invoice or other payment obligation, and the Parties will resolve such dispute in accordance with <u>Article 17</u> (Dispute Resolution; Governing Law).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 12</div>
    <div style="text-align: center; font-weight: bold;">INTELLECTUAL PROPERTY</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf8c012db0b9646c6b953de14b86c5280" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Inventions</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7a0112740d8a45aaa625f36c7d17479a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ownership of Background Intellectual Property</font>.&#160; As between the Parties, and subject to the licenses granted under this Agreement, each Party retains all rights, title, and interests in and to all
              Patent Rights and Know-How that such Party owns or Controls as of the Effective Date or that it develops or otherwise acquires after the Effective Date outside the performance of the activities under this Agreement.&#160; As between the Parties,
              each Party shall be solely responsible for any remuneration that may be due to such Party&#8217;s or its Affiliates&#8217; inventors under any applicable inventor remuneration laws.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze51154ce284640b0a312a1c9ceba4e12" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ownership of Arising Intellectual Property</font>.&#160; As between the Parties, ownership of all Collaboration Know-How and Collaboration Patent Rights will be as follows:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z671f22c43fe7461ea9bae68650c2a95a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Ionis will solely own or Control any and all (i) Collaboration Know-How that is developed or invented solely by Ionis or employees of Ionis or its Affiliates or its or their licensees (other than Ono), Sublicensees, or subcontractors, or
              any Persons contractually required to assign or license such Collaboration Know-How to Ionis or any Affiliate of Ionis (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Know-How</font>&#8221;), and (ii) Patent Rights that
              Cover the Ionis Collaboration Know-How (&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Patent Rights</font>&#8221;), and will retain all of its rights thereto, subject to any rights or licenses expressly granted by Ionis
              to Ono under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z941b7adeaeed455987fce18a4cb54600" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Ono will solely own or Control any and all (i) Collaboration Know-How that is developed or invented solely by Ono or employees of Ono or its Affiliates or [***]&#160; or any Affiliate of Ono (&#8220;<font style="font-weight: bold; font-style: italic;">Ono Collaboration Know-How</font>&#8221;), and (ii) Patent Rights that Cover the Ono Collaboration Know-How (&#8220;<font style="font-weight: bold; font-style: italic;">Ono Collaboration Patent Rights</font>&#8221;), and will retain all of its
              rights thereto, subject to any rights or licenses expressly granted by Ono to Ionis under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z1ee829df424744639bc2df6dce81520f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Each Party will own an equal, undivided share of all Joint Collaboration Technology.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z81add94da9f14e5792ab5fe753400da5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>As between the Parties, each Party shall be solely responsible for any remuneration that may be due to such Party&#8217;s or its Affiliates&#8217; inventors under any applicable inventor remuneration laws.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z06bd8a05eb524cac9689ca374e9c1845" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ownership of Trademarks</font>.&#160; As between the Parties, Ono has the sole right in the Territory, at its sole cost and in its sole discretion, to (a) select the trademark(s), service mark(s), logo(s), and
              other source identifier(s) to be used on or in connection with Commercialization of the Licensed Products in the Territory, and (b) apply for, prosecute, and maintain any registrations for the Licensed Products in the Territory.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">23</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z07798918aa3d42b19fa6f5d7c08bd0a2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.1.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Disclosure; Inventorship</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf236922328e146468db8cf81c69f537c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-size: 12pt;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Invention Disclosure</font>.&#160; Each Party will promptly disclose to the other Party all Inventions within the Collaboration Know-How developed or invented during the Term by or on behalf of such Party, in
              each case, as soon as practicably possible.&#160; Each Party will also promptly respond to reasonable requests from the other Party for additional information relating thereto.&#160; Ionis Collaboration Know-How shall be considered the Confidential
              Information of Ionis, and, subject to <u>Section 2.5</u> (Improvement Enabling License), Ono Collaboration Know-How shall be considered the Confidential Information of Ono.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zffbf8e40c74042c1991ac2ded2af7e13" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-size: 12pt;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Inventions by a Party</font>.&#160; Inventorship for Inventions and discoveries (including Know-How) first invented or developed during the course of the performance of activities under this Agreement will be
              determined in accordance with United States Patent Laws for determining inventorship.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z55b792d6065a44c7b2e9ef95c51a4cb2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top; font-size: 12pt;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Joint Research Agreement under the Leahy-Smith America Invents Act</font>.&#160; If a Party intends to invoke its rights under 35 U.S.C. &#167; 102(c) of the Leahy-Smith America Invents Act, then it will notify the
              other Party and neither Party will make an election under such provision when exercising its rights under this <u>Article 12</u> (Intellectual Property) without the prior written consent of the other Party (such consent not to be
              unreasonably withheld, conditioned, or delayed), and the Parties will use reasonable efforts to cooperate and coordinate their activities with respect to any submissions, filings or other activities in support thereof.&#160; The Parties
              acknowledge and agree that this Agreement is a &#8220;<font style="font-style: italic;">joint research agreement</font>&#8221; as defined in 35 U.S.C. &#167; 100(h).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb4bcffe931d94aa9b7876e945360c7b9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.1.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Practice Under and Other Use of Joint Collaboration Technology</font>.&#160; Subject to the rights granted under and the restrictions set forth in this Agreement (including the licenses granted under <u>Article
                2</u> (Licenses)), each Party will be entitled to the free use and enjoyment of all Joint Collaboration Technology and neither Party will have any obligation to account to the other Party for profits, or to obtain any approval of the other
              Party to license, assign, or otherwise exploit any Joint Collaboration Technology by reason of joint ownership thereof.&#160; Each Party hereby waives any right it may have under the Applicable Law of any jurisdiction to require any such approval
              or accounting.&#160; To the extent any further consent is required to enable a Party to so license or exploit its interest in the Joint Collaboration Technology, the other Party will grant consent promptly upon request.&#160; Without limitation, each
              Party will cooperate with the other Party if the Parties determine to apply patent protection in any jurisdiction for any Joint Collaboration Technology and will obtain the cooperation of the individual inventors of any such Joint
              Collaboration Technology.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z76b4d6c6542a4b588b4421e98c419196" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.1.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Employee Assignment</font>.&#160; Ono and its Affiliates will[***] enter into an agreement with each of its employees performing activities under this Agreement that (a) compels prompt disclosure to Ono [***] of
              all Collaboration Know-How and Collaboration Patent Rights discovered, developed, invented, or filed by such employee during any performance under this Agreement; and (b) automatically assigns to Ono [***] all rights, title, and interests in
              and to all Collaboration Know-How and Collaboration Patent Rights, and requires each employee to execute all documents and take such other actions as may be necessary to effectuate such assignment.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">24</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z22330cc5376e48d58f3eaf8cc89f2885" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Patent Prosecution</font><font style="color: #000000;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za705b9565a294d4a80bcd9584fea8382" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Joint </font>[***]<font style="font-weight: bold;">, and Ionis Patent Rights</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z42fc48e6f66f442bafa9a2e592a2c67e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Right to Prosecute</font>.&#160; As between the Parties, Ionis will have the (i) first right to control the Patent Prosecution of all [***], and (ii) sole right, in its sole discretion, to control the Patent
              Prosecution of all Ionis Core Technology Patents and Ionis Manufacturing and Analytical Patents (collectively, ((i) and (ii)), the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Prosecuted Patent Rights</font>&#8221;).&#160; Upon Ionis&#8217;
              reasonable request, Ono will obtain any necessary assignment documents for Ionis with respect to the Patent Prosecution of Ionis Prosecuted Patent Rights, will render all signatures that will be necessary for such patent filings, and will
              assist Ionis in all other reasonable ways that are necessary for the issuance of Ionis Prosecuted Patent Rights as well as for the Patent Prosecution of Ionis Prosecuted Patent Rights.&#160; Ono will be responsible for [***] of the reasonable
              costs and expenses incurred with respect to the Patent Prosecution of the [***].&#160; Ionis will be responsible for [***] of the reasonable costs and expenses incurred with respect to the Patent Prosecution of the [***] and for [***] of the
              reasonable costs and expenses incurred with respect to the Patent Prosecution of [***].&#160; Ono will be responsible for [***] of the reasonable costs and expenses incurred by or on behalf of Ionis with respect to the Patent Prosecution of the
              [***], and Ono will reimburse Ionis for such costs within [***] after receiving an invoice [***] for such costs.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z1e621287e23d43d3b542af28ab9b73b7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Review and Consult</font>.&#160; Ionis will keep Ono reasonably informed regarding the Patent Prosecution of the [***] and will [***].&#160; In addition, Ionis will provide Ono with drafts of proposed substantive
              filings with any patent authority in connection with the Patent Prosecution of the [***] for Ono&#8217;s review and comment as early as practicable and at least [***] prior to the submission of such proposed filings, which comments (if any) Ono
              must provide no later than [***] after receipt of the applicable draft filing.&#160; Ionis will consider in good faith Ono&#8217;s reasonable comments on the Patent Prosecution of the [***], but Ionis will have final decision-making authority regarding
              Patent Prosecution of all Ionis Prosecuted Patent Rights. </div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z53404af52d0b42008bce8f3039bb3ed2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Abandonment</font>.&#160; If, at any time during the Term, Ionis decides to cease the Patent Prosecution of [***], then Ionis will provide written notice to Ono of such decision at least [***] prior to the date
              that such applicable [***] will become abandoned.&#160; If, at any time during the Term, Ionis decides to cease the Patent Prosecution of [***], then Ionis will provide written notice to Ono of such decision within [***] after the date that Ionis
              decides or instructs to abandon the applicable [***].&#160; Unless such written notice with respect to [***] includes a reasonable strategic reason for ceasing such Patent Prosecution (<font style="font-style: italic;">e.g.</font>, continuing such
              Patent Prosecution would adversely affect Ionis&#8217; Patent Prosecution or litigation strategy), Ono may, upon written notice to Ionis, assume the Patent Prosecution of such [***] at Ono&#8217;s sole cost and expense.&#160; Without limiting the foregoing,
              with respect to any such [***] abandoned by Ionis, Ionis [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">25</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z1e68c7b86f7b4673a9c4cd30e18ea0c9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***] <font style="font-weight: bold;">and Ono Patent Rights</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zed124f82f7694f07a26522fdd1d5d6e9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Right to Prosecute</font>.&#160; As between the Parties, Ono will have the (i) first right, in its sole discretion, to control the Patent Prosecution of all [***] and (ii) sole right, in its sole discretion, to
              control the Patent Prosecution of all Ono Patent Rights (collectively, ((i) and (ii)), the &#8220;<font style="font-weight: bold; font-style: italic;">Ono Prosecuted Patent Rights</font>&#8221;).&#160; Upon Ono&#8217;s reasonable request, Ionis will obtain any
              necessary assignment documents for Ono with respect to the Patent Prosecution of the Ono Prosecuted Patent Rights, will render all signatures that will be necessary for such patent filings, and will assist Ono, at Ono&#8217;s cost, in all other
              reasonable ways that are necessary for the Patent Prosecution and issuance of the Ono Prosecuted Patent Rights.&#160; Ono will be responsible for [***] of the costs and expenses incurred with respect to the Patent Prosecution of the Ono Prosecuted
              Patent Rights.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5694b37758bc4fb0a6d93f5a83843b45" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Review and Consult</font>.&#160; Ono will keep Ionis reasonably informed regarding the Patent Prosecution of the [***] and will [***].&#160; In addition, Ono will provide Ionis with drafts of all proposed substantive
              filings with any patent authority in connection with the Patent Prosecution of the [***] for Ionis&#8217; review and comment as early as practicable and at least [***] prior to the submission of such proposed filings, which comments (if any) Ionis
              must provide no later than [***] after receipt of the applicable draft filing.&#160; Ono will consider in good faith Ionis&#8217; reasonable comments on the Patent Prosecution of the [***] but Ono will have final decision-making authority regarding
              Patent Prosecution of all Ono Prosecuted Patent Rights.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze6578d0bba264de5b224245861b1cfcf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Abandonment</font>.&#160; If, at any time during the Term, Ono decides to cease the Patent Prosecution of [***], then, Ono will provide written notice to Ionis of such decision at least [***] prior to the date
              that such Patent Right will become abandoned.&#160; Unless such written notice includes a reasonable strategic reason for ceasing such Patent Prosecution (<font style="font-style: italic;">e.g.</font>, continuing such Patent Prosecution would
              adversely affect Ono&#8217;s Patent Prosecution or litigation strategy), Ionis may, upon written notice to Ono, assume the Patent Prosecution of any such Patent Right at Ionis&#8217; sole cost and expense.&#160; Without limiting the foregoing, with respect to
              any such [***] abandoned by Ono, Ono [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zfa06771489de4035a64b30f80a856d3b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Enforcement Against Third Party Infringement or Misappropriation</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc5dc82a7820a4928bd650fe6ac674e6f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.3.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Notice of Infringement or Misappropriation</font>.&#160; Each Party will promptly notify the other of any apparent, threatened, or actual Competitive Infringement of which it becomes aware.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9d15b84973fc45f5a933a7810fdd2ad4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ono&#8217;s Enforcement Right</font>.&#160; Ono will have the (a) first right, but not the obligation, to enforce any [***], and (b) sole right to enforce any [***], in each case ((a) and (b)), against any Competitive
              Infringement at its own cost and expense and using counsel of its own choice; <font style="font-style: italic;">provided </font>that (i) with respect to [***], Ionis will be entitled to attend any substantive meetings, hearings, or other
              proceedings related to such infringement or misappropriation suit (together with its own counsel, at its own cost and expense) and to review and comment on all substantive documents related to such infringement or misappropriation suit prior
              to filing or submission of such documents, and (ii) with respect to [***], Ono shall keep Ionis reasonably informed of the status of any substantive meetings, hearings, or other proceedings related to such infringement or misappropriation
              suit to the extent without adverse effect on such suit.&#160; If Ono fails to initiate a suit or take other action to abate any such Competitive Infringement with respect to [***] within the earlier of: (x) [***] and (y) [***], or if Ono
              discontinues the prosecution of any such action after filing without abating such infringement, then, in either case, Ionis will have the second right, but not the obligation, to attempt to resolve such Competitive Infringement, at its own
              cost and expense, including the filing of an infringement or misappropriation suit, as applicable, to enforce the applicable Patent Rights or Know-How using counsel of its own choice.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">26</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z6116191b2c9944f7a4957fac2234b197" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.3.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis&#8217; Enforcement Right</font>. Ionis will have the (a) sole right, but not the obligation, to enforce any [***], and (b) first right to enforce any [***], in each case ((a) and (b)) against any
              Competitive Infringement at its own cost and expense and using counsel of its own choice; <font style="font-style: italic;">provided </font>that Ionis informs Ono of the status of enforcement of [***] related to the Licensed Compound or
              Licensed Product.&#160; Ionis shall keep Ono reasonably informed of the status of any substantive meetings, hearings, or other proceedings related to such infringement or misappropriation suit, to the extent without adverse effect on such suit.&#160;
              If Ionis fails to initiate a suit or take other action to abate any such Competitive Infringement with respect to [***] within the earlier of (x) [***] and (y) [***], or if Ionis discontinues the prosecution of any such action after filing
              without abating such infringement, then, in either case, Ono will have the second right, but not the obligation, to attempt to resolve such Competitive Infringement, at its own cost and expense, including the filing of an infringement or
              misappropriation suit, as applicable, to enforce the applicable Patent Rights or Know-How using counsel of its own choice.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z456f99908cf849bd99757b0b8ebfe12d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.3.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Allocation of Recoveries</font>.&#160; Any recoveries resulting from an enforcement action relating to a claim of Competitive Infringement will be first applied against payment of each Party&#8217;s costs and expenses
              in connection therewith.&#160; Any such recoveries in excess of such costs and expenses will be allocated as follows: (a) if the recoveries relate to [***], and (b) if the recoveries relate to [***]. Other than the above, the recoveries will be
              allocated to the Parties as follows: (x) if Ono initiates such suit, action, or proceeding, then such recoveries will [***], and (y) if Ionis initiates such suit, action, or proceeding, then such recoveries will [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zfd540ab6ce024d1d9c3421c4d0501b01" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.3.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cooperation; Procedures</font>.&#160; At the request and expense of the Party bringing an infringement or misappropriation action under this <u>Section 12.3</u> (Enforcement Against Third Party Infringement or
              Misappropriation), the other Party will provide reasonable assistance and cooperation in any such action (including entering into a common interest agreement if reasonably deemed necessary by any Party) and agrees to be joined as a party to
              the suit if necessary for the initiating Party to bring or continue an infringement or misappropriation action hereunder.&#160; In addition, the Party bringing an infringement or misappropriation action under this <u>Section 12.3</u> (Enforcement
              Against Third Party Infringement or Misappropriation) will provide the other Party with copies of all pleadings and other documents in advance of filing with the court and will consider reasonable input from the other Party during the course
              of the action.&#160; Neither Party may [***].&#160; The Parties will reasonably assist each other and cooperate with each other, at their own cost and expense, in any such investigation, pre-litigation preparation, or litigation to ensure that there is
              an aligned global litigation and enforcement strategy.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbbe0210f9dd6462fb055bb087a9901e0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Defense of Third Party Challenges</font>. Each Party will promptly notify the other Party in writing after becoming aware of an actual or threatened challenge by a Third Party of any Ionis Patent Right, Ono
              Patent Right, or Joint Collaboration Patent Right (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Third Party Challenge</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">27</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z3bf92f50ed81493384bbbe3cabaf4402" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.4.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ono&#8217;s Right to Defend</font>.&#160; Subject to the terms of <u>Section 12.4.3</u> (Cooperation; Procedures) and of any applicable license pursuant to which Ionis Controls any Patent Right, and except as may be
              otherwise agreed by the Parties, Ono will have the (a) sole right, but not the obligation, to control the defense of any Third Party Challenge relating to an [***], and (b) first right, but not the obligation, to control the defense of any
              Third Party Challenge relating to [***], and to compromise, litigate, settle, or otherwise dispose of any such challenge at its own cost and expense using counsel of its own choice; <font style="font-style: italic;">provided </font>that<font style="font-style: italic;">&#160;</font>Ionis will be entitled to attend any substantive meetings, hearings, or other proceedings related to such Third Party Challenge of [***] (together with its own counsel, at its own cost and expense) and to
              review and comment on all substantive documents related to such Third Party Challenge of [***].&#160; If Ono fails to initiate or continue the defense of such Third Party Challenge of [***] within [***] after the notice provided under <u>Section
                12.4</u> (Defense of Third Party Challenges), or otherwise abandons or elects not to continue any such defense once initiated, then Ionis will have the second right, but not the obligation, to control the defense of such Third Party
              Challenge relating to [***] at its own cost and expense using counsel of its own choice.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za54b6c94b55f42e7832c56763531d307" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.4.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis&#8217; Right to Defend</font>.&#160; Subject to the terms of <u>Section 12.4.3</u> (Cooperation; Procedures), and except as may be otherwise agreed by the Parties,<font style="font-weight: bold; font-style: italic;">&#160;</font>Ionis will have the (i) sole right, but not the obligation, to control the defense of any Third Party Challenge relating to an [***], and (ii) first right to control the defense of any Third Party Challenge relating to
              [***], and, in each case ((i) and (ii)), to compromise, litigate, settle, or otherwise dispose of any such challenge, in each case, at its own cost and expense using counsel of its own choice; <font style="font-style: italic;">provided </font>that

              Ono will be entitled to attend any substantive meetings, hearings, or other proceedings related to such Third Party Challenge of any [***] (together with its own counsel, at its own cost and expense) and to review and comment on all
              substantive documents related to such Third Party Challenge of any [***].&#160; If Ionis fails to initiate the defense of such Third Party Challenge of [***] within [***] after the notice provided under <u>Section 12.4</u> (Defense of Third Party
              Challenges), or otherwise abandons or elects not to continue any such defense once initiated, then Ono will have the second right, but not the obligation, to control the defense of such Third Party Challenge of any [***] at its own cost and
              expense using counsel of its own choice.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z8f5397fe441b41f99d42590ebec83321" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.4.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cooperation; Procedures</font>.&#160; At the request and expense of the Party controlling the defense of any Third Party Challenge under this <u>Section 12.4</u> (Defense of Third Party Challenges), the other
              Party will provide reasonable assistance and cooperation in any such action.&#160; In addition, the Party controlling the defense of any Third Party Challenge under this <u>Section 12.4</u> (Defense of Third Party Challenges) will provide the
              other Party with copies of all pleadings and other documents to be filed with the court and will consider reasonable input from the other Party during the course of the action.&#160; Ono may not settle any action or proceeding brought or defended
              under this <u>Section 12.4</u> (Defense of Third Party Challenges) or knowingly take any other action in the course thereof without Ionis&#8217; prior consent, unless such action or proceeding solely concerns the [***].&#160; Ionis may not settle any
              action or proceeding brought or defended under this <u>Section 12.4</u> (Defense of Third Party Challenges) or knowingly take any other action in the course thereof without Ono&#8217;s prior consent, unless such action or proceeding solely
              concerns the [***].&#160; The Parties will reasonably assist each other and cooperate with each other, at their own cost and expense, in any such investigation, pre-litigation preparation, or litigation to ensure that there is an aligned global
              litigation strategy.&#160; Notwithstanding the above, in the case of any invalidity or unenforceability claims arising in an enforcement action under <u>Section 12.3</u> (Enforcement Against Third Party Infringement or Misappropriation), the
              Party controlling the enforcement action pursuant to <u>Section 12.3</u> (Enforcement Against Third Party Infringement or Misappropriation) shall control the response to such invalidity or unenforceability claims, <font style="font-style: italic;">provided</font> that such Party may not admit invalidity or unenforceability of any Patent Right Controlled by the other Party without the prior written consent of the other Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">28</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z9db9efd786c448b8a9e1fe55f9c4245f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Third Party Infringement Claims</font><font style="color: #000000;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zff2c3816586e493d8769e07f504238f2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.5.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Infringement Claim; Challenges of Third-Party IP</font>.&#160; If a Third Party asserts that a Patent Right controlled by it is, or will be, infringed by the Exploitation of a Licensed Product in the Territory
              in accordance with this Agreement, then the Party first obtaining knowledge of such claim will promptly provide the other Party with prompt written notice thereof and the related facts in reasonable detail.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z989d46bed106431986bb815d709a1a8a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.5.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Responsibility to Defend</font>.&#160; During the Term of this Agreement, if a Third Party asserts that a Patent Right controlled by such Third Party is infringed, or will be infringed, by the Exploitation of a
              Licensed Product, then, subject to <u>Article 15</u> (Indemnification), Ono will have the first right, but not the obligation, to defend such claim using counsel of its own choosing.&#160; If Ono does not take affirmative steps to defend such
              claim within [***] (or such shorter period of time as is legally required to answer to such claim), then Ionis may defend such claim.&#160; The Party defending such claim will (a) keep the other Party reasonably informed regarding any such
              assertion, including by providing the other Party with copies of all pleadings and other documents filed in any proceeding relating to such claim, (b) consider reasonable input from the other Party during the course of the claim, and (c)
              provide the other Party with the opportunity to attend any substantive meetings, hearings, or other proceedings related to such claim (together with its own counsel, at its own expense) and to review and comment on all substantive documents
              related to such claim prior to filing or submission of such documents.&#160; The Parties will reasonably assist each other and cooperate and share information with respect to any such claim.&#160; Each Party will bear its own costs and expenses with
              respect to any such claim.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0e89a6e6f45b4fcd8ff9d4a9bd7d6768" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.5.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Settlement</font>.&#160; Subject to <u>Article 15</u> (Indemnification), neither Party will pursue or enter into any settlement or license agreement with any Third Party with respect to the Patent Rights that
              are the subject of a claim brought by a Third Party that a Patent Right controlled by such Third Party is infringed by the Exploitation of a Licensed Product without the other Party&#8217;s prior written consent, not to be unreasonably withheld,
              conditioned, or delayed.&#160; Subject to <u>Article 15</u> (Indemnification), [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc4330cef3aaf48718b080850cd327399" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Patent Challenges of Third Party Patent Rights</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zfc16b9a8bc734666b4149210597522f5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.6.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Notice of Third Party Patent Right</font>.&#160; If either Party becomes aware of a Third Party Patent Right that might form the basis for a claim that the Exploitation of a Licensed Product infringes, or will
              infringe, such Patent Right, then the Party first obtaining knowledge of such Patent Right will promptly provide the other Party with written notice thereof and the related facts in reasonable detail, and the Parties will promptly meet to
              discuss the matter.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">29</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z90e4042958b04ed68256d37b4a2d84b0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.6.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Challenges of Third Party Patents</font>.&#160; Ionis will have the first right, but not the obligation, to initiate a challenge of such Third Party Patent Right if such Patent Right would be an [***] if it were
              Controlled by Ionis, and if Ionis notifies Ono that it does not intend to initiate such a challenge, then Ono will have the second right, but not the obligation to do so.&#160; With respect to all other Third Party Patent Rights, Ono will have the
              first right, but not the obligation, to initiate a challenge of such Third Party Patent Right, and if Ono notifies Ionis that it does not intend to initiate such a challenge, then Ionis will have the second right, but not the obligation, to
              do so.&#160; The Party initiating such challenge will (a) keep the other Party reasonably informed regarding any such challenge, including by providing the other Party with copies of all pleadings and other documents filed in any proceeding
              relating to such challenge, (b) consider reasonable input from the other Party during the course of the challenge, and (c) provide the other Party with the opportunity to attend any substantive meetings, hearings, or other proceedings related
              to such challenge (together with its own counsel, at its own cost and expense) and to review and comment on all substantive documents related to such challenge prior to filing or submission of such documents.&#160; The Parties will reasonably
              assist each other and cooperate and share information with respect to any such challenge.&#160; Each Party will bear its own costs and expenses with respect to any such challenge.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z962d713aad9d480784ca79325aa38719" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">12.6.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Restrictions on Settlement</font>.&#160; Neither Party nor its Affiliates will pursue or enter into any settlement or license agreement with any Third Party with respect to the Patent Rights that are the subject
              of such challenge without the other Party&#8217;s prior written consent.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z71425deb4c8a43498f45a0ca906cf9de" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Orange Book Listing</font>.&#160; Following the Effective Date, [***] will select which Patent Rights licensed to Ono under this Agreement will be listed in the Orange Book and will promptly cause such Patent
              Rights to be listed in the Orange Book.&#160; [***] will have final decision-making authority to select which Patent Rights will be listed in the Orange Book; <font style="font-style: italic;">provided, however</font>, that [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z07a9140ccc6547ac93d86cffb3987740" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Patent Term Extensions</font>.&#160; With respect to supplemental protection certificates or any similar system for extending the term of Patent Rights that are in existence as of the Effective Date or that
              become available during the Term (&#8220;<font style="font-weight: bold; font-style: italic;">Patent Term Extensions</font>&#8221;), Ono will have sole rights for making all decisions regarding such supplemental protection certificates that become
              available as a result of the Regulatory Approval of a Licensed Product for the Ono Patent Rights, [***] licensed hereunder; <font style="font-style: italic;">provided</font> that, with respect to the [***], Ono will consult with Ionis with
              respect to such decisions and [***] the reasonable comments and concerns of Ionis, and Ionis shall fully cooperate with Ono in any necessary procedures with respect thereto.&#160; Ionis shall provide Ono with an opportunity to consult with respect
              to which Patent Rights may be extended in the country where multiple Patent Rights may be extended.&#160; Ono will be responsible for [***]% of the costs and expenses incurred with respect to the Patent Term Extensions of the [***], and for [***]%
              of the costs and expenses incurred by or on behalf of Ono with respect to the Patent Term Extensions of the [***].&#160; Ionis will be responsible for [***]% of the costs and expenses incurred with respect to the Patent Term Extensions of the
              [***] and for [***]% of the reasonable costs and expenses incurred by or on behalf of Ono with respect to the Patent Term Extensions of the [***], and Ionis will reimburse Ono for such costs within [***] after receiving an invoice [***] for
              such costs.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9d70c1bf7952485e85a4753f1d2508b8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Unified Patent Court</font>.&#160; The Parties shall determine through mutual consultation regarding the opting-out or opting-in of the Ionis Patent Rights, the Ono Patent Rights, and the Joint Collaboration
              Patent Rights into the jurisdiction of the Unified Patent Court or the registration of Patent Rights with unitary effect.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">30</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z7cc4eb5659924146859d7b81f76e4feb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">12.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Common Interest</font>.&#160; The Parties stipulate and agree that, with regard to such prosecution, maintenance, enforcement, and defense the interests of the Parties as collaborators and licensor and licensee
              are to obtain the strongest patent protection possible, and as such, are aligned and are legal in nature.&#160; The Parties stipulate and agree that they have not waived, and nothing in this Agreement constitutes a waiver of, any legal privilege
              concerning the Patent Rights under this <u>Article 12</u> (Intellectual Property), including privilege under the common interest doctrine and similar or related doctrines. Notwithstanding any provision to the contrary set forth in this
              Agreement, to the extent a Party has a good faith belief that any information required to be disclosed by such Party to the other Party under this <u>Article 12</u> (Intellectual Property) is protected by attorney-client privilege or any
              other applicable legal privilege or immunity, such Party will not be required to disclose such information and the Parties will in good faith cooperate to agree upon a procedure (including entering into a specific common interest agreement,
              disclosing such information on a &#8220;for counsel eyes only&#8221; basis or similar procedure) under which such information may be disclosed without waiving or breaching such privilege or immunity.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 13</div>
    <div style="text-align: center; font-weight: bold;">REPRESENTATIONS, WARRANTIES, AND COVENANTS</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9c58d5c45b8e4d13a59d9a2ab6df421b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Mutual Representations and Warranties</font>.&#160; Each of Ono and Ionis hereby represents and warrants to the other Party, as of the Execution Date and as of the Effective Date, that:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za49d6b9ba090447fb088523068aa5321" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>It is a corporation or limited company duly organized, validly existing, and in good standing under the laws of the jurisdiction of its organization, and it has the full right, power, and authority to enter into this Agreement and to
              perform its obligations hereunder.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3fde455cfbfd4fb884c87f933ff4e6d5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>All consents, approvals, and authorizations from all Governmental Authorities or other Third Parties required to be obtained by such Party in connection with this Agreement have been obtained.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z12d91a3aeb87485ba9df0e01b120dbc3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The execution, delivery, and performance of this Agreement by it has been duly authorized by all requisite corporate action.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc1511fa13a2c475d84ee21cf1509ccd3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.1.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The execution and delivery of this Agreement and the performance of its obligations hereunder (a) do not conflict with or violate any requirement of Applicable Law or any provision of its articles of incorporation, bylaws, limited
              partnership agreement, or any similar instrument, as applicable, in any material way, and (b) do not conflict with, violate, or breach or constitute a default or require any consent under, any Applicable Law or any contractual obligation or
              court or administrative order by which it is bound.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7602473ba519420493add5168d9f53fb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.1.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="color: #000000;">It has not been </font>debarred or suspended under 21 U.S.C. &#167;335(a) or (b)<font style="color: #000000;">, is not the subject of a conviction described in Section 306 of the FD&amp;C Act,</font> has not been
              and is not excluded from a federal or governmental health care program, debarred from federal contracting, convicted of or pled <font style="font-style: italic;">nolo contendere</font> to any felony, or to any federal or state legal
              violation (including misdemeanors) relating to prescription drug products or fraud, is not subject to OFAC sanctions or on the OFAC list of specially designated nationals, <font style="color: #000000;">and is not subject to any similar
                sanction of any Governmental Authority in the Territory</font> (&#8220;<font style="font-weight: bold; font-style: italic;">Debarred/Excluded</font>&#8221;)<font style="color: #000000;">, and no proceeding that could result in it being
                Debarred/Excluded is pending, and neither it nor any of its Affiliates has used, in any capacity in the performance of obligations relating to the Licensed Products, any </font>employee, <font style="color: #000000;">subcontractor,
                consultant, </font>agent, representative, <font style="color: #000000;">or other Person who has been Debarred/Excluded</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zdbefa44557154dee9251b495ffe39fb6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.1.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***] there are no legal claims, judgments, or settlements against or owed by it or any of its Affiliates, or pending or, to its Knowledge, threatened, legal claims or litigation, in each case, relating to antitrust, anti-competition, or
              anti-corruption law violations.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Additional Ionis Warranties and Covenants</font>.&#160; Ionis hereby represents and warrants to Ono, as of the Execution Date and as of the Effective Date, and where applicable, covenants to Ono, that:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">31</font></div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z4910c9fa044f4b50a811691981cbabe2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>It has the right under the Ionis Technology to grant to Ono the licenses set forth in this Agreement, and it has not granted any license or other right under the Ionis Technology that is inconsistent with the licenses granted to Ono
              hereunder.&#160; Without limiting the foregoing, Ionis has not granted any other licenses to Ionis Product-Specific Technology, or to Ionis Core Technology that would conflict with the licenses granted to Ono under <u>Section 2.1.1</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-variant: small-caps;"><u>Appendix 2</u></font><font style="color: #000000;"> (Ionis Core Technology Patents), </font><font style="font-variant: small-caps;"><u>Appendix 3</u></font> (Ionis Manufacturing and Analytical
              Patents), and <font style="font-variant: small-caps;"><u>Appendix 4</u></font> (Ionis Product-Specific Patents), collectively, list all Ionis Patent Rights existing as of the Effective Date that are necessary or reasonably useful to Exploit
              the Licensed Product in the Territory in the manner contemplated as of the Effective Date and in the form existing as of the Effective Date.&#160; With respect to any such Ionis Patent Right identified as being solely owned by Ionis, Ionis owns
              all rights, title, and interests in and to such Ionis Patent Rights.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>All issued Patent Rights within the Ionis Patent Rights are in full force and effect, have been filed, prosecuted and maintained in good faith, and, to Ionis&#8217; Knowledge, are valid and enforceable.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb591e911e6c9461da2cf41724441e46d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>There is no pending or, to Ionis&#8217; Knowledge, threatened litigation, nor has Ionis received any written notice from any Third Party, asserting or alleging that the Exploitation of the Licensed Products prior to the Execution Date infringed
              or misappropriated the intellectual property rights of such Third Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z8f96c890485642dfa10ee54be413bab7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-variant: small-caps;"><u>Schedule</u></font><u> 13.2.5</u> (Existing Third-Party IP Agreements) sets forth all Existing Third-Party IP Agreements in effect as of the Execution Date, redacted copies of which have been
              provided to Ono prior to the date hereof, and any such redactions are of information not necessary to disclose to understand the implications of such Existing Third-Party IP Agreements to this Agreement.&#160; Other than the Existing Third-Party
              IP Agreements, as of the Execution Date there are no agreements between Ionis and any Third Party pursuant to which Ionis Controls any Ionis Technology licensed to Ono under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
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          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>There are no pending, or to Ionis&#8217; Knowledge, threatened, adverse actions, suits, proceedings, judgments, orders, decrees, or settlements against or owed by Ionis or any of its Affiliates involving the Ionis Technology.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze3f5793ea327431bbb340f03cea5ecf9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>To Ionis&#8217; Knowledge, no Third Party is infringing or misappropriating any Ionis Technology as such Ionis Technology relates to the Licensed Compounds in the form existing as of the Effective Date or in any manner that would adversely
              affect Ono&#8217;s rights under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Ionis obtained assignments from the inventors of all inventorship rights relating to the Ionis Patent Rights that are solely owned by Ionis, or assignments of such Patent Rights by operation of Applicable Law, and all such assignments of
              inventorship rights are valid and enforceable.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>To Ionis&#8217; Knowledge, the Development or Commercialization of the Licensed Compound in the form existing as of the Effective Date does not infringe or misappropriate the intellectual property rights of any Third Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">32</font></div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z5b360c677a7a4f4b850d5b9a44627044" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Ionis&#8217; Development of the Licensed Products in the Ongoing Clinical Trial has, to Ionis&#8217; Knowledge, been conducted in material conformance with the protocol for the Ongoing Clinical Trial, in good scientific manner, in accordance with GLP
              and GCP, as applicable, in compliance with Professional Requirements and Applicable Law, and in such a manner as to enable Ono to conduct further Development, Manufacture, Commercialization of, and to seek Regulatory Approvals for, the
              Licensed Products in the Field in the Territory.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.11</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Ionis [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.12</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The Ionis Technology owned by Ionis, and, to Ionis&#8217; Knowledge, the Ionis Technology licensed by Ionis was not funded by the USA federal government or otherwise subject to any rights of the USA federal government under the Bayh-Dole Act.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.13</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>During the Term, Ionis will not [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.2.14</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Ionis [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Additional Ono Warranties</font>.&#160; Ono represents and warrants to Ionis, as of the Execution Date and as of the Effective Date that:</div>
          </td>
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    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.3.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>There are no [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Ono [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z46525c83731e4d749889b424e56c2e60" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Additional Covenants</font>.&#160; Each of Ono and Ionis hereby covenant to the other:</div>
          </td>
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    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0449ecf38e0944a39fc90401a93335f1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

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          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.4.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Assignment of Inventions</font>.&#160; Each Party will require all its and its Affiliates&#8217; employees to assign all Inventions that are developed or invented by such employees under this Agreement according to
              the ownership principles described in <u>Section 12.1</u> (Ownership).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zae94536581924999a2d63a22fa0183d0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.4.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Compliance with Law</font>. It will, and will require that its Affiliates, comply with all Applicable Law and, to the extent applicable, Professional Requirements, with respect to the performance of its
              obligations under this Agreement, including, as applicable, the Approved Labeling,<font style="color: #000000;"> the European Data Protection Directive 95/46/EC, the European General Data Protection Regulation (Regulation (EU) 2016/679), and
                any other applicable national data protection, cybersecurity, or privacy legislation.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3fa213de107348128bd2ff1232eafd33" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

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          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.4.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Bribery</font>; <font style="font-weight: bold;">FCPA Compliance</font>.&#160; It will not in the future offer, promise, pay, authorize, or give, money or anything of value, directly or indirectly, to any
              Government Official or Other Covered Party for the purpose, pertaining to this Agreement, of: (a) influencing any act or decision of the Government Official or Other Covered Party; (b) inducing the Government Official or Other Covered Party
              to do or omit to do an act in violation of a lawful duty; (c) securing any improper advantage; or (d) inducing the Government Official or Other Covered Party to influence the act or decision of a government or government instrumentality, in
              order to obtain or retain business, or direct business to, any Person, in each case, in any way related to this Agreement.&#160; In performing under this Agreement, it and its Affiliates agree to comply with all applicable anti-corruption laws,
              including the Foreign Corrupt Practices Act of 1977<font style="color: #000000;"> and the UK Bribery Act 2010</font>, as amended from time-to-time; the anti-corruption laws of the Territory; and all laws enacted to implement the Organization
              for Economic Co-operation and Development Convention on Combating Bribery of Foreign Officials in International Business Transactions.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">33</font></div>
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      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z42eb482ea269499caa1871c52f8d90c2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.4.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Restricted Countries</font>.&#160; Neither it nor its Affiliates will export, transfer, or sell any Licensed Product (a) to any country or territory that is subject to comprehensive economic sanctions
              administered by OFAC, unless the sale of such Licensed Product would be permissible if Ono or its Affiliates or Sublicensees were subject to OFAC&#8217;s jurisdiction, (b) to any other country or territory in which such activity would violate
              Applicable Law in the U.S., (c) to any Restricted Party unless the sale of such Licensed Product would be permissible if Ono or its Affiliates or Sublicensees was subject to OFAC&#8217;s jurisdiction, or (d) in such a manner that would violate the
              Global Trade Control Laws.</div>
          </td>
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    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">13.4.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Debarred/Excluded Persons</font>.&#160; It will not engage, in any capacity in connection with this Agreement or any ancillary agreements, any officer, employee, contractor, consultant, agent, representative, or
              other Person who has been Debarred/Excluded.&#160; Each Party will inform the other Party in writing promptly if it or any Person engaged by it or any of its Affiliates who is performing any obligations under this Agreement or any ancillary
              agreements is Debarred/Excluded, or if any action, suit, claim, investigation, or legal or administrative proceeding is pending or, to each Party&#8217;s Knowledge, is threatened, pursuant to which a Party, any of its Affiliates or any such Person
              performing obligations hereunder or thereunder may become Debarred/Excluded.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z65756493ec9442799f0e3398040f0a9e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Disclaimer</font>.&#160; EXCEPT AS EXPRESSLY SET FORTH IN THIS <u>ARTICLE 13 </u>(REPRESENTATIONS, WARRANTIES, AND COVENANTS), THE INTELLECTUAL PROPERTY RIGHTS PROVIDED BY IONIS ARE PROVIDED &#8220;AS IS&#8221; AND
              WITHOUT WARRANTY.&#160; EXCEPT AS EXPRESSLY SET FORTH IN THIS <u>ARTICLE 13 </u>(REPRESENTATIONS, WARRANTIES, AND COVENANTS), EACH OF THE PARTIES EXPRESSLY DISCLAIMS ANY AND ALL WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING THE
              WARRANTIES OF DESIGN, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, VALIDITY, OR ENFORCEABILITY OF THEIR RESPECTIVE INTELLECTUAL PROPERTY RIGHTS, AND NONINFRINGEMENT OF THE INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES, ARISING FROM A
              COURSE OF DEALING, USAGE, OR TRADE PRACTICES, IN ALL CASES WITH RESPECT THERETO.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">13.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Limitation of Liability</font>.&#160; NEITHER OF THE PARTIES WILL BE ENTITLED TO RECOVER FROM THE OTHER PARTY ANY SPECIAL, INCIDENTAL, INDIRECT, CONSEQUENTIAL, OR PUNITIVE DAMAGES OR DAMAGES FOR LOSS OF PROFIT,
              LOSS OF REVENUE, OR LOST OPPORTUNITY IN CONNECTION WITH THIS AGREEMENT, ITS PERFORMANCE OR LACK OF PERFORMANCE HEREUNDER, OR ANY LICENSE GRANTED HEREUNDER, EXCEPT TO THE EXTENT THE DAMAGES RESULT FROM A BREACH OF THE OBLIGATIONS OF A PARTY
              UNDER <u>ARTICLE 14</u> (CONFIDENTIALITY) OR <u>ARTICLE 3</u> (EXCLUSIVITY), MISAPPROPRIATION OR INFRINGEMENT OF INTELLECTUAL PROPERTY OWNED OR CONTROLLED BY THE OTHER PARTY, OR AMOUNTS REQUIRED TO BE PAID TO A THIRD PARTY AS
              PART OF A CLAIM FOR WHICH A PARTY PROVIDES INDEMNIFICATION UNDER <u>ARTICLE 15</u> (INDEMNIFICATION).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 14</div>
    <div style="text-align: center; font-weight: bold;">CONFIDENTIALITY</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zfc6a8c5969d047a083f745ba04a6c44f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Duty of Confidence</font>.&#160; Subject to the other provisions of this <u>Article 14</u> (Confidentiality):</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z8f547efdb14e47ae8d952e0102a53c2c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>except to the extent expressly authorized by this Agreement, all Confidential Information disclosed by a Party or its Affiliates (the &#8220;<font style="font-weight: bold; font-style: italic;">Disclosing Party</font>&#8221;) will be maintained in
              confidence and otherwise safeguarded, and not published or otherwise disclosed, by the Party (and its Affiliates) receiving such information (the &#8220;<font style="font-weight: bold; font-style: italic;">Receiving Party</font>&#8221;);</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">34</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zbbeda1aba52b4251a4b852bdbed561d5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the Receiving Party will treat all Confidential Information provided by the Disclosing Party, at a minimum, with the same degree of care as the Receiving Party uses for its own similar information, but in no event less than a reasonable
              degree of care;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7c74a1b9e0e542c682e5c473cb42b46e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the Receiving Party may only use any Confidential Information of the Disclosing Party for the purposes of performing its obligations or exercising its rights under this Agreement;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z14bb38f250d0400387dde77fe0ec9ead" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.1.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>a Receiving Party may only disclose Confidential Information of the Disclosing Party to: (a) such Receiving Party&#8217;s Affiliates, and potential and actual licensees and Sublicensees; and (b) employees, directors, officers, agents,
              contractors, consultants, attorneys, accountants, banks, investors, and advisors of the Receiving Party and its Affiliates, licensees, and Sublicensees, in each case ((a) and (b)), to the extent reasonably necessary for the purposes of, and
              for those matters undertaken pursuant to, this Agreement; <font style="font-style: italic;">provided </font>that such Persons are bound by legally enforceable obligations of confidentiality and non-use with respect to the Disclosing Party&#8217;s
              Confidential Information, or subject to professional ethical obligations of confidentiality, no less stringent than the confidentiality and non-use obligations set forth in this Agreement, except that the term of such obligation will be
              customary for such recipient of Confidential Information.&#160; Each Party will remain responsible for any failure by its Affiliates, licensees, and Sublicensees, and its and its Affiliates&#8217;, licensees&#8217;, and Sublicensees&#8217; respective employees,
              directors, officers, agents, consultants, attorneys, accountants, banks, investors, advisors, and contractors, in each case, to treat such Confidential Information as required under this <u>Section 14.1</u> (Duty of Confidence) (as if such
              Persons were Parties directly bound to the requirements of this <u>Section 14.1</u> (Duty of Confidence)); and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd9706b16ac0e47c99f8d23abb7f4354e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.1.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>each Party will promptly notify the other Party of any misuse or unauthorized disclosure of the other Party&#8217;s Confidential Information.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z001b20eb952b49e98d948e2779c818a2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.1.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>The confidentiality, non-use, and non-disclosure obligations set forth in this <u>Section 14.1</u> (Duty of Confidence) will be in full force and effect from the Effective Date until [***] after expiration or termination of this
              Agreement, <font style="font-style: italic;">provided</font> that, with respect to any Know-How that is a trade secret and is identified as such by the Disclosing Party at the time of disclosure, the obligations of this <u>Section 14.1</u>
              (Duty of Confidence) will continue for so long as such Know-How remains a trade secret.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf91b6292e4bd457ebfa41320f8a82b0f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Confidential Information</font>.&#160; The Ionis Know-How will be the Confidential Information of Ionis.&#160; The Joint Collaboration Know-How and the terms of this Agreement will be the Confidential Information of
              both Parties, with each Party deemed to be the Receiving Party of such information.&#160; The Ono Know-How will be the Confidential Information of Ono.&#160; Except as provided in <u>Section 14.4</u> (Authorized Disclosures) and <u>Section 14.7</u>
              (Publicity; Use of Names), neither Party nor its Affiliates may disclose the existence or the terms of this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z90178f4188aa4d23b0f0bf0ac851c040" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Exemptions</font>.&#160; Information of a Disclosing Party will not be the Confidential Information of such Disclosing Party to the extent that the Receiving Party can demonstrate through competent evidence that
              such information:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z34e159f2ced143dcbde57291c7166b3b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.3.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>was already known by the Receiving Party or any of its Affiliates without an obligation of confidentiality at the time of its receipt from the Disclosing Party, and not through a prior disclosure by or on behalf of the Disclosing Party, as
              documented by the Receiving Party&#8217;s business records;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">35</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zb82e4061359e4efd8485d71064d2f22e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.3.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>was generally available to the public or otherwise part of the public domain before its receipt from the Disclosing Party;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6b12783402cd4fa493a2ec593fa6e723" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.3.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>became generally available to the public or otherwise part of the public domain after its disclosure by the Disclosing Party other than through any act or omission of the Receiving Party or any of its Affiliates or disclosees in breach of
              this Agreement;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc9eb0700c2124fddbe4e11251c976c3a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.3.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>is subsequently disclosed to the Receiving Party or any of its Affiliates without obligation of confidentiality by a Third Party who may rightfully do so and is not under a conflicting obligation of confidentiality to the Disclosing Party;
              or</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbcd552d4772f4cdd9224095e2316719e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.3.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>is developed by the Receiving Party or any of its Affiliates independently and without use of or reference to any Confidential Information received from the Disclosing Party, as documented by the Receiving Party&#8217;s business records.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 36pt;">No combination of features or disclosures will be deemed to fall within the foregoing exclusions merely because individual features are published or available to the general public or in the rightful
      possession of the Receiving Party unless the combination itself and principle of operation are published or available to the general public or in the rightful possession of the Receiving Party.</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6fa688c6398e4073acb292e6f10cd770" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Authorized Disclosures</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z73688fc9d69942c29af1cfb1a9c8264e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.4.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Permitted Circumstances</font>.&#160; Notwithstanding the obligations set forth in <u>Section 14.1</u> (Duty of Confidence) and <u>Section 14.6</u> (Publication and Listing of Clinical Trials), a Party may
              disclose the other Party&#8217;s Confidential Information (including this Agreement and the terms herein) to the extent such disclosure is reasonably necessary in the following situations:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3c8106a8e85c4487a82c39c91e416c5c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>the prosecution or enforcement of Ionis Patent Rights or Collaboration Patent Rights, in each case, as contemplated by this Agreement;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z94d7978a4fc047ec870a0ce38b8e190c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Regulatory Submissions and other filings or communications with Governmental Authorities (including Regulatory Authorities), as necessary for the Exploitation of the Licensed Products in accordance with the rights and obligations of the
              applicable Party under this Agreement;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6f87090242c44a52a338db46c30f42b2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>disclosure of this Agreement, its terms, and the status and results of Exploitation of the Licensed Products to actual or <font style="font-style: italic;">bona fide</font> potential investors, acquirors, (sub)licensees, lenders, and
              other financial or commercial partners (including in connection with any royalty financing transaction), and their respective attorneys, accountants, banks, investors, and advisors, solely for the purpose of evaluating or carrying out an
              actual or potential investment, acquisition, (sub)license, debt transaction, or collaboration; <font style="font-style: italic;">provided </font>that,<font style="font-style: italic;">&#160;</font>in each such case, (i) such Persons are bound by
              obligations of confidentiality and non-use, or subject to professional ethical obligations of confidentiality, at least as stringent as those set forth in <u>Article 14</u> (Confidentiality), [***] and (ii) the scope of any such disclosure
              is limited to the maximum extent practicable for the particular context in which it is being disclosed;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">36</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="za75bd8907ab14047b8b85500774c08ab" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>such disclosure is required to comply with Applicable Law (whether generally or in pursuit of an application for listing of securities) including the United States Securities and Exchange Commission or equivalent foreign agency or
              regulatory body, or otherwise required by judicial or administrative process, <font style="font-style: italic;">provided </font>that in each such event, as promptly as reasonably practicable and to the extent not prohibited by Applicable
              Law or judicial or administrative process, such Party will notify the other Party of such required disclosure and provide a draft of the disclosure to the other Party reasonably in advance of such filing or disclosure for the other Party&#8217;s
              review and comment.&#160; The non-disclosing Party will provide any comments as soon as practicable, and the disclosing Party will consider in good faith any timely comments provided by the non-disclosing Party; <font style="font-style: italic;">provided

              </font>that the disclosing Party may or may not accept such comments in its sole discretion.&#160; Confidential Information that is disclosed in order to comply with Applicable Law or by judicial or administrative process pursuant to this <u>Section

                14.4.1(d)</u>, in each case, will remain otherwise subject to the confidentiality and non-use provisions of this <u>Article 14</u> (Confidentiality) with respect to the Party disclosing such Confidential Information, and such Party will
              take all steps reasonably necessary, including seeking of confidential treatment or a protective order for a period of at least [***] (to the extent permitted by Applicable Law or Governmental Authority), to ensure the continued confidential
              treatment of such Confidential Information, and each Party will be responsible for its own legal and other External Costs in connection with any such filing or disclosure pursuant to this <u>Section 14.4.1(d)</u>; or</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb065a13ef4b04e73a2b383134cc09bf4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(e)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>disclosure pursuant to <u>Section 14.6</u> (Publication and Listing of Clinical Trials) and <u>Section 14.7</u> (Publicity; Use of Name).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3e9433cf1a934b57992ab102283cdd44" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.4.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>If and whenever any Confidential Information is disclosed in accordance with this <u>Section 14.4</u> (Authorized Disclosures), such disclosure will not cause any such information to cease to be Confidential Information except to the
              extent that such disclosure results in a public disclosure of such information (other than by breach of this Agreement).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z10d4645af36248f29e886d360f41f502" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Publications</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9af8f8ac45c54cbead26992be4e56aac" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.5.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ono&#8217;s Right to Publish</font>.&#160; After the Effective Date, Ono will have the right to publicly present or publish any Clinical Trial data, non-clinical or preclinical data, or any associated results or
              conclusions generated by or on behalf of Ionis or Ono pursuant to this Agreement (each such proposed presentation or publication, an &#8220;<font style="font-weight: bold; font-style: italic;">Ono Publication</font>&#8221;), [***], and solely to the
              extent such publication or presentation is, with respect to any data generated by or on behalf of Ionis, approved in advance by Ionis[***].&#160; If Ono desires to publicly present or publish an Ono Publication in accordance with the foregoing
              sentence, then Ono will provide Ionis (including Ionis&#8217; Liaison and all Ionis members of the JSC) with a copy of such proposed Ono Publication at least [***] prior to the earlier of its presentation or intended submission for publication, and
              Ionis will have [***] after receiving such proposed Ono Publication to review and provide comments thereto (such applicable [***] period, the &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Review Period</font>&#8221;).&#160; [***].&#160;
              Notwithstanding any provision to the contrary set forth in this Agreement, Ono will (i) [***], and (ii) [***].&#160; Ono will provide Ionis a copy of any Ono Publication at the time of the submission or presentation thereof.&#160; Ono agrees to
              determine the authorship of all Ono Publications in accordance with all applicable International Committee of Medical Journal Editors (ICMJE) guidelines.&#160; Ono will require its Affiliates and Sublicensees to comply with the obligations of this
              <u>Section 14.5</u> (Publications) as if they were Ono, and Ono will be liable for any non-compliance of such Persons.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">37</font></div>
      <div class="BRPFPageBreak" style="page-break-after: always;">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
      <div class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z25d9d60d59fa4951808d63868bc118b6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.5.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Ionis&#8217; Right to Publish</font>.&#160; Ionis will have the right to publicly present or publish any Clinical Trial data, non-clinical or preclinical data, or any associated results or conclusions generated by or
              on behalf of Ionis pursuant to this Agreement (each such proposed presentation or publication, an &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Publication</font>&#8221;) [***].&#160; If Ionis desires to publicly present or publish a Ionis
              Publication in accordance with the foregoing sentence, then Ionis will provide Ono (including Ono&#8217;s Liaison and all Ono members of the JSC) with a copy of such proposed Ionis Publication [***] with respect to Ionis Publications to be made in
              2025 after the Effective Date, and with respect to any Ionis Publication to be made after 2025, at least [***] prior to the earlier of its presentation or intended submission for publication.&#160; Ono will have [***] (or a shorter period of time,
              as may be specified by Ionis for Ionis Publications to be made in 2025, considering the deadlines for such Ionis Publications) after receiving such proposed Ionis Publication to review and provide comments thereto (such applicable period, the
              &#8220;<font style="font-weight: bold; font-style: italic;">Ono Review Period</font>&#8221;).&#160; [***].&#160; Notwithstanding any provision to the contrary set forth in this Agreement, Ionis will (i) [***], (ii) [***] and (iii) [***]. &#160;Ionis will provide Ono a
              copy of any Ionis Publication at the time of the submission or presentation thereof.&#160; Ionis agrees to determine the authorship of all Ionis Publications in accordance with all applicable International Committee of Medical Journal Editors
              (ICMJE) guidelines.&#160; Ionis will require its Affiliates and Sublicensees to comply with the obligations of this <u>Section 14.5</u> (Publications) as if they were Ionis, and Ionis will be liable for any non-compliance of such Persons.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z4050866598e141ce9bc13979abd79925" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.5.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Subsequent Publications</font>.&#160; After any Ono Publication or Ionis Publication has been published or publicly presented in accordance with <u>Section 14.5.1</u> (Ono&#8217;s Right to Publish) or <u>Section
                14.5.2</u> (Ionis&#8217; Right to Publish), as applicable, either Party may make subsequent publications or presentations of the content of such previously published Ono Publication or Ionis Publication without further approval or review by the
              other Party; <font style="font-style: italic;">provided</font>, that such subsequent publication or presentation does not include any new data, information, or conclusions, or present the content in a form or matter that materially alters
              the conclusion or subject matter of the previous publication or public presentation.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z56eea9f9b6d64ca2b34828159bb5a725" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Publication and Listing of Clinical Trials</font>.&#160; With respect to the listing of Clinical Trials or the publication of Clinical Trial results for the Licensed Products and to the extent applicable to a
              Party&#8217;s activities conducted under this Agreement, each Party will comply with (a) the Pharmaceutical Research and Manufacturers of America (PhRMA) Guidelines on the listing of Clinical Trials and the Publication of Clinical Trial results,
              and (b) any Applicable Law or applicable court order, stipulations, consent agreements, and settlements entered into by such Party.&#160; The Parties agree that any such listings or publications made pursuant to this <u>Section 14.6</u>
              (Publication and Listing of Clinical Trials) will be considered a Publication for purposes of this Agreement and will be subject to <u>Section 14.5</u> (Publications).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">38</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="ze0b05ff346d54eda8ffb63045b9deb09" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Publicity; Use of Names</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z53650f09cc1d45d496cd6e63d0831109" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.7.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Press Release</font>.&#160; Each Party may issue a press release announcing this Agreement, on such date and time and in such form, in each case, as may be agreed by the Parties.&#160; Other than such press release
              and the public disclosures permitted by this <u>Section 14.7</u> (Publicity; Use of Names) and <u>Section 14.4</u> (Authorized Disclosures), the Parties agree that the portions of any other news release or other public announcement relating
              to this Agreement or the performance hereunder that would disclose information other than that already in the public domain will require prior review and approval by both Parties (with such approval not to be unreasonably withheld,
              conditioned, or delayed).&#160; However, the Parties agree that after (a) a disclosure pursuant to <u>Section 14.7</u> (Publicity; Use of Names) or <u>Section 14.4</u> (Authorized Disclosures) or (b) the issuance of a press release (including
              the initial press release) or other public announcement pursuant to this <u>Section 14.7.1</u> (Press Release) that has been reviewed and approved by the other Party, the disclosing Party may make subsequent public disclosures reiterating
              such information without having to obtain the other Party&#8217;s prior consent and approval so long as the information in such press release or other public announcement remains true, correct, and the most current information with respect to the
              subject matters set forth therein.&#160; Similarly, after a Publication has been made available to the public, each Party may post such Publication or a link to it on its corporate website or social media platforms (or any website managed by such
              Party in connection with a Clinical Trial for the Licensed Products, as appropriate) without the prior written consent of the other Party, so long as the information in such Publication remains true, correct, and the most current information
              with respect to the subject matters set forth therein.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb6fa500785e74b15a47d4f320b43a361" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.7.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Disclosures by Ionis</font>.&#160; Notwithstanding any provision to the contrary set forth in this Agreement, Ionis has the right to publicly disclose (in written, oral, or other form): (a) the achievement of
              any Milestone Event under this Agreement (including the amount, payment, and timing of any such Milestone Event); (b) the commencement, completion, material data, or key results of any Clinical Trials for the Licensed Products conducted by or
              on behalf of Ionis; and (c) the achievement of Regulatory Approval for any Licensed Product throughout the world.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0dc3636c57854298a9801fcef2095928" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.7.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Use of Names</font>.&#160; Each Party will have the right to use the other Party&#8217;s name and logo in presentations, its website, collateral materials, and corporate overviews to describe the collaboration
              relationship, as well as in taglines of press releases issued pursuant to this <u>Section 14.7</u> (Publicity; Use of Names); <font style="font-style: italic;">provided </font>that [***], and each Party will [***].&#160; Except as permitted
              under this <u>Section 14.7</u> (Publicity; Use of Names) or with the prior express written permission of the other Party, neither Party will use the name, trademark, trade name, or logo of the other Party or its Affiliates or their
              respective employees in any publicity, promotion, news release, or disclosure relating to this Agreement or its subject matter except as may be required by Applicable Law.&#160; </div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z03d307a355fc403895295150d87109dd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">14.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Acknowledgement</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zfd88766c10354a89b52517b2ee042b75" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.8.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Ono [***].&#160; Ionis will [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z22038eb8d83a48288d34d34ac1088836" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">14.8.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].&#160; As such, Ono agrees that it will [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; margin-left: 4.5pt; font-weight: bold;">ARTICLE 15</div>
    <div style="text-align: center; margin-left: 4.5pt; font-weight: bold;">INDEMNIFICATION</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0dcaaf7a0e414bac9f6e0bc5f3e74efa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Indemnification by Ionis</font>.&#160; Ionis will indemnify, hold harmless, and defend Ono and its Affiliates and their respective directors, officers, employees, and agents (each, a &#8220;<font style="font-weight: bold; font-style: italic;">Ono Indemnitee</font>&#8221;) from and against any and all Third Party suits, claims, actions, or demands (&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Claims</font>&#8221;) and all liabilities, expenses,
              or losses (including reasonable attorneys&#8217; fees, court costs, witness fees, damages, judgments, fines, and amounts paid in settlement) arising therefrom (&#8220;<font style="font-weight: bold; font-style: italic;">Losses</font>&#8221;) to the extent that
              the applicable Third Party Claims and such Losses arise out of (a) a breach of this Agreement by Ionis, (b) the Exploitation of the Licensed Products by or on behalf of Ionis or any of its Affiliates, licensees (not including Ono or its
              Affiliates, Sublicensees, or its subcontractors), Sublicensees, or subcontractors (i) prior to the Effective Date, (ii) in connection with the Ongoing Clinical Trial, or (iii) after any early termination of the Agreement in accordance with <u>Article

                16</u> (Term and Termination), or (c) the negligence or willful misconduct of any Ionis Indemnitee.&#160; Notwithstanding the foregoing, Ionis will not have any obligation to indemnify Ono Indemnitees to the extent that any Losses arise out of
              any Third Party Claim for which Ono is responsible for indemnifying Ionis pursuant to <u>Section 15.2</u> (Indemnification by Ono).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">39</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z4dfb2cbc66964f918e023767c93d0508" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Indemnification by Ono</font>.&#160; Ono will indemnify, hold harmless, and defend Ionis and its Affiliates, and their respective directors, officers, employees, and agents (each, an &#8220;<font style="font-weight: bold; font-style: italic;">Ionis Indemnitee</font>&#8221;) from and against any and all Losses, to the extent that the applicable Third Party Claims and such Losses arise out of (a) a breach of this Agreement by Ono, (b) the Exploitation of the
              Licensed Products by or on behalf of Ono or any of its Affiliates, Sublicensees, or subcontractors, or (c) the negligence or willful misconduct of any Ono Indemnitee<font style="color: #000000;">.&#160; </font>Notwithstanding any provision to the
              contrary set forth in this Agreement,<font style="color: #000000;">&#160;</font>Ono <font style="color: #000000;">will not have any obligation to indemnify the Ionis Indemnitees to the extent that any&#160;</font>Losses arise out of any Third Party
              Claim for which Ionis is responsible for indemnifying Ono pursuant to <u>Section 15.1</u> (Indemnification by Ionis).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3e1ce6ebbdca41b68e783c0d8c919c44" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Indemnification Procedure</font>.&#160; If either Party is seeking indemnification under <u>Section 15.1</u> (Indemnification by Ionis) or <u>Section 15.2</u> (Indemnification by Ono) (the &#8220;<font style="font-weight: bold; font-style: italic;">Indemnified Party</font>&#8221;), then it will inform the other Party (the &#8220;<font style="font-weight: bold; font-style: italic;">Indemnifying Party</font>&#8221;) of the Third Party Claim giving rise to
              such indemnification obligations within [***] after receiving written notice of the Third Party Claim (it being understood and agreed, however, that the failure or delay by an Indemnified Party to give such notice of a Third Party Claim will
              not affect the Indemnifying Party&#8217;s indemnification obligations hereunder except to the extent the Indemnifying Party will have been actually and materially prejudiced as a result of such failure or delay to give notice).&#160; The Indemnifying
              Party will have the right to assume the defense of any such Third Party Claim for which it is obligated to indemnify the Indemnified Party.&#160; The Indemnified Party will cooperate with the Indemnifying Party and the Indemnifying Party&#8217;s insurer
              as the Indemnifying Party may reasonably request, and at the Indemnifying Party&#8217;s cost and expense.&#160; The Indemnified Party will have the right to participate, with counsel of its choice, in the defense of any Third Party Claim that has been
              assumed by the Indemnifying Party, which participation will be at the Indemnified Party&#8217;s expense unless (a) the Indemnifying Party has agreed to pay such fees and expenses, (b) the Indemnifying Party has failed to employ counsel reasonably
              satisfactory to the Indemnified Party in a timely manner, or (c) the Indemnified Party has been advised by counsel that there are actual or potential conflicting interests between the Indemnifying Party and the Indemnified Party, including
              situations in which there are one or more legal defenses available to the Indemnified Party that are different from or additional to those available to the Indemnifying Party.&#160; Neither Party will have the obligation to indemnify the other
              Party in connection with any settlement made without the Indemnifying Party&#8217;s written consent, which consent will not be unreasonably withheld, conditioned, or delayed.&#160; The Indemnifying Party will not admit any fault or negligence on the
              part of the Indemnified Party, or impose any obligation on, or otherwise materially adversely affect, the Indemnified Party, without the Indemnified Party&#8217;s prior written consent, which consent will not be unreasonably withheld, conditioned,
              or delayed.&#160; If the Parties cannot agree as to the application of <u>Section 15.1 </u>(Indemnification by Ionis) or <u>Section 15.2</u> (Indemnification by Ono) as to any Third Party Claim, then, pending resolution of the dispute pursuant
              to <u>Article 17</u> (Dispute Resolution; Governing Law), the Parties may conduct separate defenses of such Third Party Claims, with each Party retaining the right to claim indemnification from the other Party in accordance with <u>Section
                15.1</u> (Indemnification by Ionis) or <u>Section 15.2</u> (Indemnification by Ono), as applicable, upon resolution of the underlying Third Party Claim.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">40</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="ze0140abda03a49a69452b7a0c643cb10" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">15.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Insurance</font>.&#160; Each Party will, at its own expense, procure and maintain insurance, including product liability insurance, adequate to cover its obligations hereunder and that is consistent with normal
              business practices of prudent companies similarly situated at all times during which any Licensed Product is being clinically tested in human subjects or commercially distributed or sold by such Party pursuant to this Agreement.&#160; It is
              understood that such insurance will not be construed to create a limit of either Party&#8217;s liability with respect to its indemnification obligations under this <u>Article 15</u> (Indemnification).&#160; Each Party will provide the other Party with
              written evidence of such insurance upon request.&#160; Each Party will provide the other Party with [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 16</div>
    <div style="text-align: center; font-weight: bold;">TERM AND TERMINATION</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd1bcd7be449a4dcda71c4bafaa2ed610" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Term</font>.&#160; The term of this Agreement will begin on the Effective Date and, unless earlier terminated in accordance with this <u>Article 16</u> (Term and Termination), will continue, on a Licensed
              Product-by-Licensed Product and country-by-country basis, until the expiration of the Royalty Term for such Licensed Product in such country (the &#8220;<font style="font-weight: bold; font-style: italic;">Term</font>&#8221;).&#160; If the Effective Date has
              not occurred by the [***] following the Execution Date, then this Agreement may be terminated by either Party upon written notice to the other Party, <font style="font-style: italic;">provided</font> that a Party shall not be entitled to
              terminate this Agreement pursuant to this sentence if such Party is in breach of this Agreement and such breach has caused the Effective Date not to occur by the [***] following the Execution Date.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z11aef9cdb615458484bdcfeef8e35013" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Termination for Material Breach</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z409c8b4ae3dc469d9a7a53434f9a874f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.2.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Material Breach</font>.&#160; If either Party believes in good faith that the other is in material breach of this Agreement, then the non-breaching Party may deliver notice of such breach to the other Party
              stating the cause and proposed remedy (&#8220;<font style="font-weight: bold; font-style: italic;">Breach Notification</font>&#8221;).&#160; For any breach arising from a failure to make a payment set forth in this Agreement, the allegedly breaching Party
              will have [***] from the receipt of the applicable Breach Notification to cure such breach.&#160; For all breaches other than a failure to make a payment as set forth in this Agreement, the allegedly breaching Party will have [***] from the date
              of the Breach Notification to cure such breach.&#160; If the allegedly breaching Party fails to cure the applicable breach within the applicable period set forth above, then the Party originally delivering the Breach Notification may terminate
              this Agreement effective on written notice of termination to such allegedly breaching Party.&#160; The Parties stipulate and agree, for purposes of this <u>Section 16.2</u> (Termination for Material Breach), that a material breach by Ono, its
              Affiliates or Sublicensees of [***].&#160; The Parties further stipulate and agree, for purposes of this <u>Section 16.2</u> (Termination for Material Breach), that a material breach by Ionis, its Affiliates or Sublicensees of [***].</div>
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    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
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          <td style="width: 35.1pt; vertical-align: top;">16.2.2</td>
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            <div><font style="font-weight: bold;">Disagreement as to Material Breach</font>.&#160; Notwithstanding <u>Section 16.2.1</u> (Material Breach), if the Parties, reasonably and in good faith, disagree as to whether there has been a material breach of
              this Agreement, then: (a) the Party that disputes whether there has been a material breach may contest the allegation by referring such matter, within the cure period applicable to such alleged material breach, for resolution in accordance
              with <u>Article 17</u> (Dispute Resolution; Governing Law); (b) the relevant cure period with respect to such alleged material breach will be tolled from the date on which the Party that disputes whether there has been a material breach
              notifies the other Party of such dispute and through the resolution of such dispute in accordance with <u>Article 17</u> (Dispute Resolution; Governing Law); and (c) during the pendency of such dispute, all of the terms and conditions of
              this Agreement will remain in effect and the Parties will continue to perform all of their respective obligations hereunder.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Termination by Ono for Convenience</font>. At any time after payment of the Upfront Payment and until [***], Ono will have the right to terminate the Agreement in its entirety upon [***] prior written
              notice.&#160; After [***], Ono will have the right to terminate the Agreement in its entirety upon [***] prior written notice.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z375beae8a7af48e986872f33c83a2437" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Termination for Patent Challenge</font>. Except to the extent unenforceable under Applicable Law, Ionis may terminate this Agreement in its entirety by providing written notice of termination to Ono if Ono
              or its Affiliates (individually or in association with any Person) contests or assists a Third Party in contesting the scope, validity, or enforceability of any Ionis Patent Right anywhere in the world in any court, tribunal, arbitration
              proceeding, or other proceeding, including the U.S. Patent and Trademark Office, the U.S. International Trade Commission, the European Patent Office, the European Patent Court, or any national court or patent office in Europe (a &#8220;<font style="font-weight: bold; font-style: italic;">Patent Challenge</font>&#8221;).&#160; If there is a Patent Challenge, then Ionis will provide prompt written notice of such Patent Challenge to Ono, and Ionis may immediately terminate this Agreement by
              providing written notice of such termination to Ono.&#160; If termination of this Agreement pursuant to this <u>Section 16.5</u> (Termination for Patent Challenge) is not an available remedy under Applicable Law, then [***]; <font style="font-style: italic;">provided, however</font>, that nothing in this <u>Section 16.5</u>&#160; (Termination for Patent Challenge) prevents Ono or its Affiliates from taking any of the actions referred to in this <u>Section 16.5</u>&#160;
              (Termination for Patent Challenge), and <font style="font-style: italic;">provided further </font>that [***].&#160; If [***].&#160; As used herein, a Patent Challenge includes: (i) filing an action under 28 U.S.C. &#167;&#167; 2201-2202 seeking a declaration
              of invalidity or unenforceability of any such Patent Right; (ii) filing, or joining in, a petition under 35 U.S.C. &#167; 311 to institute <font style="font-style: italic;">inter partes</font> review of any such Patent Right; (iii) filing, or
              joining in, a petition under 35 U.S.C. &#167; 321 to institute post-grant review of any such Patent Right or any portion thereof; (iv) filing or commencing any opposition, nullity, or similar proceedings challenging the validity of any such Patent
              Right in the Territory; or (v) any foreign equivalent of clauses (i), (ii), (iii), or (iv).&#160; [***].&#160; It is understood and agreed by the Parties that [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Termination for Insolvency</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z24609d58dcbc46c6b1d75289e047dc87" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.6.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Each Party will have the right to terminate this Agreement upon delivery of written notice to the other Party if (a) such other Party files in any court or agency pursuant to any statute or regulation of any jurisdiction a petition in
              bankruptcy or insolvency or for reorganization or similar arrangement for the benefit of creditors or for the appointment of a receiver or trustee of such other Party or its assets, (b) such other Party is served with an involuntary petition
              against it in any insolvency proceeding and such involuntary petition has not been stayed or dismissed within [***] of its filing, or (c) such other Party makes an assignment of substantially all of its assets for the benefit of its
              creditors.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbf3254a2894c437c9ca1c3d35f6148fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.6.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>All rights and licenses granted under or pursuant to any section of this Agreement are and will otherwise be deemed to be for purposes of Section 365(n) of Title 11, United States Code (the &#8220;<font style="font-weight: bold; font-style: italic;">Bankruptcy Code</font>&#8221;) licenses of rights to &#8220;intellectual property&#8221; as defined in Section 101(35A) of the Bankruptcy Code.&#160; The Parties will retain and may fully exercise all their respective rights and elections under the
              Bankruptcy Code.&#160; Upon the bankruptcy of any Party, the non-bankrupt Party will further be entitled to a complete duplicate of, or complete access to, any such intellectual property, and such, if not already in its possession, will be
              promptly delivered to the non-bankrupt Party, unless the bankrupt Party elects in writing to continue, and continues, to perform all its obligations under this Agreement.</div>
          </td>
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    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
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    <table cellspacing="0" cellpadding="0" id="zdfd43d57a8ca4d54a5d66ce3f0c74978" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Full Force and Effect During Notice Period</font>.&#160; This Agreement will remain in full force and effect until the expiration of the applicable termination notice period.&#160; For clarity, if Ono or any of its
              Affiliates or Sublicensees achieve any Milestone Events during the termination notice period, then the corresponding Milestone Payment is accrued and Ono will remain responsible for the payment of such Milestone Payment even if the due date
              of such Milestone Payment occurs after the effective date of the termination.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z298598c62dae4661a9b0c3a48e21c7ae" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Effects of Termination</font>.&#160; Upon any expiration or termination of this Agreement, each Party will destroy (at the other Party&#8217;s election) all Confidential Information of the other Party in its
              possession upon termination of this Agreement, and, if applicable, the Receiving Party will provide a written confirmation of such destruction within [***] of such request.&#160; Notwithstanding the foregoing or any provision to the contrary set
              forth in this Agreement, (a) the foregoing terms of this <u>Section 16.8</u> (Effects of Termination) will not apply to any Confidential Information that is necessary to allow the Receiving Party to perform its obligations or exercise any of
              its rights that expressly survive the applicable termination of this Agreement, and the Receiving Party may retain one copy of such Confidential Information for its legal archives; and (b) the Receiving Party will not be required to destroy
              electronic files containing such Confidential Information that are made in the ordinary course of its business information back-up procedures pursuant to its electronic record retention and destruction practices that apply to its own general
              electronic files and information.&#160; Further, if this Agreement is terminated by either Party pursuant to <u>Section 16.2</u> (Termination for Material Breach) or <u>Section 16.6</u> (Termination for Insolvency), by Ono pursuant to <u>Section

                16.3</u> (Termination by Ono for Convenience), or by Ionis pursuant to <u>Section 16.4</u> (Cessation of Development and Commercialization), or <u>Section 16.5</u> (Termination for Patent Challenge), then all rights in the Licensed
              Products will revert to Ionis, and the following will apply with respect to the Licensed Products:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zfbe6b91a9ebf40ac8eb669b4d9f9624b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Termination of Licenses</font>.&#160; As of the effective date of termination of this Agreement, all rights licensed to Ono under <u>Section 2.1</u> (Grant of Licenses to Ono) or otherwise under this Agreement
              (except for the licenses granted under <u>Section 2.5</u> (Improvement Enabling License)), in each case, will each terminate, but each Party will retain its joint ownership interests in the Joint Collaboration Technology.&#160; Subject to <u>Section

                16.8.7</u> (Appointment as Exclusive Distributor) and <u>Section 16.8.2</u> (Effects of Termination on Sublicenses), Ono and its Affiliates and Sublicensees will cease selling Licensed Products that are the subject of such termination.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z4d7f4011ae304efe9804248aac561fa2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Effects of Termination on Sublicenses</font>.&#160; If this Agreement is terminated for any reason, then any sublicense granted hereunder by Ono, will, at the Sublicensee&#8217;s request within [***] of such
              termination, survive such termination; <font style="font-style: italic;">provided</font> that (a) the relevant Sublicensee is not in breach of any of its obligations under such sublicense, (b) Ionis is not required to assume any obligations
              or liabilities (contingent or otherwise) not set forth in this Agreement, (c) such Sublicensee agrees in writing to comply with all of the terms and conditions of this Agreement to the extent applicable to the rights originally sublicensed to
              it by Ono, and (d) such Sublicensee agrees to assume all of Ono&#8217;s financial obligations under this Agreement to the extent applicable to the rights.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">43</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>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z26ffabcee4ef467e93798420a89140bc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Reversion License</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 72pt;"><br>
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          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">License Grant</font>.&#160; Ionis will have, and Ono hereby grants to Ionis, effective upon such termination, a worldwide, exclusive, perpetual, irrevocable, and sublicensable (through multiple tiers) license
              under any Patent Rights and Know-How Controlled by Ono as of the effective date of such termination, other than any Ono Technology, that are necessary or actually used to Exploit the Licensed Products, solely to Exploit the Licensed Products
              in the Territory (the &#8220;<font style="font-weight: bold; font-style: italic;">Reversion License</font>&#8221;), which license will be (a) royalty-bearing if [***] and (b) [***].&#160; Except as otherwise provided in <u>Section 16.8.7</u> (Appointment as
              Exclusive Distributor), Ono will not Commercialize any Licensed Product in the Territory upon and following the effective date of termination of this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z2cab772004eb4203b514784088bcdc7d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
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            <div><font style="font-weight: bold;">Reversion Royalty</font>.&#160; If this Agreement is terminated by Ono under <u>Section </u><u>16.2</u> (Termination for Material Breach), then, promptly following notice of termination, the Parties will
              negotiate in good faith and agree on a reasonable royalty to be paid by Ionis to Ono in consideration of the Reversion License, taking into account, among other things, [***].&#160; If the Parties are unable to agree on the royalty rate for the
              Reversion License within [***] after the effective date of termination, then either Party may refer such matter for resolution pursuant to<font style="font-weight: bold;">&#160;</font><font style="font-variant: small-caps;"><u>Schedule</u></font><u>
                16.8.3(b)</u> (Reversion Royalties Dispute Resolution).&#160; The terms of <u>Section 11.3.2</u> (Royalty Adjustments) and <u>Section 11.3.4</u> (Royalty Payments and Reports) will apply to the payment and reporting of any royalties described
              in this <u>Section 16.8.3(b)</u> (Reversion Royalties), <font style="font-style: italic;">mutatis mutandis</font>.&#160; </div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z4dac6da8c6634fa18e56252ce6bc4610" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Transition Services</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z8274a5a6c71e4528a2b3a4cc324fa4a2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
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          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Scope</font>.&#160; Ionis may request that Ono perform transition activities with respect to any Licensed Products that are necessary or reasonably useful to (i) provide patients with continued access to the
              Licensed Products, (ii) transition the responsibilities under all Regulatory Approvals and ongoing Clinical Trials for Licensed Products to Ionis or its designee, or (iii) transition the then-current supply process and responsibilities for
              the Licensed Products to Ionis or its designee.&#160; If Ionis requests that Ono perform any such transition activities, then the Parties will enter into a transition agreement for Ono to perform transition services[***] and such activities, the &#8220;<font style="font-weight: bold; font-style: italic;">Transition Services</font>&#8221;).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6d5cd8ec001843888a627e0e2d51b9cc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Transition Plan</font>.&#160; Ionis may elect to have Ono perform the Transition Services by providing written notice to Ono no later than the later of (i) [***] following the effective date of the termination
              and (ii) [***] following [***].&#160; If Ionis requests that Ono perform the Transition Services, then Ionis will propose a transition plan setting forth the Transition Services to be performed by Ono, and promptly after such request, the Parties
              will negotiate and enter into a transition plan [***]. While Ono is providing Transition Services, Ono and Ionis will mutually agree on talking points and a communication plan to key stakeholders, including customers, specialty pharmacies,
              physicians, Regulatory Authorities, patient advocacy groups, payors, and clinical study investigators, and Ono will make all such communication to such entities and individuals in accordance with the mutually agreed talking points.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3d133a0369d945a6b69a35034f2174f7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Costs</font>.&#160; Ionis will pay Ono for the Transition Services [***].&#160; In addition, Ionis will reimburse [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc3d536acecdb414f917252ced3931794" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Assignment and Disclosure</font>.&#160; To the extent requested by Ionis following the date that a Party provides notice of termination of this Agreement, Ono will promptly (and in any event no later than [***]
              after the effective date of termination unless agreed otherwise in the Transition Plan):</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">44</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z2b079b66e8004a4abe89cdce492dd69f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>provide to Ionis for its review unredacted copies of all clinical trial agreements and distribution agreements (to the extent assignable and not cancelled), in each case, that are necessary or reasonably useful for the Exploitation of the
              Licensed Products, and, following such review, upon Ionis&#8217; request, assign and transfer to Ionis or its designee all of Ono&#8217;s rights, title, and interests in and to any such agreements;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z017d95501a154fd6aa70dc49d667c3ea" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>assign or amend, as appropriate, any agreements or arrangements with Third Party vendors (including distributors) solely related to the Licensed Products or, to the extent any such Third Party agreement or arrangement is not assignable to
              Ionis, reasonably cooperate with Ionis to arrange to continue to provide such services for a reasonable time after termination of this Agreement to facilitate the orderly transition of all Commercialization and other activities then being
              performed by or on behalf of Ono or its Affiliates or Sublicensees for the Licensed Products to Ionis or its designee;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zcadee74989aa4b5ab807407ab97cbff9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>assign and transfer to Ionis or its designee, as of the effective date of termination, all of Ono&#8217;s rights, title, and interests in and to the trademarks used for the Licensed Products (other than any corporate trademarks of Ono) and any
              domain names associated with such trademarks (to the extent that Ono or its Affiliates has any), and promptly provide to Ionis all login and password information necessary to maintain such domain names;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z13321dab2fed4ae8aeed4d4cb26c5007" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>assign and transfer to Ionis or its designee all of Ono&#8217;s rights, title, and interests in and to any promotional materials, training materials, medical education materials, and all other literature or other materials related to the
              Licensed Products used to support Commercialization of such Licensed Products, and copyrights and any registrations for the foregoing; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z2ac2994dd92c4bf99e173b663594f22e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 72pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(e)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>disclose to Ionis or its designee all documents, records, and materials that embody any of the foregoing and that are controlled by Ono or that Ono is able to obtain using reasonable efforts.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 72pt;">Subject to <u>Section 16.8.11</u> (Termination by Ono for Breach), Ono will be responsible for [***] the assignments set forth in this <u>Section 16.8.5</u><font style="color: #000000;">&#160;</font>(Assignment

      and Disclosure).&#160; To the extent that any agreement or other asset described in this <u>Section 16.8.5</u> (Assignment and Disclosure) is not assignable by Ono, then such agreement or other asset will not be assigned, and upon the request of Ionis,
      Ono will take such steps as may be necessary to allow Ionis to obtain and to enjoy the benefits of such agreement or other asset, in the form of a license or other right to the extent Ono has the right and ability to do so.&#160; For clarity, Ionis will
      have the right to request that Ono take any or all of the foregoing actions in whole or in part, or with respect to all or any portion of the assets set forth in the foregoing provisions.</div>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">45</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z1cb2513efa5f41df900677266026fca3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Regulatory Submissions and Regulatory Approvals</font>.&#160; Ono will and hereby does, and will cause its Affiliates and Sublicensees to, (a) no later than [***] after the effective date of termination of this
              Agreement, at Ionis&#8217; request either (i) assign and transfer to Ionis or its designee all of Ono&#8217;s rights, title, and interests in and to all Regulatory Submissions, Regulatory Approvals, and Reimbursement Approvals, or (ii) withdraw all
              Regulatory Submissions, Regulatory Approvals, and Reimbursement Approvals, in each case ((i) or (ii)), solely for the Licensed Products that are the subject of termination, and (b) to the extent assignment pursuant to clause (a)(i) is delayed
              or is not permitted by the applicable Regulatory Authority, permit Ionis to cross-reference and rely upon any such Regulatory Submissions, Regulatory Approvals, and Reimbursement Approvals filed by Ono or any of its Affiliates or
              Sublicensees.&#160; Ono will execute and deliver, or will cause to be executed and delivered, to Ionis or its designee such endorsements, assignments, commitments, acknowledgements, and other documents as may be necessary to assign, convey,
              transfer, and deliver to Ionis or its designee all of Ono&#8217;s or its applicable Affiliate&#8217;s or designee&#8217;s rights, title, and interests in and to all such assigned Regulatory Submissions, Regulatory Approvals, and Reimbursement Approvals,
              including submitting to each applicable Regulatory Authority or other Governmental Authority a letter or other necessary documentation (with copy to Ionis) notifying such Regulatory Authority or other Governmental Authority of, or otherwise
              giving effect to, the transfer of ownership to Ionis of all such assigned Regulatory Submissions, Regulatory Approvals, and Reimbursement Approvals.&#160; In addition, upon Ionis&#8217; written request, Ono will provide to Ionis copies of all material
              related documentation, including material non-clinical, preclinical, and clinical data related to the Licensed Products that are held by or reasonably available to Ono or its Affiliates or Sublicensees.&#160; Subject to <u>Section 16.8.11</u>
              (Termination by Ono for Breach), Ono shall conduct the activities set forth in this <u>Section 16.8.6</u> (Regulatory Submissions and Regulatory Approvals) [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z43fb2d7e6840473c81b39cfd23e121df" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Appointment as Exclusive Distributor</font>.&#160; If Ono is Commercializing any Licensed Product as of the applicable effective date of termination, then, [***], either (a) Ono will appoint Ionis or its
              designee as its exclusive distributor of such Licensed Product in such country and grant Ionis or its designee the right to appoint sub-distributors, or (b) Ono will have the continued right to sell the Licensed Products from its inventory; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that Ono&#8217;s obligations under this Agreement with respect to the Licensed Products that Ono sells, including the obligation to pay Royalties to
              Ionis hereunder, will continue in full force and effect during such period.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zcf5eecd8057843d58301ff3a16d3ee4a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Know-How Transfer Support</font>.&#160; In furtherance of the assignment of Know-How pursuant to <u>Section 16.8.5</u> (Assignment and Disclosure), Ono will, for a period of [***] from the effective date of
              such termination, provide such consultation or other assistance, as Ionis may reasonably request to assist Ionis in becoming familiar with such Know-How in order for Ionis to undertake further Exploitation of the Licensed Products [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z07a5249f15a74beabaebb6ed2dfb3fb9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Inventory</font>.&#160; At Ionis&#8217; election and request, unless Ionis elects to grant to Ono the continued right to sell the Licensed Products from its inventory pursuant to clause (b) of <u>Section 16.8.7</u>
              (Appointment as Exclusive Distributor), Ono will transfer to Ionis or its designee some or all inventory of the Licensed Products (including all final product, bulk drug substance, intermediates, works-in-process, formulation materials,
              reference standards, drug product clinical reserve samples, packaged retention samples, and the like) then in the possession or Control of Ono, its Affiliates or Sublicensees; <font style="font-style: italic;">provided </font>that [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za9e72b68d3954eb99b856a535f19ef1d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Wind Down and Transition</font>.&#160; Ono will be responsible, [***], for the wind-down of Ono&#8217;s and its Affiliates&#8217; and its Sublicensees&#8217; activities with respect to the Licensed Products.&#160; In accordance with
              Ionis&#8217; election under <u>Section 16.8.6(a)(i)</u> (Regulatory Submissions and Regulatory Approvals), Ono will, and will cause its Affiliates and Sublicensees to, reasonably cooperate with Ionis to facilitate orderly transition to Ionis or
              its designee of all Commercialization and other activities then being performed by or on behalf of Ono or its Affiliates or Sublicensees for the Licensed Products, including reasonably cooperating with Ionis to transfer all Commercialization
              and other activities to Ionis or its designee and continuing to perform such activities on Ionis&#8217; behalf for a reasonable time after termination of this Agreement until such transfer is completed.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">46</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z7efcc363fe9645259723a2d558d3761c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.11</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Termination by Ono</font>&#160;<font style="font-weight: bold;">for Breach</font>.&#160; Notwithstanding any provision to the contrary in this <u>Section 16.8</u> (Effects of Termination), if Ono terminates this
              Agreement pursuant to <u>Section 16.2</u> (Termination for Material Breach), then [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze2a603acfffa4cae8e76b59ea74a6736" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 35.1pt; vertical-align: top;">16.8.12</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Other Assistance; Further Assurances</font>.&#160; Without limiting the assistance to be provided under <u>Section 16.8.8</u> (Know-How Transfer Support), Ono will provide any other assistance reasonably
              requested by Ionis for the purpose of allowing Ionis or its designee to proceed expeditiously with the Exploitation of the Licensed Products for a period of [***] after the effective date of termination of this Agreement.&#160; Ono will execute
              all documents and take all such further actions as may be reasonably requested by Ionis in order to give effect to the requirements in this <u>Section 16.8</u> (Effects of Termination).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z08c90b326f574a1c8722df934f485462" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">16.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Survival; Accrued Rights</font>.&#160; Expiration or termination of this Agreement will not relieve the Parties of any liability that accrued hereunder prior to the effective date of such expiration or
              termination nor preclude either Party from pursuing all rights and remedies it may have hereunder or at law or in equity with respect to any breach of this Agreement, nor prejudice either Party&#8217;s right to obtain performance of any
              obligation.&#160; Without limiting the foregoing, the following provisions of this Agreement will survive the expiration or termination of this Agreement: <u>Section 2.4</u> (Responsibility for Sublicensees and Subcontractors), <u>Section 2.5</u>
              (Improvement Enabling License), <u>Section 2.6</u> (No Other Rights and Retained Rights), <u>Section 7.9</u> (Development Records), <u>Section 8.2</u> (Correspondence with Regulatory Authorities), <u>Section 8.10.1</u>, <u>Section </u><u>11.2.3</u>
              (Notice and Payment), <u>Section 11.3.4(b)</u> (Royalty Report) (solely with respect to the report covering the final Calendar Quarter prior to expiration or termination of the Agreement), <u>Section 11.3.4(c)</u> (Royalty Payments) (solely
              with respect to Royalties dur for the final Calendar Quarter prior to expiration or termination of the Agreement), <u>Section 11.4</u> (Other Amounts Payable), <u>Section 11.5</u> (Financial Records and Audits), <u>Section 11.6</u> (No
              Refunds), <u>Section 11.8</u> (Method of Payment; Exchange Rate), <u>Section 11.9</u> (Blocked Payments), <u>Section 11.10</u> (Taxes), <u>Section 11.11</u> (Late Payments; Disputed Payments), <u>Article 12</u> (Intellectual Property), <u>Section

                13.5</u> (Disclaimer), <u>Section 13.6</u> (Limitation of Liability), <u>Article 14</u> (Confidentiality), <u>Article 15</u> (Indemnification), <u>Article 16</u> (Term and Termination), <u>Article 17</u> (Dispute Resolution; Governing
              Law), and <u>Article 18</u> (Miscellaneous).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 17</div>
    <div style="text-align: center; font-weight: bold;">DISPUTE RESOLUTION; GOVERNING LAW</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z2bd98229866346828948f3da435390bd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">17.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Executive Officers; Disputes</font>.&#160; Each Party will ensure that an Executive Officer is designated for such Party at all times during the Term for dispute resolution purposes and will promptly notify the
              other Party of any change in its designated Executive Officer.&#160; Except as expressly set forth in this Agreement, if a dispute arises under, in relation to, or in connection with, this Agreement (except for disputes arising at the JSC, which
              will be resolved in accordance with <u>Section 4.3</u> (Decision-Making)), then the Parties will refer such dispute to their Executive Officers, and such Executive Officers or designees will attempt in good faith to resolve such dispute.&#160; If
              the Parties are unable to resolve any such dispute within [***] after referring such dispute to the designated Executive Officers pursuant to this <u>Section 17.1</u> (Executive Officers; Disputes), then either Party will have the right to
              pursue any and all remedies available at law or equity, as set forth in <u>Section 17.2</u> (Arbitration) or <u>Section 17.3</u> (Intellectual Property Disputes), as applicable.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">47</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z2fa793d9a2ed4352954c039a80a1b679" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">17.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Arbitration</font>.&#160; Except as otherwise expressly set forth in<font style="font-weight: bold;">&#160;</font>this Agreement, if the Executive Officers do not resolve a dispute within [***] after such dispute is
              referred to them in accordance with <u>Section 17.1</u> (Executive Officers Disputes), then, either Party may at any time after such [***] period submit such dispute to be finally settled by arbitration administered by the International
              Chamber of Commerce (the &#8220;<font style="font-weight: bold; font-style: italic;">ICC</font>&#8221;) in accordance with its Rules of Arbitration in effect at the time of the arbitration, except as modified by this <u>Section 17.2</u> (Arbitration)
              (the &#8220;<font style="font-weight: bold; font-style: italic;">Arbitration</font>&#8221;).&#160; The Arbitration will be governed by the Applicable Law of the State of New York. The language of the arbitration will be English.&#160; The Arbitration will be heard
              and determined by three arbitrators who are retired judges or attorneys with at least 20 years of relevant experience in the pharmaceutical and biotechnology industry, each of whom will be impartial and independent and will not have worked
              for or on behalf of either Party for at least [***].&#160; Each Party will appoint one arbitrator and the third arbitrator will be selected by the two Party-appointed arbitrators, or, failing agreement within [***] following appointment of the
              second arbitrator, by the ICC.&#160; Such Arbitration will take place in New York, NY.&#160; The Arbitration award so given will, absent manifest error, be a final and binding determination of the dispute, will be fully enforceable in any court of
              competent jurisdiction, and will not include any damages expressly prohibited by <u>Section 13.6</u> (Limitation of Liability).&#160; Ionis will pay the fees, costs, and expenses for the arbitrator it chooses, Ono will pay the fees, costs, and
              expenses for the arbitrator it chooses, and the Parties will share payment for the third arbitrator.&#160; Except in a proceeding to enforce the results of the Arbitration or as otherwise required by Applicable Law or securities exchange, neither
              Party nor any arbitrator may disclose the existence, content, or results of any Arbitration hereunder without the prior written consent of both Parties. </div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5449040a404544988f2c6c0fa66f994f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">17.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Intellectual Property Disputes</font>.&#160; Notwithstanding any provision to the contrary set forth in this Agreement, if a dispute arises under this Agreement with respect to the validity, scope,
              enforceability, or ownership of any Patent Right or other intellectual property rights, and such dispute is not resolved in accordance with <u>Section 17.1</u> (Executive Officers; Disputes), then such dispute will be [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3cb89e5435924f7e8111f9b87bf3ba7e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">17.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Equitable Remedies</font>.&#160; Notwithstanding any provision to the contrary set forth in this Agreement, the Parties each stipulate and agree that (a) the other Party&#8217;s Confidential Information includes
              highly sensitive trade secret information such that a breach of <u>Article 14</u> (Confidentiality) by a Party will cause irrevocable harm for which monetary damages would not provide a sufficient remedy; and (b) in such case of such breach
              of <u>Article 14</u> (Confidentiality), the non-breaching Party will be entitled to seek equitable relief, including specific performance, temporary or permanent restraining orders, preliminary injunction, permanent injunction, or other
              equitable relief without the posting of any bond or other security, from any court of competent jurisdiction.&#160; In addition, and notwithstanding any provision to the contrary set forth in this Agreement, if there is any other actual or
              threatened breach hereunder, then the aggrieved Party may seek equitable relief (including specific performance, temporary or permanent restraining orders, or other equitable relief) from any court of competent jurisdiction without first
              submitting to the dispute resolution procedures set forth in <u>Article 17</u> (Dispute Resolution; Governing Law).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z176db33d00524e978a606083ebcc5715" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">17.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Governing Law; English Language</font>.&#160; This Agreement and all amendments, modifications, alterations, or supplements hereto, and the rights of the Parties, will be construed under and governed by the laws
              of [***], exclusive of its conflicts of laws principles.&#160; This Agreement has been prepared in the English language and the English language will control its interpretation.&#160; All consents, notices, reports, and other written documents to be
              delivered or provided by a Party under this Agreement will be in the English language (and the Party delivering or providing such consent, notice, report, or other written document shall bear the cost of translating such consent, notice,
              report, or other written document into English if not originally prepared in English), and if there is any conflict between the provisions of any document and the English language translation thereof, then the terms of the English language
              translation will control.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">48</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-weight: bold;">ARTICLE 18</div>
    <div style="text-align: center; font-weight: bold;">MISCELLANEOUS</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z61915dfac60a49b6868b92f07a60f1ab" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Assignment</font>.&#160; This Agreement may not be assigned or otherwise transferred, nor may any right or obligation hereunder be assigned or transferred, by either Party without the prior written consent of
              the other Party.&#160; Notwithstanding the foregoing, (a) Ionis may assign its rights to receive payments under this Agreement to one or more Persons without consent of Ono (including as part of a royalty monetization transaction) with prior
              notice to Ono, and (b) either Party may, without consent of the other Party, assign this Agreement and its rights and obligations hereunder (i) in whole or in part to an Affiliate of such Party (for so long as such Affiliate remains an
              Affiliate), or (ii) in whole to its successor-in-interest in connection with the sale of all or substantially all of its assets, whether in a merger, acquisition, or similar transaction or series of related transactions.&#160; If there is an
              assignment pursuant to the foregoing clauses (b)(i) or (b)(ii), then such assignment will only be effective if the Person to whom this Agreement is assigned agrees in writing to assume all of the assigning Party&#8217;s obligations under this
              Agreement and the assigning Party provides written notice of such assignment to the non-assigning Party within [***] after the effective date of such assignment.&#160; Any attempted assignment of this Agreement in violation of this <u>Section
                18.1</u> (Assignment) will be null, void, and of no legal effect.&#160; Any permitted assignee will assume all assigned obligations of its assignor under this Agreement.&#160; This Agreement will be binding on and will inure to the benefit of the
              permitted successors and assigns of the Parties.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z93198724d8214be69f47f9aedaa83200" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Entire Agreement; Amendment</font>.&#160; This Agreement, together with all exhibits and schedules attached hereto, constitutes the entire agreement between the Parties with respect to the subject matter hereof,
              and supersedes and merges all prior and contemporaneous negotiations, representations, and understandings regarding the same, (including that certain mutual confidential disclosure agreement between the Parties dated [***] (&#8220;<font style="font-weight: bold; font-style: italic;">Confidential Disclosure Agreement</font>&#8221;)).&#160; All information shared by the Parties pursuant to the Confidential Disclosure Agreement will be Confidential Information under this Agreement from
              and after the Effective Date, and the use and disclosure thereof will be governed by <u>Article 14</u> (Confidentiality).&#160; This Agreement may not be modified or amended, except by another agreement in writing executed by duly authorized
              signatories of each Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">49</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z5903bb6ac9314ff78bb4a558acd23ea8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Strict Construction; Interpretation</font>.&#160; This Agreement has been prepared jointly and will not be strictly construed against either Party.&#160; Ambiguities, if any, in this Agreement will not be
              construed against any Party, irrespective of which Party may be deemed to have authored the ambiguous provision.&#160; Except where the context expressly requires otherwise, (a) whenever any provision of this Agreement uses the term &#8220;including&#8221;
              (or &#8220;includes&#8221;), such term will be deemed to mean &#8220;including without limitation&#8221; and &#8220;including but not limited to&#8221; (or &#8220;includes without limitations&#8221; and &#8220;includes but is not limited to&#8221;) regardless of whether the words &#8220;without limitation&#8221;
              or &#8220;but not limited to&#8221; actually follow the term &#8220;including&#8221; (or &#8220;includes&#8221;); (b) &#8220;herein,&#8221; &#8220;hereby,&#8221; &#8220;hereunder,&#8221; &#8220;hereof,&#8221; and other equivalent words will refer to this Agreement in its entirety and not solely to the particular portion of
              this Agreement in which any such word is used; (c) all definitions set forth herein will be deemed applicable whether the words defined are used herein in the singular or the plural; (d) wherever used herein, any pronoun or pronouns will be
              deemed to include both the singular and plural and to cover all genders; (e) the recitals set forth at the start of this Agreement, along with the schedules and exhibits to this Agreement, and the terms and conditions incorporated in such
              recitals and schedules and exhibits will be deemed integral parts of this Agreement and all references in this Agreement to this Agreement will encompass such recitals and schedules and exhibits and the terms and conditions incorporated in
              such recitals and schedules and exhibits; <font style="font-style: italic;">provided</font> that if there is any conflict between the terms and conditions of this Agreement and any terms and conditions set forth in the recitals, schedules,
              or exhibits, then the terms and conditions of this Agreement will control; (f) if there is any conflict between the terms and conditions of this Agreement and any terms and conditions that may be set forth on any order, invoice, verbal
              agreement, or otherwise, then the terms and conditions of this Agreement will govern; (g) unless otherwise provided, all references to Sections, Articles, and Schedules in this Agreement are to Sections, Articles, and Schedules of and to this
              Agreement; (h) any reference to any federal, national, state, local, or foreign statute or law will be deemed to also refer to all rules and regulations promulgated thereunder, and any reference to any law, rule, or regulation will be deemed
              to include the then&#8209;current amendments thereto or any replacement or successor law, rule, or regulation thereof; (i) wherever used, the word &#8220;shall&#8221; and the word &#8220;will&#8221; are each understood to be imperative or mandatory in nature and are
              interchangeable with one another; (j) the term &#8220;or&#8221; will be interpreted in the inclusive sense commonly associated with the term &#8220;and/or&#8221;; (k) references to a particular Person include such Person&#8217;s successors and assigns to the extent not
              prohibited by this Agreement; (l) the section headings and captions used herein are inserted for convenience of reference only and will not be construed to create obligations, benefits, or limitations; (m) any definition of or reference to
              any agreement, instrument, or other document herein will be construed as referring to such agreement, instrument, or other document as from time to time amended, supplemented, or otherwise modified (subject to any restrictions on such
              amendments, supplements, or modifications set forth herein); (n) the word &#8220;notice&#8221; means notice in writing (whether or not specifically stated) and will include notices, consents, approvals, and other written communications contemplated under
              this Agreement; and (o) provisions that require that a Party, the Parties, or any committee hereunder &#8220;agree,&#8221; &#8220;consent,&#8221; or &#8220;approve&#8221; or the like will require that such agreement, consent, or approval be specific and in writing, whether by
              written agreement, letter, approved minutes, or otherwise (but excluding e&#8209;mail and instant messaging).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbb85a5d641ad4f27a629d59086cd6296" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Severability</font>.&#160; If any provision of this Agreement is declared invalid by a court of last resort or by any court or other governmental body, the decision of which is not appealed within the time
              provided by law, then this Agreement will be deemed to have been terminated only as to the portion thereof that relates to the provision invalidated by that decision and only in the relevant jurisdiction, and this Agreement will remain in
              force in all other respects and all other jurisdictions; <font style="font-style: italic;">provided, however</font>, that if the provision so invalidated is essential to the Agreement as a whole, then the Parties will negotiate in good faith
              to amend the terms hereof as nearly as practical to carry out the original intent of the Parties, and, failing such amendment, either Party may submit the matter for resolution pursuant to <u>Article 17</u><font style="color: #000000;">&#160;</font>(Dispute

              Resolution; Governing Law).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z2f64ee30916c444fa0544bd6721d840e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Force Majeure</font>.&#160; Neither Party will be held liable or responsible to the other Party nor be deemed to be in default under, or in breach of any provision of, this Agreement for failure or delay in
              fulfilling or performing any obligation (other than a payment obligation) of this Agreement when such failure or delay is due to force majeure.&#160; For purposes of this Agreement, &#8220;<font style="font-weight: bold; font-style: italic;">Force
                Majeure</font>&#8221; is defined as any cause beyond the control of the affected Party and without the fault or negligence of such Party, which may include acts of God; material changes in Applicable Law; war; civil commotion; destruction of
              production facilities or materials by fire, flood, earthquake, explosion or storm; labor disturbances; epidemic; pandemic; quarantine; and failure of public utilities or common carriers.&#160; Notwithstanding the foregoing, a Party will not be
              excused from making payments owed hereunder due to any such Force Majeure circumstances affecting such Party.&#160; In such event the Party affected by such force majeure will immediately notify the other Party of such inability and of the period
              for which such inability is expected to continue.&#160; The Party giving such notice will thereupon be excused from such of its obligations under this Agreement as it is thereby disabled from performing for so long as it is so disabled for up to a
              maximum of [***], after which time the Parties will promptly meet to discuss in good faith how to best proceed in a manner that maintains and abides by the Agreement.&#160; To the extent possible, each Party will use reasonable efforts to minimize
              the duration of any Force Majeure.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">50</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z17136e8aa3304f3a9391382731c3e4f1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Notices</font>.&#160; All notices that are required or permitted hereunder will be in writing and sufficient if delivered by internationally-recognized overnight courier or sent by registered or certified mail,
              postage prepaid, return receipt requested, and in each case, addressed as follows (with a courtesy copy sent by email, which will not constitute notice):</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 50.4pt;">If to Ionis:</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt;">Ionis Pharmaceuticals, Inc.</div>
    <div style="margin-left: 72pt;">[***]</div>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 50.4pt;"><font style="font-style: italic;">With a copy (which will not constitute notice for purposes of this Agreement) to</font>:</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt;">[***]</div>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 50.4pt;">If to Ono:</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt;">Ono Pharmaceutical Co., Ltd.</div>
    <div style="margin-left: 72pt;">[***]</div>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 50.4pt;"><font style="font-style: italic;">With a copy (which will not constitute notice for purposes of this Agreement) to</font>:</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt;">[***]</div>
    <div style="margin-left: 72pt;"> <br>
    </div>
    <div style="margin-left: 72pt;">[***]</div>
    <div>&#160;</div>
    <div style="text-align: justify; margin-left: 72pt;">or to such other address as the Party to whom notice is to be given may have furnished to the other Party in writing in accordance with this <u>Section 18.6</u> (Notices).&#160; Any such notice will be
      deemed to have been given: (a) on the [***] after dispatch if sent by internationally-recognized overnight courier; or (b) on the [***] after dispatch if sent by registered or certified mail, postage prepaid, return receipt requested.</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za874b9f2de20441897179aef737deca0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Further Assurances</font>.&#160; The Parties agree to reasonably cooperate with each other in connection with any actions required to be taken as part of their respective obligations under this Agreement, and
              will (a) furnish to each other such further information; (b) execute and deliver to each other such other documents; and (c) do such other acts and things (including working collaboratively to correct any clerical, typographical, or other
              similar errors in this Agreement), all as the other Party may reasonably request for the purpose of carrying out the intent of this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zefdbc9d4d30d4496ad8306025523474a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Performance by Affiliates</font>.&#160; If Ono or Ionis performs any or all of its obligations or exercises any or all of its rights under this Agreement through any Affiliate, then Ono and Ionis each hereby
              guarantees the performance by its Affiliates of its obligations under this Agreement and will cause its Affiliates to comply with the provisions of this Agreement in connection with such performance.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3d435ce4f071472ca5d37515e22cc926" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Agency</font>.&#160; Neither Party is, nor will be deemed to be an employee, agent, or representative of the other Party for any purpose.&#160; Each Party is an independent contractor, not an employee or partner of
              the other Party.&#160; Neither Party will have the authority to speak for, represent, or obligate the other Party in any way without prior written authority from the other Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">51</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zb1f1329336f848a08e5035002aef2cfd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Binding Effect; No Third-Party Beneficiaries or Obligors</font>.&#160; As of the Effective Date, this Agreement will be binding upon and inure to the benefit of the Parties and their respective permitted
              successors and assigns.&#160; Except as set forth in <u>Article 15</u> (Indemnification), no Person other than Ionis, Ono, and their respective permitted successors and assigns hereunder will be deemed an intended beneficiary hereunder, nor have
              any right to enforce any obligation of any Party to this Agreement, nor will any Person other than Ionis and Ono and their respective permitted successors and assigns have any obligations to any Party under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc8b1b4388fc24ff48629d877d85bd5b3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.11</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">No Waiver</font>.&#160; Any omission or delay by either Party at any time to enforce any right or remedy reserved to it, or to require performance of any of the terms, covenants, or provisions hereof, by the
              other Party, will not constitute a waiver of such Party&#8217;s rights to the future enforcement of its rights under this Agreement.&#160; Any waiver by a Party of a particular breach or default by the other Party will not operate or be construed as a
              waiver of any subsequent breach or default by the other Party.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z156d3a17cf254783b517234c1bd33012" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.12</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Cumulative Remedies</font>.&#160; No remedy referred to in this Agreement, including termination of this Agreement, is intended to be exclusive, but each will be cumulative and in addition to any other remedy
              referred to in this Agreement or otherwise available under law.&#160; Without limiting the foregoing, neither Party will be entitled to recover any liabilities, expenses, or losses (including reasonable attorneys&#8217; fees, court costs, witness fees,
              damages, judgments, fines, and amounts paid in settlement) to the extent that such Party has already recovered such liabilities, expenses, or losses pursuant to other provisions of this Agreement, including recoveries under <u>Section 15.1</u>
              (Indemnification by Ionis) or <u>Section 15.2</u> (Indemnification by Ono).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zffbecfd2342546f89d8072fe826e4291" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">18.13</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="font-weight: bold;">Counterparts</font>.&#160; This Agreement may be executed in one or more counterparts, all of which taken together will be regarded as one and the same instrument.&#160; Each Party may execute this Agreement in
              Adobe&#8482; Portable Document Format (PDF) sent by electronic mail.&#160; PDF signatures of authorized signatories of the Parties will be deemed to be original signatures, will be valid and binding upon the Parties, and, upon delivery, will constitute
              due execution of this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: center; font-style: italic;">[Remainder of page intentionally left blank.&#160; Signature page follows.]</div>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">52</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-weight: bold;">IN WITNESS WHEREOF,</font> the Parties have executed this Agreement through their duly authorized representatives to be effective as of the Effective Date.</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" border="0" id="zd1c5823a70bb4c4780d906aaa316ede1" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

        <tr>
          <td style="vertical-align: top;" colspan="2">
            <div style="text-align: justify; font-variant: small-caps; font-weight: bold;">
              <div style="text-align: left; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
            </div>
          </td>
          <td style="width: 10%; vertical-align: top;">&#160;</td>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; color: #000000; font-variant: small-caps; font-weight: bold;">
              <div style="text-align: left; font-weight: bold;">ONO PHARMACEUTICAL CO., LTD.</div>
            </div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="vertical-align: top;" colspan="3" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 3%; vertical-align: top; padding-bottom: 2px;">
            <div style="text-align: justify; color: #000000;">By:</div>
          </td>
          <td style="width: 37%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">
            <div style="text-align: justify; color: rgb(0, 0, 0); font-style: italic; margin-left: 9pt;">/s/ Brett Monia</div>
          </td>
          <td style="width: 10%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
          <td style="width: 3%; vertical-align: top; padding-bottom: 2px;">
            <div style="text-align: justify; color: #000000;">By:</div>
          </td>
          <td style="width: 43%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">
            <div style="text-align: justify; color: rgb(0, 0, 0); font-style: italic; margin-left: 9pt;">/s/ Toichi Takino</div>
          </td>
          <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="vertical-align: top;" colspan="3" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="2">
            <div style="text-align: justify; color: #000000;">Name:&#160; Brett Monia</div>
          </td>
          <td style="width: 10%; vertical-align: top;">&#160;</td>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; color: #000000;">Name:&#160; Toichi Takino</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="vertical-align: top;" colspan="3" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" colspan="2">
            <div style="text-align: justify; color: #000000;">Title:&#160; Chief Executive Officer</div>
          </td>
          <td style="width: 10%; vertical-align: top;">&#160;</td>
          <td style="vertical-align: top;" colspan="3">
            <div style="text-align: justify; color: #000000;">Title: &#160;Representative Director, President and Chief Operating Officer</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">53</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-weight: bold;"><u>Appendix 1</u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Definitions</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt;">For purposes of this Agreement, whether used in the singular or plural, the following terms will have the meanings set forth below:</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z63b32e2e068348a7903af0f215a659e8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.1</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Accounting Standards</font>&#8221; means, with respect to a Party or its Affiliate or Sublicensee, GAAP or IFRS, as such Person uses for its financial reporting standards from time to time,
              in each case, as consistently applied.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za9313f03d27f4b628ad75574e1fb0215" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.2</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Additional Know-How Transfer</font>&#8221; has the meaning set forth in <u>Section 6.2</u> (Additional Know-How Transfer).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5aaf58935ff145f993a9fa89f6137495" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.3</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Affiliate</font>&#8221; means, with respect to a Person, any corporation or other business entity controlled by, controlling, or under common control with such Person, with &#8220;control&#8221; meaning
              (a) direct or indirect beneficial ownership of more than 50% of the voting stock or other ownership interest of, or more than 50% interest in the income of, the applicable entity, or (b) the possession, directly or indirectly, of the power to
              direct the management or policies of the applicable entity, whether through the ownership of voting securities or other equity rights, by contract relating to voting rights or corporate governance, or otherwise.&#160; Notwithstanding the
              foregoing, &#8220;Affiliates&#8221; will not include, with respect to an entity, <font style="font-style: italic;">bona fide</font> venture capital investors in such entity or <font style="font-style: italic;">bona fide</font> institutional investors
              in such entity, in each case, that routinely make venture capital investments for the potential financial return on such investments and not with any view to acquisition or for other strategic purpose, or Affiliates of such venture capital or
              institutional investors.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z369acb1b5f2746cd8719c8e83dcd6738" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.4</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="color: #000000;">&#8220;</font>[***]<font style="color: #000000;">&#8221;</font> means [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z39d6e833bfb04bb1970dda71294633e1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.5</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Annual Net Sales</font>&#8221; means the Net Sales for a Fiscal Year.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z146eb37c14944e1699f41b069aa322c2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.6</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Antitrust Authorities</font>&#8221; has the meaning set forth in <u>Section 5.2.1</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zec9b7b1043fe4407901d42d29dee96bf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.7</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Antitrust Filings</font>&#8221; has the meaning set forth in <u>Section 5.2.1</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z05f34f5ce3fb46569a2397b056ae7629" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.8</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Applicable Law</font>&#8221; means applicable (with respect to the particular activity, task, or obligation under this Agreement to which such term applies) laws, statutes, rules,
              regulations, and other pronouncements having the effect of law of any Governmental Authority that may be in effect from time to time, including for clarity any applicable rules, regulations, guidelines, or other requirements of data
              protection, privacy, or any Regulatory Authority that may be in effect from time to time.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z90dc8f97fa654e6cb376333101787470" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.9</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Approved Labeling</font>&#8221; means, with respect to a Licensed Product and a jurisdiction: (a) the applicable Regulatory Authority-approved full prescribing information for such Licensed
              Product in such jurisdiction; and (b) the applicable Regulatory Authority-approved labels and other written, printed, or graphic materials on any container, wrapper, or any package insert that is used with or for such Licensed Product in such
              jurisdiction.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z07ca4eb7f89f4f829e1b64a1ed07ee9c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.10</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Arbitration</font>&#8221; has the meaning set forth in <u>Section 17.2</u> (Arbitration).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">54</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z86969b1c2fe641a383fe76be02350a76" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.11</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">ASO</font>&#8221; means a [***] oligonucleotide compound, or analog or variant thereof that is at least [***] bases long and is designed to inhibit expression of a gene target via the
              binding, partially or wholly, of such compound to the RNA transcript of such gene target.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc0ff2a4a8fd74e208b1fef33ccf8227b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.12</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Bankruptcy Code</font>&#8221; has the meaning set forth in <u>Section 16.6.2</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zcaaca101627844189ec35ad5cd0e362f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.13</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Business Day</font>&#8221; means a day other than a Saturday, Sunday, or a day on which banking institutions in California or Japan are required by Applicable Law to remain closed, a day that
              is a legal holiday in California or Japan, or any day within Ionis&#8217; corporate holidays (for Ionis&#8217; obligations and response times) or Ono&#8217;s corporate holidays (for Ono&#8217;s obligations and response times).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7c99fe75927a49daabec3f44b59ceca4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.14</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Calendar Quarter</font>&#8221; means, with respect to the first Calendar Quarter during the Term, the period beginning on the Effective Date and ending on the last day of the Calendar Quarter
              within which the Effective Date falls, and thereafter each successive period of three calendar months ending on (and including) each of March 31, June 30, September 30, and December 31; except that the last Calendar Quarter during the Term
              will end upon the expiration of the Term.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zfd6936b78d4f457a8a9c5d7b82a57b0d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.15</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Calendar Year</font>&#8221; means the period of 12 consecutive calendar months beginning on January 1 and ending on December 31; except that (a) the first Calendar Year during the Term will
              begin on the Effective Date and end on December 31 of the Calendar Year within which the Effective Date falls, and (b) the last Calendar Year during the Term will end upon expiration of the Term.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z049b41ab3ffb46d5a525f98512d85310" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.16</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Change of Control</font>&#8221; means, with respect to a Party, that: (a) any Third Party acquires directly or indirectly the beneficial ownership of any voting security of such Party, or if
              the percentage ownership of such Third Party in the voting securities of such Party is increased through stock redemption, cancellation, or other recapitalization, and immediately after such acquisition or increase such Third Party is,
              directly or indirectly, the beneficial owner of voting securities representing more than 50% of the total voting power of all of the then outstanding voting securities of such Party; (b) a merger, consolidation, recapitalization, or
              reorganization of such Party is consummated that would result in shareholders or equity holders of such Party immediately prior to such transaction owning 50% or less of the outstanding voting securities of the surviving entity (or its parent
              entity) immediately following such transaction; or (c) the sale or transfer to a Third Party, in one or more related transactions, of all or substantially all of such Party&#8217;s consolidated assets taken as a whole.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z4a23f50cda444c0f82a92ff2d9e63d29" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.17</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Clinical Trial</font>&#8221; means any clinical trial in humans.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z1d14e095a6f2433083eeaedd3263f496" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.18</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">CMC</font>&#8221; means chemistry, manufacturing, and controls.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc1ce9d42fa144456a4ae4cf822b37766" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.19</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Collaboration Know-How</font>&#8221; means all Know-How developed or invented by a Party&#8217;s or its Affiliates&#8217;, [***] either alone or jointly with the other Party&#8217;s or its Affiliates&#8217;, [***]
              in each case, in the performance of activities under this Agreement during the Term.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd42569aab1934bd4ba0fc83b1093b0f3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.20</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Collaboration Patent Rights</font>&#8221; means any Patent Right that (a) has a priority date after the Effective Date and (b) Covers any Invention included in the Collaboration Know-How.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbe0682e7bd32476198a6f85e2e2292fd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.21</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Commercialization</font>&#8221; means any and all activities directed to the marketing, promotion, distribution, pricing, reimbursement, offering for sale, and sale of a pharmaceutical or
              biologic product and interacting with Regulatory Authorities following receipt of Regulatory Approval in the applicable country for such pharmaceutical or biologic product regarding the foregoing, including [***], but excluding activities
              directed to [***].&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Commercialize</font>,&#8221; &#8220;<font style="font-weight: bold; font-style: italic;">Commercializing</font>,&#8221; and &#8220;<font style="font-weight: bold; font-style: italic;">Commercialized</font>&#8221;
              will be construed accordingly.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">55</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zc143edd278734cebbf70e66fbf568248" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.22</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Commercially Reasonable Efforts</font>&#8221; means, with respect to the Exploitation of a Licensed Product by a Party, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.23</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Competitive Infringement</font>&#8221; means any actual or alleged infringement, unauthorized use, misappropriation or threatened infringement or misappropriation by a Third Party with
              respect to any Ionis Technology, Ono Technology, or Joint Collaboration Technology by reason of the [***] of an [***] designed to bind to the RNA encoded by TMPRSS6.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.24</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Confidential Disclosure Agreement</font>&#8221; has the meaning set forth in <u>Section 18.2</u> (Entire Agreement; Amendment<font style="font-weight: bold;">)</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.25</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Confidential Information</font>&#8221; means, subject to <u>Section 14.3</u> (Exemptions), (a) the terms of this Agreement, and (b) Know-How and any technical, scientific, trade, research,
              Manufacturing, business, financial, marketing, product, supplier, intellectual property, and other non-public or proprietary data or information (including unpublished patent applications) that may be disclosed by the Disclosing Party to the
              Receiving Party pursuant to this Agreement (including information disclosed prior to the Effective Date pursuant to the Confidential Disclosure Agreement), that is specifically marked or designated as confidential or, if disclosed orally,
              confirmed by a written summary thereof (which may consist of a copy of slides used in an oral presentation) sent to the Receiving Party promptly after such oral disclosure; <font style="font-style: italic;">provided, however</font>, that the
              failure to so mark or summarize Confidential Information will not compromise or alter its confidential status if a reasonable person in the industry would recognize, based on its content or the context of its disclosure, that such disclosure
              was intended as confidential.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z81804d74e15b443684660bfee0166617" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.26</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Control</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Controlled</font>&#8221; means the possession by a Party (whether by ownership, license, or otherwise other than
              pursuant to this Agreement) of, (a) with respect to any materials or other tangible Know-How, the legal authority or right to physical possession of such materials or tangible Know-How, with the right to provide such materials or tangible
              Know-How to the other Party on the terms set forth herein, (b) with respect to Patent Rights, Regulatory Approvals, Regulatory Submissions, intangible Know-How, or other intellectual property, the legal authority or right to grant a license,
              sublicense, access, or right to use (as applicable) to the other Party under such Patent Rights, Regulatory Approvals, Regulatory Submissions, intangible Know-How, or other intellectual property on the terms set forth herein, in each case
              ((a) and (b)), without breaching or otherwise violating the terms of any arrangement or agreement with a Third Party in existence as of the time such Party or its Affiliates would first be required hereunder to grant the other Party such
              access, right to use, license, or sublicense or incurring any additional payment obligations to a Third Party as a result of such access, right to use, license, or sublicense, other than payment obligations incurred under an agreement entered
              into in accordance with <u>Section 2.8</u> (Future Third-Party IP Agreements), and (c) with respect to any product, the possession by a Party of the ability (whether by sole or joint ownership, license, or otherwise, other than pursuant to
              the licenses granted under this Agreement) to grant an exclusive license or sublicense of Patent Rights that Cover such product or proprietary Know-How that is used in connection with the Exploitation of such product.&#160; Notwithstanding the
              foregoing, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.27</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Cost Overrun</font>&#8221; has the meaning set forth in <u>Section 7.6.3</u> (Cost Overruns).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z91d923ad6b284ba589a6f1f6043e22fb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.28</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Cover</font>&#8221; means, with respect to a particular subject matter at issue and a relevant Patent Right or individual claim in such Patent Right, as applicable, that the manufacture, use,
              sale, offer for sale, or importation of such subject matter would fall within the scope of one or more claims in such Patent Right.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">56</font></div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.29</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Debarred/Excluded</font>&#8221; has the meaning set forth in <u>Section 13.1.5</u> (Mutual Representations and Warranties<font style="font-weight: bold;">)</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc87bbf5869a34060b0a4e632fdfdd70e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.30</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Development</font>&#8221; means all internal and external research, development and regulatory activities regarding pharmaceutical or biologic products, including (a) [***], and (b) [***] for
              the purpose of submission to a Regulatory Authority to obtain authorization to conduct Clinical Trials and to obtain, support, or maintain Regulatory Approval of a pharmaceutical or biologic product, but excluding activities [***].&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Develop</font>,&#8221; &#8220;<font style="font-weight: bold; font-style: italic;">Developing</font>,&#8221; and &#8220;<font style="font-weight: bold; font-style: italic;">Developed</font>&#8221; will be construed
              accordingly.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z239809c43e8b470b943e30aa209970cd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.31</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Development Milestone Event</font>&#8221; has the meaning set forth in <u>Section 11.2.1</u> (Development Milestone Payments).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6a8944396ccb413ca7518f64c52b3bd0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.32</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Development Milestone Payment</font>&#8221; has the meaning set forth in <u>Section 11.2.1</u> (Development Milestone Payments).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zdb844f0b29474659a1cbf1c0789602d4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.33</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Disclosing Party</font>&#8221; has the meaning set forth in <u>Section </u><u>14.1</u>&#160;(Duty of Confidence<font style="font-weight: bold;">)</font>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z798920e91f15402e8a2a65f5dcd1a508" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.34</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Effective Date</font>&#8221; has the meaning set forth in <u>Section 5.1</u> (Closing).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.35</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">EMA</font>&#8221; means the European Medicines Agency or any successor agency thereto.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc6d95833300647f2aae68dacb0ac9ec1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.36</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; means [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5007016086c24c809e622cf043165cf8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.37</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">European Union</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">E.U.</font>&#8221; means the economic, scientific, and political organization of member states of the European
              Union as it may be constituted from time to time.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z703fcaadc59a4135a38344e71f0aab1f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.38</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Execution Date</font>&#8221; has the meaning set forth in the Preamble to this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9b316ad830464217a50ee5321de6ed44" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.39</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Executive Officer</font>&#8221; means (a) with respect to Ono, [***] and (b) with respect to Ionis, [***]<font style="font-weight: bold;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf5d2f7abb51043358a0438e1fec530ff" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.40</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Existing Third-Party IP Agreement</font>&#8221; means any agreement between Ionis (or any of its Affiliates) and any Third Party entered into prior to the Effective Date under which such
              Third Party grants Ionis (or any of its Affiliates) a license to any of the Ionis Technology that is sublicensed to Ono hereunder as of the Effective Date or during the Term.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z2fc13db726394ac48ea2b36acd937096" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.41</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Exploit</font>&#8221; means to make, have made, use, offer to sell, sell, Develop, Manufacture, Commercialize, or otherwise exploit.&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Exploitation</font>&#8221;
              will be construed accordingly.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z1ea98d6c27354e909e68ed8e814ed848" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.42</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">External Costs</font>&#8221; means, with respect to a Party, expenses paid to Third Parties (or payable to Third Parties and accrued in accordance with such Party&#8217;s Accounting Standards) by
              such Party (or its Affiliate) in consideration of the performance of activities under this Agreement, and excluding any Internal Costs.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbb64b3930b1b4ce6a9823ed976a3144d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.43</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">FD&amp;C Act</font>&#8221; means the United States Federal Food, Drug and Cosmetic Act, as amended from time-to-time, together with any rules, regulations, and requirements promulgated
              thereunder (including all additions, supplements, extensions, and modifications thereto).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze2284d55b0a94df381500822a064e887" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.44</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">FDA</font>&#8221; means the U.S. Food and Drug Administration or any successor agency thereto.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">57</font></div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z5fcb5d21bdc14004b33a4098eb42a30d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.45</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Field</font>&#8221; means the treatment, prevention, or diagnosis of any diseases and conditions in humans.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z84dc97c9f61c44ffbe6204f8e98d61d9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.46</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Fill</font>&#8221; means the process of adding the Licensed Compound to a container, such as a vial, syringe, or cartridge, prior to Packaging and Labeling such Licensed Compound for
              distribution.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf7d63694991e4401817cf46f8617234c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.47</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">First Commercial Sale</font>&#8221; means, with respect to a Licensed Product in a country, the first sale for end use or consumption to a Third Party of such Licensed Product in such country
              by Ono, or its Affiliates or Sublicensees after the receipt of Regulatory Approval in the Field for such Licensed Product by the relevant Regulatory Authority in such country.&#160; First Commercial Sale excludes any sale or other distribution for
              use in a [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0e41326f22fd456d9abc6674dafa7f38" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.48</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Fiscal Year</font>&#8221; means a twelve-month accounting period that begins on April 1 and ends on March 31.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.49</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Flash Report</font>&#8221; has the meaning set forth in <u>Section 11.3.4(a)</u> (Flash Reports).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zcc08796f7a0b4874b20eafed447c7ad3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.50</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Follow-On Compound</font>&#8221; has the meaning set forth in <u>Section 2.9.1</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.51</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">FTE</font>&#8221; means the equivalent of the work of one duly qualified employee of a Party full time for one year (consisting of a total of [***] hours per year) carrying out [***] under
              this Agreement.&#160; Overtime, and work on weekends, holidays and the like will not be counted with any multiplier (<font style="font-style: italic;">e.g.</font>, time-and-a-half or double time) toward the number of hours that are used to
              calculate the FTE contribution, and no individual may be charged at greater than one FTE, regardless of that individual&#8217;s hours worked during that year.&#160; The portion of an FTE billable by a Party for one employee during a given accounting
              period will be determined by dividing the number of hours worked directly by such employee on the work to be conducted under this Agreement during such accounting period by the number of FTE hours applicable for such accounting period based
              on [***] working hours per Calendar Year.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z93e44417ed0b4b0b9650b5a8bcf074a3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.52</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">FTE Rate</font>&#8221; means, for a given Calendar Year, the rate that a Party charges for an FTE with the appropriate technical skill for such Calendar Year. For the avoidance of doubt, such
              FTE Rate will [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb8b64d35c0564eed9a362b616e82c174" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.53</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Full Royalty Rate</font>&#8221; has the meaning set forth in <u>Section 11.3.1</u> (Royalty Rate).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf148ebe852de4857ae0b97737435906a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.54</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Future Third Party IP</font>&#8221; has the meaning set forth in <u>Section 2.8.1</u> (Identification of Future Third Party Patent Rights).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z31939580fe384047b0e623e003e7bc68" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.55</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">GAAP</font>&#8221; means the generally accepted accounting principles in the United States.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5c6f2885cfd8411fb22eea91618f2bd0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.56</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Generic Product</font>&#8221; means, with respect to a Licensed Product in a country, a pharmaceutical product (other than such Licensed Product) that (a) is sold by a Third Party other than
              a Sublicensee under license from Ono in such country, (b) is authorized for use in such country in one or more of the indications for which such Licensed Product has Regulatory Approval in such country; and (c) contains the same active
              pharmaceutical ingredient(s) as such Licensed Product.&#160; A product will not be considered to be a Generic Product if (i) Ono or any of its Affiliates was involved in or authorized the Development or Commercialization of such product, (ii) Ono
              or any of its Affiliates has granted a license to such Third Party in respect of such product, or (iii) such product is Commercialized in a country by any Person who obtained such product in such country in a chain of distribution that is
              initiated by Ono or any of its Affiliates or Sublicensees under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">58</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>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z7fc3d670823a41fda2be62d8784f14b8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.57</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section [***]</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb878691ccc534f73acd8bfd4e62fbf59" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.58</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Global Trade Control Laws</font>&#8221; means the U.S. Export Administration Regulations, the U.S. International Traffic in Arms Regulations, the economic sanctions regulations administered
              by the U.S. Treasury Department&#8217;s Office of Foreign Assets Control, E.U. Council Regulations on export controls, including Nos. 428/2009, 267/2012, other E.U. Council sanctions regulations, as implemented in the E.U. member states, United
              Nations sanctions policies, and all relevant regulations made under any of the foregoing.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5df3ee276e2a46dc9a136d25d7e3e686" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.59</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Good Clinical Practices</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">GCP</font>&#8221; means the then-current good clinical practice standards, practices, and procedures
              promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9b027eb3c82e4fdd988743e758196880" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.60</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Good Laboratory Practices</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">GLP</font>&#8221; means the then-current good laboratory practice standards, practices, and
              procedures promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3cfebf66fe194811a5c4133a9e446812" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.61</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Good Manufacturing Practices</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">GMP</font>&#8221; means the then-current good manufacturing practice standards, practices, and
              procedures promulgated or endorsed by the applicable Regulatory Authority as set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time-to-time.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9c2344e209e34bbfbf950ae1d06730d0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.62</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Government Official</font>&#8221; means any official, officer, employee, or representative of: (a) any federal, state, provincial, administrative division, county, or municipal government or
              any department or agency thereof; (b) any public international organization or any department or agency thereof; or (c) any company or other entity owned or controlled by any government or Governmental Authority.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc33791e1433e479783fa0548592dbcd3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.63</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Governmental Authority</font>&#8221; means any court, agency, department, authority, tribunal, or other instrumentality of any supra-national, national, state, provincial, county, city, or
              other political subdivision.&#160; For clarity, Governmental Authorities include all Regulatory Authorities.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6419a3471c7045bd986087d7c95fcb0c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.64</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">HSR Act</font>&#8221; means the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended, and the rules and regulations promulgated thereunder.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd0a414c7b2dd48669f915c3ee4db790a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.65</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">HSR Clearance</font>&#8221; has the meaning set forth in <u>Section 5.1</u> (Closing).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z18c4656968434642be032fece3824812" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.66</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">ICC</font>&#8221; has the meaning set forth in <u>Section 17.2</u> (Arbitration).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc164159295ab48019873aaba885f98a9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.67</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">IFRS</font>&#8221; means International Financial Reporting Standards, consistently applied.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7b588277bb634c8398020297a5cbf0ad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.68</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">IND</font>&#8221; means an Investigational New Drug application required pursuant to 21 C.F.R. Part 312 or any comparable filings outside of the U.S. required to commence human clinical
              trials in such country, and all supplements or amendments that may be filed with respect to the foregoing.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zaedc14637d604eb4b34a1343ee12c701" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.69</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Indemnified Party</font>&#8221; has the meaning set forth in <u>Section 15.3</u> (Indemnification Procedure).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z728f584d71184bbca8de3924f3a3b717" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.70</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Indemnifying Party</font>&#8221; has the meaning set forth in <u>Section 15.3</u> (Indemnification Procedure).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">59</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zc93005c7f014495bb03447c35d40a542" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.71</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Initial Know-How Transfer</font>&#8221; has the meaning set forth in <u>Section 6.1</u> (Initial Know-How Transfer).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze367f42676fa44f7aa037dfacb936b8b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.72</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="color: #000000;">&#8220;</font><font style="font-weight: bold; font-style: italic; color: #000000;">Initiation</font><font style="color: #000000;">&#8221;</font> means dosing of the first patient in a Clinical Trial.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd349f685f499460796e4801785cc467a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.73</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Internal Costs</font>&#8221; means, for any period of time, the product obtained by multiplying (a) the total FTEs (or portion thereof) devoted to the performance of activity under this
              Agreement during such period, by (b) the applicable FTE Rate for such period; <font style="font-style: italic;">provided</font> that in determining the total number of FTEs, the applicable Party may rely on estimates as long as the method of
              calculating such estimates is consistently applied.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z968219c788044f498c3d100cd77331de" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.74</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Invention</font>&#8221; means any new process, method, composition of matter, article of manufacture that is conceived or first reduced to practice (whether or not patentable).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z223bb39199af487fbd0ac9aa69b68c94" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.75</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Know-How</font>&#8221;<font style="font-weight: bold; font-style: italic;">&#160;</font>has the meaning set forth in <u>Section 12.1.2(a).</u></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf3b9bedc2b9148dfacf60fba3fcad8ee" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.76</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Collaboration Patent Rights</font>&#8221; has the meaning set forth in <u>Section 12.1.2(a).</u></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za601e8c711ff48f2a243730630648bbd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.77</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Core Technology</font>&#8221; means Ionis Core Technology Know-How and the Ionis Core Technology Patents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za37442004526404ca0e67bb2a49b59c1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.78</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Core Technology Know-How</font>&#8221; means all Know-How, excluding Ionis Product-Specific Know-How, Ionis Manufacturing and Analytical Know-How, and Ionis&#8217; interest in any Joint
              Collaboration Know-How, that (a) is Controlled by Ionis or its Affiliates on the Execution Date or at any time during the Term, (b) is necessary or reasonably useful to Exploit a Licensed Product, and (c) relates generally to
              oligonucleotides, but <font style="font-style: italic;">excluding</font> any Know-How to the extent solely related to any active pharmaceutical ingredient that is not a Licensed Compound.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z4b0e4023d1ed4cdcb7ff242a4f3f3367" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.79</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Core Technology Patents</font>&#8221; means any Patent Rights, excluding Ionis Product-Specific Patents, Ionis Manufacturing and Analytical Patents, and Ionis&#8217; interest in any Joint
              Collaboration Patent Rights, that (a) are Controlled by Ionis or its Affiliates on the Execution Date or at any time during the Term, (b) are necessary or reasonably useful to Exploit a Licensed Product and (c) claim subject matter generally
              applicable to oligonucleotides, but <font style="font-style: italic;">excluding</font> any Patent Rights to the extent solely related to any active pharmaceutical ingredient that is not a Licensed Compound.&#160; <font style="color: #000000;">A
                list of the </font>Ionis Core Technology Patents <font style="color: #000000;">as of the </font>Execution Date <font style="color: #000000;">is set forth on </font><font style="font-variant: small-caps; color: #000000;"><u>Appendix 2</u></font><font style="color: #000000;"> (Ionis Core Technology Patents)</font>; <font style="font-style: italic;">provided</font> that, any Patent Right existing as of the Effective Date that otherwise would be included in the definition of Ionis Core
              Technology Patents but is not included on <font style="font-variant: small-caps; color: #000000;"><u>Appendix 2</u></font>&#160;<font style="color: #000000;">(Ionis Core Technology Patents) </font>will still be considered an Ionis Core
              Technology Patent<font style="color: #000000;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd895c00b11954166b70de2e6a7816ff9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.80</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Indemnitees</font>&#8221; has the meaning set forth in <u>Section 15.2</u> (Indemnification by Ono).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z4075ffab3d3445ecb58196f947854aa8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.81</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Internal Oligonucleotide Safety Database</font>&#8221; has the meaning set forth in <u>Section 8.10.1</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb5dfe743d37847969dec4f39421c206a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.82</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Know-How</font>&#8221; means the Ionis Core Technology Know-How, Ionis Manufacturing and Analytical Know-How, and Ionis Product-Specific Know-How.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zed9d4f9188664248b28050de51835d06" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.83</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Manufacturing and Analytical Know-How</font>&#8221; means Know-How, excluding Ionis&#8217; interest in any Joint Collaboration Know-How, that (a) is Controlled by Ionis or its Affiliates on
              the Execution Date or at any time during the Term, (b) is necessary or reasonably useful to Exploit a Licensed Compound or Licensed Product, and (c) relates to the synthesis or analysis of oligonucleotides generally, including a Licensed
              Product, but <font style="font-style: italic;">excluding</font> any Know-How to the extent solely related to any active pharmaceutical ingredient that is not a Licensed Compound.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">60</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>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
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    <table cellspacing="0" cellpadding="0" id="z196348119d4f4c70a7cc7128e9b5fbc8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.84</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Manufacturing and Analytical Patents</font>&#8221; means Patent Rights, excluding Ionis&#8217; interest in any Joint Collaboration Patent Rights, that (a) are Controlled by Ionis or its
              Affiliates on the Execution Date or at any time during the Term, (b) are necessary or reasonably useful to Manufacture a Licensed Product, and (c) claim (i) methods and materials used in the synthesis or analysis of an oligonucleotide
              regardless of sequence or chemical modification, (ii) methods of manufacturing components of an oligonucleotide, and (iii) methods and materials used in Manufacturing a Licensed Product, but <font style="font-style: italic;">excluding</font>
              any Patent Rights to the extent solely related to any active pharmaceutical ingredient that is not a Licensed Compound.&#160; A list of Ionis Manufacturing and Analytical Patents as of the Execution Date is set forth on <font style="font-variant: small-caps;"><u>Appendix 3</u></font> (Ionis Manufacturing and Analytical Patents); <font style="font-style: italic;">provided</font> that, any Patent Right existing as of the Execution Date that otherwise would be included in the
              definition of Ionis Manufacturing and Analytical Patent but is not included on <font style="font-variant: small-caps;"><u>Appendix 3</u>&#160;</font>(Ionis Manufacturing and Analytical Patents) will still be considered an Ionis Manufacturing and
              Analytical Patent.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc963356c8f5740228249f7cb612ab657" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.85</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Manufacturing and Analytical Technology</font>&#8221; means Ionis Manufacturing and Analytical Know-How and Ionis Manufacturing and Analytical Patents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5372c21b72b148c3b8055c859f4ab199" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.86</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Patent Rights</font>&#8221; means the Ionis Core Technology Patents, Ionis Manufacturing and Analytical Patents, and Ionis Product-Specific Patents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0db5a85fbe9243449be238a229854b0c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.87</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product-Specific Know-How</font>&#8221; means all Know-How, excluding Ionis&#8217; interest in any Joint Collaboration Know-How, that is (a) Controlled by Ionis or its Affiliates on the
              Execution Date or at any time during the Term, (b) necessary or reasonably useful to Exploit a Licensed Product in the Field, and (c) specifically relating to (i) the composition of matter of a Licensed Product or (ii) methods of using a
              Licensed Product for the Field, but <font style="font-style: italic;">excluding</font> any Know-How to the extent solely related to any active pharmaceutical ingredient that is not a Licensed Compound; <font style="font-style: italic;">provided</font>
              however, such Know-How that (x) consists of subject matter applicable to oligonucleotide compounds or products in general or (y) relates to an [***] compound that does not specifically modulate expression of TMPRSS6 via the binding, partially
              or wholly, of such compound to RNA encoded by TMPRSS6, will not be considered Ionis Product-Specific Know-How, and in each case of (x) and (y), such Know-How will be considered Ionis Core Technology Know-How.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z87e47d4a1812433295889157cbd115fb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.88</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product-Specific Patents</font>&#8221; means all Product-Specific Patents, excluding Ionis&#8217; interest in any Joint Collaboration Patent Rights, that are (a) Controlled by Ionis or its
              Affiliates on the Execution Date or at any time during the Term and (b) necessary or reasonably useful to Exploit a Licensed Product, but <font style="font-style: italic;">excluding</font> any Patent Rights to the extent solely related to
              any active pharmaceutical ingredient that is not a Licensed Compound; <font style="font-style: italic;">provided</font>, however, that such Patent Rights that include only claims that are directed to (i) subject matter applicable to
              oligonucleotide compounds or products in general or (ii) an [***] compound that does not specifically modulate expression of TMPRSS6 via the binding, partially or wholly, of such compound to RNA encoded by TMPRSS6, will not be considered
              Ionis Product-Specific Patents, and in each case of (i) and (ii), such Patent Rights will be considered Ionis Core Technology Patents<font style="color: #000000;">.&#160; A list of </font>Ionis Product-Specific Patents <font style="color: #000000;">as of the </font>Execution Date <font style="color: #000000;">is set forth on </font><font style="font-variant: small-caps;"><u>Appendix 4</u></font> (Ionis Product-Specific Patents); <font style="font-style: italic;">provided</font>
              that, any Patent Right existing as of the Execution Date that otherwise would be included in the definition of Ionis Product-Specific Patent but is not included on <font style="font-variant: small-caps;"><u>Appendix 4</u>&#160;</font>(Ionis
              Product-Specific Patents) will still be considered an Ionis Product-Specific Patent<font style="color: #000000;">.</font></div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">61</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z2762ef88e09346eaa74ee8c757b96154" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.89</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Product-Specific Technology</font>&#8221; means Ionis Product-Specific Know-How and Ionis Product-Specific Patents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc5fb37356dcb495888afe9905b294b48" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.90</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Publication</font>&#8221; has the meaning set forth in <u>Section 14.5.2</u> (Ionis&#8217; Right to Publish).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z985a4b4c779d4f10b8a8b0e2654bb345" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.91</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Review Period</font>&#8221; has the meaning set forth in <u>Section 14.5.1</u> (Ono&#8217;s Right to Publish).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb6f752bb5d254587ac29c31f30d601e3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.92</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ionis Technology</font>&#8221; means the Ionis Know-How, the Ionis Patent Rights, and Ionis&#8217; interest in the Joint Collaboration Technology.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z893cc1cfbc144455ba49f43bb8feffb8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.93</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">IRS</font>&#8221; has the meaning set forth in <u>Section 11.10.3</u> (Tax Cooperation).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc13358984cfb4d828e4a820a74efaf5f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.94</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration </font>[***] <font style="font-weight: bold; font-style: italic;">Technology</font>&#8221; means Joint Collaboration [***] Technology Know-How and Joint Collaboration
              [***] Technology Patents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z45be39d740d24bd6ac81001d763f4d83" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.95</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration </font>[***] <font style="font-weight: bold; font-style: italic;">Technology Know-How</font>&#8221; means all Joint Collaboration Know-How, excluding Joint Collaboration
              [***] Know-How and Joint Collaboration [***] Know-How, that [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z13b7a854c7c84766b6b1ac32302ed9ed" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.96</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration </font>[***] <font style="font-weight: bold; font-style: italic;">Technology Patents</font>&#8221; means any Joint Collaboration Patent Rights, excluding Joint
              Collaboration [***] Patents and Joint Collaboration Manufacturing and Analytical Patents, that [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf40fcf65629c4e4792738b51a02e43b4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.97</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration Know-How</font>&#8221; means all Collaboration Know-How that is developed or invented jointly by a Party&#8217;s or its Affiliates&#8217;, [***], on the one hand, and the other
              Party&#8217;s or its Affiliates&#8217;, [***], on the other hand.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z34a6be4f60414127a11c08ce77b8b770" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.98</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration </font>[***] <font style="font-weight: bold; font-style: italic;">Know-How</font>&#8221; means Joint Collaboration Know-How that [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5529b739ea434ecbac1fad9575668a3a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.99</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><u>&#8220;</u><font style="font-weight: bold; font-style: italic;">Joint Collaboration </font>[***] <font style="font-weight: bold; font-style: italic;">Patents</font>&#8221; means Joint Collaboration Patent Rights that [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zae239b99cc9e479485944418581c7b98" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.100</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration </font>[***] <font style="font-weight: bold; font-style: italic;">Technology</font>&#8221; means Joint Collaboration [***] Know-How and Joint Collaboration [***]
              Patents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zd1d17333218e4b40b3b2902959570068" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.101</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration Patent Rights</font>&#8221; means all Collaboration Patent Rights that Cover Joint Collaboration Know-How.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z613712dd27fe4d5d8f5c074bfeac0fb8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.102</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration </font>[***] <font style="font-weight: bold; font-style: italic;">Know-How</font>&#8221; means Joint Collaboration Know-How that [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6ebf4f04b748437abffcb0b72881cd4d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.103</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration </font>[***] <font style="font-weight: bold; font-style: italic;">Patents</font>&#8221; means Joint Collaboration Patent Rights that [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z0a59562468b04e5db33211c190617da6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.104</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration </font>[***] <font style="font-weight: bold; font-style: italic;">Technology</font>&#8221; means Joint Collaboration [***] Know-How and Joint Collaboration [***]
              Patents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf0e444eabba64cc1be6f33b9ad0ff313" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.105</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Joint Collaboration Technology</font>&#8221; means the Joint Collaboration Know-How and the Joint Collaboration Patent Rights.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.106</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">JSC</font>&#8221; has the meaning set forth in <u>Section 4.1.1</u> (Formation and Purpose of the JSC).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.107</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">JSC Co-Chairperson</font>&#8221; has the meaning set forth in <u>Section 4.1.2</u> (Membership<font style="font-weight: bold;">)</font>.</div>
          </td>
        </tr>

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    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">62</font></div>
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      <div class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zd0abab8b544b41bdae726ce56b9641d2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.108</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Know-How</font>&#8221; means proprietary Inventions, discoveries, trade secrets, materials, information, experience, data, formulas, procedures, technology, results, and other intellectual
              property (whether or not patentable), including practices, knowledge, know-how, experience and test data (including physical, chemical, biological, toxicological, pharmacological, clinical and veterinary data), correspondence, regulatory
              materials (including regulatory submissions, regulatory filings, and correspondence with Regulatory Authorities), dosage regimens, assays, diagnostics, product specifications, manufacturing techniques and costs, platform data, platform
              technology, analytical and quality control data and marketing, pricing and distribution costs, and sales practices, methods, data, and descriptions.&#160; Notwithstanding the foregoing, any Know-How that is Covered by Patent Rights shall not be
              deemed as Know-How.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.109</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Knowledge</font>&#8221; means the actual knowledge, without any inquiry or investigation, of (a) with respect to Ionis, its [***]; and (b) with respect to Ono, its [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zcfe2e440c0a3422ab09756841f8b6a3e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.110</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Liaison</font>&#8221; has the meaning set forth in <u>Section 4.6</u> (Liaisons).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb7f777419cb840d8855850654ec7a8eb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.111</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="color: #000000;">&#8220;</font><font style="font-weight: bold; font-style: italic; color: #000000;">Licensed CMO</font><font style="color: #000000;">&#8221;</font> means a contract manufacturing organization to whom Ionis has granted a
              license under Ionis&#8217; manufacturing intellectual property to manufacture oligonucleotides.&#160; A list of the current Licensed CMOs as of the Execution Date is attached as <font style="font-variant: small-caps;"><u>Schedule</u></font><u> 10.4</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z209663b157fa49b59771fd3d7306a948" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.112</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Licensed Compound</font>&#8221; means any ASO designed to bind to the RNA encoded by TMPRSS6 discovered by Ionis prior to the Effective Date of the Agreement, which for clarity includes the
              GalNAc-conjugated ASO known as sapablursen (the structure of which is set forth in <font style="font-variant: small-caps;"><u>Appendix 5</u>)</font>, including any solvates, salts, esters, metabolites, acid forms, base forms, radioisomers,
              steroisomers, racemates, tautomers, polymorphs, hydrates and crystalline forms thereof; and any such ASOs designed to bind to the RNA encoded by TMPRSS6 discovered by Ionis prior to the Effective Date that are backups or derivatives or
              modifications of sapablursen.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.113</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div><font style="color: #000000;">&#8220;</font><font style="font-weight: bold; font-style: italic; color: #000000;">Licensed Patent</font><font style="color: #000000;">&#8221;</font> means (a) the Ionis Product-Specific Patents, (b) the Ionis Core
              Technology Patents, (c) the Ionis Manufacturing and Analytical Patents, and (d) Ionis&#8217; and its Affiliate&#8217;s interest in any Joint Collaboration Patent Rights.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.114</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Licensed Product</font>&#8221; means any pharmaceutical product that contains, comprises, or incorporates a Licensed Compound as an active pharmaceutical ingredient, in all current and future
              formulations and in any dosage strengths, presentations, or package configuration, and for any mode of administration, whether alone or in combination with other active pharmaceutical ingredients, components, or devices.&#160; Any pharmaceutical
              product that contains the same active pharmaceutical ingredient within the scope of the Licensed Compound, whether alone or in combination with other active pharmaceutical ingredients shall be deemed as one and the same product regardless of
              the different formulation or route of administration.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7fb41a40b9444484a20641715701d96b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.115</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Losses</font>&#8221; has the meaning set forth in <u>Section 15.1</u> (Indemnification by Ionis).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9b15cbde65bb40fc97e0b44d001c5e28" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.116</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">MAA</font>&#8221; means any (a) New Drug Application as defined in the FD&amp;C Act, (b) a marketing authorization application filed with (i) the EMA under the centralized EMA filing
              procedure to gain approval to market a biopharmaceutical in the E.U., or (ii) a Regulatory Authority in any country in the E.U. if the centralized EMA filing procedure is not used to gain approval to market a biopharmaceutical in the E.U., or
              (c) substantially similar application or submission to those set forth in clause (a) or clause (b) filed with a Regulatory Authority in a country or group of countries to obtain Regulatory Approval to Commercialize a biopharmaceutical or
              diagnostic product in that country or in that group of countries, in each case ((a) through (c)), including any amendments thereto, and supplemental applications, but excluding Reimbursement Approval applications.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">63</font></div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zfcb4d1d58a4e4356a7c7949b670c0ac0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.117</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; means[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc4b40d516bbd407cbed354bf6086485d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.118</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacture</font>&#8221; means activities directed to manufacturing, having manufactured, processing, packaging, labeling, filling, finishing, assembly, quality assurance, quality control,
              testing, and release, shipping, importing, exporting, or storage of any pharmaceutical or biologic product (or any components or process steps involving any product or any companion diagnostic), placebo, or comparator agent, as the case may
              be, including qualification, validation, and scale-up, pre-clinical, clinical, and commercial manufacture and analytic development, product characterization, and stability testing, but excluding activities directed to Development, or
              Commercialization.&#160; &#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing</font>&#8221; and &#8220;<font style="font-weight: bold; font-style: italic;">Manufactured</font>&#8221; will be construed accordingly.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z21e5c0dd49834f2cb2ddc8764e185c96" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.119</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; means, with respect to a Licensed Product, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z8a75f8536f1843e28e5bb1eb78ff003d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.120</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Manufacturing Technology Transfer</font>&#8221;<font style="font-weight: bold; font-style: italic;">&#160;</font>has the meaning set forth in <u>Section 6.3</u> (Manufacturing Technology
              Transfer).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.121</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Milestone Event</font>&#8221; means a Development Milestone Event or a Sales Milestone Event, individually or collectively as the context requires.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za9dac728e133453d9c8c1267bd264548" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.122</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Milestone Payment</font>&#8221; means a Development Milestone Payment or a Sales Milestone Payment, individually or collectively as the context requires.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zad72eb3469fb4a7c81937c8b9de987f1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.123</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; means [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z487dd108da7b45f78c16b3c15cd3baa6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.124</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section [***]</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6d322c3de3134332a26e56d1462e675f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.125</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Net Sales</font>&#8221; means, with respect to any Licensed Product, the amount billed by Ono or its Affiliates or Sublicensees (each a &#8220;<font style="font-weight: bold; font-style: italic;">Selling

                Party</font>&#8221;) for sales of such Licensed Product in arm&#8217;s length transactions to Third Parties in the Territory, after deduction (if not already deducted in the amount invoiced) of the following items with respect to sales of such Licensed
              Product:</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5882dc4429f84438b7937239043eb639" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(a)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Normal and customary trade, quantity, or cash discounts (including 340B drug pricing program) to non-affiliated brokers, agents or customers to the extent actually allowed and taken, <font style="font-style: italic;">provided</font> that
              [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
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          </td>
          <td style="width: 36pt; vertical-align: top;">(b)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Actual amounts repaid or credited by reason of rejections or returns ([***]);</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(c)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>To the extent separately stated on purchase orders, invoices, or other documents of sale, any taxes or other governmental charges paid and levied on the production, sale, transportation, delivery, or use of the Licensed Products;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(d)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Rebates, fees, and chargeback payments required to sell products granted to managed health care organizations, group purchasing organizations, pharmacy benefit managers (or equivalent thereof), national, state/provincial, local, and other
              governments, their agencies/purchasers/reimbursement providers, or to trade customers;</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">64</font></div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zc0331814c47345459187cb2d045357d3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(e)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***] lump sum of the gross amount invoiced for Net Sales of the Licensed Product to cover outbound transportation costs prepaid or allowed and costs of insurance in transit, with the exclusion of [***];</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(f)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Any invoiced amounts that are not collected, including bad debts; <font style="font-style: italic;">provided</font> that the following deductions are not allowed in the calculation of Net Sales: [***]; and</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z4e9ef755332048dfb64765e7d81204d5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt;"><br>
          </td>
          <td style="width: 36pt; vertical-align: top;">(g)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>Any mandatory sales-based contributions actually made for [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 36pt;">If a Selling Party [***], then [***].</div>
    <div>&#160;</div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 36pt;">Net Sales will not include [***].</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z72b9569b0d904532b600f3568147f9af" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.126</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Non-Manufacturing Technology Transfer</font>&#8221; has the meaning set forth in <u>Section 6.2</u> (Additional Know-How Transfer).</div>
          </td>
        </tr>

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    <div>&#160;</div>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ongoing Clinical Trial Extension</font>&#8221; has the meaning set forth in <u>Section 7.2</u> (Extension of Ongoing Clinical Trial).</div>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ono Indemnitees</font>&#8221; has the meaning set forth in <u>Section 15.1</u> (Indemnification by Ionis).</div>
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    <div>&#160;</div>
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    <div>&#160;</div>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ono Publication</font>&#8221; has the meaning set forth in <u>Section 14.5.1</u> (Ono&#8217;s Right to Publish).</div>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Ono Review Period</font>&#8221; has the meaning set forth in <u>Section 14.5.2</u> (Ionis&#8217; Right to Publish).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.139</td>
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            <div>&#8220;[***]&#8221; means [***].</div>
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            <div>&#8220;[***]&#8221; means [***].</div>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Other Covered Party</font>&#8221; means any political party or party official, or any candidate for political office.</div>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Package and Label</font>&#8221; means primary, secondary, or tertiary packaging and labeling of a Licensed Product for sale or use in a country, including the Approved Labeling and insertion
              of materials such as patient inserts, patient medication guides, and professional inserts and any other written, printed, or graphic materials accompanying such Licensed Product and any brand security or anti-counterfeiting measures included
              in the packaging elements for such licensed Product considered to be part of the finished packaged Licensed Product, and all testing and release thereof.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.144</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Party Vote</font>&#8221; has the meaning set forth in <u>Section 4.3.1</u> (General Decision-Making Process).</div>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Patent Challenge</font>&#8221; has the meaning set forth in <u>Section 16.5</u> (Termination for Patent Challenge).</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.146</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Patent Prosecution</font>&#8221; means activities directed to (a) preparing, filing, and prosecuting applications (of all types) for any Patent Right, (b) maintaining any Patent Right, and
              (c) deciding whether to abandon or maintain any Patent Right.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.147</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Patent Rights</font>&#8221; means (a) all patents, patent applications, and utility models in any country or jurisdiction, including provisional applications, priority applications, and
              international applications, (b) any and all patents that have issued or in the future issue from the foregoing patent applications, (c) any and all substitutions, renewals, registrations, confirmations, revalidations, reissues, and
              re-examinations of the foregoing patents or patent applications, and (d) extensions, restorations, supplemental protection certificates, and the like based on any of the foregoing patents or patent applications.</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.148</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Patent Term Extensions</font>&#8221; has the meaning set forth in <u>Section 12.8</u> (Patent Term Extensions).</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.149</td>
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            <div><font style="color: #000000;">&#8220;</font><font style="font-weight: bold; font-style: italic; color: #000000;">Permitted Licenses</font><font style="color: #000000;">&#8221;</font> means (a) licenses granted by Ionis after the Effective Date to any
              Third Party under the Ionis Core Technology Patents or Ionis Manufacturing and Analytical Patents (but not under the Ionis Product-Specific Patents) solely to (i) conduct nonclinical research, or (ii) enable such Third Party to manufacture or
              formulate oligonucleotides, where such Third Party is primarily engaged in providing contract manufacturing services or services and is not primarily engaged in drug discovery, development or commercialization of therapeutics; and (b)
              material transfer agreements with academic collaborators or non-profit institutions solely to conduct non-commercial research.</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.150</td>
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              or agency, or any other entity or body, or an individual.</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.151</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Pharmacovigilance Agreement</font>&#8221; means an agreement regarding receipt, investigation, and reporting of product complaints, adverse events, product recalls, and any other information
              related to the safety of the Licensed Products in the Territory.</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.152</td>
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            <div><font style="color: #000000;">&#8220;</font><font style="font-weight: bold; font-style: italic; color: #000000;">Pivotal Clinical Trial</font><font style="color: #000000;">&#8221;</font> means, with respect to a Licensed Product, (a) a Clinical Trial
              performed to gain evidence with statistical significance of the efficacy of such Licensed Product in a target population and to obtain expanded evidence of safety for such Licensed Product that is needed to evaluate the overall benefit-risk
              relationship of such Licensed Product, to form the basis for approval of an MAA by a Regulatory Authority and to provide an adequate basis for physician labeling, as described in 21 C.F.R. &#167; 312.21(c), as amended from time to time, or the
              corresponding regulation in jurisdictions other than the United States; or (b) a Clinical Trial that satisfies the requirements of 21 C.F.R. &#167; 312.21(c) and is a registration trial on a sufficient number of patients designed to establish
              statistically significant efficacy and safety of such Licensed Product for its target patient population, and to determine warnings, precautions, and adverse reactions that are associated with such Licensed Product in the dosage range to be
              prescribed, for the purpose of enabling the preparation and submission of application for an MAA to the competent Regulatory Authorities in a given country, as evidenced by (i) an agreement with or statement from the FDA on a Special Protocol
              Assessment or equivalent in another country, (ii) other guidance or minutes issued by the FDA for such registration trial or equivalent in another country, or (iii) Ono&#8217;s public statements, in each case ((i)-(iii)), where the results of such
              Clinical Trial are intended (if supportive) to be used to establish both safety and efficacy of such Licensed Product in patients that are the subject of such trial and serve as the basis for obtaining initial or supplemental Regulatory
              Approval of such Licensed Product.</div>
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    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.153</td>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.154</td>
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            <div><font style="color: #000000;">&#8220;</font><font style="font-weight: bold; font-style: italic; color: #000000;">Product-Specific Know-How</font><font style="color: #000000;">&#8221;</font> means, all Know-How that is (a) Controlled by a Party or its
              Affiliates on the Execution Date or at any time during the Term, (b) necessary or reasonably useful to Exploit a Licensed Product in the Field, and (c) specifically relating to (i) the composition of matter of a Licensed Product or (ii)
              methods of using a Licensed Product for the Field, but <font style="font-style: italic;">excluding</font> any Know-How to the extent solely related to any active pharmaceutical ingredient that is not a Licensed Compound; <font style="font-style: italic;">provided</font> however, such Know-How that is Controlled by Ionis and (x) consists of subject matter applicable to oligonucleotide compounds or products in general or (y) relates to an [***] compound that does
              not specifically modulate expression of TMPRSS6 via the binding, partially or wholly, of such compound to RNA encoded by TMPRSS6, will not be considered Product-Specific Know-How, and in each case of (x) and (y), such Know-How will be
              considered Ionis Core Technology Know-How.</div>
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    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.155</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Product-Specific Patents</font>&#8221; means Patent Rights Controlled by a Party or any of its Affiliates on or after the Effective Date claiming: (a) the specific composition of matter of a
              Licensed Product, or (b) methods of using such a Licensed Product.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.156</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Professional Requirements</font>&#8221; means (a) the codes and standards of the European Accreditation Council for Continuing Medical Education (EACCME) and the European Federation of
              Pharmaceutical Industries and Associations (EFPIA), (b) the codes of the Prescription Medicines Code of Practice Authority (PMCPA) and the Association of the British Pharmaceutical Industry (ABPI), (c) FDA&#8217;s regulations, guidance, and
              enforcement letters concerning the advertising of prescription drug products, (d) the American Medical Association&#8217;s Guidelines on Gifts to Physicians from Industry, (e) the Accreditation Council for Continuing Medical Education (ACCME)
              Standards for Commercial Support of Continuing Medical Education, (f) the Pharmaceutical Supply Chain Initiative (PSCI) and Pharmaceutical Industry Principles for Responsible Supply Chain Management, (g) the Code on Interactions with
              Healthcare Professionals promulgated by the Pharmaceutical Research and Manufacturers of America (PhRMA Code), (h) the Department of Health and Human Services Office of Inspector General Compliance Program Guidance for Pharmaceutical
              Manufacturers (OIG Compliance Guidance), and (i) all other accepted national and international pharmaceutical industry codes of practice in and for the relevant countries in the Territory, as any of the foregoing may be amended from
              time-to-time.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">67</font></div>
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        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z48810e88ad85432c994bcc2f243f5801" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.157</td>
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            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Publication</font>&#8221; has the meaning set forth in <u>Section 14.5</u> (Publications).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z8e723beaad174435875bdf0b81a49c00" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.158</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Receiving Party</font>&#8221; has the meaning set forth in <u>Section 14.1.1</u> (Duty of Confidence).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6c535b6324ec4ddfbd06479512044a36" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.159</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Reduction Circumstances</font>&#8221; has the meaning set forth in <u>Section 11.3.3(c)</u> ([***]).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zbd94925ee6b64cd89ae7b6a2601bb220" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.160</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Approval</font>&#8221; means, with respect to a particular country or other regulatory jurisdiction, any approval of an MAA or other approval, product, or establishment license,
              registration, or authorization of any Regulatory Authority necessary for the commercial sale of a pharmaceutical, diagnostic, or biologic product in such country or other regulatory jurisdiction, excluding, in each case, [***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6f4e1243d06a41e2850ba0dfc361d770" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.161</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Authority</font>&#8221; means, in a particular country or jurisdiction, any applicable Governmental Authority involved in granting Regulatory Approval in such country or
              jurisdiction, including (a) in the U.S., the FDA and any other applicable Governmental Authority in the U.S. having jurisdiction over any pharmaceutical, diagnostic, or biologic product, (b) in the E.U., the EMA and any other applicable
              Governmental Authority in the E.U. having jurisdiction over any pharmaceutical, diagnostic, or biologic product, and (c) in other countries, other analogous Governmental Authorities having jurisdiction over any pharmaceutical, diagnostic, or
              biologic product.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z1037b466f9c94632a5e08683fb57fd56" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.162</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Exclusivity</font>&#8221; means, with respect to a Licensed Product in a country, the period of time during which: (a) Ono or its Affiliate or Sublicensee has been granted the
              exclusive legal right by a Regulatory Authority (or is otherwise entitled to the exclusive legal right by operation of Applicable Law) in such country to market and sell such Licensed Product, and such right precludes a Third Party from
              making such Licensed Product available for purchase for any indication; or (b) the data and information submitted by Ono or its Affiliate or Sublicensee to the relevant Regulatory Authority in such country for purposes of obtaining Regulatory
              Approval may not be referenced, or relied upon in any way by a Third Party or such Regulatory Authority to support the Regulatory Approval or marketing of any product by a Third Party in such country, or if such data and information is
              referenced, or relied upon to support a Regulatory Approval granted to a Third Party in such country, the product may not be placed on the market for any indication.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za931ceb677014b97bcc628ead69ecea1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.163</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Regulatory Submission</font>&#8221; means any filing, application, or submission with any Regulatory Authority in support of the Development, Manufacture, Commercialization, or other
              Exploitation of a pharmaceutical, diagnostic, or biologic product (including to obtain, support, or maintain Regulatory Approval from that Regulatory Authority), and all written or electronic correspondence or communication with or from the
              relevant Regulatory Authority, as well as minutes of any material meetings, telephone conferences, or discussions with the relevant Regulatory Authority.&#160; Regulatory Submissions include all INDs, MAAs, and other applications for Regulatory
              Approval and their equivalents.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">68</font></div>
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      <div class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="zc6ec9ca98d65422d97dcd51d124fdafd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.164</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Reimbursement Approval</font>&#8221; means any approval, agreement, determination, or other decision by the applicable Governmental Authority in a given country that establishes prices
              charged to end-users for pharmaceutical, diagnostic, or biologic products at which such pharmaceutical, diagnostic, or biologic products will be reimbursed by the Regulatory Authorities or other applicable Governmental Authorities in such
              country or any other approvals related to pricing, reimbursement, or access to a pharmaceutical, diagnostic, or biologic product (including all activities related to tenders and contracts).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za91df1f29d894b55b064b041487f9eb1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.165</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Restricted Party</font>&#8221; means any individual or entity on one or more of the Restricted Party Lists.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z378857e0585544018743fa6ffb8907ec" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.166</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Restricted Party List</font>&#8221; means the list of sanctioned entities maintained by the United Nations; the Specially Designated Nationals and Blocked Persons List, the Foreign Sanctions
              Evaders List and the Sectoral Sanctions Identifications List, all administered by OFAC; the U.S. Denied Persons List, the U.S. Entity List, and the U.S. Unverified List, all administered by the U.S. Department of Commerce; and the entities
              subject to restrictive measures and the consolidated list of Persons, Groups, and Entities Subject to E.U. Financial Sanctions, as implemented by the E.U. Common Foreign &amp; Security Policy.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z86ba12c2e8e743dfba7afeeca51fbea7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.167</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Review Period</font>&#8221; has the meaning set forth in <u>Section 14.5.1</u> (Ono&#8217;s Right to Publish).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7066d390f3e14532aad392e861d7bf3f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.168</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section [***]</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb710dd2023694db594c231c07ec580a2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.169</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;[***]&#8221; has the meaning set forth in <u>Section [***]</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5263f35aef4f4f59a72a58db8e313a28" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.170</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Royalties</font>&#8221; has the meaning set forth in <u>Section 11.3.1</u> (Royalty Rate).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc5eb12b8b6e0461185a5185b3310fdf8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.171</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Royalty Report</font>&#8221; has the meaning set forth in <u>Section </u><u>11.3.4(b)</u> (Royalty Report).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb005e09760f14d348c18c8c32eb6f961" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.172</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Royalty Term</font>&#8221; has the meaning set forth in <u>Section </u><u>11.3.2(a)</u> (Royalty Term).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z573b2572ea4c40e9b5776224c0e1e483" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.173</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Sales Milestone Event</font>&#8221; has the meaning set forth in <u>Section 11.2.2</u> (Sales Milestone Payments).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z08cddff8b09340d4aefecf104cf0bedf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.174</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Sales Milestone Payment</font>&#8221; has the meaning set forth in <u>Section 11.2.2</u> (Sales Milestone Payments).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z5cb6665d4a224ee5bcb99aedc0f5c804" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.175</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Selling Party</font>&#8221; has the meaning set forth in <u>Section 1.125</u> (Net Sales) of this <font style="font-variant: small-caps;"><u>Appendix</u></font><u> 1</u>.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z4b3ac84902034f778ab7b95d4ad71654" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.176</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Sublicensee</font>&#8221; means, with respect to a Party, any Affiliate or Third Party to which such Party or its Affiliate grants a sublicense under any of the rights licensed to the
              applicable Party under this Agreement.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9bee6f84727f4a008195085634a741b3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.177</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Tax</font>&#8221; or &#8220;<font style="font-weight: bold; font-style: italic;">Taxes</font>&#8221; means any present or future taxes, levies, imposts, duties, charges, assessments or fees of any nature
              (including any interest thereon), including value add, sales, excise or similar taxes.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z1ffcfd60e7a34113bf1332862246ca20" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.178</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Taxation Forms</font>&#8221; means Form 3 and Form 17 posted in the WEB of National Tax Agency in Japan and certification of residence issued by the IRS.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z618b3690652349979797a4093282fbfc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.179</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Technology Transfers</font>&#8221; has the meaning set forth in <u>Section 6.4</u> (Technology Transfer Costs and Support).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z8c70264e50d24275b8688311fc5f93cc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.180</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Term</font>&#8221; has the meaning set forth in <u>Section 16.1</u> (Term).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zda6c554d577a4913a3aeb94886da80db" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.181</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Territory</font>&#8221; means worldwide.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">69</font></div>
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      <div class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="z8e02c40045e04e838b0d3d62d06d6cfb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.182</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party</font>&#8221; means any Person other than a Party or its Affiliates.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
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        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.183</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Claims</font>&#8221; has the meaning set forth in <u>Section 15.1</u> (Indemnification by Ionis).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z047ba52182454ec4b45b3ff34e699a1d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.184</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Challenge</font>&#8221; has the meaning set forth in <u>Section 12.4</u> (Defense of Third Party Challenges).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zc5f4d6c3c36e4ce29b3bf8c98e27866d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.185</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Third Party Payment</font>&#8221; means, with respect to the Licensed Product, any (a) payments (including upfront payments, milestone payments, license fees, and royalties) made by Ono or
              its Affiliate to a Third Party (i) pursuant to an agreement between Ono or its Affiliate and such Third Party entered into following the Effective Date in accordance with <u>Section 2.8.2</u> (Future Third Party [***]) or <u>Section
                2.8.4(b)</u> (Ono Step-In Right) to obtain rights to Patent Rights or Know-How from such Third Party that are necessary to Develop or Commercialize the Licensed Product in the form the Licensed Product exists as of the Effective Date or
              (ii) pursuant to an agreement between Ono or its Affiliate and such Third Party, or otherwise, entered into after the Effective Date, as part of a settlement or to satisfy a judgement in accordance with <u>Section 12.5.3</u> (Settlement), or
              (b) amounts for which Ono reimburses Ionis under an agreement entered into by Ionis following the Effective Date in accordance with <u>Section 2.8.3(b)</u> (Ionis Step-In Right) to obtain rights to Patent Rights or Know-How from such Third
              Party that are necessary to Develop or Commercialize the Licensed Product in the form the Licensed Product exists as of the Effective Date, in each case ((a) and (b)) that are directly in consideration for or reasonably allocable to a license
              or sublicense (as applicable) to Ono or its Affiliate under, or are paid in settlement or to satisfy a judgment of a claim relating to, Patent Rights or Know-How controlled by such Third Party that are necessary to Develop or Commercialize
              the Licensed Product in the form the Licensed Product exists as of the Effective Date.</div>
          </td>
        </tr>

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    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="ze40d4f23eb9c4dcf971760c2776cd863" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.186</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">TMPRSS6</font>&#8221; means the human transmembrane serine protease 6 gene (NCBI Gene ID: 164656; Ensembl Gene ID: ENSG00000187045), including all mutants, polymorphisms, and fragments
              thereof.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za3a9236785c843c4970def0c06679ad5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.187</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">USA</font>&#8221; means the United States of America (including all possessions and territories thereof, including Puerto Rico).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9c903878faa840ccadd4875f517f405c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.188</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">U.S. Dollars</font>&#8221; or &#8220;<font style="font-weight: bold;">$</font>&#8221; means the legal tender of the USA.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z43c84d61e3f74a5dba3880fcbff96a65" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.189</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Valid Claim</font>&#8221; means: (a) a claim of an issued and unexpired patent (as may be adjusted through a patent term adjustment or extended through supplementary protection certificate or
              patent term extension or the like) that has not been revoked, held invalid, or held unenforceable by a patent office or other Governmental Authority of competent jurisdiction in a final and non-appealable judgment (or judgment from which no
              appeal was taken within the allowable time period); or (b) a pending claim of an unissued, pending patent application, which claim has not been pending for more than [***] years, unless and until such claim becomes an issued claim of an
              issued patent in which case it will again be considered a Valid Claim under the foregoing clause (a), <font style="font-style: italic;">provided</font> that such [***]-year period will be tolled for the duration of any adverse proceeding
              (e.g., appeals during examination or any appeal thereof) with respect to the patent application at issue.</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z15b2a7bfd6a34590a7d3b148337b77f1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.190</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Withheld Amount</font>&#8221; has the meaning set forth in <u>Section 11.10.2</u> (Withholding Tax).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z218f1fb5b08b4d0eb94cba6972d7821d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 36pt; vertical-align: top; font-weight: bold;">1.191</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>&#8220;<font style="font-weight: bold; font-style: italic;">Working Group</font>&#8221; has the meaning set forth in <u>Section 4.1.1</u> (Formation and Purpose of the JSC).</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">70</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">
      <div><u>APPENDIX 2</u></div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u> <br>
      </u></div>
    <div style="text-align: center; font-weight: bold;">Ionis Core Technology Patents</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" border="0" id="zaeba049100f74a20ad5ba516703a1ec1" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

        <tr>
          <td style="width: 17.22%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Ionis File No.</div>
          </td>
          <td style="width: 15.74%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Country/Treaty</div>
          </td>
          <td style="width: 18.68%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Application No./</div>
            <div style="text-align: center; font-weight: bold;">Patent No.</div>
          </td>
          <td style="width: 13.51%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Filing Date</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Grant Date</div>
          </td>
          <td style="width: 20%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Title</div>
          </td>
        </tr>
        <tr>
          <td style="width: 17.22%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 20%; 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>
        </tr>
        <tr>
          <td style="width: 17.22%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 20%; 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>
        </tr>
        <tr>
          <td style="width: 17.22%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 20%; 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>
        </tr>
        <tr>
          <td style="width: 17.22%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
          <td style="width: 20%; 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>
        </tr>
        <tr>
          <td style="width: 17.22%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
          <td style="width: 20%; 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>
        </tr>
        <tr>
          <td style="width: 17.22%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
          <td style="width: 20%; 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>
        </tr>
        <tr>
          <td style="width: 17.22%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
          <td style="width: 20%; 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>
        </tr>
        <tr>
          <td style="width: 17.22%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 20%; 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>
        </tr>
        <tr>
          <td style="width: 17.22%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
          <td style="width: 20%; 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>
        </tr>
        <tr>
          <td style="width: 17.22%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
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            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17.22%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17.22%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17.22%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17.22%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17.22%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17.22%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 15.74%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18.68%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.51%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 13.94%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
          <td style="width: 20%; 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>
        </tr>

    </table>
    <div><br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">71</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">
      <div><u>APPENDIX 3<br>
        </u></div>
    </div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Ionis Manufacturing and Analytical Patents</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" border="0" id="z90e8a65dfc1647a2b7b316be4416910b" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

        <tr>
          <td style="width: 17%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Ionis File No.</div>
          </td>
          <td style="width: 15%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Country</div>
          </td>
          <td style="width: 8.46%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Status</div>
          </td>
          <td style="width: 18%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Application No./</div>
            <div style="text-align: center; font-weight: bold;">Patent No.</div>
          </td>
          <td style="width: 10.98%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Filing Date</div>
          </td>
          <td style="width: 10.98%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Grant Date</div>
          </td>
          <td style="width: 20%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Title</div>
          </td>
        </tr>
        <tr>
          <td style="width: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
          <td style="width: 20%; 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>
        </tr>
        <tr>
          <td style="width: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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><br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">72</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <table cellspacing="0" cellpadding="0" id="ze332e85e0b9a4590aac0f2671a49981a" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

        <tr>
          <td style="width: 17%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Ionis File No.</div>
          </td>
          <td style="width: 15%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Country</div>
          </td>
          <td style="width: 8.46%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Status</div>
          </td>
          <td style="width: 18%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Application No./</div>
            <div style="text-align: center; font-weight: bold;">Patent No.</div>
          </td>
          <td style="width: 10.98%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Filing Date</div>
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          <td style="width: 10.98%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Grant Date</div>
          </td>
          <td style="width: 20%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Title</div>
          </td>
        </tr>
        <tr>
          <td style="width: 17%; 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>
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          <td style="width: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</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>
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        </tr>
        <tr>
          <td style="width: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
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          <td style="width: 18%; 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>
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          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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            <div style="text-align: center;">[***]</div>
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          <td style="width: 15%; 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>
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          <td style="width: 18%; 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>
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          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
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          <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>
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            <div style="text-align: center;">[***]</div>
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          <td style="width: 15%; 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>
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          <td style="width: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <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>
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            <div style="text-align: center;">[***]</div>
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          <td style="width: 15%; 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);">
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          <td style="width: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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          <td style="width: 18%; 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>
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          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
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          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
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          <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>
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          <td style="width: 17%; 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>
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          <td style="width: 15%; 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>
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          <td style="width: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
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          <td style="width: 18%; 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>
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          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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            <div style="text-align: center;">[***]</div>
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          <td style="width: 17%; 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: 15%; 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>
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          <td style="width: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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          <td style="width: 18%; 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);">
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          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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          <td style="width: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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          <td style="width: 18%; 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>
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          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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          <td style="width: 10.98%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
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            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</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: 17%; 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: 15%; 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: 8.46%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 18%; 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: 10.98%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.98%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
          <td style="width: 20%; 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>
        </tr>

    </table>
    <div><br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">73</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>APPENDIX 4<br>
      </u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Ionis Product-Specific Patents</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z7f550cfba01240c8aba7e9bf751bb80a" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

        <tr>
          <td style="width: 14.89%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Ionis File No.</div>
          </td>
          <td style="width: 11.43%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Country</div>
          </td>
          <td style="width: 7.91%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Status</div>
          </td>
          <td style="width: 17.58%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Application No./</div>
            <div style="text-align: center; font-weight: bold;">Patent No.</div>
          </td>
          <td style="width: 9.43%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Date Filed</div>
          </td>
          <td style="width: 10.06%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Grant Date</div>
          </td>
          <td style="width: 28.69%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Title</div>
          </td>
        </tr>
        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
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          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
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            <div style="text-align: center;">[***]</div>
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            <div style="text-align: center;">[***]</div>
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          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
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            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
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        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
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          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
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          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
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            <div style="text-align: center;">[***]</div>
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        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
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          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">74</font></div>
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      <div class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
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        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Ionis File No.</div>
          </td>
          <td style="width: 11.43%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Country</div>
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            <div style="text-align: center; font-weight: bold;">Application No./</div>
            <div style="text-align: center; font-weight: bold;">Patent No.</div>
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          <td style="width: 9.43%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Date Filed</div>
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          <td style="width: 10.06%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Grant Date</div>
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          <td nowrap="nowrap" style="width: 28.69%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">Title</div>
          </td>
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        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
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        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
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            <div style="text-align: center;">[***]</div>
          </td>
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            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td nowrap="nowrap" style="width: 14.89%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 11.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 7.91%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 17.58%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 9.43%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
          <td style="width: 10.06%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">&#160;</td>
          <td nowrap="nowrap" style="width: 28.69%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">75</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-weight: bold;"><u>APPENDIX 5</u><u></u></div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">Sapablursen Structure</div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: normal;">[***]</div>
    <div style="text-align: center;"> <br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">76</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-weight: bold;"><u>APPENDIX 6</u><u></u></div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">Prior Agreements</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" id="zec4be67c721347aaa642760afa27b20b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

        <tr>
          <td style="width: 18pt;">&#160;</td>
          <td style="width: 18pt; vertical-align: top;">1.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z69fbe4e04a8a455982cc224dcd8f5f26" 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;">2.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z78d357fe58254b6e990446d9095d98b0" 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;">3.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z50cbd97a38d645e4951db9cca212d8f1" 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;">4.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zec9255d0f43e4e1b8231bd6d870fd756" 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;">5.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z452aa1036ed84a979c32e74dba8a35c9" 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;">6.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zfde7c6985ba4496285f425f85cb25fb2" 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;">7.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z9a06fe20548c4604b8f74009f12cddb5" 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;">8.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z6f116fc9e4704b1fbc606449a0dc96d0" 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;">9.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="za47d20f01e534132935a63d461524718" 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;">10.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zf86f8a3b80e54414854b2aa80c9dadd7" 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;">11.</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div>[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">77</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">
      <div style="font-weight: bold;"><u>SCHEDULE 6.1</u></div>
    </div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">[***]</div>
    <div>&#160;</div>
    <div>[***]</div>
    <div> <br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">78</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">
      <div style="font-weight: bold;"><u>SCHEDULE 6.4</u></div>
    </div>
    <div>&#160;</div>
    <div style="text-align: center;">[***]</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="text-align: center;">[***]</div>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">79</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-weight: bold;">
      <div style="font-weight: bold;"><u>SCHEDULE 7.1</u></div>
      <u></u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Ongoing Clinical Trial Development Plan</div>
    <div>&#160;</div>
    <div style="font-variant: small-caps; font-weight: bold;">[***]</div>
    <div><br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">80</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-weight: bold;">
      <div style="font-weight: bold;"><u>SCHEDULE 7.2</u></div>
      <u></u></div>
    <div><br>
    </div>
    <div style="text-align: center; font-weight: bold;">Extension of Ongoing Clinical Trial &#8211; Estimated Development Plan and Costs</div>
    <div style="font-variant: small-caps; font-weight: bold;">[***]</div>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">81</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-variant: small-caps;">
      <div style="font-weight: bold;"><u>SCHEDULE 10.1 (A)</u></div>
      <u></u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps;">
      <div style="font-weight: bold;">MANUFACTURING HISTORY AND CURRENT INVENTORY</div>
    </div>
    <div>&#160;</div>
    <div style="text-align: justify;">[***]</div>
    <div style="text-align: justify;"> <br>
    </div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">82</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-variant: small-caps;"><font style="font-weight: bold;"><u>SCHEDULE 10.1 (B)</u></font><u></u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">[***]</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">[***]</div>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">83</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;"><u>SCHEDULE 10.4<br>
      </u></div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">Licensed CMOs</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z75e1240f46d84d87a11139752c19fd1e" 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;">1.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: normal;">[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zba982b40957f41ba9b791d1d4ba0d552" 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;">2.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: normal;">[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z3ffeb36f177b4e52b808ffb499ab535f" 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;">3.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: normal;">[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z906a6b2591244cb983471c289b1902db" 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;">4.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: normal;">[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="z012b3a41db9148ad97619364ad4066f8" 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;">5.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: normal;">[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" id="zb6492d0c9da34b0b88a8a9b676631b58" 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;">6.</td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-weight: normal;">[***].</div>
          </td>
        </tr>

    </table>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">84</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
        <div style="text-align: right; font-style: italic; font-weight: bold;">Execution Version</div>
      </div>
    </div>
    <div style="text-align: center; font-variant: small-caps; font-weight: bold;">
      <div style="font-weight: bold;"><u>SCHEDULE 13.1.6</u></div>
    </div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">[***]</div>
    <div>&#160;</div>
    <div style="text-align: center; font-weight: bold;">[***]</div>
    <div>&#160;</div>
    <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">85</font></div>
      <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 class="BRPFPageHeader" style="width: 100%;">
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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>
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    <div>&#160;</div>
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  <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;" class="BRPFPageNumber">88</font></div>
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<DOCUMENT>
<TYPE>EX-31.1
<SEQUENCE>4
<FILENAME>ex31-1.htm
<DESCRIPTION>EXHIBIT 31.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 25.3.1.5296
         Copyright 1995 - 2025 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:956881ca-11d1-4726-85b7-68a37548513a"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><font style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></font>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="z527e4e66a70441ac8d575e43b8c00552"><tr><td style="width: 18pt;"></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;">I have reviewed this Quarterly Report on Form 10-Q 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="zf9341ed7e1af4b62b332897f45daee0e"><tr><td style="width: 18pt;"></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;">Based on my knowledge, this quarterly 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 quarterly 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="z716d3ae233be429494d12c3ba2ff4e7c"><tr><td style="width: 18pt;"></td><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;">Based on my knowledge, the condensed consolidated financial statements, and other financial information included in this quarterly report, fairly present in all material respects the financial condition, condensed consolidated results of operations and condensed consolidated cash flows of the registrant as of, and for, the periods presented in this quarterly 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="z0dd8db6570814d7fb81909ecac35eabe"><tr><td style="width: 18pt;"></td><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;">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="z79d9b362fbfb4430a7b45f9b91604d62"><tr><td style="width: 36pt;"></td><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;">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="z506cdd45ea2045c7a5066e7bcd4c305f"><tr><td style="width: 36pt;"></td><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;">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="zb3f2a2de289b4e2da179b9c78158d571"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">c)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="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="z30565ee049b74f4e87a31e39d562bf8d"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">d)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="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="zbd670ed181ee42d58e35094f6db7ee15"><tr><td style="width: 18pt;"></td><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;">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="zf303aa3cce17478fb820564295b53d59"><tr><td style="width: 36pt;"></td><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;">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="zcf84d074865b471c872a576b7f7abe94"><tr><td style="width: 36pt;"></td><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;">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;</div><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#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="zbf99548d32484aa5b1eb9c3f1cdec72c"><tr><td style="width: 27.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dated: April 30, 2025</div></td><td style="width: 72.41%; 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: 27.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td style="width: 72.41%; 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: 27.59%; 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: 72.41%; 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: 27.59%; 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: 72.41%; 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: 27.59%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Chief Executive Officer</div></td><td style="width: 72.41%; 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 style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></div></div></body></html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-31.2
<SEQUENCE>5
<FILENAME>ex31-2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals, Inc.
         Document created using Broadridge PROfile 25.3.1.5296
         Copyright 1995 - 2025 Broadridge -->
  </head><body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><div id="TRGRSegment:9770b480-fdae-48ad-8dab-7c414e81bcac"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><font style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;"><hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none" noshade="noshade" align="center"></font>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. Hougen, 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="zabdddabef804417ebf3732e03e2ee90f"><tr><td style="width: 18pt;"></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;">I have reviewed this Quarterly Report on Form 10-Q 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="zdf650fdd14534420ace1b35c14cb3af5"><tr><td style="width: 18pt;"></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;">Based on my knowledge, this quarterly 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 quarterly 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="z37a67db2fa8348b38796fbac2b6ec711"><tr><td style="width: 18pt;"></td><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;">Based on my knowledge, the condensed consolidated financial statements, and other financial information included in this quarterly report, fairly present in all material respects the financial condition, condensed consolidated results of operations and condensed consolidated cash flows of the registrant as of, and for, the periods presented in this quarterly 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="zec049484bf904878b5217079a2829c01"><tr><td style="width: 18pt;"></td><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;">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="z335681fbc66842fd972012db5f39a13c"><tr><td style="width: 36pt;"></td><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;">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="zc545d2940bdb45ea95814059258b652e"><tr><td style="width: 36pt;"></td><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;">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="zfcf054ed28ec4116baec71600270e340"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">c)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="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="z3c13bb2d726e4a618a6d0e3d45579b57"><tr><td style="width: 36pt;"></td><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">d)</td><td style="width: auto; vertical-align: top; text-align: justify;"><div style="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; 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  <xs:element name="AccruedInLicensingFeesCurrent" id="ions_AccruedInLicensingFeesCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
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  <xs:element name="ResearchDevelopmentAndPatentExpensesMember" id="ions_ResearchDevelopmentAndPatentExpensesMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
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  <xs:element name="UpfrontPaymentAchieved" id="ions_UpfrontPaymentAchieved" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" id="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" />
  <xs:element name="DrugDiscoveryExpenses" id="ions_DrugDiscoveryExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="MedicalAffairsExpenses" id="ions_MedicalAffairsExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="ResearchAndDevelopmentSupportExpenses" id="ions_ResearchAndDevelopmentSupportExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
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  <xs:element name="DrugDevelopmentExpenses" id="ions_DrugDevelopmentExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="ManufacturingAndDevelopmentChemistryExpenses" id="ions_ManufacturingAndDevelopmentChemistryExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
</xs:schema>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.CAL
<SEQUENCE>8
<FILENAME>ions-20250331_cal.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION CALCULATION LINKBASE
<TEXT>
<XBRL>
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<DOCUMENT>
<TYPE>EX-101.LAB
<SEQUENCE>10
<FILENAME>ions-20250331_lab.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
<TEXT>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Depreciation" xlink:to="us-gaap_Depreciation" xlink:title="label: Depreciation to us-gaap_Depreciation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Depreciation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Depreciation_lbl1" xml:lang="en-US" id="us-gaap_Depreciation_lbl1">Depreciation</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfFinancingCosts_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfFinancingCosts_lbl1" xml:lang="en-US" id="us-gaap_AmortizationOfFinancingCosts_lbl1">Amortization of Debt Issuance Costs</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_AmortizationOfIntangibleAssets" xlink:label="AmortizationOfIntangibleAssets" xlink:title="AmortizationOfIntangibleAssets" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AmortizationOfIntangibleAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AmortizationOfIntangibleAssets_lbl1" xml:lang="en-US" id="us-gaap_AmortizationOfIntangibleAssets_lbl1">Amortization of Intangible Assets</link:label>
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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:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EarningsPerShareBasic" xlink:label="EarningsPerShareBasic" xlink:title="EarningsPerShareBasic" />
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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_CashAndCashEquivalentsAtCarryingValue" xlink:label="CashAndCashEquivalentsAtCarryingValue" xlink:title="CashAndCashEquivalentsAtCarryingValue" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl1" xml:lang="en-US" id="us-gaap_CashAndCashEquivalentsAtCarryingValue_lbl1">Cash and Cash Equivalents, at Carrying Value</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_InterestPaidNet" xlink:label="InterestPaidNet" xlink:title="InterestPaidNet" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesAuthorized" xlink:to="us-gaap_CommonStockSharesAuthorized" xlink:title="label: CommonStockSharesAuthorized to us-gaap_CommonStockSharesAuthorized" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesAuthorized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockSharesAuthorized_lbl1" xml:lang="en-US" id="us-gaap_CommonStockSharesAuthorized_lbl1">Common Stock, Shares Authorized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesAuthorized" xlink:to="us-gaap_CommonStockSharesAuthorized_lbl1" xlink:title="label: CommonStockSharesAuthorized to us-gaap_CommonStockSharesAuthorized_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesIssued" xlink:label="CommonStockSharesIssued" xlink:title="CommonStockSharesIssued" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesIssued" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockSharesIssued" xml:lang="en-US" id="us-gaap_CommonStockSharesIssued">Common stock, shares issued (in shares)</link:label>
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesIssued_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockSharesIssued_lbl1" xml:lang="en-US" id="us-gaap_CommonStockSharesIssued_lbl1">Common Stock, Shares, Issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesIssued" xlink:to="us-gaap_CommonStockSharesIssued_lbl1" xlink:title="label: CommonStockSharesIssued to us-gaap_CommonStockSharesIssued_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesOutstanding" xlink:label="CommonStockSharesOutstanding" xlink:title="CommonStockSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesOutstanding" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CommonStockSharesOutstanding" xml:lang="en-US" id="us-gaap_CommonStockSharesOutstanding">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_CommonStockSharesOutstanding" xlink:title="label: CommonStockSharesOutstanding to us-gaap_CommonStockSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockSharesOutstanding_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockSharesOutstanding_lbl1" xml:lang="en-US" id="us-gaap_CommonStockSharesOutstanding_lbl1">Common Stock, Shares, Outstanding</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockSharesOutstanding" xlink:to="us-gaap_CommonStockSharesOutstanding_lbl1" xlink:title="label: CommonStockSharesOutstanding to us-gaap_CommonStockSharesOutstanding_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockValue" xlink:label="CommonStockValue" xlink:title="CommonStockValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockValue" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_CommonStockValue" xml:lang="en-US" id="us-gaap_CommonStockValue">Common stock, $0.001 par value; 300,000,000 shares authorized, 159,041,259 and 157,908,815 shares issued and outstanding at March 31, 2025 (unaudited) and December 31, 2024, respectively</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockValue" xlink:to="us-gaap_CommonStockValue" xlink:title="label: CommonStockValue to us-gaap_CommonStockValue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockValue_lbl1" xml:lang="en-US" id="us-gaap_CommonStockValue_lbl1">Common Stock, Value, Issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommonStockValue" xlink:to="us-gaap_CommonStockValue_lbl1" xlink:title="label: CommonStockValue to us-gaap_CommonStockValue_lbl1" />
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_ComprehensiveIncomeNetOfTax" xml:lang="en-US" id="us-gaap_ComprehensiveIncomeNetOfTax">Comprehensive loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_ComprehensiveIncomeNetOfTax" xlink:title="label: ComprehensiveIncomeNetOfTax to us-gaap_ComprehensiveIncomeNetOfTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ComprehensiveIncomeNetOfTax_lbl1" xml:lang="en-US" id="us-gaap_ComprehensiveIncomeNetOfTax_lbl1">Comprehensive Income (Loss), Net of Tax, Attributable to Parent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_ComprehensiveIncomeNetOfTax_lbl1" xlink:title="label: ComprehensiveIncomeNetOfTax to us-gaap_ComprehensiveIncomeNetOfTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CorporateDebtSecuritiesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CorporateDebtSecuritiesMember" xml:lang="en-US" id="us-gaap_CorporateDebtSecuritiesMember">Corporate Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CorporateDebtSecuritiesMember" xlink:to="us-gaap_CorporateDebtSecuritiesMember" xlink:title="label: CorporateDebtSecuritiesMember to us-gaap_CorporateDebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CorporateDebtSecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CorporateDebtSecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_CorporateDebtSecuritiesMember_lbl1">Corporate Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CorporateDebtSecuritiesMember" xlink:to="us-gaap_CorporateDebtSecuritiesMember_lbl1" xlink:title="label: CorporateDebtSecuritiesMember to us-gaap_CorporateDebtSecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="CostOfGoodsAndServicesSold" xlink:title="CostOfGoodsAndServicesSold" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfGoodsAndServicesSold" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold">Cost of sales</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSold" xlink:to="us-gaap_CostOfGoodsAndServicesSold" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfGoodsAndServicesSold_lbl1" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold_lbl1">Cost of Goods and Services Sold</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSold" xlink:to="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostOfSalesPolicyTextBlock" xlink:label="CostOfSalesPolicyTextBlock" xlink:title="CostOfSalesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesPolicyTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfSalesPolicyTextBlock" xml:lang="en-US" id="us-gaap_CostOfSalesPolicyTextBlock">Cost of Sales</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesPolicyTextBlock_lbl1">Cost of Goods and Service [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfSalesPolicyTextBlock" xlink:to="us-gaap_CostOfSalesPolicyTextBlock_lbl1" xlink:title="label: CostOfSalesPolicyTextBlock to us-gaap_CostOfSalesPolicyTextBlock_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_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">Convertible Debt</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/verboseLabel" xlink:title="us-gaap_DebtInstrumentFaceAmount" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount">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_DebtInstrumentFaceAmount" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentFaceAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtInstrumentFaceAmount_lbl1" xml:lang="en-US" id="us-gaap_DebtInstrumentFaceAmount_lbl1">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_lbl1" xlink:title="label: DebtInstrumentFaceAmount to us-gaap_DebtInstrumentFaceAmount_lbl1" />
    <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/terseLabel" xlink:title="us-gaap_DebtInstrumentInterestRateStatedPercentage" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateStatedPercentage">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_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/label" xlink:title="us-gaap_DebtInstrumentInterestRateStatedPercentage1" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateStatedPercentage1">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_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" />
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    <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" />
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    <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_DebtSecuritiesMember" xlink:label="DebtSecuritiesMember" xlink:title="DebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtSecuritiesMember" xml:lang="en-US" id="us-gaap_DebtSecuritiesMember">Available-for-sale Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesMember" xlink:to="us-gaap_DebtSecuritiesMember" xlink:title="label: DebtSecuritiesMember to us-gaap_DebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesMember_lbl1">Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesMember" xlink:to="us-gaap_DebtSecuritiesMember_lbl1" xlink:title="label: DebtSecuritiesMember to us-gaap_DebtSecuritiesMember_lbl1" />
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EarningsPerShareDiluted" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EarningsPerShareDiluted" xml:lang="en-US" id="us-gaap_EarningsPerShareDiluted">Diluted net loss 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="EarningsPerShareDiluted" xlink:to="us-gaap_EarningsPerShareDiluted" xlink:title="label: EarningsPerShareDiluted to us-gaap_EarningsPerShareDiluted" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConsolidationPolicyTextBlock" xlink:label="ConsolidationPolicyTextBlock" xlink:title="ConsolidationPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConsolidationPolicyTextBlock" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConsolidationPolicyTextBlock" xml:lang="en-US" id="us-gaap_ConsolidationPolicyTextBlock">Consolidation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationPolicyTextBlock" xlink:to="us-gaap_ConsolidationPolicyTextBlock" xlink:title="label: ConsolidationPolicyTextBlock to us-gaap_ConsolidationPolicyTextBlock" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" xlink:label="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" xlink:title="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount">Capitalized stock-based compensation expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" xlink:title="label: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount to us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_lbl1" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_lbl1">Share-Based Payment Arrangement, Amount Capitalized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_lbl1" xlink:title="label: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount to us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="AllocatedShareBasedCompensationExpense" xlink:title="AllocatedShareBasedCompensationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AllocatedShareBasedCompensationExpense" xml:lang="en-US" id="us-gaap_AllocatedShareBasedCompensationExpense">Stock-based compensation expense, net of amounts capitalized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AllocatedShareBasedCompensationExpense" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense" xlink:title="label: AllocatedShareBasedCompensationExpense to us-gaap_AllocatedShareBasedCompensationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xml:lang="en-US" id="us-gaap_AllocatedShareBasedCompensationExpense_lbl1">Share-Based Payment Arrangement, Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AllocatedShareBasedCompensationExpense" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense_lbl1" xlink:title="label: AllocatedShareBasedCompensationExpense to us-gaap_AllocatedShareBasedCompensationExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems">Share-Based Payment Arrangement, Expensed and Capitalized, Amount [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="label: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems to us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockMember" xlink:label="EmployeeStockMember" xlink:title="EmployeeStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeStockMember" xml:lang="en-US" id="us-gaap_EmployeeStockMember">ESPP [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockMember" xlink:to="us-gaap_EmployeeStockMember" xlink:title="label: EmployeeStockMember to us-gaap_EmployeeStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeStockMember_lbl1" xml:lang="en-US" id="us-gaap_EmployeeStockMember_lbl1">Employee Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockMember" xlink:to="us-gaap_EmployeeStockMember_lbl1" xlink:title="label: EmployeeStockMember to us-gaap_EmployeeStockMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensation" xlink:label="ShareBasedCompensation" xlink:title="ShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensation" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensation" xml:lang="en-US" id="us-gaap_ShareBasedCompensation">Stock-based compensation expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensation" xlink:to="us-gaap_ShareBasedCompensation" xlink:title="label: ShareBasedCompensation to us-gaap_ShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensation_lbl1">Share-Based Payment Arrangement, Noncash Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensation" xlink:to="us-gaap_ShareBasedCompensation_lbl1" xlink:title="label: ShareBasedCompensation to us-gaap_ShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationAbstract" xlink:label="ShareBasedCompensationAbstract" xlink:title="ShareBasedCompensationAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationAbstract" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAbstract">Stock-based Compensation Expense [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAbstract" xlink:to="us-gaap_ShareBasedCompensationAbstract" xlink:title="label: ShareBasedCompensationAbstract to us-gaap_ShareBasedCompensationAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationAbstract_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationAbstract_lbl1">Share-Based Payment Arrangement, Noncash Expense [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationAbstract" xlink:to="us-gaap_ShareBasedCompensationAbstract_lbl1" xlink:title="label: ShareBasedCompensationAbstract to us-gaap_ShareBasedCompensationAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquitySecuritiesMember" xlink:label="EquitySecuritiesMember" xlink:title="EquitySecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesMember" xml:lang="en-US" id="us-gaap_EquitySecuritiesMember">Equity Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesMember" xlink:to="us-gaap_EquitySecuritiesMember" xlink:title="label: EquitySecuritiesMember to us-gaap_EquitySecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesMember_lbl1">Equity Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesMember" xlink:to="us-gaap_EquitySecuritiesMember_lbl1" xlink:title="label: EquitySecuritiesMember to us-gaap_EquitySecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GainLossOnInvestments" xlink:label="GainLossOnInvestments" xlink:title="GainLossOnInvestments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainLossOnInvestments" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_GainLossOnInvestments" xml:lang="en-US" id="us-gaap_GainLossOnInvestments">Gain (loss) on investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnInvestments" xlink:to="us-gaap_GainLossOnInvestments" xlink:title="label: GainLossOnInvestments to us-gaap_GainLossOnInvestments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GainLossOnInvestments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GainLossOnInvestments_lbl1" xml:lang="en-US" id="us-gaap_GainLossOnInvestments_lbl1">Gain (Loss) on Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GainLossOnInvestments" xlink:to="us-gaap_GainLossOnInvestments_lbl1" xlink:title="label: GainLossOnInvestments to us-gaap_GainLossOnInvestments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementAbstract" xlink:label="IncomeStatementAbstract" xlink:title="IncomeStatementAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeStatementAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeStatementAbstract" xml:lang="en-US" id="us-gaap_IncomeStatementAbstract">CONSOLIDATED STATEMENTS OF OPERATIONS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeStatementAbstract" xlink:to="us-gaap_IncomeStatementAbstract" xlink:title="label: IncomeStatementAbstract to us-gaap_IncomeStatementAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxDisclosureTextBlock" xlink:label="IncomeTaxDisclosureTextBlock" xlink:title="IncomeTaxDisclosureTextBlock" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncomeTaxDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_IncomeTaxDisclosureTextBlock_lbl1">Income Tax Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncomeTaxDisclosureTextBlock" xlink:to="us-gaap_IncomeTaxDisclosureTextBlock_lbl1" xlink:title="label: IncomeTaxDisclosureTextBlock to us-gaap_IncomeTaxDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxesPaidNet" xlink:label="IncomeTaxesPaidNet" xlink:title="IncomeTaxesPaidNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncomeTaxesPaidNet" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncomeTaxesPaidNet" xml:lang="en-US" id="us-gaap_IncomeTaxesPaidNet">Income taxes paid (refunds received)</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities">Accrued compensation</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xlink:title="label: IncreaseDecreaseInOtherEmployeeRelatedLiabilities to us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" />
    <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_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_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_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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xlink:title="label: LiabilitiesAndStockholdersEquity to us-gaap_LiabilitiesAndStockholdersEquity_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquityAbstract">LIABILITIES AND STOCKHOLDERS' EQUITY</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:title="label: LiabilitiesAndStockholdersEquityAbstract to us-gaap_LiabilitiesAndStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1">Liabilities and Equity [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xlink:title="label: LiabilitiesAndStockholdersEquityAbstract to us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" />
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivities" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivities">Net cash provided by 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" xlink:title="label: NetCashProvidedByUsedInFinancingActivities to us-gaap_NetCashProvidedByUsedInFinancingActivities" />
    <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 provided by 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" />
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    <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/terseLabel" 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/totalLabel" 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_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_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:label="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:title="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xml:lang="en-US" id="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock">Organization and Basis of Presentation</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock" xlink:to="us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_lbl1" xlink:title="label: OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock to us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock_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_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/label" xlink:title="us-gaap_OtherNonoperatingIncomeExpense" xml:lang="en-US" id="us-gaap_OtherNonoperatingIncomeExpense">Other income</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:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:label="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xml:lang="en-US" id="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities">Proceeds from sale of short-term investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:to="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:title="label: ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities to us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1">Proceeds from Sale and Maturity of Debt Securities, Available-for-Sale</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities" xlink:to="us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" xlink:title="label: ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities to us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromConvertibleDebt" xlink:label="ProceedsFromConvertibleDebt" xlink:title="ProceedsFromConvertibleDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromConvertibleDebt" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromConvertibleDebt" xml:lang="en-US" id="us-gaap_ProceedsFromConvertibleDebt">Proceeds from issuance of convertible senior notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromConvertibleDebt" xlink:to="us-gaap_ProceedsFromConvertibleDebt" xlink:title="label: ProceedsFromConvertibleDebt to us-gaap_ProceedsFromConvertibleDebt" />
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfWarrants" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProceedsFromIssuanceOfWarrants" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfWarrants">Proceeds from issuance of warrants</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfWarrants" xlink:to="us-gaap_ProceedsFromIssuanceOfWarrants" xlink:title="label: ProceedsFromIssuanceOfWarrants to us-gaap_ProceedsFromIssuanceOfWarrants" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1">Proceeds from Issuance of Warrants</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromIssuanceOfWarrants" xlink:to="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" xlink:title="label: ProceedsFromIssuanceOfWarrants to us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="PropertyPlantAndEquipmentNet" xlink:title="PropertyPlantAndEquipmentNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentNet" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentNet" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentNet">Property, plant and equipment, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentNet" xlink:to="us-gaap_PropertyPlantAndEquipmentNet" xlink:title="label: PropertyPlantAndEquipmentNet to us-gaap_PropertyPlantAndEquipmentNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentNet_lbl1" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentNet_lbl1">Property, Plant and Equipment, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentNet" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_lbl1" xlink:title="label: PropertyPlantAndEquipmentNet to us-gaap_PropertyPlantAndEquipmentNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsToAcquireIntangibleAssets" xlink:label="PaymentsToAcquireIntangibleAssets" xlink:title="PaymentsToAcquireIntangibleAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireIntangibleAssets" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_PaymentsToAcquireIntangibleAssets" xml:lang="en-US" id="us-gaap_PaymentsToAcquireIntangibleAssets">Acquisition of licenses and other assets, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireIntangibleAssets" xlink:to="us-gaap_PaymentsToAcquireIntangibleAssets" xlink:title="label: PaymentsToAcquireIntangibleAssets to us-gaap_PaymentsToAcquireIntangibleAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1">Payments to Acquire Intangible Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireIntangibleAssets" xlink:to="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xlink:title="label: PaymentsToAcquireIntangibleAssets to us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xml:lang="en-US" id="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment">Purchases of property, plant and equipment</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_RetainedEarningsAccumulatedDeficit" xlink:label="RetainedEarningsAccumulatedDeficit" xlink:title="RetainedEarningsAccumulatedDeficit" />
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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_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" xlink:label="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" xlink:title="ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:title="label: AvailableForSaleSecuritiesDebtSecuritiesCurrent to us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtSecuritiesCurrent to us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfSegmentReportingInformationBySegmentTextBlock" xlink:to="us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl1" xlink:title="label: ScheduleOfSegmentReportingInformationBySegmentTextBlock to us-gaap_ScheduleOfSegmentReportingInformationBySegmentTextBlock_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SegmentReportingInformationLineItems" xlink:to="us-gaap_SegmentReportingInformationLineItems" xlink:title="label: SegmentReportingInformationLineItems to us-gaap_SegmentReportingInformationLineItems" />
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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_SellingGeneralAndAdministrativeExpense" xlink:label="SellingGeneralAndAdministrativeExpense" xlink:title="SellingGeneralAndAdministrativeExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpense" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpense" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpense">Selling, general and administrative</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpense1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpense1" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpense1">Selling, general and administrative</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_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" />
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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_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:title="ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
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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_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <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:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:title="label: ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable to us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShortTermInvestments" xlink:label="ShortTermInvestments" xlink:title="ShortTermInvestments" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShortTermInvestments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShortTermInvestments_lbl1" xml:lang="en-US" id="us-gaap_ShortTermInvestments_lbl1">Short-Term Investments</link:label>
    <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_SignificantAccountingPoliciesTextBlock" xlink:label="SignificantAccountingPoliciesTextBlock" xlink:title="SignificantAccountingPoliciesTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SignificantAccountingPoliciesTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SignificantAccountingPoliciesTextBlock" xml:lang="en-US" id="us-gaap_SignificantAccountingPoliciesTextBlock">Significant Accounting Policies</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantAccountingPoliciesTextBlock" xlink:to="us-gaap_SignificantAccountingPoliciesTextBlock" xlink:title="label: SignificantAccountingPoliciesTextBlock to us-gaap_SignificantAccountingPoliciesTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1" xml:lang="en-US" id="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1">Significant Accounting Policies [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SignificantAccountingPoliciesTextBlock" xlink:to="us-gaap_SignificantAccountingPoliciesTextBlock_lbl1" xlink:title="label: SignificantAccountingPoliciesTextBlock to us-gaap_SignificantAccountingPoliciesTextBlock_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_StockholdersEquityAbstract" xlink:label="StockholdersEquityAbstract" xlink:title="StockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockholdersEquityAbstract" xml:lang="en-US" id="us-gaap_StockholdersEquityAbstract">Stockholders' equity:</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityAbstract" xlink:to="us-gaap_StockholdersEquityAbstract_lbl1" xlink:title="label: StockholdersEquityAbstract to us-gaap_StockholdersEquityAbstract_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventTypeAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventTypeAxis" xml:lang="en-US" id="us-gaap_SubsequentEventTypeAxis">Subsequent Event Type [Axis]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventTypeDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventTypeDomain" xml:lang="en-US" id="us-gaap_SubsequentEventTypeDomain">Subsequent Event Type [Domain]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrentAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AssetsCurrentAbstract" xml:lang="en-US" id="us-gaap_AssetsCurrentAbstract">Current 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_FairValueInputsLevel2Member" xlink:label="FairValueInputsLevel2Member" xlink:title="FairValueInputsLevel2Member" />
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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_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" />
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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" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeStockOptionMember_lbl1" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember_lbl1">Employee Stock Option [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl1" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl1" />
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RealizedInvestmentGainsLosses" xlink:role="http://www.xbrl.org/2009/role/negatedTerseLabel" xlink:title="us-gaap_RealizedInvestmentGainsLosses" xml:lang="en-US" id="us-gaap_RealizedInvestmentGainsLosses">Loss (gain) on investments</link:label>
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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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:label="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="StockIssuedDuringPeriodSharesShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation">Issuance of common stock in connection with employee stock plans, net (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1">Shares Issued, Shares, Share-Based Payment Arrangement, after Forfeiture</link:label>
    <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" />
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementBusinessSegmentsAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementBusinessSegmentsAxis" xml:lang="en-US" id="us-gaap_StatementBusinessSegmentsAxis">Segments [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementBusinessSegmentsAxis" xlink:to="us-gaap_StatementBusinessSegmentsAxis" xlink:title="label: StatementBusinessSegmentsAxis to us-gaap_StatementBusinessSegmentsAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherLiabilitiesDisclosureTextBlock" xlink:label="OtherLiabilitiesDisclosureTextBlock" xlink:title="OtherLiabilitiesDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherLiabilitiesDisclosureTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherLiabilitiesDisclosureTextBlock" xml:lang="en-US" id="us-gaap_OtherLiabilitiesDisclosureTextBlock">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="OtherLiabilitiesDisclosureTextBlock" xlink:to="us-gaap_OtherLiabilitiesDisclosureTextBlock" xlink:title="label: OtherLiabilitiesDisclosureTextBlock to us-gaap_OtherLiabilitiesDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherLiabilitiesDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherLiabilitiesDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_OtherLiabilitiesDisclosureTextBlock_lbl1">Other Liabilities Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherLiabilitiesDisclosureTextBlock" xlink:to="us-gaap_OtherLiabilitiesDisclosureTextBlock_lbl1" xlink:title="label: OtherLiabilitiesDisclosureTextBlock to us-gaap_OtherLiabilitiesDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CollaborativeArrangementDisclosureTextBlock" xlink:label="CollaborativeArrangementDisclosureTextBlock" xlink:title="CollaborativeArrangementDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CollaborativeArrangementDisclosureTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CollaborativeArrangementDisclosureTextBlock" xml:lang="en-US" id="us-gaap_CollaborativeArrangementDisclosureTextBlock">Collaborative Arrangements and Licensing Agreements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementDisclosureTextBlock" xlink:to="us-gaap_CollaborativeArrangementDisclosureTextBlock" xlink:title="label: CollaborativeArrangementDisclosureTextBlock to us-gaap_CollaborativeArrangementDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1">Collaborative Arrangement Disclosure [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementDisclosureTextBlock" xlink:to="us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" xlink:title="label: CollaborativeArrangementDisclosureTextBlock to us-gaap_CollaborativeArrangementDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostsAndExpensesAbstract" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract">Expenses:</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" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract" />
    <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>
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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_CostsAndExpenses" xlink:label="CostsAndExpenses" xlink:title="CostsAndExpenses" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_CostsAndExpenses" xml:lang="en-US" id="us-gaap_CostsAndExpenses">Total operating expenses</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpenses_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl1">Costs and Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl1" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl1" />
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xml:lang="en-US" id="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract">Supplemental disclosures of non-cash investing and financing 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_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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract" />
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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: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" />
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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_AccountsPayableCurrent" xlink:label="AccountsPayableCurrent" xlink:title="AccountsPayableCurrent" />
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    <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>
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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_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" />
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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" />
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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_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:label="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" xlink:title="ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Fair Value Assumptions, Expected Term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1 to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_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/terseLabel" 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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1">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_lbl1" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1 to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_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/label" 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_NumberOfOperatingSegments1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NumberOfOperatingSegments1" xml:lang="en-US" id="us-gaap_NumberOfOperatingSegments1">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_NumberOfOperatingSegments1" xlink:title="label: NumberOfOperatingSegments to us-gaap_NumberOfOperatingSegments1" />
    <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/verboseLabel" xlink:title="us-gaap_SellingGeneralAndAdministrativeExpensesMember" xml:lang="en-US" id="us-gaap_SellingGeneralAndAdministrativeExpensesMember">Selling, General and Administrative Expense [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_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">Statement of Financial Position Location, Balance [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/terseLabel" 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:label xlink:type="resource" xlink:label="us-gaap_InvestmentTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentTextBlock_lbl1">Investment [Text Block]</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_lbl1" xlink:title="label: InvestmentTextBlock to us-gaap_InvestmentTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherCurrentLiabilitiesMember" xlink:label="OtherCurrentLiabilitiesMember" xlink:title="OtherCurrentLiabilitiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherCurrentLiabilitiesMember" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherCurrentLiabilitiesMember" xml:lang="en-US" id="us-gaap_OtherCurrentLiabilitiesMember">Other Current Liabilities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherCurrentLiabilitiesMember" xlink:to="us-gaap_OtherCurrentLiabilitiesMember" xlink:title="label: OtherCurrentLiabilitiesMember to us-gaap_OtherCurrentLiabilitiesMember" />
    <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" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConvertibleDebtTableTextBlock" xlink:label="ConvertibleDebtTableTextBlock" xlink:title="ConvertibleDebtTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtTableTextBlock" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtTableTextBlock" xml:lang="en-US" id="us-gaap_ConvertibleDebtTableTextBlock">Convertible Senior Notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtTableTextBlock" xlink:to="us-gaap_ConvertibleDebtTableTextBlock" xlink:title="label: ConvertibleDebtTableTextBlock to us-gaap_ConvertibleDebtTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtTableTextBlock_lbl1">Convertible Debt [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtTableTextBlock" xlink:to="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xlink:title="label: ConvertibleDebtTableTextBlock to us-gaap_ConvertibleDebtTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherNoncurrentLiabilitiesTableTextBlock" xlink:label="OtherNoncurrentLiabilitiesTableTextBlock" xlink:title="OtherNoncurrentLiabilitiesTableTextBlock" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherNoncurrentLiabilitiesTableTextBlock" xlink:to="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock" xlink:title="label: OtherNoncurrentLiabilitiesTableTextBlock to us-gaap_OtherNoncurrentLiabilitiesTableTextBlock" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherNoncurrentLiabilitiesTableTextBlock" xlink:to="us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1" xlink:title="label: OtherNoncurrentLiabilitiesTableTextBlock to us-gaap_OtherNoncurrentLiabilitiesTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage">Vesting percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Award Vesting Rights, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardDateAxis" xlink:label="AwardDateAxis" xlink:title="AwardDateAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AwardDateAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AwardDateAxis" xml:lang="en-US" id="us-gaap_AwardDateAxis">Award Date [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AwardDateAxis" xlink:to="us-gaap_AwardDateAxis" xlink:title="label: AwardDateAxis to us-gaap_AwardDateAxis" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AwardDateDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AwardDateDomain" xml:lang="en-US" id="us-gaap_AwardDateDomain">Award Date [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_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl1" xlink:title="label: AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax to us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl1" xlink:title="label: AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax to us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:label="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" xlink:title="AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract" />
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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_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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" xlink:title="label: AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract to us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract" />
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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: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_ContractWithCustomerAssetNetCurrent" xlink:label="ContractWithCustomerAssetNetCurrent" xlink:title="ContractWithCustomerAssetNetCurrent" />
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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_OperatingLeaseLiabilityNoncurrent" xlink:label="OperatingLeaseLiabilityNoncurrent" xlink:title="OperatingLeaseLiabilityNoncurrent" />
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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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" />
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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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:label="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" xlink:title="DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiUnrealizedLoss" xlink:to="us-gaap_EquitySecuritiesFvNiUnrealizedLoss" xlink:title="label: EquitySecuritiesFvNiUnrealizedLoss to us-gaap_EquitySecuritiesFvNiUnrealizedLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1">Equity Securities, FV-NI, Unrealized Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFvNiUnrealizedLoss" xlink:to="us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" xlink:title="label: EquitySecuritiesFvNiUnrealizedLoss to us-gaap_EquitySecuritiesFvNiUnrealizedLoss_lbl1" />
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GranteeStatusAxis" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GranteeStatusAxis" xml:lang="en-US" id="us-gaap_GranteeStatusAxis">Grantee Status [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GranteeStatusAxis" xlink:to="us-gaap_GranteeStatusAxis" xlink:title="label: GranteeStatusAxis to us-gaap_GranteeStatusAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GranteeStatusDomain" xlink:label="GranteeStatusDomain" xlink:title="GranteeStatusDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_GranteeStatusDomain" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_GranteeStatusDomain" xml:lang="en-US" id="us-gaap_GranteeStatusDomain">Grantee Status [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GranteeStatusDomain" xlink:to="us-gaap_GranteeStatusDomain" xlink:title="label: GranteeStatusDomain to us-gaap_GranteeStatusDomain" />
    <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" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedPaymentArrangementEmployeeMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedPaymentArrangementEmployeeMember" xml:lang="en-US" id="us-gaap_ShareBasedPaymentArrangementEmployeeMember">Employees [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementEmployeeMember" xlink:to="us-gaap_ShareBasedPaymentArrangementEmployeeMember" xlink:title="label: ShareBasedPaymentArrangementEmployeeMember to us-gaap_ShareBasedPaymentArrangementEmployeeMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1">Share-Based Payment Arrangement, Employee [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementEmployeeMember" xlink:to="us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" xlink:title="label: ShareBasedPaymentArrangementEmployeeMember to us-gaap_ShareBasedPaymentArrangementEmployeeMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:label="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:title="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent">Amortized cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostCurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1">Debt Securities, Available-for-Sale, Amortized Cost, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostCurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostCurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:label="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:title="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent">Amortized cost</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1">Debt Securities, Available-for-Sale, Amortized Cost, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" xlink:to="us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" xlink:title="label: DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent to us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:label="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:title="OperatingLeaseRightOfUseAssetAmortizationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense">Amortization of 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="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:to="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:title="label: OperatingLeaseRightOfUseAssetAmortizationExpense to us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1">Operating Lease, Right-of-Use Asset, Periodic Reduction</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLeaseRightOfUseAssetAmortizationExpense" xlink:to="us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" xlink:title="label: OperatingLeaseRightOfUseAssetAmortizationExpense to us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquitySecuritiesFVNIAbstract" xlink:label="EquitySecuritiesFVNIAbstract" xlink:title="EquitySecuritiesFVNIAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFVNIAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EquitySecuritiesFVNIAbstract" xml:lang="en-US" id="us-gaap_EquitySecuritiesFVNIAbstract">Equity Securities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFVNIAbstract" xlink:to="us-gaap_EquitySecuritiesFVNIAbstract" xlink:title="label: EquitySecuritiesFVNIAbstract to us-gaap_EquitySecuritiesFVNIAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EquitySecuritiesFVNIAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EquitySecuritiesFVNIAbstract_lbl1" xml:lang="en-US" id="us-gaap_EquitySecuritiesFVNIAbstract_lbl1">Equity Securities, FV-NI [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquitySecuritiesFVNIAbstract" xlink:to="us-gaap_EquitySecuritiesFVNIAbstract_lbl1" xlink:title="label: EquitySecuritiesFVNIAbstract to us-gaap_EquitySecuritiesFVNIAbstract_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_ExecutiveOfficerMember" xlink:label="ExecutiveOfficerMember" xlink:title="ExecutiveOfficerMember" />
    <link:label xlink:type="resource" xlink:label="srt_ExecutiveOfficerMember" xlink:role="http://www.xbrl.org/2003/role/label" 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: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_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductOrServiceAxis" xlink:to="srt_ProductOrServiceAxis" xlink:title="label: ProductOrServiceAxis to srt_ProductOrServiceAxis" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_CoverAbstract" xlink:label="CoverAbstract" xlink:title="CoverAbstract" />
    <link:label xlink:type="resource" xlink:label="dei_CoverAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CoverAbstract" xml:lang="en-US" id="dei_CoverAbstract">Cover [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CoverAbstract" xlink:to="dei_CoverAbstract" xlink:title="label: CoverAbstract to dei_CoverAbstract" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_DocumentType" xlink:label="DocumentType" xlink:title="DocumentType" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentType" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentType" xml:lang="en-US" id="dei_DocumentType">Document Type</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentType" xlink:to="dei_DocumentType" xlink:title="label: DocumentType to dei_DocumentType" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_DocumentQuarterlyReport" xlink:label="DocumentQuarterlyReport" xlink:title="DocumentQuarterlyReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentQuarterlyReport" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentQuarterlyReport" xml:lang="en-US" id="dei_DocumentQuarterlyReport">Document Quarterly Report</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentQuarterlyReport" xlink:to="dei_DocumentQuarterlyReport" xlink:title="label: DocumentQuarterlyReport to dei_DocumentQuarterlyReport" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_DocumentTransitionReport" xlink:label="DocumentTransitionReport" xlink:title="DocumentTransitionReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentTransitionReport" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentTransitionReport" xml:lang="en-US" id="dei_DocumentTransitionReport">Document Transition Report</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentTransitionReport" xlink:to="dei_DocumentTransitionReport" xlink:title="label: DocumentTransitionReport to dei_DocumentTransitionReport" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityInteractiveDataCurrent" xlink:label="EntityInteractiveDataCurrent" xlink:title="EntityInteractiveDataCurrent" />
    <link:label xlink:type="resource" xlink:label="dei_EntityInteractiveDataCurrent" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityInteractiveDataCurrent" xml:lang="en-US" id="dei_EntityInteractiveDataCurrent">Entity Interactive Data Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityInteractiveDataCurrent" xlink:to="dei_EntityInteractiveDataCurrent" xlink:title="label: EntityInteractiveDataCurrent to dei_EntityInteractiveDataCurrent" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_AmendmentFlag" xlink:label="AmendmentFlag" xlink:title="AmendmentFlag" />
    <link:label xlink:type="resource" xlink:label="dei_AmendmentFlag" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AmendmentFlag" xml:lang="en-US" id="dei_AmendmentFlag">Amendment Flag</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmendmentFlag" xlink:to="dei_AmendmentFlag" xlink:title="label: AmendmentFlag to dei_AmendmentFlag" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_DocumentFiscalYearFocus" xlink:label="DocumentFiscalYearFocus" xlink:title="DocumentFiscalYearFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalYearFocus" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalYearFocus" xml:lang="en-US" id="dei_DocumentFiscalYearFocus">Document Fiscal Year Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalYearFocus" xlink:to="dei_DocumentFiscalYearFocus" xlink:title="label: DocumentFiscalYearFocus to dei_DocumentFiscalYearFocus" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_DocumentFiscalPeriodFocus" xlink:label="DocumentFiscalPeriodFocus" xlink:title="DocumentFiscalPeriodFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalPeriodFocus" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalPeriodFocus" xml:lang="en-US" id="dei_DocumentFiscalPeriodFocus">Document Fiscal Period Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalPeriodFocus" xlink:to="dei_DocumentFiscalPeriodFocus" xlink:title="label: DocumentFiscalPeriodFocus to dei_DocumentFiscalPeriodFocus" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_DocumentPeriodEndDate" xlink:label="DocumentPeriodEndDate" xlink:title="DocumentPeriodEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentPeriodEndDate" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentPeriodEndDate" xml:lang="en-US" id="dei_DocumentPeriodEndDate">Document Period End Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentPeriodEndDate" xlink:to="dei_DocumentPeriodEndDate" xlink:title="label: DocumentPeriodEndDate to dei_DocumentPeriodEndDate" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityRegistrantName" xlink:label="EntityRegistrantName" xlink:title="EntityRegistrantName" />
    <link:label xlink:type="resource" xlink:label="dei_EntityRegistrantName" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityRegistrantName" xml:lang="en-US" id="dei_EntityRegistrantName">Entity Registrant Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityRegistrantName" xlink:to="dei_EntityRegistrantName" xlink:title="label: EntityRegistrantName to dei_EntityRegistrantName" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityCentralIndexKey" xlink:label="EntityCentralIndexKey" xlink:title="EntityCentralIndexKey" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCentralIndexKey" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCentralIndexKey" xml:lang="en-US" id="dei_EntityCentralIndexKey">Entity Central Index Key</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCentralIndexKey" xlink:to="dei_EntityCentralIndexKey" xlink:title="label: EntityCentralIndexKey to dei_EntityCentralIndexKey" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityFileNumber" xlink:label="EntityFileNumber" xlink:title="EntityFileNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFileNumber" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFileNumber" xml:lang="en-US" id="dei_EntityFileNumber">Entity File Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityFileNumber" xlink:to="dei_EntityFileNumber" xlink:title="label: EntityFileNumber to dei_EntityFileNumber" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2024/dei-2024.xsd#dei_EntityTaxIdentificationNumber" xlink:label="EntityTaxIdentificationNumber" xlink:title="EntityTaxIdentificationNumber" />
    <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_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_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="ions-20250331.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/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0PercentMember" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember">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" 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/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl2">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_lbl2" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.xsd#ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" xlink:label="LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" xlink:title="LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_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. Used to reflect the noncurrent portion of the liability (due after one year or beyond the operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl1" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl1">Liability Related to Sale of Future Royalties, Net, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl1" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent">Liability related to sale of future royalties, net - Non-current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl2" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent_lbl2">Liability related to sale of future royalties, net</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20250331.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>
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    <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-20250331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, within Two Years, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" />
    <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-20250331.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_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1">Available-for-sale Securities, Debt Maturities, Total, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" />
    <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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage">After one year but within two years</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl">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.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, after Two Through Three and One Half Years, Percentage</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage">After two years but within three and a half years</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20250331.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:loc xlink:type="locator" xlink:href="ions-20250331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange2" xlink:to="ions_MaximumContractMaturityPeriodRange2" xlink:title="label: MaximumContractMaturityPeriodRange2 to ions_MaximumContractMaturityPeriodRange2" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange3" xlink:to="ions_MaximumContractMaturityPeriodRange3" xlink:title="label: MaximumContractMaturityPeriodRange3 to ions_MaximumContractMaturityPeriodRange3" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.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-20250331.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-20250331.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-20250331.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-20250331.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-20250331.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-20250331.xsd#ions_CapitalAndPatentExpendituresIncurredButNotYetPaid" xlink:label="CapitalAndPatentExpendituresIncurredButNotYetPaid" xlink:title="CapitalAndPatentExpendituresIncurredButNotYetPaid" />
    <link:label xlink:type="resource" xlink:label="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid_lbl" xml:lang="en-US" id="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid_lbl">Future cash outflow to pay for purchases of fixed assets and patents that have occurred.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CapitalAndPatentExpendituresIncurredButNotYetPaid" xlink:to="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid_lbl" xlink:title="label: CapitalAndPatentExpendituresIncurredButNotYetPaid to ions_CapitalAndPatentExpendituresIncurredButNotYetPaid_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid_lbl1" xml:lang="en-US" id="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid_lbl1">Capital and Patent Expenditures Incurred but Not Yet Paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CapitalAndPatentExpendituresIncurredButNotYetPaid" xlink:to="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid_lbl1" xlink:title="label: CapitalAndPatentExpendituresIncurredButNotYetPaid to ions_CapitalAndPatentExpendituresIncurredButNotYetPaid_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid" xml:lang="en-US" id="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid">Amounts accrued for capital and patent expenditures</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CapitalAndPatentExpendituresIncurredButNotYetPaid" xlink:to="ions_CapitalAndPatentExpendituresIncurredButNotYetPaid" xlink:title="label: CapitalAndPatentExpendituresIncurredButNotYetPaid to ions_CapitalAndPatentExpendituresIncurredButNotYetPaid" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.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/negatedLabel" xlink:title="ions_RoyaltyPayments" xml:lang="en-US" id="ions_RoyaltyPayments">Royalty payments to Royalty Pharma</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember">1% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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:loc xlink:type="locator" xlink:href="ions-20250331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1">Debt Instrument, Convertible, 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_lbl1" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" />
    <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-20250331.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 conversion feature embedded in the debt instrument and the impact of the purchased hedges in the call spread transaction.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1">Debt Instrument, Convertible, Conversion Price including call spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:role="http://www.xbrl.org/2003/role/terseLabel" 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-20250331.xsd#ions_DebtInstrumentConvertibleSharesSubjectToConversion" xlink:label="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:title="DebtInstrumentConvertibleSharesSubjectToConversion" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl">The number of shares of common stock subject to conversion if the debt was converted to equity.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:to="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xlink:title="label: DebtInstrumentConvertibleSharesSubjectToConversion to ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1">Debt Instrument, Convertible, Shares Subject to Conversion</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:to="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xlink:title="label: DebtInstrumentConvertibleSharesSubjectToConversion to ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion">Total shares of common stock subject to conversion (in shares)</link:label>
    <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-20250331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread_lbl" xlink:title="label: CallSpread to ions_CallSpread_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CallSpread_lbl1" xml:lang="en-US" id="ions_CallSpread_lbl1">Call Spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread_lbl1" xlink:title="label: CallSpread to ions_CallSpread_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CallSpread" xml:lang="en-US" id="ions_CallSpread">Cost of call spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread" xlink:title="label: CallSpread to ions_CallSpread" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.xsd#ions_AccruedClinicalExpenses" xlink:label="AccruedClinicalExpenses" xlink:title="AccruedClinicalExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedClinicalExpenses_lbl" xml:lang="en-US" id="ions_AccruedClinicalExpenses_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for clinical 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="AccruedClinicalExpenses" xlink:to="ions_AccruedClinicalExpenses_lbl" xlink:title="label: AccruedClinicalExpenses to ions_AccruedClinicalExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedClinicalExpenses_lbl1" xml:lang="en-US" id="ions_AccruedClinicalExpenses_lbl1">Accrued clinical expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalExpenses" xlink:to="ions_AccruedClinicalExpenses_lbl1" xlink:title="label: AccruedClinicalExpenses to ions_AccruedClinicalExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalExpenses" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedClinicalExpenses" xml:lang="en-US" id="ions_AccruedClinicalExpenses">Clinical expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalExpenses" xlink:to="ions_AccruedClinicalExpenses" xlink:title="label: AccruedClinicalExpenses to ions_AccruedClinicalExpenses" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.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-20250331.xsd#ions_GrantedIn2025Member" xlink:label="GrantedIn2025Member" xlink:title="GrantedIn2025Member" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2025Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GrantedIn2025Member_lbl" xml:lang="en-US" id="ions_GrantedIn2025Member_lbl">Awards granted in 2025.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedIn2025Member" xlink:to="ions_GrantedIn2025Member_lbl" xlink:title="label: GrantedIn2025Member to ions_GrantedIn2025Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2025Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GrantedIn2025Member_lbl1" xml:lang="en-US" id="ions_GrantedIn2025Member_lbl1">Granted in 2025 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedIn2025Member" xlink:to="ions_GrantedIn2025Member_lbl1" xlink:title="label: GrantedIn2025Member to ions_GrantedIn2025Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2025Member" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GrantedIn2025Member" xml:lang="en-US" id="ions_GrantedIn2025Member">Granted in 2025 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedIn2025Member" xlink:to="ions_GrantedIn2025Member" xlink:title="label: GrantedIn2025Member to ions_GrantedIn2025Member" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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" />
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    <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" />
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    <link:loc xlink:type="locator" xlink:href="ions-20250331.xsd#ions_ResearchDevelopmentAndPatentExpensesMember" xlink:label="ResearchDevelopmentAndPatentExpensesMember" xlink:title="ResearchDevelopmentAndPatentExpensesMember" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpensesMember" xlink:to="ions_ResearchDevelopmentAndPatentExpensesMember" xlink:title="label: ResearchDevelopmentAndPatentExpensesMember to ions_ResearchDevelopmentAndPatentExpensesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.xsd#ions_GrantedIn2024Member" xlink:label="GrantedIn2024Member" xlink:title="GrantedIn2024Member" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2024Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GrantedIn2024Member_lbl" xml:lang="en-US" id="ions_GrantedIn2024Member_lbl">Awards granted in 2024.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_GrantedIn2024Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GrantedIn2024Member_lbl1" xml:lang="en-US" id="ions_GrantedIn2024Member_lbl1">Granted in 2024 [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20250331.xsd#ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent" xlink:label="LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent" xlink:title="LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent_lbl" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent_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. Used to reflect the current portion of the liability (due within one year or within the normal operating cycle if longer).</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent">Less: Current portion</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent" xlink:to="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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>
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    <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/periodStartLabel" xlink:title="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet" xml:lang="en-US" id="ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet">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" xlink:title="label: LiabilityRelatedToSaleOfFutureRoyaltiesNet to ions_LiabilityRelatedToSaleOfFutureRoyaltiesNet" />
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    <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:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.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-20250331.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-20250331.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-20250331.xsd#ions_RoyaltyRevenueMonetizationAbstract" xlink:label="RoyaltyRevenueMonetizationAbstract" xlink:title="RoyaltyRevenueMonetizationAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyRevenueMonetizationAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyRevenueMonetizationAbstract_lbl1" xml:lang="en-US" id="ions_RoyaltyRevenueMonetizationAbstract_lbl1">Royalty Revenue Monetization [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyRevenueMonetizationAbstract" xlink:to="ions_RoyaltyRevenueMonetizationAbstract_lbl1" xlink:title="label: RoyaltyRevenueMonetizationAbstract to ions_RoyaltyRevenueMonetizationAbstract_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyRevenueMonetizationAbstract" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyRevenueMonetizationAbstract" xml:lang="en-US" id="ions_RoyaltyRevenueMonetizationAbstract">Royalty Revenue Monetization [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyRevenueMonetizationAbstract" xlink:to="ions_RoyaltyRevenueMonetizationAbstract" xlink:title="label: RoyaltyRevenueMonetizationAbstract to ions_RoyaltyRevenueMonetizationAbstract" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.xsd#ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:label="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:title="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl" xml:lang="en-US" id="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl">The maximum amount of annual sales on which royalty payments are paid under the royalty purchase agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" xlink:to="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl" xlink:title="label: MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid to ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid_lbl" />
    <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-20250331.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-20250331.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-20250331.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-20250331.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/terseLabel" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine">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" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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/2003/role/terseLabel" xlink:title="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" xml:lang="en-US" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties">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" xlink:title="label: PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties to ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.xsd#ions_TryngolzaMember" xlink:label="TryngolzaMember" xlink:title="TryngolzaMember" />
    <link:label xlink:type="resource" xlink:label="ions_TryngolzaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TryngolzaMember_lbl" xml:lang="en-US" id="ions_TryngolzaMember_lbl">TRYNGOLZA (olezarsen) is a medicine for the treatment of familial chylomicronemia syndrome, or FCS.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TryngolzaMember" xlink:to="ions_TryngolzaMember_lbl" xlink:title="label: TryngolzaMember to ions_TryngolzaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TryngolzaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TryngolzaMember_lbl1" xml:lang="en-US" id="ions_TryngolzaMember_lbl1">TRYNGOLZA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TryngolzaMember" xlink:to="ions_TryngolzaMember_lbl1" xlink:title="label: TryngolzaMember to ions_TryngolzaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TryngolzaMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TryngolzaMember" xml:lang="en-US" id="ions_TryngolzaMember">TRYNGOLZA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TryngolzaMember" xlink:to="ions_TryngolzaMember" xlink:title="label: TryngolzaMember to ions_TryngolzaMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.xsd#ions_OtherRoyaltiesMember" xlink:label="OtherRoyaltiesMember" xlink:title="OtherRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_OtherRoyaltiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OtherRoyaltiesMember_lbl" xml:lang="en-US" id="ions_OtherRoyaltiesMember_lbl">Revenue from other royalties excluding SPINRAZA and WAINUA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherRoyaltiesMember" xlink:to="ions_OtherRoyaltiesMember_lbl" xlink:title="label: OtherRoyaltiesMember to ions_OtherRoyaltiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OtherRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OtherRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_OtherRoyaltiesMember_lbl1">Other Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherRoyaltiesMember" xlink:to="ions_OtherRoyaltiesMember_lbl1" xlink:title="label: OtherRoyaltiesMember to ions_OtherRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OtherRoyaltiesMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OtherRoyaltiesMember" xml:lang="en-US" id="ions_OtherRoyaltiesMember">Other Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherRoyaltiesMember" xlink:to="ions_OtherRoyaltiesMember" xlink:title="label: OtherRoyaltiesMember to ions_OtherRoyaltiesMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.xsd#ions_TegsediAndWaylivraMember" xlink:label="TegsediAndWaylivraMember" xlink:title="TegsediAndWaylivraMember" />
    <link:label xlink:type="resource" xlink:label="ions_TegsediAndWaylivraMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TegsediAndWaylivraMember_lbl" xml:lang="en-US" id="ions_TegsediAndWaylivraMember_lbl">TEGSEDI (inotersen) is a Generation 2+ antisense drug to treat people with hereditary TTR amyloidosis, or hATTR, a rare, progressive, fatal disease. WAYLIVRA is a drug designed to treat two severe and rare, genetically defined diseases, familial chylomicronemia syndrome, or FCS, and familial partial lipodystrophy, or FPL.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TegsediAndWaylivraMember" xlink:to="ions_TegsediAndWaylivraMember_lbl" xlink:title="label: TegsediAndWaylivraMember to ions_TegsediAndWaylivraMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TegsediAndWaylivraMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TegsediAndWaylivraMember_lbl1" xml:lang="en-US" id="ions_TegsediAndWaylivraMember_lbl1">TEGSEDI and WAYLIVRA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TegsediAndWaylivraMember" xlink:to="ions_TegsediAndWaylivraMember_lbl1" xlink:title="label: TegsediAndWaylivraMember to ions_TegsediAndWaylivraMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TegsediAndWaylivraMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TegsediAndWaylivraMember" xml:lang="en-US" id="ions_TegsediAndWaylivraMember">TEGSEDI and WAYLIVRA Revenue, Net [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TegsediAndWaylivraMember" xlink:to="ions_TegsediAndWaylivraMember" xlink:title="label: TegsediAndWaylivraMember to ions_TegsediAndWaylivraMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.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-20250331.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-20250331.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-20250331.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/verboseLabel" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">Number of 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-20250331.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-20250331.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>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstraZenecaCollaborationWainuaMember" xlink:to="ions_AstraZenecaCollaborationWainuaMember_lbl1" xlink:title="label: AstraZenecaCollaborationWainuaMember to ions_AstraZenecaCollaborationWainuaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AstraZenecaCollaborationWainuaMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AstraZenecaCollaborationWainuaMember" xml:lang="en-US" id="ions_AstraZenecaCollaborationWainuaMember">WAINUA (Eplontersen) Collaboration with AstraZeneca [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" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1">Collaborative Arrangement and Licensing Agreement [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAbstract to ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.xsd#ions_OnoCollaborationMember" xlink:label="OnoCollaborationMember" xlink:title="OnoCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_OnoCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OnoCollaborationMember_lbl" xml:lang="en-US" id="ions_OnoCollaborationMember_lbl">Collaboration agreement entered into with Ono Pharmaceutical, Ltd (Ono) in March 2025 to develop and commercialize sapablursen, an investigational RNA-targeted medicine for the potential treatment of polycythemia vera, a rare and potentially life-threatening hematologic disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OnoCollaborationMember" xlink:to="ions_OnoCollaborationMember_lbl" xlink:title="label: OnoCollaborationMember to ions_OnoCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OnoCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OnoCollaborationMember_lbl1" xml:lang="en-US" id="ions_OnoCollaborationMember_lbl1">Ono Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OnoCollaborationMember" xlink:to="ions_OnoCollaborationMember_lbl1" xlink:title="label: OnoCollaborationMember to ions_OnoCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OnoCollaborationMember" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OnoCollaborationMember" xml:lang="en-US" id="ions_OnoCollaborationMember">Ono Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OnoCollaborationMember" xlink:to="ions_OnoCollaborationMember" xlink:title="label: OnoCollaborationMember to ions_OnoCollaborationMember" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.xsd#ions_UpfrontPaymentAchieved" xlink:label="UpfrontPaymentAchieved" xlink:title="UpfrontPaymentAchieved" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentAchieved_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontPaymentAchieved_lbl" xml:lang="en-US" id="ions_UpfrontPaymentAchieved_lbl">The amount of upfront payments achieved 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="UpfrontPaymentAchieved" xlink:to="ions_UpfrontPaymentAchieved_lbl" xlink:title="label: UpfrontPaymentAchieved to ions_UpfrontPaymentAchieved_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentAchieved_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontPaymentAchieved_lbl1" xml:lang="en-US" id="ions_UpfrontPaymentAchieved_lbl1">Upfront payment achieved</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentAchieved" xlink:to="ions_UpfrontPaymentAchieved_lbl1" xlink:title="label: UpfrontPaymentAchieved to ions_UpfrontPaymentAchieved_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentAchieved" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontPaymentAchieved" xml:lang="en-US" id="ions_UpfrontPaymentAchieved">Upfront payment achieved</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentAchieved" xlink:to="ions_UpfrontPaymentAchieved" xlink:title="label: UpfrontPaymentAchieved to ions_UpfrontPaymentAchieved" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.xsd#ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration_lbl">The maximum amount of development, regulatory and 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="MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration_lbl1">Maximum amount of development, regulatory and sales 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="MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration">Maximum amount of development, regulatory and sales 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="MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" xlink:title="label: MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration" />
    <link:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.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-20250331.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:loc xlink:type="locator" xlink:href="ions-20250331.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-20250331.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>
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    <link:loc xlink:type="locator" xlink:href="ions-20250331.xsd#ions_ManufacturingAndDevelopmentChemistryExpenses" xlink:label="ManufacturingAndDevelopmentChemistryExpenses" xlink:title="ManufacturingAndDevelopmentChemistryExpenses" />
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<TYPE>EX-101.PRE
<SEQUENCE>11
<FILENAME>ions-20250331_pre.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
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<XBRL>
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  <link:roleRef roleURI="http://www.xbrl.org/2009/role/netLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/net-2009-12-16.xsd#netLabel" />
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Document and Entity Information - shares<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2025</div></th>
<th class="th"><div>Apr. 24, 2025</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_dei_CoverAbstract', window );"><strong>Cover [Abstract]</strong></a></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_dei_DocumentType', window );">Document Type</a></td>
<td class="text">10-Q<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_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_DocumentQuarterlyReport', window );">Document Quarterly Report</a></td>
<td class="text">true<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_dei_DocumentPeriodEndDate', window );">Document Period End Date</a></td>
<td class="text">Mar. 31,  2025<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_dei_CurrentFiscalYearEndDate', window );">Current Fiscal Year End Date</a></td>
<td class="text">--12-31<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_dei_DocumentFiscalYearFocus', window );">Document Fiscal Year Focus</a></td>
<td class="text">2025<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<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_DocumentFiscalPeriodFocus', window );">Document Fiscal Period Focus</a></td>
<td class="text">Q1<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_dei_DocumentTransitionReport', window );">Document Transition Report</a></td>
<td class="text">false<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_dei_EntityFileNumber', window );">Entity File Number</a></td>
<td class="text">000-19125<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_dei_EntityRegistrantName', window );">Entity Registrant Name</a></td>
<td class="text">Ionis Pharmaceuticals, Inc.<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_dei_EntityCentralIndexKey', window );">Entity Central Index Key</a></td>
<td class="text">0000874015<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_dei_EntityIncorporationStateCountryCode', window );">Entity Incorporation, State or Country Code</a></td>
<td class="text">DE<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_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>
</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_EntityAddressAddressLine1', window );">Entity Address, Address Line One</a></td>
<td class="text">2855 Gazelle Court<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_dei_EntityAddressCityOrTown', window );">Entity Address, City or Town</a></td>
<td class="text">Carlsbad<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_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>
</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_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="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>
</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_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="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>
</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_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="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>
</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_dei_EntityFilerCategory', window );">Entity Filer Category</a></td>
<td class="text">Large Accelerated Filer<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_dei_EntitySmallBusiness', window );">Entity Small Business</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_EntityEmergingGrowthCompany', window );">Entity Emerging Growth Company</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_EntityShellCompany', window );">Entity Shell Company</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_EntityCommonStockSharesOutstanding', window );">Entity Common Stock, Shares Outstanding</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">159,159,099<span></span>
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<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>
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<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">
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<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">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CoverAbstract</td>
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<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">
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<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">
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<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">
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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>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">
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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>Boolean flag that is true only for a form used as an quarterly 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-Q<br> -Number 240<br> -Section 308<br> -Subsection a<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ 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_DocumentQuarterlyReport</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_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_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_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>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>14
<FILENAME>R2.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;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED BALANCE SHEETS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Mar. 31, 2025</div></th>
<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_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">$ 264,192<span></span>
</td>
<td class="nump">$ 242,077<span></span>
</td>
</tr>
<tr class="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">1,880,960<span></span>
</td>
<td class="nump">2,055,579<span></span>
</td>
</tr>
<tr class="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">39,707<span></span>
</td>
<td class="nump">92,188<span></span>
</td>
</tr>
<tr class="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">11,502<span></span>
</td>
<td class="nump">12,512<span></span>
</td>
</tr>
<tr class="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">222,571<span></span>
</td>
<td class="nump">217,934<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">2,418,932<span></span>
</td>
<td class="nump">2,620,290<span></span>
</td>
</tr>
<tr class="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">102,925<span></span>
</td>
<td class="nump">94,251<span></span>
</td>
</tr>
<tr class="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">159,269<span></span>
</td>
<td class="nump">161,856<span></span>
</td>
</tr>
<tr class="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">131,822<span></span>
</td>
<td class="nump">127,278<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">2,812,948<span></span>
</td>
<td class="nump">3,003,675<span></span>
</td>
</tr>
<tr class="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">17,456<span></span>
</td>
<td class="nump">42,964<span></span>
</td>
</tr>
<tr class="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">26,575<span></span>
</td>
<td class="nump">69,614<span></span>
</td>
</tr>
<tr class="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">102,735<span></span>
</td>
<td class="nump">108,438<span></span>
</td>
</tr>
<tr class="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">126<span></span>
</td>
<td class="nump">34<span></span>
</td>
</tr>
<tr class="re">
<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">81,097<span></span>
</td>
<td class="nump">78,989<span></span>
</td>
</tr>
<tr class="ro">
<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">22,304<span></span>
</td>
<td class="nump">9,279<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_LiabilitiesCurrent', window );">Total current liabilities</a></td>
<td class="nump">250,293<span></span>
</td>
<td class="nump">309,318<span></span>
</td>
</tr>
<tr class="ro">
<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">140,678<span></span>
</td>
<td class="nump">156,504<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_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent', window );">Liability related to sale of future royalties, net</a></td>
<td class="nump">536,141<span></span>
</td>
<td class="nump">542,212<span></span>
</td>
</tr>
<tr class="ro">
<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">159,392<span></span>
</td>
<td class="nump">161,805<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherLiabilitiesNoncurrent', window );">Long-term obligations</a></td>
<td class="nump">55,671<span></span>
</td>
<td class="nump">51,924<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_Liabilities', window );">Total liabilities</a></td>
<td class="nump">2,337,222<span></span>
</td>
<td class="nump">2,415,324<span></span>
</td>
</tr>
<tr class="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>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<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, 159,041,259 and 157,908,815 shares issued and outstanding at March 31, 2025 (unaudited) and December 31, 2024, respectively</a></td>
<td class="nump">159<span></span>
</td>
<td class="nump">158<span></span>
</td>
</tr>
<tr class="re">
<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">2,901,262<span></span>
</td>
<td class="nump">2,868,812<span></span>
</td>
</tr>
<tr class="ro">
<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">(28,949)<span></span>
</td>
<td class="num">(30,811)<span></span>
</td>
</tr>
<tr class="re">
<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">(2,396,746)<span></span>
</td>
<td class="num">(2,249,808)<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_StockholdersEquity', window );">Total stockholders' equity</a></td>
<td class="nump">475,726<span></span>
</td>
<td class="nump">588,351<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_LiabilitiesAndStockholdersEquity', window );">Total liabilities and stockholders' equity</a></td>
<td class="nump">2,812,948<span></span>
</td>
<td class="nump">3,003,675<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="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">565,721<span></span>
</td>
<td class="nump">565,026<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="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">$ 629,326<span></span>
</td>
<td class="nump">$ 628,535<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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. Used to reflect the noncurrent portion of the liability (due after one year or beyond the 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_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent</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>
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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 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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_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_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>
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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>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>
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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>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>
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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>
<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_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>
<td style="white-space:nowrap;">us-gaap_Liabilities</td>
</tr>
<tr>
<td style="padding-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_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>
<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 944<br> -SubTopic 210<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(25))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478777/944-210-S99-1<br><br>Reference 3: 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 4: 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 5: 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 6: 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(23))<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147478546/942-210-S99-1<br><br>Reference 7: 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(32))<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_LiabilitiesAndStockholdersEquity</td>
</tr>
<tr>
<td style="padding-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_LiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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>
<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(21))<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 810<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/1943274/2147481203/810-10-50-3<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 810<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481231/810-10-45-25<br><br>Reference 4: 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-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><br>Reference 21: 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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>
<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_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>
</tr>
<tr>
<td style="padding-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_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_OtherLiabilitiesNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 after 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(24))<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>
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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 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>
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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 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>
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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 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>
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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>instant</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 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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquity</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 );">- 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>
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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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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares<br></strong></div></th>
<th class="th"><div>Mar. 31, 2025</div></th>
<th class="th"><div>Dec. 31, 2024</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_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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<tr class="ro">
<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>
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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_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="nump">159,041,259<span></span>
</td>
<td class="nump">157,908,815<span></span>
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<td class="nump">159,041,259<span></span>
</td>
<td class="nump">157,908,815<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_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="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>
</tr>
<tr class="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>
</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="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>
</tr>
<tr class="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">0.00%<span></span>
</td>
<td class="nump">0.00%<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_CommonStockParOrStatedValuePerShare">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockParOrStatedValuePerShare</td>
</tr>
<tr>
<td style="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_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>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
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<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_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>
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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_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>
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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> 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_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>
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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>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2025</div></th>
<th class="th"><div>Mar. 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_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue:</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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 131,612<span></span>
</td>
<td class="nump">$ 119,497<span></span>
</td>
</tr>
<tr class="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>
</tr>
<tr class="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">1,463<span></span>
</td>
<td class="nump">2,151<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_ResearchDevelopmentAndPatentExpense', window );">Research, development and patent</a></td>
<td class="nump">200,759<span></span>
</td>
<td class="nump">214,215<span></span>
</td>
</tr>
<tr class="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">76,250<span></span>
</td>
<td class="nump">52,644<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">278,472<span></span>
</td>
<td class="nump">269,010<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">(146,860)<span></span>
</td>
<td class="num">(149,513)<span></span>
</td>
</tr>
<tr class="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>
</tr>
<tr class="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">24,667<span></span>
</td>
<td class="nump">26,285<span></span>
</td>
</tr>
<tr class="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">(4,108)<span></span>
</td>
<td class="num">(4,151)<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">(18,822)<span></span>
</td>
<td class="num">(17,959)<span></span>
</td>
</tr>
<tr class="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 );">Gain (loss) on investments</a></td>
<td class="num">(2,164)<span></span>
</td>
<td class="nump">2,333<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_OtherNonoperatingIncomeExpense', window );">Other income</a></td>
<td class="nump">465<span></span>
</td>
<td class="nump">277<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_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest', window );">Loss before income tax expense</a></td>
<td class="num">(146,822)<span></span>
</td>
<td class="num">(142,728)<span></span>
</td>
</tr>
<tr class="ro">
<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 expense</a></td>
<td class="num">(116)<span></span>
</td>
<td class="num">(75)<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="num">$ (146,938)<span></span>
</td>
<td class="num">$ (142,803)<span></span>
</td>
</tr>
<tr class="ro">
<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">$ (0.93)<span></span>
</td>
<td class="num">$ (0.98)<span></span>
</td>
</tr>
<tr class="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">$ (0.93)<span></span>
</td>
<td class="num">$ (0.98)<span></span>
</td>
</tr>
<tr class="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">158,735<span></span>
</td>
<td class="nump">145,538<span></span>
</td>
</tr>
<tr class="re">
<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">158,735<span></span>
</td>
<td class="nump">145,538<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>
</tr>
<tr class="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>
</tr>
<tr class="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">$ 76,168<span></span>
</td>
<td class="nump">$ 59,593<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 );">Product Sales, Net [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_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue:</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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">6,287<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=us-gaap_RoyaltyMember', window );">Royalty Revenue [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_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue:</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_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">64,166<span></span>
</td>
<td class="nump">49,385<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>
</tr>
<tr class="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>
</tr>
<tr class="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">5,715<span></span>
</td>
<td class="nump">10,208<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>
</tr>
<tr class="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>
</tr>
<tr class="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">55,444<span></span>
</td>
<td class="nump">59,904<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>
</tr>
<tr class="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>
</tr>
<tr class="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">45,031<span></span>
</td>
<td class="nump">49,345<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>
</tr>
<tr class="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>
</tr>
<tr class="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">$ 10,413<span></span>
</td>
<td class="nump">$ 10,559<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>
<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_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>
</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_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>
<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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-Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-7<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482689/260-10-45-2<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482689/260-10-45-60B<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 250<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 4<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483443/250-10-50-4<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<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_EarningsPerShareBasic</td>
</tr>
<tr>
<td style="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_EarningsPerShareDiluted">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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>
</tr>
<tr>
<td style="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_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>
</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_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;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2025</div></th>
<th class="th"><div>Mar. 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_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>
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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">$ (146,938)<span></span>
</td>
<td class="num">$ (142,803)<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 debt securities, net of tax</a></td>
<td class="nump">1,630<span></span>
</td>
<td class="num">(2,205)<span></span>
</td>
</tr>
<tr class="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="nump">232<span></span>
</td>
<td class="num">(114)<span></span>
</td>
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<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_ComprehensiveIncomeNetOfTax', window );">Comprehensive loss</a></td>
<td class="num">$ (145,076)<span></span>
</td>
<td class="num">$ (145,122)<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 );">- 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">
<tr>
<td><strong> Name:</strong></td>
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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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</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 );">- 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>
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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>
<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 10A<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 220<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-10A<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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-10A<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-10A<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481839/830-10-45-9<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 35<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482014/830-20-35-3<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481694/830-30-45-12<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_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax</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_StatementOfIncomeAndComprehensiveIncomeAbstract</td>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONDENSED 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>
</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>
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<td class="nump">$ 386,686<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_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">(142,803)<span></span>
</td>
<td class="num">(142,803)<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">(2,205)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(2,205)<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">(114)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(114)<span></span>
</td>
</tr>
<tr class="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">23,609<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">23,611<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_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans, net (in shares)</a></td>
<td class="nump">1,504<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">31,340<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">31,340<span></span>
</td>
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<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 Mar. 31, 2024</a></td>
<td class="nump">$ 146<span></span>
</td>
<td class="nump">2,270,047<span></span>
</td>
<td class="num">(34,964)<span></span>
</td>
<td class="num">(1,938,714)<span></span>
</td>
<td class="nump">296,515<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 Mar. 31, 2024</a></td>
<td class="nump">145,845<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<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, 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>
<tr class="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">(146,938)<span></span>
</td>
<td class="num">(146,938)<span></span>
</td>
</tr>
<tr class="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">1,630<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">1,630<span></span>
</td>
</tr>
<tr class="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">232<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">232<span></span>
</td>
</tr>
<tr class="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">$ 1<span></span>
</td>
<td class="nump">2,241<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">2,242<span></span>
</td>
</tr>
<tr class="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">1,132<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">30,209<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">30,209<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 Mar. 31, 2025</a></td>
<td class="nump">$ 159<span></span>
</td>
<td class="nump">$ 2,901,262<span></span>
</td>
<td class="num">$ (28,949)<span></span>
</td>
<td class="num">$ (2,396,746)<span></span>
</td>
<td class="nump">$ 475,726<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 Mar. 31, 2025</a></td>
<td class="nump">159,041<span></span>
</td>
<td class="text">&#160;<span></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_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>
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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_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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>
</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_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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>
<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 10A<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 220<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-10A<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://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-10A<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 220<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482790/220-10-45-10A<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481839/830-10-45-9<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 20<br> -Name Accounting Standards Codification<br> -Section 35<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482014/830-20-35-3<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 830<br> -SubTopic 30<br> -Name Accounting Standards Codification<br> -Section 45<br> -Paragraph 12<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481694/830-30-45-12<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_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>
</tr>
</table></div>
</div></td></tr>
</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_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>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-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_StockIssuedDuringPeriodValueShareBasedCompensationGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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, 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>
</tr>
<tr>
<td style="padding-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_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">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquity</td>
</tr>
<tr>
<td style="padding-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>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2025</div></th>
<th class="th"><div>Mar. 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_NetCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Operating activities:</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_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (146,938)<span></span>
</td>
<td class="num">$ (142,803)<span></span>
</td>
</tr>
<tr class="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>
</tr>
<tr class="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">2,228<span></span>
</td>
<td class="nump">2,547<span></span>
</td>
</tr>
<tr class="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">2,587<span></span>
</td>
<td class="nump">2,465<span></span>
</td>
</tr>
<tr class="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">582<span></span>
</td>
<td class="nump">639<span></span>
</td>
</tr>
<tr class="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 discount on investments, net</a></td>
<td class="num">(7,108)<span></span>
</td>
<td class="num">(9,257)<span></span>
</td>
</tr>
<tr class="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">1,642<span></span>
</td>
<td class="nump">1,667<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">(12,891)<span></span>
</td>
<td class="num">(6,623)<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">18,670<span></span>
</td>
<td class="nump">17,806<span></span>
</td>
</tr>
<tr class="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">29,718<span></span>
</td>
<td class="nump">31,340<span></span>
</td>
</tr>
<tr class="ro">
<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 (gain) on investments</a></td>
<td class="nump">1,849<span></span>
</td>
<td class="num">(2,332)<span></span>
</td>
</tr>
<tr class="re">
<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">61<span></span>
</td>
<td class="nump">133<span></span>
</td>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="re">
<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">52,481<span></span>
</td>
<td class="nump">92,638<span></span>
</td>
</tr>
<tr class="ro">
<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="nump">1,010<span></span>
</td>
<td class="nump">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_IncreaseDecreaseInOtherOperatingAssets', window );">Other current and long-term assets</a></td>
<td class="num">(12,366)<span></span>
</td>
<td class="nump">11,048<span></span>
</td>
</tr>
<tr class="ro">
<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">92<span></span>
</td>
<td class="nump">59<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInAccruedIncomeTaxesPayable', window );">Income taxes</a></td>
<td class="num">(25,968)<span></span>
</td>
<td class="num">(13,869)<span></span>
</td>
</tr>
<tr class="ro">
<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="num">(43,039)<span></span>
</td>
<td class="num">(46,190)<span></span>
</td>
</tr>
<tr class="re">
<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="nump">333<span></span>
</td>
<td class="num">(42,887)<span></span>
</td>
</tr>
<tr class="ro">
<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">(13,718)<span></span>
</td>
<td class="num">(46,818)<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_NetCashProvidedByUsedInOperatingActivities', window );">Net cash used in operating activities</a></td>
<td class="num">(150,775)<span></span>
</td>
<td class="num">(149,938)<span></span>
</td>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="re">
<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">(311,068)<span></span>
</td>
<td class="num">(519,001)<span></span>
</td>
</tr>
<tr class="ro">
<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">494,755<span></span>
</td>
<td class="nump">600,836<span></span>
</td>
</tr>
<tr class="re">
<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">(12,577)<span></span>
</td>
<td class="num">(4,493)<span></span>
</td>
</tr>
<tr class="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">(651)<span></span>
</td>
<td class="num">(1,237)<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 provided by investing activities</a></td>
<td class="nump">170,459<span></span>
</td>
<td class="nump">76,105<span></span>
</td>
</tr>
<tr class="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>
</tr>
<tr class="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">2,241<span></span>
</td>
<td class="nump">23,609<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_RepaymentsOfSecuredDebt', window );">Principal payments on mortgage debt</a></td>
<td class="num">(42)<span></span>
</td>
<td class="num">(39)<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 financing activities</a></td>
<td class="nump">2,199<span></span>
</td>
<td class="nump">23,570<span></span>
</td>
</tr>
<tr class="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="nump">232<span></span>
</td>
<td class="num">(114)<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="nump">22,115<span></span>
</td>
<td class="num">(50,377)<span></span>
</td>
</tr>
<tr class="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 period</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_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at end of period</a></td>
<td class="nump">264,192<span></span>
</td>
<td class="nump">348,889<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_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>
</tr>
<tr class="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">92<span></span>
</td>
<td class="nump">95<span></span>
</td>
</tr>
<tr class="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">(400)<span></span>
</td>
<td class="nump">13<span></span>
</td>
</tr>
<tr class="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>
</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_CapitalAndPatentExpendituresIncurredButNotYetPaid', window );">Amounts accrued for capital and patent expenditures</a></td>
<td class="nump">$ 460<span></span>
</td>
<td class="nump">$ 924<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_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>
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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>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>
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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_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_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_IncreaseDecreaseInAccruedIncomeTaxesPayable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 period in the amount due for taxes based on the reporting entity's earnings or attributable to the entity's income earning process (business presence) within a given jurisdiction.</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_IncreaseDecreaseInAccruedIncomeTaxesPayable</td>
</tr>
<tr>
<td style="padding-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_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>
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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_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>
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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>
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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_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>
</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 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>
</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>
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<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>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of realized gain (loss) on investment.</p></div>
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<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>
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<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>
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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;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Basis of Presentation<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</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_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTextBlock', window );">Organization and Basis of Presentation</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1.&#160; Organization and 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; font-weight: bold;">Organization and Business 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;">We incorporated in California on January 10, 1989. In conjunction with our initial public offering, we reorganized as a Delaware
    corporation in April 1991. We are a leader in the discovery and development of RNA-targeted 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; 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;">We prepared the unaudited interim condensed consolidated financial statements for the three months ended&#160;March 31, 2025 and 2024 on the same basis as the audited financial statements for the year ended December 31, 2024. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at
    such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these
    financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2024
    included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div>

<div><br/>
  </div>

<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 condensed 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="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_716d7f6d27dd450bb3559e4e755739ee">single</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</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 <span style="-sec-ix-hidden:Fact_95a745ba91854ab0bbf27d495728685c">single</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>operating segment. Refer to Note 14, <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; 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We prepare our condensed consolidated financial statements in
      conformity with accounting principles generally accepted in the United States, or </span>U.S., that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying
    notes. Actual results could differ from our estimates.</div>
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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>The entire disclosure for organization, consolidation and basis of presentation of financial statements 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/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480424/946-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 946<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147480424/946-10-50-2<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 810<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org/810/tableOfContent<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 205<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org/205/tableOfContent<br></p></div>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</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_AccountingPoliciesAbstract', window );"><strong>Significant Accounting Policies [Abstract]</strong></a></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_SignificantAccountingPoliciesTextBlock', window );">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;">2.&#160; Significant Accounting Policies</div>

<div><br/>
  </div>

<div style="display:none;"><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 accounting policies for revenue recognition related to product sales, net and cost of sales as a result of our
    launch of TRYNGOLZA in the U.S. Our other significant accounting policies have not changed substantially from those included in our Annual Report on Form 10-K for the year ended December 31, 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; font-style: italic; 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; font-style: italic;">Product Sales, Net</div>

<div><br/>
  </div>

<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 revenue from product sales when the customer obtains control of our product in the amount of the transaction price, which is
    the amount that reflects the consideration which we expect to receive. We estimate reserves for variable consideration related to applicable discounts, rebates, chargebacks and other allowances included in our agreements with customers, payors and
    other third parties. We include the amount of variable consideration in the transaction price to the extent that it is probable that a significant reversal in the amount of the cumulative revenue recognized will not occur in a future period. If actual
    results vary significantly from our estimates, we adjust our estimates in the period that we become aware of such variances.</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; 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="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales for a newly launched product, such as TRYNGOLZA, does not include the full cost of manufacturing until we manufacture and
    sell additional inventory after exhausting pre-launch inventory, which we previously recorded as research and development, or R&amp;D, expense.</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;">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 Accounting Standards Codification, or ASC, Topic 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. We adopted the reporting requirements in our 2024 Annual Report on Form 10-K and in this Quarterly Report on Form 10-Q for the first quarter of 2025. Refer to Note 14, <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/>
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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 do not expect any recently issued accounting standards other than those included in our Annual Report on Form 10-K for the year ended December 31, 2024 to have a material impact to our financial results.</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/disclosureRef<br> -Topic 235<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147483426/235-10-50-1<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Topic 235<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org/235/tableOfContent<br></p></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3. Supplemental Financial Data</div>

<div><br/>
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<div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventories</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 inventories consisted of the following (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;">


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    <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>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2025</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;">December 31, 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>

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  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; 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; 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">
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    <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;">640</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">
          <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; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,557</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%; white-space: nowrap;" valign="bottom">
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        </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;">8,744</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%; 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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" 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; 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;">2,118</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;">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>

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  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
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        </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;">11,502</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>
        </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;">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>

  </tr>


</table>

<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: left; text-indent: 36pt; 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: left; 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; 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; 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;">March 31, 2025</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;">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: 76%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Clinical expenses</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;">67,614</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;">77,436</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%; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In-licensing expenses</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;">7,374</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;">7,951</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; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial expenses</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;">7,257</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;">3,589</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; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other miscellaneous expenses</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,490</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; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19,462</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; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total accrued liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; 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 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Revenues<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;">4. Revenues</div>

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    <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>

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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>

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    <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>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; 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: 2px; 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>

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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>

    <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">&#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">
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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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">38,455</div>
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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: 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">&#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;">9,372</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">
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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>

    <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;">6,784</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;">9,805</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>

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  <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">&#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: 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">&#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: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA revenue, net</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;">5,715</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;">8,628</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: 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;" 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;">1,580</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: 2px; background-color: #CCEEFF;" 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; 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;">5,715</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;">10,208</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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">76,168</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;">59,593</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: 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%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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: 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">45,031</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;">49,345</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: 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; 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;">10,413</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;">10,559</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: 2px;" 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;" 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;">55,444</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;">59,904</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: left; text-indent: -9pt; 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; 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;">131,612</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;">119,497</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; font-weight: bold;"><span style="text-decoration: underline;">Revenue Sources</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 are sources of revenue and when we typically recognize 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-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;">In December 2024, the U.S. Food and Drug Administration, or FDA, approved TRYNGOLZA (olezarsen) for the treatment of familial
    chylomicronemia syndrome, or FCS. Following the approval, we launched TRYNGOLZA and began earning revenue from TRYNGOLZA sales. We recognize product sales, net of variable considerations related to applicable discounts and allowances, when the customer
    obtains control of our product.</div>

<div><br/>
  </div>

<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 earn royalty payments primarily on net sales of SPINRAZA, WAINUA and QALSODY.</div>

<div><br/>
  </div>

<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 earn commercial revenue from TEGSEDI and WAYLIVRA sales under our distribution agreements with Swedish Orphan Biovitrum AB, or Sobi. In
    addition, we receive royalties from PTC Therapeutics International Limited, or PTC, for TEGSEDI and WAYLIVRA sales. 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>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 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; 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 that may involve 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></span> 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.</div>

<div><br/>
  </div>

<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></span> We
    consider milestone payments to be variable consideration and include them 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.</div>

<div><br/>
  </div>

<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.</div>

<div><br/>
  </div>

<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></span> 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.</div>

<div><br/>
  </div>

<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.</div>

<div><br/>
  </div>

<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 Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or 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 Topic 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>, or 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 selling, general and administrative, or SG&amp;A, expense and R&amp;D expense, 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; 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 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>
</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">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure of revenue from contract with customer to transfer good or service and to transfer nonfinancial asset. Includes, but is not limited to, disaggregation of revenue, credit loss recognized from contract with customer, judgment and change in judgment related to contract with customer, and asset recognized from cost incurred to obtain or fulfill contract with customer. Excludes insurance and lease contracts.</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 9<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-9<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 10<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-10<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 15<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-15<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 12<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-12<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 12<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-12<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 12<br> -Subparagraph (c)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-12<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 12<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-12<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 12<br> -Subparagraph (e)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-12<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 606<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 13<br> -Subparagraph (b)(2)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479806/606-10-50-13<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>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<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">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</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_CollaborativeArrangementsAndLicensingAgreementsAbstract', 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_CollaborativeArrangementDisclosureTextBlock', window );">Collaborative Arrangements and Licensing Agreements</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">5.&#160; Collaborative Arrangements and Licensing 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Below, we have included our Ono collaboration, which is the
      only collaboration that had either substantive changes or was new from those included in Part IV, Item 15, Note 4, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and
      Licensing Agreements</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024.</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; font-weight: bold;">Ono</div>

<div><br/>
  </div>

<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 March 2025, we entered into an agreement with Ono Pharmaceutical, Ltd, or Ono, to develop and commercialize sapablursen, an
    investigational RNA-targeted medicine for the potential treatment of polycythemia vera, or PV, a rare and potentially life-threatening hematologic disease. We are responsible for completing the ongoing Phase 2 IMPRSSION study, while Ono will be solely
    responsible for subsequent development, regulatory filings and commercialization of sapablursen.</div>

<div><br/>
  </div>

<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 our sapablursen collaboration, we are eligible to receive up to $940 million, which is comprised of a $280 million upfront payment and up
    to $660 million in development, regulatory and sales milestone payments. In addition, we are eligible to receive royalties in the mid-teen
    percentage range on net 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;">In April 2025, we achieved a $280
    million upfront payment when this transaction received clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, or HSR Act.</div>
<span></span>
</td>
</tr>
</table>
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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>The entire disclosure for collaborative arrangements in which the entity is a participant, including a) information about the nature and purpose of such arrangements; b) its rights and obligations thereunder; c) the accounting policy for collaborative arrangements; and d) the income statement classification and amounts attributable to transactions arising from the collaborative arrangement between participants.</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> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -SubTopic 10<br> -Topic 808<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479402/808-10-50-1<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -SubTopic 10<br> -Topic 808<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147479402/808-10-50-1<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Name Accounting Standards Codification<br> -Topic 808<br> -Publisher FASB<br> -URI https://asc.fasb.org/808/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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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basic and Diluted Net Loss Per Share<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</div></th></tr>
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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_EarningsPerShareTextBlock', window );">Basic and Diluted Net Loss Per Share</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6. 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-weight: bold;">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 calculated our basic net loss per share for the three months ended&#160;March 31, 2025 and 2024 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 three months ended&#160;March 31, 2025 and 2024, 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>

<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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.75 percent convertible senior notes, or 1.75% Notes;</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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent convertible senior notes, or 0% Notes;</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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the 0% Notes;</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: left;">
          <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: left;">
          <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: left;">
          <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: left;">
          <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 three months ended&#160;March 31, 2024, common stock underlying the 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>, and n<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ote hedges related to the </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes </span>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;">Additionally, as of March 31, 2025
    and 2024, we had warrants related to our 0%
    and 0.125% Notes outstanding. 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.</div>
<span></span>
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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>The entire disclosure for earnings per share.</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 (c)<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> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org/260/tableOfContent<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 2<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-2<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 260<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 3<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482662/260-10-50-3<br></p></div>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</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_InvestmentTextBlock', window );">Investments</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7.&#160; 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 March 31, 2025:</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: left; 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>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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</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%;" valign="bottom">
          <div style="text-align: left; 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">27</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; 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_f12cc57cfa544d218ac6c26f9aae5797">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;">6</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">
          <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; 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;" 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;">100</div>
        </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>

  </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 March 31, 2025,
    94 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 debt 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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We invest in debt securities</span> 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;">At March 31, 2025, we had an
    equity ownership interest of less than 20 percent in seven private companies and three public companies with which we conduct business.</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;">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; text-indent: 6.5pt;">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; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">March 31, 2025</span></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;"><span style="text-decoration: underline;">Available-for-sale debt securities:</span></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;">516,458</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;">299</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;">(247</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;">516,510</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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">120,961</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;">156</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;">(32</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;">121,085</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: 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;">592,770</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;">393</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 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">592,893</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;" 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;" 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;">3,072</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;">2</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;">3,074</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: 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;">1,233,261</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;">850</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;">(549</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;">1,233,562</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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">471,479</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;">1,086</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;">(1,009</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;">471,556</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: 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;">61,184</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;">188</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;">(116</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;">61,256</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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">145,922</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;">373</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</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;">146,243</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: 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 states of the U.S. and political subdivisions of the 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">&#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;">1,595</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</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;">1,596</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;" 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</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;">698</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>

    <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;">698</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: 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;">Total debt 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: #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;">680,878</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;">1,648</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;">(1,177</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;">681,349</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;" 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 debt securities</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,914,139</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,498</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,726</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,914,911</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: 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;"><span style="text-decoration: underline;">Equity securities:</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">&#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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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: 52%;" 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%;" 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;">11,897</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;">41</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;">(8,856</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;">3,082</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: 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;">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: #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;">23,115</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;">25,001</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;">(7,093</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;">41,023</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;" valign="bottom">
          <div style="text-align: left; text-indent: 9pt; margin-left: 9pt; 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;" 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;">35,012</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;">25,042</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;">(15,949</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;">44,105</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: 52%; padding-bottom: 4px; 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 debt and equity securities</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;">1,949,151</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;">27,540</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;">(17,675</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;">1,959,016</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>

<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; text-indent: 6.5pt;">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; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">December 31, 2024</span></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;"><span style="text-decoration: underline;">Available-for-sale debt securities:</span></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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">143,647</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;">287</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;">(39</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;">143,895</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: 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;" 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;" 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;">7,516</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</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;">7,524</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: 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;">Total debt 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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">439,561</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;">723</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;">(2,275</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;">438,009</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: 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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">149,086</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</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;">(476</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;">148,734</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: 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;" valign="bottom">
          <div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt securities with a maturity of more than one year</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;">654,600</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;">984</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;">(3,042</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;">652,542</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: 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 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">
          <div style="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%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</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">&#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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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: 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;" 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;" 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;">23,115</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;">25,001</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;">(7,093</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;">41,023</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: 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;">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">&#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;">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">&#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;">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">&#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;">(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">&#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;">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;" 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 debt and equity securities</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;">2,091,870</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;">27,618</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;">(17,194</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;">2,102,294</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="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 condensed
            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 three months ended&#160;March 31, 2025, we recorded a $2.2 million net unrealized loss
            in our condensed consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies.</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<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</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;">The following is a summary of our investments we consider to be temporarily impaired at March 31, 2025 (in thousands, except for number of investments):</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">&#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; 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;">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;" 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;">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; 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;">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; 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;">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; 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;">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; 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;">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; 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;">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;" 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;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">244</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;">466,130</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;">(1,236</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;">9,945</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;">(20</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;">476,075</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;">(1,256</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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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">&#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;">45,578</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;">(148</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">45,578</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;">(148</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;" 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;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">271,642</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;">(266</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">
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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="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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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;">Debt securities issued by states of the U.S. and political subdivisions of the states</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;">2</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">
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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">
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        </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>

    <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;">471</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>

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    <td style="vertical-align: bottom; width: 16%; 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;">Total temporarily impaired securities</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;">312</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>

    <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;">783,821</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;">(1,650</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>
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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>
        </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;">22,876</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;">(76</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>
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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>
        </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;">806,697</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>

    <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">
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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;">(1,726</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">
          <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;">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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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8.&#160; Fair Value Measurements</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 tables present the major security types we held at March 31, 2025 and December 31, 2024 that we regularly measure and
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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; 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;">At</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 31, 2025</div>
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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;">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="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;">Significant Other</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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    <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;">Cash equivalents (1)</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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          <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;">176,876</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;">176,876</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;">&#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;">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;">988,066</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;">988,066</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: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</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;">182,341</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;">182,341</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;">Debt securities issued by the U.S. Treasury (3)</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;">739,136</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;">739,136</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 (3)</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;">4,670</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;">4,670</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 (3)</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;">698</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;">698</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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</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;">3,082</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;">3,082</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;">2,094,869</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;">919,094</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;">1,175,775</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"> </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, 2024</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: left; 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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (3)</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: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</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>
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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;">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">
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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;">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>

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          <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 (3)</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>
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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">
          <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 (3)</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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</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>
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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>
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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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  <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>
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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;">2,241,716</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">
          <div style="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>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following footnotes reference lines in our condensed consolidated balance sheets:</div>

<div><br/>
  </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>

    <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.</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;">$34.0 million was included in cash and cash equivalents, with the difference included in short-term investments.</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 short-term investments.</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;">Included in other current assets.</div>
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  </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 $559.0 million and $623.0 million at March 31, 2025, respectively.
    Our 1.75% Notes and 0% Notes had a
    fair value of $569.3 million and $612.8
    million at December 31, 2024, 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>
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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;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stock-based Compensation Expense<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</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_DisclosureOfCompensationRelatedCostsSharebasedPaymentsAbstract', 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_DisclosureOfCompensationRelatedCostsShareBasedPaymentsTextBlock', 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;">9. 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;">The following table summarizes stock-based compensation expense for the three months ended&#160;March 31, 2025 and 2024 (in thousands):</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 76%; 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;">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;">100</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;">204</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;">Research, development and patent expense</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;">20,298</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;">22,225</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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative 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;">9,320</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;">8,911</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: 2px;" valign="bottom">
          <div style="text-align: left; 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%; 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;">29,718</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;">31,340</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: 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;">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;">491</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: 76%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; 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;">30,209</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;">31,340</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;">As of March 31, 2025, total
    unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $51.9 million, $117.1 million and $17.8 million, respectively.
    Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures, including any PRSUs that do not vest. We expect to recognize the cost of stock-based compensation
    expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.3 years, 1.8 years and 1.9 years, 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;">Refer to Part IV, Item 15, Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization







      and Significant Accounting Policies</span>, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 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 three months ended&#160;March 31, 2025 and 2024, 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Options:</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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 76%; 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;">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;">4.0</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: 76%;" valign="bottom">
          <div style="text-align: left; 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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; 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;">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;">41.9</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">44.0</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;" valign="bottom">
          <div style="text-align: left; 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>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
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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="vertical-align: bottom; width: 1%; background-color: #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%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RSUs:</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 weighted-average grant date fair value of RSUs granted to employees for the three months ended&#160;March 31, 2025 and 2024 was $33.21 and $53.54 per share, respectively.</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; font-style: italic;">PRSUs:</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;">Under the terms of the PRSUs we granted in 2025 and 2024, 100 percent of the PRSUs may vest at the end of the three-year performance period based on our relative
    total shareholder return, or 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
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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;">The weighted-average grant date fair value of PRSUs we granted to our executive officers for the three months ended&#160;March 31, 2025 and 2024 was $48.81 and $78.41 per share, respectively.</div>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
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<div style="text-align: left; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">10.&#160; 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 recorded income tax expense of $0.1
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<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 of our net deferred tax assets.</div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for income tax.</p></div>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Liability Related to Sale of Future Royalties<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</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_OtherLiabilitiesDisclosureAbstract', window );"><strong>Liability Related to Sale of Future Royalties [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_OtherLiabilitiesDisclosureTextBlock', 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;">11. 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 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. 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, our medicine in
    development to treat patients with elevated lipoprotein(a)-driven cardiovascular disease. 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;">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 March 31, 2025 and 2024, the estimated effective interest rate under the agreement was 13.5 percent.</div>

<div><br/>
  </div>

<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 our liability related to sale of future royalties (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: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties, net as of December 31, 2024</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;">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>

  </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;">Royalty payments to Royalty Pharma</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;">(12,891</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;">Interest expense 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;">18,670</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%; padding-bottom: 2px;" 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;" 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;">152</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: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties, net as of March 31, 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;">548,143</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%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion (1)</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;">(12,002</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: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties, net as of March 31, 2025 &#8211; Non-current</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;">536,141</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>

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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;">Included in other current liabilities in our condensed consolidated balance sheet.</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;">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>
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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>The entire disclosure for other liabilities.</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 210<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(24))<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 405<br> -Name Accounting Standards Codification<br> -Publisher FASB<br> -URI https://asc.fasb.org/405/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>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Convertible Debt<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</div></th></tr>
<tr class="re">
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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_DebtDisclosureTextBlock', window );">Convertible Debt</a></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">12. Convertible Debt</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; font-style: italic;">1.75 Percent
    Convertible Senior Notes</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;">In 2023, we completed a $575.0
    million offering of our 1.75% Notes. We used $532.7
    million of the net proceeds from the issuance of our 1.75% Notes to repurchase and settle our 0.125% Notes, which matured 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;">At March 31, 2025, we had the following 1.75% Notes outstanding (in millions except interest rate and price per share data):</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;">


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    <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;">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;">9.3</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_ac460e99cb6b43a8b64e987880ed0dd5">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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">1.75</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;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">2.3</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="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: 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 percent 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 March 31, 2025, we had the following <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> 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;">3.2</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_edbb9fb31e834f86ad026d22e567df04">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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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>

  <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;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">0.5</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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes by increasing the effective conversion price on our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes. We increased our effective conversion price to $76.39
    with the same number of underlying shares as our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%&#160;</span>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 <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes, our note hedges are subject to adjustment. Additionally, our note hedges
    are exercisable upon conversion of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes. The note
    hedges will expire upon maturity of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes, or April
    2026. The warrants will expire in July 2026. The note hedges and warrants are separate transactions and are not part of the terms of our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> Notes. The holders of the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">0%</span> 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
    condensed consolidated balance sheets. Refer to Part IV, Item 15, Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span>, of our audited
    financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 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.</div>
<span></span>
</td>
</tr>
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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>
<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 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (b)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481544/470-10-50-6<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 470<br> -SubTopic 10<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147481544/470-10-50-6<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Topic 405<br> -SubTopic 40<br> -Name Accounting Standards Codification<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147477092/405-40-50-1<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> 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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;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">14. 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_92f78800150c4bacb3c7033e970a29cb">single</span>
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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 4, <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="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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    <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="text-align: left; 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>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Insider Trading Arrangements<br></strong></div></th>
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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 1<br></p></div>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Basis of Presentation (Policies)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</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_BasisOfAccountingPolicyPolicyTextBlock', window );">Basis of Presentation</a></td>
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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 prepared the unaudited interim condensed consolidated financial statements for the three months ended&#160;March 31, 2025 and 2024 on the same basis as the audited financial statements for the year ended December 31, 2024. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at
    such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these
    financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2024
    included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.</div>
<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_ConsolidationPolicyTextBlock', window );">Consolidation</a></td>
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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 our condensed 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>
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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_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_716d7f6d27dd450bb3559e4e755739ee">single</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</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 <span style="-sec-ix-hidden:Fact_95a745ba91854ab0bbf27d495728685c">single</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>operating segment. Refer to Note 14, <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>
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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_UseOfEstimates', window );">Use of Estimates</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-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;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We prepare our condensed consolidated financial statements in
      conformity with accounting principles generally accepted in the United States, or </span>U.S., that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying
    notes. Actual results could differ from our estimates.</div>
<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for basis of accounting, or basis of presentation, used to prepare the financial statements (for example, US Generally Accepted Accounting Principles, Other Comprehensive Basis of Accounting, IFRS).</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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<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 );">- 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>Disclosure of accounting policy for segment reporting.</p></div>
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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 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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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Significant Accounting Policies (Policies)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</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_AccountingPoliciesAbstract', window );"><strong>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_RevenueFromContractWithCustomerPolicyTextBlock', window );">Revenue Recognition</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; 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; font-style: italic;">Product Sales, Net</div>

<div><br/>
  </div>

<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 revenue from product sales when the customer obtains control of our product in the amount of the transaction price, which is
    the amount that reflects the consideration which we expect to receive. We estimate reserves for variable consideration related to applicable discounts, rebates, chargebacks and other allowances included in our agreements with customers, payors and
    other third parties. We include the amount of variable consideration in the transaction price to the extent that it is probable that a significant reversal in the amount of the cumulative revenue recognized will not occur in a future period. If actual
    results vary significantly from our estimates, we adjust our estimates in the period that we become aware of such variances.</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="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;">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="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales for a newly launched product, such as TRYNGOLZA, does not include the full cost of manufacturing until we manufacture and
    sell additional inventory after exhausting pre-launch inventory, which we previously recorded as research and development, or R&amp;D, 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_NewAccountingPronouncementsPolicyPolicyTextBlock', window );">Recent Accounting Standards</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-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 Accounting Standards Codification, or ASC, Topic 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. We adopted the reporting requirements in our 2024 Annual Report on Form 10-K and in this Quarterly Report on Form 10-Q for the first quarter of 2025. Refer to Note 14, <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;">We do not expect any recently issued accounting standards other than those included in our Annual Report on Form 10-K for the year ended December 31, 2024 to have a material impact to our financial results.</div>
<span></span>
</td>
</tr>
</table>
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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>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 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">
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<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>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Basic and Diluted Net Loss Per Share (Policies)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</div></th></tr>
<tr class="re">
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<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
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<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-weight: bold;">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 calculated our basic net loss per share for the three months ended&#160;March 31, 2025 and 2024 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">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 three months ended&#160;March 31, 2025 and 2024, 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/>
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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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.75 percent convertible senior notes, or 1.75% Notes;</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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent convertible senior notes, or 0% Notes;</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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Note hedges related to the 0% Notes;</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: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</div>
        </td>

  </tr>


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  </tr>


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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>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Stock Purchase Plan, or ESPP.</div>
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  </tr>


</table>

<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;">For the three months ended&#160;March 31, 2024, common stock underlying the 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>, and n<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ote hedges related to the </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes </span>would also have had an anti-dilutive effect on net loss per share.</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;">Additionally, as of March 31, 2025
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Supplemental Financial Data (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2025</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_ScheduleOfInventoryCurrentTableTextBlock', window );">Inventories</a></td>
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<div style="text-align: justify; margin-left: 36pt; 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>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventories consisted of the following (in thousands):</div>

<div><br/>
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  <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>

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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;">December 31, 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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; 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; 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">
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    <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;">640</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">
          <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; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,557</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%; white-space: nowrap;" 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>
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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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,744</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%; 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;">6,679</div>
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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: 76%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" 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; 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;">2,118</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;">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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; white-space: nowrap;" 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; 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;">11,502</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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    <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;">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>

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<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-weight: bold;">Accrued Liabilities</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;">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; 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; 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;">March 31, 2025</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;">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: 76%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Clinical expenses</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;">67,614</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;">77,436</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%; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In-licensing expenses</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;">7,374</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;">7,951</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; white-space: nowrap;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial expenses</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;">7,257</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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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 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; white-space: nowrap;" valign="bottom">&#160;</td>

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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Revenues (Tables)<br></strong></div></th>
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    <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>

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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="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>

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    <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>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <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="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>
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    <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>

  </tr>

  <tr>

    <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>

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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">&#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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48,010</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="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">9,372</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">
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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: 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,784</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;">9,805</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>

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  <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">&#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;">64,166</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;">49,385</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>

    <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">&#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: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA revenue, net</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;">5,715</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;">8,628</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: 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;" 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;">1,580</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>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" 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; 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;">5,715</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;">10,208</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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">76,168</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;">59,593</div>
        </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: 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">&#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">
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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;">45,031</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;">49,345</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: 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; 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;">10,413</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;">10,559</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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" 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>
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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;">55,444</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;">59,904</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>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <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 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;">131,612</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>

    <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;">119,497</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>

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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2025</div></th></tr>
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<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 March 31, 2025:</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: left; 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>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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</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%;" valign="bottom">
          <div style="text-align: left; 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">27</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; 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_f12cc57cfa544d218ac6c26f9aae5797">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;">6</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">
          <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; 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;" 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;">100</div>
        </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>

  </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_UnrealizedGainLossOnInvestmentsTableTextBlock', window );">Summary of Investments</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;">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; text-indent: 6.5pt;">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; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">March 31, 2025</span></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;"><span style="text-decoration: underline;">Available-for-sale debt securities:</span></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;">516,458</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;">299</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;">(247</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;">516,510</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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">120,961</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;">156</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;">(32</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;">121,085</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: 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;">592,770</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;">393</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;">(270</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;">592,893</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;" 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;" 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;">3,072</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;">2</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;">3,074</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: 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;">Total debt 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;">1,233,261</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">
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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;">(549</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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    <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;">1,233,562</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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%;" 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;">471,479</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;">1,086</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;">(1,009</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;">471,556</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: 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;">61,184</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;">188</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;">(116</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;">61,256</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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">145,922</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;">373</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</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;">146,243</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: 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 states of the U.S. and political subdivisions of the 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">&#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;">1,595</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</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;">1,596</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;" 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</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;">698</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>

    <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;">698</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: 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;">Total debt 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: #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;">680,878</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;">1,648</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;">(1,177</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;">681,349</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;" 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 debt securities</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,914,139</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,498</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,726</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">
          <div style="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;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,914,911</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: 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;"><span style="text-decoration: underline;">Equity securities:</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">&#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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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: 52%;" 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%;" 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;">11,897</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;">41</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;">(8,856</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;">3,082</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: 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;">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: #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;">23,115</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;">25,001</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;">(7,093</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;">41,023</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;" valign="bottom">
          <div style="text-align: left; text-indent: 9pt; margin-left: 9pt; 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;" 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;">35,012</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;">25,042</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;">(15,949</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;">44,105</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: 52%; padding-bottom: 4px; 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 debt and equity securities</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;">1,949,151</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;">27,540</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;">(17,675</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;">1,959,016</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>

<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; text-indent: 6.5pt;">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; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-indent: 0pt;">December 31, 2024</span></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;"><span style="text-decoration: underline;">Available-for-sale debt securities:</span></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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">143,647</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;">287</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;">(39</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;">143,895</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: 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;" 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;" 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;">7,516</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</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;">7,524</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: 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;">Total debt 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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">439,561</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;">723</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;">(2,275</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;">438,009</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: 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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">149,086</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</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;">(476</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;">148,734</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: 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;" valign="bottom">
          <div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt securities with a maturity of more than one year</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;">654,600</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;">984</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;">(3,042</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;">652,542</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: 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 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">
          <div style="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%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Equity securities:</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">&#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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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: 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;" 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;" 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;">23,115</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;">25,001</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;">(7,093</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;">41,023</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: 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;">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">&#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;">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">&#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;">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">&#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;">(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">&#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;">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;" 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 debt and equity securities</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;">2,091,870</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;">27,618</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;">(17,194</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;">2,102,294</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="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 condensed
            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 three months ended&#160;March 31, 2025, we recorded a $2.2 million net unrealized loss
            in our condensed consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies.</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<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</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;">The following is a summary of our investments we consider to be temporarily impaired at March 31, 2025 (in thousands, except for number of investments):</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">&#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; 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;">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 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>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
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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>

    <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>
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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>

    <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>
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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;">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; 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;">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; 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;">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; 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;">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;" 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;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">244</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;">466,130</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;">(1,236</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;">9,945</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;">(20</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;">476,075</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;">(1,256</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%;" 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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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">&#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;">45,578</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;">(148</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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;">45,578</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;">(148</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;" 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;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">271,642</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;">(266</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;">12,931</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;">(56</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;">284,573</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;">(322</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%; padding-bottom: 2px;" 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;" 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;">2</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;">471</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">
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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;">&#8212;</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;">471</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">
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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="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;">312</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>

    <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">
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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">
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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%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,650</div>
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          <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; 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;">22,876</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>

    <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;">(76</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">
          <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; 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">
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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">
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,726</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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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements (Tables)<br></strong></div></th>
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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 March 31, 2025 and December 31, 2024 that we regularly measure and
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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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          <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="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;">Significant Other</div>
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          <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>

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    <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;">Cash equivalents (1)</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">
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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;">176,876</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;">176,876</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;">&#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>

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    <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;">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>

    <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;">988,066</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;">&#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;">988,066</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: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</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;">182,341</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;">182,341</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;">Debt securities issued by the U.S. Treasury (3)</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;">739,136</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;">739,136</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 (3)</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;">4,670</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;">4,670</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 (3)</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;">698</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;">698</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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</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;">3,082</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;">3,082</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;">2,094,869</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;">919,094</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;">1,175,775</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"> </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, 2024</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: left; 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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (3)</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: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (3)</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: 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 (3)</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">
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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%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: 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: 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 (3)</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>
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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">
          <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 (3)</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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</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>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following footnotes reference lines in our condensed consolidated balance sheets:</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: 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.</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;">$34.0 million was included in cash and cash equivalents, with the difference included in short-term investments.</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 short-term investments.</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;">
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        </td>

  </tr>


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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stock-based Compensation Expense (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
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<tr><th class="th"><div>Mar. 31, 2025</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;">The following table summarizes stock-based compensation expense for the three months ended&#160;March 31, 2025 and 2024 (in thousands):</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><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>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 76%; 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;">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;">100</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;">204</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;">20,298</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;">22,225</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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative 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;">9,320</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;">8,911</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: 2px;" valign="bottom">
          <div style="text-align: left; 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%; 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;">29,718</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;">31,340</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: 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;">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;">491</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: 76%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; 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;">30,209</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;">31,340</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_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for Stock Options</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;">Employee Stock Options:</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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 76%; 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;">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;">4.0</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: 76%;" valign="bottom">
          <div style="text-align: left; 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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; 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;">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;">41.9</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>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; 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;">44.0</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;" valign="bottom">
          <div style="text-align: left; 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>

  </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_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for ESPP</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;">ESPP:</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;">Three Months Ended</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">March 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;">2025</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;">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: 76%; 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;">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;">4.3</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;">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>

  </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;">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>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; 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;">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;">41.3</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;">38.4</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;" valign="bottom">
          <div style="text-align: left; 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 months</div>
        </td>

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          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of allocation of amount expensed and capitalized for award under share-based payment arrangement to statement of income or comprehensive income and statement of financial position. Includes, but is not limited to, corresponding line item in financial statement.</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> -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">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the significant assumptions used during the year to estimate the fair value of employee stock purchase plans, including, but not limited to: (a) expected term, (b) expected volatility of the entity's shares, (c) expected dividends, (d) risk-free rate(s), and (e) discount for post-vesting restrictions.</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 (f)(2)<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>
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<td style="white-space:nowrap;">us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock</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 the significant assumptions used during the year to estimate the fair value of stock options, including, but not limited to: (a) expected term of share options and similar instruments, (b) expected volatility of the entity's shares, (c) expected dividends, (d) risk-free rate(s), and (e) discount for post-vesting restrictions.</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 (f)(2)<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">
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<td style="white-space:nowrap;">us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock</td>
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<head>
<title></title>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Liability Related to Sale of Future Royalties (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</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_OtherLiabilitiesDisclosureAbstract', window );"><strong>Liability Related to Sale of Future Royalties [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_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;">The following table sets forth information on our liability related to sale of future royalties (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: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties, net as of December 31, 2024</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;">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>

  </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;">Royalty payments to Royalty Pharma</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;">(12,891</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;">Interest expense 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;">18,670</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%; padding-bottom: 2px;" 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;" 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;">152</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: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties, net as of March 31, 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;">548,143</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%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion (1)</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;">(12,002</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: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Liability related to sale of future royalties, net as of March 31, 2025 &#8211; Non-current</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;">536,141</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/>
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  <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 other current liabilities in our condensed consolidated balance sheet.</div>
        </td>

  </tr>


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<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">
<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 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">
<tr>
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</DOCUMENT>
<DOCUMENT>
<TYPE>XML
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<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;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Convertible Debt (Tables)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</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_DebtInstrumentAxis=ions_ConvertibleSeniorNotes175PercentMember', window );">1.75% 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 March 31, 2025, 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;" 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>

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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 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_ConvertibleDebtTableTextBlock', window );">Convertible Senior Notes</a></td>
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<div style="display:none;"><br/></div>
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  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
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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="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%; background-color: #CCEEFF;" valign="bottom">&#160;</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 table sets forth information on segment profit or loss, including significant segment expenses (in thousands):</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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  <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>

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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">&#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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  <tr>

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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>

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  <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">&#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: 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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,946</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;">125,751</div>
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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: 76%; 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;">Medical affairs</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;">5,642</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;">4,676</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>

    <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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,281</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;">11,441</div>
        </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: 76%; 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>
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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;">20,553</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;">21,946</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>

    <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">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66,980</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;">43,733</div>
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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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    <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;">29,796</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;">24,630</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>

  </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%; 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>
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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;">(146,938</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="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;">(142,803</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 );">- 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_SegmentReportingAbstract</td>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Basis of Presentation (Details)<br></strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
</tr>
<tr><th class="th">
<div>Mar. 31, 2025 </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>
<td class="nump">1<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_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>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</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_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract</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>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<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>Mar. 31, 2025</div></th>
<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_InventoryNetAbstract', window );"><strong>Inventory [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_InventoryRawMaterials', window );">Raw materials</a></td>
<td class="nump">$ 640<span></span>
</td>
<td class="nump">$ 5,557<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryWorkInProcess', window );">Work in process</a></td>
<td class="nump">8,744<span></span>
</td>
<td class="nump">6,679<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryFinishedGoods', window );">Finished goods</a></td>
<td class="nump">2,118<span></span>
</td>
<td class="nump">276<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_InventoryNet', window );">Total inventories</a></td>
<td class="nump">$ 11,502<span></span>
</td>
<td class="nump">$ 12,512<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_InventoryFinishedGoods">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryFinishedGoods</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>
<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>
</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_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>
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<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_InventoryNetAbstract</td>
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<td>na</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_InventoryRawMaterials">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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>
</tr>
<tr>
<td style="padding-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>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_InventoryWorkInProcess">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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>
</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>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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<html>
<head>
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<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;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<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>Mar. 31, 2025</div></th>
<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_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_AccruedClinicalExpenses', window );">Clinical expenses</a></td>
<td class="nump">$ 67,614<span></span>
</td>
<td class="nump">$ 77,436<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">7,374<span></span>
</td>
<td class="nump">7,951<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">7,257<span></span>
</td>
<td class="nump">3,589<span></span>
</td>
</tr>
<tr class="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">20,490<span></span>
</td>
<td class="nump">19,462<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">$ 102,735<span></span>
</td>
<td class="nump">$ 108,438<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedClinicalExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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_AccruedClinicalExpenses</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>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<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="2">3 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2025 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2024 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($) </div>
<div>Component </div>
<div>PerformanceObligation</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DisaggregationOfRevenueAbstract', window );"><strong>Revenues [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 131,612<span></span>
</td>
<td class="nump">$ 119,497<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>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetAndLiabilityAbstract', 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>
</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="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_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="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_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of performance obligations | PerformanceObligation</a></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="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_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>
</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="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>
</tr>
<tr class="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">$ 76,168<span></span>
</td>
<td class="nump">59,593<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 );">Product Sales, 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>
</tr>
<tr class="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>
</tr>
<tr class="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">6,287<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_TryngolzaMember', window );">TRYNGOLZA [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_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>
</tr>
<tr class="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">6,287<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=us-gaap_RoyaltyMember', window );">Royalty [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_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>
</tr>
<tr class="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">64,166<span></span>
</td>
<td class="nump">49,385<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>
</tr>
<tr class="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>
</tr>
<tr class="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">48,010<span></span>
</td>
<td class="nump">38,455<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>
</tr>
<tr class="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>
</tr>
<tr class="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">9,372<span></span>
</td>
<td class="nump">1,125<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_OtherRoyaltiesMember', window );">Other 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_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>
</tr>
<tr class="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">6,784<span></span>
</td>
<td class="nump">9,805<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>
</tr>
<tr class="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>
</tr>
<tr class="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">5,715<span></span>
</td>
<td class="nump">10,208<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_TegsediAndWaylivraMember', 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>
</tr>
<tr class="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>
</tr>
<tr class="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">5,715<span></span>
</td>
<td class="nump">8,628<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>
</tr>
<tr class="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>
</tr>
<tr class="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">0<span></span>
</td>
<td class="nump">1,580<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>
</tr>
<tr class="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>
</tr>
<tr class="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">55,444<span></span>
</td>
<td class="nump">59,904<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>
</tr>
<tr class="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>
</tr>
<tr class="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">45,031<span></span>
</td>
<td class="nump">49,345<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>
</tr>
<tr class="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>
</tr>
<tr class="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">$ 10,413<span></span>
</td>
<td class="nump">$ 10,559<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>
<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_ContractWithCustomerAssetAndLiabilityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ContractWithCustomerAssetAndLiabilityAbstract</td>
</tr>
<tr>
<td style="padding-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_DisaggregationOfRevenueAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_DisaggregationOfRevenueAbstract</td>
</tr>
<tr>
<td style="padding-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_TypeOfArrangementAxis=ions_AstraZenecaCollaborationWainuaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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>
</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_CommercialMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_CommercialMember</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> 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></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=us-gaap_ProductMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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=us-gaap_ProductMember</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> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></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 );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_TryngolzaMember</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>
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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_ProductOrServiceAxis=us-gaap_RoyaltyMember</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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<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>
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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 );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_WainusRoyaltiesMember</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>
</tr>
<tr>
<td><strong> Balance Type:</strong></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>
<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_OtherRoyaltiesMember</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>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_OtherCommercialMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_OtherCommercialMember</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> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_TegsediAndWaylivraMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_TegsediAndWaylivraMember</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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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_OtherMember">
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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;">srt_ProductOrServiceAxis=ions_OtherMember</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_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ResearchAndDevelopmentRevenueMember</td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_CollaborativeAgreementRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_CollaborativeAgreementRevenueMember</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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<tr>
<td><strong> Data Type:</strong></td>
<td>na</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 border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_WainuaJointDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_WainuaJointDevelopmentRevenueMember</td>
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<DOCUMENT>
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<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements (Details) - Ono Collaboration [Member] - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Apr. 30, 2025</div></th>
<th class="th"><div>Mar. 31, 2025</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>
</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">$ 940<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_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration', window );">Maximum amount of upfront payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">280<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_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development, regulatory and sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 660<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_OnoCollaborationMember', window );">Subsequent Event [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_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>
</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_UpfrontPaymentAchieved', window );">Upfront payment achieved</a></td>
<td class="nump">$ 280<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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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;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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, regulatory and 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_MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration</td>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance 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 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>
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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>instant</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 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>
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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: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></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 achieved 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_UpfrontPaymentAchieved</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_TypeOfArrangementAxis=ions_OnoCollaborationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_OnoCollaborationMember</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_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember</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>51
<FILENAME>R39.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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</head>
<body>
<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Basic and Diluted Net Loss Per Share (Details)<br></strong></div></th>
<th class="th"><div>Mar. 31, 2025</div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Mar. 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_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>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareDilutedAbstract', window );"><strong>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>
</tr>
<tr class="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="nump">1.75%<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>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareDilutedAbstract', window );"><strong>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>
</tr>
<tr class="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>
</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>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareDilutedAbstract', window );"><strong>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>
</tr>
<tr class="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="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_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_EarningsPerShareDilutedAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_EarningsPerShareDilutedAbstract</td>
</tr>
<tr>
<td style="padding-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_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>
</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>
</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_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>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>52
<FILENAME>R40.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'; }
							}</script>
</head>
<body>
<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<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">3 Months Ended</th>
</tr>
<tr><th class="th"><div>Mar. 31, 2025</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">67.00%<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">27.00%<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">6.00%<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_MaximumContractMaturityPeriodRange1', window );">Maximum contract maturity period, range 1</a></td>
<td class="text">1 year<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_MaximumContractMaturityPeriodRange2', window );">Maximum contract maturity period, range 2</a></td>
<td class="text">2 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_MaximumContractMaturityPeriodRange3', window );">Maximum contract maturity period, range 3</a></td>
<td class="text">3 years 6 months<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_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage', window );">Percentage of available-for-sale securities with a maturity of less than two years</a></td>
<td class="nump">94.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_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>
</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_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>
</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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<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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<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>
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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_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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<tr>
<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>
</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_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>
</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>
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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>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<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_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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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<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">3 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2025 </div>
<div>USD ($) </div>
<div>Company</div>
</th>
<th class="th">
<div>Dec. 31, 2024 </div>
<div>USD ($)</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_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 private 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 public 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">$ 1,233,261<span></span>
</td>
<td class="nump">$ 1,402,258<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">850<span></span>
</td>
<td class="nump">1,607<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">(549)<span></span>
</td>
<td class="num">(399)<span></span>
</td>
</tr>
<tr class="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">1,233,562<span></span>
</td>
<td class="nump">1,403,466<span></span>
</td>
</tr>
<tr class="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">680,878<span></span>
</td>
<td class="nump">654,600<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_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,648<span></span>
</td>
<td class="nump">984<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">(1,177)<span></span>
</td>
<td class="num">(3,042)<span></span>
</td>
</tr>
<tr class="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">681,349<span></span>
</td>
<td class="nump">652,542<span></span>
</td>
</tr>
<tr class="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">1,914,139<span></span>
</td>
<td class="nump">2,056,858<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">2,498<span></span>
</td>
<td class="nump">2,591<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">(1,726)<span></span>
</td>
<td class="num">(3,441)<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">1,914,911<span></span>
</td>
<td class="nump">2,056,008<span></span>
</td>
</tr>
<tr class="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="rou">
<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">25,042<span></span>
</td>
<td class="nump">25,027<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">(15,949)<span></span>
</td>
<td class="num">(13,753)<span></span>
</td>
</tr>
<tr class="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">44,105<span></span>
</td>
<td class="nump">46,286<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_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">1,949,151<span></span>
</td>
<td class="nump">2,091,870<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">27,540<span></span>
</td>
<td class="nump">27,618<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">(17,675)<span></span>
</td>
<td class="num">(17,194)<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">1,959,016<span></span>
</td>
<td class="nump">2,102,294<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">516,458<span></span>
</td>
<td class="nump">593,810<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">299<span></span>
</td>
<td class="nump">487<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">(247)<span></span>
</td>
<td class="num">(240)<span></span>
</td>
</tr>
<tr class="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">516,510<span></span>
</td>
<td class="nump">594,057<span></span>
</td>
</tr>
<tr class="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">471,479<span></span>
</td>
<td class="nump">439,561<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">1,086<span></span>
</td>
<td class="nump">723<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">(1,009)<span></span>
</td>
<td class="num">(2,275)<span></span>
</td>
</tr>
<tr class="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">471,556<span></span>
</td>
<td class="nump">438,009<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_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">120,961<span></span>
</td>
<td class="nump">143,647<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">156<span></span>
</td>
<td class="nump">287<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">(32)<span></span>
</td>
<td class="num">(39)<span></span>
</td>
</tr>
<tr class="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">121,085<span></span>
</td>
<td class="nump">143,895<span></span>
</td>
</tr>
<tr class="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">61,184<span></span>
</td>
<td class="nump">65,255<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">188<span></span>
</td>
<td class="nump">137<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">(116)<span></span>
</td>
<td class="num">(289)<span></span>
</td>
</tr>
<tr class="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">61,256<span></span>
</td>
<td class="nump">65,103<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">592,770<span></span>
</td>
<td class="nump">657,285<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">393<span></span>
</td>
<td class="nump">825<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">(270)<span></span>
</td>
<td class="num">(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_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">592,893<span></span>
</td>
<td class="nump">657,990<span></span>
</td>
</tr>
<tr class="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">145,922<span></span>
</td>
<td class="nump">149,086<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">373<span></span>
</td>
<td class="nump">124<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">(52)<span></span>
</td>
<td class="num">(476)<span></span>
</td>
</tr>
<tr class="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">146,243<span></span>
</td>
<td class="nump">148,734<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">3,072<span></span>
</td>
<td class="nump">7,516<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">2<span></span>
</td>
<td class="nump">8<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="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_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3,074<span></span>
</td>
<td class="nump">7,524<span></span>
</td>
</tr>
<tr class="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">1,595<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">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_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', 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="text">&#160;<span></span>
</td>
</tr>
<tr class="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">1,596<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=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="nump">698<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="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_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', 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">(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_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">698<span></span>
</td>
<td class="nump">696<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="reu">
<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">41<span></span>
</td>
<td class="nump">26<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">(8,856)<span></span>
</td>
<td class="num">(6,660)<span></span>
</td>
</tr>
<tr class="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">3,082<span></span>
</td>
<td class="nump">5,263<span></span>
</td>
</tr>
<tr class="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">(2,200)<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="reu">
<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">(7,093)<span></span>
</td>
</tr>
<tr class="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">$ 41,023<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 condensed
            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 three months ended&#160;March 31, 2025, we recorded a $2.2 million net unrealized loss
            in our condensed consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies.</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<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</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>
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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: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>
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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_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>
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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: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>
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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_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>
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<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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<td><strong> Period Type:</strong></td>
<td>instant</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_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>
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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>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>
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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>
</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>
</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_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>
</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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</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>
</tr>
<tr>
<td style="padding-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_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent</td>
</tr>
<tr>
<td style="padding-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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<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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<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>
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<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>
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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>
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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;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<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>Mar. 31, 2025 </div>
<div>USD ($) </div>
<div>Investment</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 783,821<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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">22,876<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_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">806,697<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_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">(1,650)<span></span>
</td>
</tr>
<tr class="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">(76)<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">$ (1,726)<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">244<span></span>
</td>
</tr>
<tr class="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">$ 466,130<span></span>
</td>
</tr>
<tr class="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">9,945<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">476,075<span></span>
</td>
</tr>
<tr class="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">(1,236)<span></span>
</td>
</tr>
<tr class="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">(20)<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">$ (1,256)<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">26<span></span>
</td>
</tr>
<tr class="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">$ 45,578<span></span>
</td>
</tr>
<tr class="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">45,578<span></span>
</td>
</tr>
<tr class="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">(148)<span></span>
</td>
</tr>
<tr class="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">$ (148)<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">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_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">$ 271,642<span></span>
</td>
</tr>
<tr class="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">12,931<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">284,573<span></span>
</td>
</tr>
<tr class="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">(266)<span></span>
</td>
</tr>
<tr class="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">(56)<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">$ (322)<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">2<span></span>
</td>
</tr>
<tr class="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">$ 471<span></span>
</td>
</tr>
<tr class="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">471<span></span>
</td>
</tr>
<tr class="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>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_AvailableForSaleSecuritiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
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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>
</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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract</td>
</tr>
<tr>
<td style="padding-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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-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_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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), 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>
</tr>
<tr>
<td style="padding-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>
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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>
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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">
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<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>
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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>
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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">
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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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<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>Mar. 31, 2025</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Mar. 31, 2024</div></th>
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<td class="th" style="border-bottom: 0px;"><sup></sup></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="nump">$ 1,914,911<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 2,056,008<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="nump">$ 44,105<span></span>
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<td class="nump">$ 46,286<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="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>
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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>
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<td class="nump">1.75%<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.75%<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.75%<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_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [Member]</a></td>
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<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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</tr>
<tr class="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>
</tr>
<tr class="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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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">$ 3,082<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 5,263<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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>[1]</sup></td>
<td class="nump">176,876<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">180,445<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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">2,094,869<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2,241,716<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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">988,066<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">1,032,066<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></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>
</tr>
<tr class="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>
</tr>
<tr class="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">34,000<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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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>[3]</sup></td>
<td class="nump">182,341<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">208,998<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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>[3]</sup></td>
<td class="nump">739,136<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">806,724<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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>[3]</sup></td>
<td class="nump">4,670<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">7,524<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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>[3]</sup></td>
<td class="nump">698<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">696<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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>[4]</sup></td>
<td class="nump">3,082<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">5,263<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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></sup></td>
<td class="nump">176,876<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">180,445<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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">919,094<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">992,432<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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">739,136<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">806,724<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</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]</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>
</tr>
<tr class="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>
</tr>
<tr class="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">3,082<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">5,263<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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></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>
</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">1,175,775<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,249,284<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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">559,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">569,300<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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">623,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">612,800<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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">988,066<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,032,066<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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">182,341<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">208,998<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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">4,670<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">7,524<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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>
</tr>
<tr class="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>
</tr>
<tr class="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">698<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">696<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></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] | 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>
</tr>
<tr class="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>
</tr>
<tr class="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">$ 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>
</tr>
<tr><td colspan="6"></td></tr>
<tr><td colspan="6"><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">Included in cash and cash equivalents.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">$34.0 million was included in cash and cash equivalents, with the difference included in short-term investments.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">Included in short-term investments.</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.</td>
</tr>
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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>Fair value portion 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 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 2: 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 (b)<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 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></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>
<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 (b)<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 (a)<br> -Publisher FASB<br> -URI https://asc.fasb.org/1943274/2147482106/820-10-50-2<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">
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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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<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>
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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>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>
<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>
<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember</td>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>56
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
<title></title>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stock-based Compensation Expense (Details) - USD ($)<br> $ / shares in Units, $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2025</div></th>
<th class="th"><div>Mar. 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_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<td class="nump">$ 29,718<span></span>
</td>
<td class="nump">$ 31,340<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">491<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_SharebasedCompensationArrangementBySharebasedPaymentAwardCompensationCost1', window );">Total stock-based compensation expense</a></td>
<td class="nump">30,209<span></span>
</td>
<td class="nump">31,340<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_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>
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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 Expense [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_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense, net of amounts capitalized</a></td>
<td class="nump">100<span></span>
</td>
<td class="nump">204<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_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentExpensesMember', window );">Research, Development and Patent Expense [Member]</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_ShareBasedCompensationAbstract', window );"><strong>Stock-based Compensation Expense [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_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense, net of amounts capitalized</a></td>
<td class="nump">20,298<span></span>
</td>
<td class="nump">22,225<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_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember', window );">Selling, General and Administrative Expense [Member]</a></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 Expense [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_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense, net of amounts capitalized</a></td>
<td class="nump">9,320<span></span>
</td>
<td class="nump">$ 8,911<span></span>
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</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 );">Stock Options [Member]</a></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="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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions', window );">Unrecognized compensation expense related to non-vested stock options</a></td>
<td class="nump">$ 51,900<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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">1 year 3 months 18 days<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_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Stock Options [Member] | Employees [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">4.50%<span></span>
</td>
<td class="nump">4.00%<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">41.90%<span></span>
</td>
<td class="nump">44.00%<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_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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="ro">
<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">4.30%<span></span>
</td>
<td class="nump">5.30%<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">41.30%<span></span>
</td>
<td class="nump">38.40%<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_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">6 months<span></span>
</td>
<td class="text">6 months<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]</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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [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_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested units</a></td>
<td class="nump">$ 117,100<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 9 months 18 days<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_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Employees [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share)</a></td>
<td class="nump">$ 33.21<span></span>
</td>
<td class="nump">$ 53.54<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>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
</tr>
<tr class="re">
<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">$ 17,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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 10 months 24 days<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_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted-average grant date fair value (in dollars per share)</a></td>
<td class="nump">$ 48.81<span></span>
</td>
<td class="nump">$ 78.41<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] | Granted in 2025 [Member] | Executive Officers [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">100.00%<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">3 years<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest', window );">Number of units guaranteed to vest (in shares)</a></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_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Granted in 2025 [Member] | Executive Officers [Member] | Minimum [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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 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>
<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_PerformanceSharesMember', window );">PRSUs [Member] | Granted in 2025 [Member] | Executive Officers [Member] | Maximum [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="nump">200.00%<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_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Granted in 2024 [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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>
<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_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest', window );">Number of units guaranteed to vest (in shares)</a></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_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Granted in 2024 [Member] | Minimum [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></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_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Granted in 2024 [Member] | Maximum [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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract', window );"><strong>RSUs and PRSUs [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 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>
<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_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_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>
</tr>
<tr>
<td style="padding-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_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsCapitalizedAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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>
</tr>
<tr>
<td style="padding-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_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_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_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_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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ShareBasedCompensationArrangementByShareBasedPaymentAwardAdditionalGeneralDisclosuresAbstract</td>
</tr>
<tr>
<td style="padding-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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract</td>
</tr>
<tr>
<td style="padding-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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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>
</tr>
<tr>
<td style="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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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 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>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate</td>
</tr>
<tr>
<td style="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_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<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>
</tr>
<tr>
<td style="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_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>
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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>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>
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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 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>
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<tr>
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<td><strong> Period Type:</strong></td>
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</tr>
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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>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1</td>
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<tr>
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<td>na</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_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember</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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<td><strong> Name:</strong></td>
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<td>na</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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<td><strong> Name:</strong></td>
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<td><strong> Name:</strong></td>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
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<tr>
<th class="th"><div>Mar. 31, 2025</div></th>
<th class="th"><div>Mar. 31, 2024</div></th>
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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_IncomeTaxExpenseBenefit', window );">Income tax (benefit) expense</a></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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<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>
</div>
</body>
</html>
</TEXT>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Liability Related to Sale of Future Royalties (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">3 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2025</div></th>
<th class="th"><div>Mar. 31, 2024</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<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_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_RoyaltyPayments', window );">Royalty payments to Royalty Pharma</a></td>
<td class="num">$ (12,891)<span></span>
</td>
<td class="num">$ (6,623)<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_InterestExpenseRelatedToSaleOfFutureRoyalties', window );">Interest expense related to sale of future royalties</a></td>
<td class="nump">18,670<span></span>
</td>
<td class="nump">$ 17,806<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_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent', window );">Liability related to sale of future royalties, net - Non-current</a></td>
<td class="nump">536,141<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 542,212<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="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_UpfrontRoyaltyPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 500,000<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_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="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 );">Transaction costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,400<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_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="nump">13.50%<span></span>
</td>
<td class="nump">13.50%<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_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Liability related to sale of future royalties, net</a></td>
<td class="nump">$ 542,212<span></span>
</td>
<td class="text">&#160;<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_RoyaltyPayments', window );">Royalty payments to Royalty Pharma</a></td>
<td class="num">(12,891)<span></span>
</td>
<td class="text">&#160;<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_InterestExpenseRelatedToSaleOfFutureRoyalties', window );">Interest expense related to sale of future royalties</a></td>
<td class="nump">18,670<span></span>
</td>
<td class="text">&#160;<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_AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties', window );">Amortization of issuance costs related to sale of future royalties</a></td>
<td class="nump">152<span></span>
</td>
<td class="text">&#160;<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_LiabilityRelatedToSaleOfFutureRoyaltiesNet', window );">Liability related to sale of future royalties, net</a></td>
<td class="nump">548,143<span></span>
</td>
<td class="text">&#160;<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_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent', window );">Liability related to sale of future royalties, net - Non-current</a></td>
<td class="nump">536,141<span></span>
</td>
<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] | Other Current Liabilities [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_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent', window );">Less: Current portion</a></td>
<td class="num">(12,002)<span></span>
</td>
<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] | 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="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] | 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="text">&#160;<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="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] | 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="text">&#160;<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="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] | 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>
</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_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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. Used to reflect the current portion of the liability (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_LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent</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_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</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. Used to reflect the noncurrent portion of the liability (due after one year or beyond the 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_LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent</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>
<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_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>
<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_TypeOfArrangementAxis=ions_RoyaltyPurchaseAgreementMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_RoyaltyPurchaseAgreementMember</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_BalanceSheetLocationAxis=us-gaap_OtherCurrentLiabilitiesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_BalanceSheetLocationAxis=us-gaap_OtherCurrentLiabilitiesMember</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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</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>59
<FILENAME>R47.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Convertible Debt (Details) - USD ($)<br> $ / shares in Units, shares in Millions, $ in Millions</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="2">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2025</div></th>
<th class="th"><div>Dec. 31, 2023</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2024</div></th>
<th class="th"><div>Mar. 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_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_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>
</tr>
<tr class="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="nump">$ 575.0<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_ProceedsFromConvertibleDebt', window );">Proceeds from issuance of convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 532.7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 575.0<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="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">$ 9.3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">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>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.75%<span></span>
</td>
<td class="nump">1.75%<span></span>
</td>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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="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>
</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_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>
</tr>
<tr class="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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_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_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>
</tr>
<tr class="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">$ 632.5<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">319.0<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_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="nump">$ 632.5<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="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">$ 3.2<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_DebtInstrumentMaturityDate', window );">Maturity date</a></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>
</tr>
<tr class="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">0.00%<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>
<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_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></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>
</tr>
<tr class="re">
<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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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_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="text">&#160;<span></span>
</td>
<td class="text">&#160;<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">10.9<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>
</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="nump">46.9<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_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">136.7<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_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="nump">89.8<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_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange', window );">Percentage of principal amount used as purchase price upon occurrence of fundamental change</a></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>
</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>
</tr>
<tr class="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>
</tr>
<tr class="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="nump">$ 309.9<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="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>
</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>
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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>
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<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 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>
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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>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</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_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>
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<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_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>
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<tr>
<td><strong> Data Type:</strong></td>
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<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_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>
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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_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_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_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>
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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>
</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>
</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_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>
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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>
</tr>
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<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>
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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>
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<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>
</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_ConvertibleSeniorNotes1PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" 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_ConvertibleSeniorNotes1PercentMember</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>
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<span style="display: none;">v3.25.1</span><table class="report" border="0" cellspacing="2" id="id2">
<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>
</tr>
<tr>
<th class="th">
<div>Mar. 31, 2025 </div>
<div>USD ($) </div>
<div>Segment</div>
</th>
<th class="th">
<div>Mar. 31, 2024 </div>
<div>USD ($)</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_SegmentReportingInformationProfitLossAbstract', window );"><strong>Segment Information [Abstract]</strong></a></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_NumberOfOperatingSegments', window );">Number of operating segments | Segment</a></td>
<td class="nump">1<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">$ 131,612<span></span>
</td>
<td class="nump">$ 119,497<span></span>
</td>
</tr>
<tr class="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">1,463<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_SellingGeneralAndAdministrativeExpense', window );">Selling, general and administrative</a></td>
<td class="nump">76,250<span></span>
</td>
<td class="nump">52,644<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">(146,938)<span></span>
</td>
<td class="num">(142,803)<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>
</tr>
<tr class="ro">
<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>
</tr>
<tr class="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">131,612<span></span>
</td>
<td class="nump">119,497<span></span>
</td>
</tr>
<tr class="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">1,363<span></span>
</td>
<td class="nump">1,952<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_DrugDiscoveryExpenses', window );">Drug discovery</a></td>
<td class="nump">26,989<span></span>
</td>
<td class="nump">28,171<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_DrugDevelopmentExpenses', window );">Drug development</a></td>
<td class="nump">112,946<span></span>
</td>
<td class="nump">125,751<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_MedicalAffairsExpenses', window );">Medical affairs</a></td>
<td class="nump">5,642<span></span>
</td>
<td class="nump">4,676<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_ManufacturingAndDevelopmentChemistryExpenses', window );">Manufacturing and development chemistry</a></td>
<td class="nump">14,281<span></span>
</td>
<td class="nump">11,441<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_ResearchAndDevelopmentSupportExpenses', window );">R&amp;D support</a></td>
<td class="nump">20,553<span></span>
</td>
<td class="nump">21,946<span></span>
</td>
</tr>
<tr class="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">66,980<span></span>
</td>
<td class="nump">43,733<span></span>
</td>
</tr>
<tr class="re">
<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="nump">29,796<span></span>
</td>
<td class="nump">24,630<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">$ (146,938)<span></span>
</td>
<td class="num">$ (142,803)<span></span>
</td>
</tr>
<tr class="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">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>
</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>
</table></div>
</div></td></tr>
</table>
<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>
</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_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>
<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 );">- 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>
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<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>
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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>
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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>
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1.&#160; Organization and 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; font-weight: bold;"&gt;Organization and Business 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;We incorporated in California on January 10, 1989. In conjunction with our initial public offering, we reorganized as a Delaware
    corporation in April 1991. We are a leader in the discovery and development of RNA-targeted 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; 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;We prepared the unaudited interim condensed consolidated financial statements for the three months ended&#160;March 31, 2025 and 2024 on the same basis as the audited financial statements for the year ended December 31, 2024. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at
    such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these
    financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2024
    included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 condensed 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="display:none;"&gt;&lt;br/&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_716d7f6d27dd450bb3559e4e755739ee"&gt;single&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&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 &lt;span style="-sec-ix-hidden:Fact_95a745ba91854ab0bbf27d495728685c"&gt;single&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;operating segment. Refer to Note 14, &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; 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We prepare our condensed consolidated financial statements in
      conformity with accounting principles generally accepted in the United States, or &lt;/span&gt;U.S., that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying
    notes. Actual results could differ from our estimates.&lt;/div&gt;
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      id="Text_81b8305cf0914dd480c3779bb834c828">
&lt;div style="display:none;"&gt;&lt;br/&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 prepared the unaudited interim condensed consolidated financial statements for the three months ended&#160;March 31, 2025 and 2024 on the same basis as the audited financial statements for the year ended December 31, 2024. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at
    such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these
    financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2024
    included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.&lt;/div&gt;
</us-gaap:BasisOfAccountingPolicyPolicyTextBlock>
    <us-gaap:ConsolidationPolicyTextBlock
      contextRef="c20250101to20250331"
      id="Text_c46fa5d2afe84cef91a6b400d35f4f37">
&lt;div style="display:none;"&gt;&lt;br/&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 condensed 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;
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    <us-gaap:SegmentReportingPolicyPolicyTextBlock
      contextRef="c20250101to20250331"
      id="Text_fa9ff58c52194407aeff743416e5c445">
&lt;div style="display:none;"&gt;&lt;br/&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_716d7f6d27dd450bb3559e4e755739ee"&gt;single&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&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 &lt;span style="-sec-ix-hidden:Fact_95a745ba91854ab0bbf27d495728685c"&gt;single&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;operating segment. Refer to Note 14, &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="c20250101to20250331"
      id="Text_a36e2aeec70b4cda8a724e271f28212e">
&lt;div style="display:none;"&gt;&lt;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;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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We prepare our condensed consolidated financial statements in
      conformity with accounting principles generally accepted in the United States, or &lt;/span&gt;U.S., that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying
    notes. Actual results could differ from our estimates.&lt;/div&gt;
</us-gaap:UseOfEstimates>
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2.&#160; Significant Accounting Policies&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Below, we have included our accounting policies for revenue recognition related to product sales, net and cost of sales as a result of our
    launch of TRYNGOLZA in the U.S. Our other significant accounting policies have not changed substantially from those included in our Annual Report on Form 10-K for the year ended December 31, 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; font-style: italic; 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; font-style: italic;"&gt;Product Sales, Net&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 revenue from product sales when the customer obtains control of our product in the amount of the transaction price, which is
    the amount that reflects the consideration which we expect to receive. We estimate reserves for variable consideration related to applicable discounts, rebates, chargebacks and other allowances included in our agreements with customers, payors and
    other third parties. We include the amount of variable consideration in the transaction price to the extent that it is probable that a significant reversal in the amount of the cumulative revenue recognized will not occur in a future period. If actual
    results vary significantly from our estimates, we adjust our estimates in the period that we become aware of such variances.&lt;/div&gt;

&lt;div&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;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="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cost of sales for a newly launched product, such as TRYNGOLZA, does not include the full cost of manufacturing until we manufacture and
    sell additional inventory after exhausting pre-launch inventory, which we previously recorded as research and development, or R&amp;amp;D, 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: left; text-indent: 36pt; 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 Accounting Standards Codification, or ASC, Topic 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. We adopted the reporting requirements in our 2024 Annual Report on Form 10-K and in this Quarterly Report on Form 10-Q for the first quarter of 2025. Refer to Note 14, &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;We do not expect any recently issued accounting standards other than those included in our Annual Report on Form 10-K for the year ended December 31, 2024 to have a material impact to our financial results.&lt;/div&gt;
</us-gaap:SignificantAccountingPoliciesTextBlock>
    <us-gaap:RevenueFromContractWithCustomerPolicyTextBlock
      contextRef="c20250101to20250331"
      id="Text_26339d82b1a04895824ad3bc299f04e1">
&lt;div style="display:none;"&gt;&lt;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;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; font-style: italic;"&gt;Product Sales, Net&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 revenue from product sales when the customer obtains control of our product in the amount of the transaction price, which is
    the amount that reflects the consideration which we expect to receive. We estimate reserves for variable consideration related to applicable discounts, rebates, chargebacks and other allowances included in our agreements with customers, payors and
    other third parties. We include the amount of variable consideration in the transaction price to the extent that it is probable that a significant reversal in the amount of the cumulative revenue recognized will not occur in a future period. If actual
    results vary significantly from our estimates, we adjust our estimates in the period that we become aware of such variances.&lt;/div&gt;
</us-gaap:RevenueFromContractWithCustomerPolicyTextBlock>
    <us-gaap:CostOfSalesPolicyTextBlock
      contextRef="c20250101to20250331"
      id="Text_902e367e553a482290197e3bdde3f501">
&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;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="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cost of sales for a newly launched product, such as TRYNGOLZA, does not include the full cost of manufacturing until we manufacture and
    sell additional inventory after exhausting pre-launch inventory, which we previously recorded as research and development, or R&amp;amp;D, expense.&lt;/div&gt;
</us-gaap:CostOfSalesPolicyTextBlock>
    <us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock
      contextRef="c20250101to20250331"
      id="Text_77f04263f8fd40e2bb811ff95d88cebe">
&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;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 Accounting Standards Codification, or ASC, Topic 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. We adopted the reporting requirements in our 2024 Annual Report on Form 10-K and in this Quarterly Report on Form 10-Q for the first quarter of 2025. Refer to Note 14, &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;We do not expect any recently issued accounting standards other than those included in our Annual Report on Form 10-K for the year ended December 31, 2024 to have a material impact to our financial results.&lt;/div&gt;
</us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock>
    <us-gaap:SupplementalBalanceSheetDisclosuresTextBlock
      contextRef="c20250101to20250331"
      id="Text_9c86d5826cfc4e50b92f86949d3b9fca">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;3. Supplemental Financial Data&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; margin-left: 36pt; 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 inventories 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; 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; 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;March 31, 2025&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;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: 76%; background-color: #CCEEFF; white-space: nowrap;" 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;Raw materials&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;640&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; white-space: nowrap;" 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%; 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;8,744&lt;/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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" 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; 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;2,118&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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; white-space: nowrap;" 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; 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;11,502&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;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;/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; 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: left; 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; 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; 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;March 31, 2025&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;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: 76%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: justify; 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; 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;67,614&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;&#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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: justify; 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%; 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;7,374&lt;/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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: justify; 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; 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;7,257&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; white-space: nowrap;" 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 miscellaneous expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; 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; 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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,490&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; 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; 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; white-space: nowrap;" 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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" 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 accrued liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="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="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 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; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;102,735&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; 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; 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%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" 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;/tr&gt;


&lt;/table&gt;
</us-gaap:SupplementalBalanceSheetDisclosuresTextBlock>
    <us-gaap:ScheduleOfInventoryCurrentTableTextBlock
      contextRef="c20250101to20250331"
      id="Text_8ca956cffe974ce9a840a246a97aa16c">
&lt;div style="text-align: justify; margin-left: 36pt; 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 inventories 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; 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; 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;March 31, 2025&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;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: 76%; background-color: #CCEEFF; white-space: nowrap;" 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;Raw materials&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;640&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; white-space: nowrap;" 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%; 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;8,744&lt;/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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" 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; 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;2,118&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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; white-space: nowrap;" 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; 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;11,502&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;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;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfInventoryCurrentTableTextBlock>
    <us-gaap:InventoryRawMaterials
      contextRef="c20250331"
      decimals="-3"
      id="Fact_9975fb0b2fa74f9e8ab81ebad8fb2237"
      unitRef="U002">640000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20241231"
      decimals="-3"
      id="Fact_e3f1efde1cdb414796dec720e17eac54"
      unitRef="U002">5557000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20250331"
      decimals="-3"
      id="Fact_e7c4b729eb5c4047a12ddaf1f657b647"
      unitRef="U002">8744000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20241231"
      decimals="-3"
      id="Fact_182d548d120f4e1daae74044c3e1bbe5"
      unitRef="U002">6679000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20250331"
      decimals="-3"
      id="Fact_b21c128f10e14f89b4963ecd92676ea1"
      unitRef="U002">2118000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20241231"
      decimals="-3"
      id="Fact_70a3a016ecb849cd9021230823cf224d"
      unitRef="U002">276000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryNet
      contextRef="c20250331"
      decimals="-3"
      id="Fact_6f6a7ebaae1b4d95ace7fcfcf1fba210"
      unitRef="U002">11502000</us-gaap:InventoryNet>
    <us-gaap:InventoryNet
      contextRef="c20241231"
      decimals="-3"
      id="Fact_3e4c02edf53745679ae7e698216e7837"
      unitRef="U002">12512000</us-gaap:InventoryNet>
    <us-gaap:ScheduleOfAccruedLiabilitiesTableTextBlock
      contextRef="c20250101to20250331"
      id="Text_2a5416376d8f443abf966ca8534832b3">
&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;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: left; 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; 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; 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;March 31, 2025&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;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: 76%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: justify; 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; 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;67,614&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;&#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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: justify; 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%; 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;7,374&lt;/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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: justify; 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; 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;7,257&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; white-space: nowrap;" 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 miscellaneous expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; 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; 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; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,490&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; 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; 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; white-space: nowrap;" 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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" 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 accrued liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="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="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 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; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;102,735&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; 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; 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%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" 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;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfAccruedLiabilitiesTableTextBlock>
    <ions:AccruedClinicalExpenses
      contextRef="c20250331"
      decimals="-3"
      id="Fact_9fa65e9eb4874e529d2b5a8558dbeefc"
      unitRef="U002">67614000</ions:AccruedClinicalExpenses>
    <ions:AccruedClinicalExpenses
      contextRef="c20241231"
      decimals="-3"
      id="Fact_e1554d35bd0e4c82aabac0d765ba6ddc"
      unitRef="U002">77436000</ions:AccruedClinicalExpenses>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20250331"
      decimals="-3"
      id="Fact_c222f622055145968e8cd08ff3a569bd"
      unitRef="U002">7374000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_7076c86dd1604e5a826b9716b8c0ca6e"
      unitRef="U002">7951000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20250331"
      decimals="-3"
      id="Fact_74d1a19cf230440593ea60ac85e2acd3"
      unitRef="U002">7257000</ions:AccruedCommercialExpensesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_0c409149156e4e1bb3090f026e0406df"
      unitRef="U002">3589000</ions:AccruedCommercialExpensesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20250331"
      decimals="-3"
      id="Fact_9ed0b35c739e48bbb51027c4ea2073ae"
      unitRef="U002">20490000</us-gaap:OtherAccruedLiabilitiesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_b95beacb8e88464e9674b3d0a46cdaf4"
      unitRef="U002">19462000</us-gaap:OtherAccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20250331"
      decimals="-3"
      id="Fact_eda2e67f42534d11b5f9b63e05969ad1"
      unitRef="U002">102735000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20241231"
      decimals="-3"
      id="Fact_e41fd559b7f64fab9ce5f7f42569b6db"
      unitRef="U002">108438000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:RevenueFromContractWithCustomerTextBlock
      contextRef="c20250101to20250331"
      id="Text_6b1d63434c574c6a8112cdba1e5b15e3">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;4. 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;During the three months ended March 31, 2025 and 2024, 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; &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;Three Months Ended&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 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;2025&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;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;" 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;/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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" 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;Product sales, net:&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%; 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;TRYNGOLZA sales, net&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;6,287&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;&#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: 76%;" 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;Total product sales, 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;6,287&lt;/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: 76%; 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;Royalty 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;/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: 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,010&lt;/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;38,455&lt;/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: -9pt; 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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,372&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;1,125&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other royalties&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;6,784&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;9,805&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: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total royalty 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;64,166&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;49,385&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 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: 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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,715&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;8,628&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;&#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: -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;" valign="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;1,580&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: 2px; background-color: #CCEEFF;" 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; 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;5,715&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;10,208&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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76,168&lt;/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;59,593&lt;/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: -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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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: 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,031&lt;/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;49,345&lt;/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: 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; 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;10,413&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;10,559&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: 2px;" 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;" valign="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;55,444&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;59,904&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: 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; 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;131,612&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;119,497&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; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Revenue Sources&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 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: justify; 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;In December 2024, the U.S. Food and Drug Administration, or FDA, approved TRYNGOLZA (olezarsen) for the treatment of familial
    chylomicronemia syndrome, or FCS. Following the approval, we launched TRYNGOLZA and began earning revenue from TRYNGOLZA sales. We recognize product sales, net of variable considerations related to applicable discounts and allowances, when the customer
    obtains control of our product.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 earn royalty payments primarily on net sales of SPINRAZA, WAINUA and 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;We earn commercial revenue from TEGSEDI and WAYLIVRA sales under our distribution agreements with Swedish Orphan Biovitrum AB, or Sobi. In
    addition, we receive royalties from PTC Therapeutics International Limited, or PTC, for TEGSEDI and WAYLIVRA sales. Refer to Part IV, Item 15, 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;, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 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; 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 that may involve 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;&lt;/span&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;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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;&lt;/span&gt; We
    consider milestone payments to be variable consideration and include them 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;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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;&lt;/span&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;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;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.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 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, 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 Topic 606, &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;, or 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 selling, general and administrative, or 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: justify; 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 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="c20250101to20250331"
      id="Text_f2e15c2700584bae9782b0e80d3a26fc">
&lt;div style="display:none;"&gt;&lt;br/&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 three months ended March 31, 2025 and 2024, 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; &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;Three Months Ended&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 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;2025&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;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;" 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;/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;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" 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;Product sales, net:&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%; 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;TRYNGOLZA sales, net&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;6,287&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;&#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: 76%;" 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;Total product sales, 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;6,287&lt;/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: 76%; 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;Royalty 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;/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: 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,010&lt;/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;38,455&lt;/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: -9pt; 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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,372&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;1,125&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other royalties&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;6,784&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;9,805&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: left; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total royalty 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;64,166&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;49,385&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: -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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 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: 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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,715&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;8,628&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;&#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: -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;" valign="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;1,580&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: 2px; background-color: #CCEEFF;" 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; 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;5,715&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;10,208&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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76,168&lt;/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;59,593&lt;/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: -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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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: 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,031&lt;/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;49,345&lt;/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: 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; 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;10,413&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;10,559&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: 2px;" 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;" valign="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;55,444&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;59,904&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: 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; 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;131,612&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;119,497&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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    <ions:UpfrontPaymentReceived
      contextRef="c20210101to20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember"
      decimals="-6"
      id="Fact_183ad00f1c244f45887d306ae2c90532"
      unitRef="U002">200000000</ions:UpfrontPaymentReceived>
    <ions:NumberOfMaterialComponents
      contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember"
      decimals="INF"
      id="Fact_784abf7441294980aecea5f51a0b2271"
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      contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember"
      decimals="INF"
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    <ions:RevenueFromContractWithCustomerTransactionPrice
      contextRef="c20211231_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember"
      decimals="-6"
      id="Fact_213c3fa8f5f94eada5849b6952e3bf1d"
      unitRef="U002">200000000</ions:RevenueFromContractWithCustomerTransactionPrice>
    <ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner
      contextRef="c20250101to20250331_TypeOfArrangementAxis_AstraZenecaCollaborationWainuaMember"
      decimals="2"
      id="Fact_2a080dd76c62479d99491c48185ab4bd"
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      id="Text_80736ca15cff42788a97f47831eeb088">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;5.&#160; Collaborative Arrangements and Licensing 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Below, we have included our Ono collaboration, which is the
      only collaboration that had either substantive changes or was new from those included in Part IV, Item 15, Note 4, &lt;/span&gt;&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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024.&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; font-weight: bold;"&gt;Ono&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 March 2025, we entered into an agreement with Ono Pharmaceutical, Ltd, or Ono, to develop and commercialize sapablursen, an
    investigational RNA-targeted medicine for the potential treatment of polycythemia vera, or PV, a rare and potentially life-threatening hematologic disease. We are responsible for completing the ongoing Phase 2 IMPRSSION study, while Ono will be solely
    responsible for subsequent development, regulatory filings and commercialization of sapablursen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 our sapablursen collaboration, we are eligible to receive up to $940 million, which is comprised of a $280 million upfront payment and up
    to $660 million in development, regulatory and sales milestone payments. In addition, we are eligible to receive royalties in the mid-teen
    percentage range on net 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;In April 2025, we achieved a $280
    million upfront payment when this transaction received clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, or HSR Act.&lt;/div&gt;
</us-gaap:CollaborativeArrangementDisclosureTextBlock>
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      contextRef="c20250331_TypeOfArrangementAxis_OnoCollaborationMember"
      decimals="-6"
      id="Fact_aede8b9ef220439980fe3002bfb04d1c"
      unitRef="U002">940000000</ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration>
    <ions:MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration
      contextRef="c20250331_TypeOfArrangementAxis_OnoCollaborationMember"
      decimals="-6"
      id="Fact_cf4f7782dc2e4bd1bbf88508bc23dd48"
      unitRef="U002">280000000</ions:MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration>
    <ions:MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration
      contextRef="c20250331_TypeOfArrangementAxis_OnoCollaborationMember"
      decimals="-6"
      id="Fact_68281c2f896147ed83de58ec367ded6b"
      unitRef="U002">660000000</ions:MaximumAmountOfDevelopmentRegulatoryAndSalesMilestonePaymentsOverTermOfCollaboration>
    <ions:UpfrontPaymentAchieved
      contextRef="c20250401to20250430_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_OnoCollaborationMember"
      decimals="-6"
      id="Fact_c07cd0091879446c949a49812609acb6"
      unitRef="U002">280000000</ions:UpfrontPaymentAchieved>
    <us-gaap:EarningsPerShareTextBlock
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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. 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-weight: bold;"&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 calculated our basic net loss per share for the three months ended&#160;March 31, 2025 and 2024 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&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 three months ended&#160;March 31, 2025 and 2024, 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: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.75 percent convertible senior notes, or 1.75% Notes;&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: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent convertible senior notes, or 0% Notes;&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: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Note hedges related to the 0% Notes;&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: left;"&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: left;"&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: left;"&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: left;"&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 three months ended&#160;March 31, 2024, common stock underlying the 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;, and n&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;ote 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;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;Additionally, as of March 31, 2025
    and 2024, we had warrants related to our 0%
    and 0.125% Notes outstanding. 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;/div&gt;
</us-gaap:EarningsPerShareTextBlock>
    <us-gaap:EarningsPerSharePolicyTextBlock
      contextRef="c20250101to20250331"
      id="Text_9471c38bb7ae4e1287d0671ecea462a6">
&lt;div style="display:none;"&gt;&lt;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;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 calculated our basic net loss per share for the three months ended&#160;March 31, 2025 and 2024 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&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 three months ended&#160;March 31, 2025 and 2024, 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: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.75 percent convertible senior notes, or 1.75% Notes;&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: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent convertible senior notes, or 0% Notes;&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: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Note hedges related to the 0% Notes;&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: left;"&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: left;"&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: left;"&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: left;"&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 three months ended&#160;March 31, 2024, common stock underlying the 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;, and n&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;ote 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;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;Additionally, as of March 31, 2025
    and 2024, we had warrants related to our 0%
    and 0.125% Notes outstanding. 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;/div&gt;
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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    <us-gaap:InvestmentTextBlock
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      id="Text_9c14342eb23f428ab65b1e5fc1fe2953">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;7.&#160; 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 March 31, 2025:&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: left; 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;67&lt;/div&gt;
        &lt;/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%;" 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;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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27&lt;/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; 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_f12cc57cfa544d218ac6c26f9aae5797"&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;6&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;
          &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; 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;" 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;100&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;
          &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 March 31, 2025,
    94 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 debt 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;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We invest in debt securities&lt;/span&gt; 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;At March 31, 2025, we had an
    equity ownership interest of less than 20 percent in seven private companies and three public companies with which we conduct business.&lt;/div&gt;

&lt;div&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;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; text-indent: 6.5pt;"&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; padding-bottom: 2px;" 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; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;March 31, 2025&lt;/span&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="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;&lt;span style="text-decoration: underline;"&gt;Available-for-sale debt securities:&lt;/span&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;&#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;516,458&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;299&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(247&lt;/div&gt;
        &lt;/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;516,510&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,961&lt;/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;156&lt;/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;(32&lt;/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;121,085&lt;/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: 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;592,770&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;393&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(270&lt;/div&gt;
        &lt;/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;592,893&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;" 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;" valign="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;3,072&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;2&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;3,074&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: 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;Total debt 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;1,233,261&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;850&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;(549&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;1,233,562&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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;471,479&lt;/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;1,086&lt;/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;(1,009&lt;/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;471,556&lt;/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: 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;61,184&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;188&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(116&lt;/div&gt;
        &lt;/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;61,256&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;145,922&lt;/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;373&lt;/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&lt;/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;146,243&lt;/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: 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 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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,595&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;1,596&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;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" 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&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;698&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;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;698&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: 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;Total debt 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: #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;680,878&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;1,648&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;(1,177&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;681,349&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;" 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 debt securities&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,914,139&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,498&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,726&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,914,911&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: 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;&lt;span style="text-decoration: underline;"&gt;Equity securities:&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;&#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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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: 52%;" 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%;" 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;11,897&lt;/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;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;td colspan="1" style="vertical-align: bottom; width: 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;(8,856&lt;/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;3,082&lt;/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: 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;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: #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;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: #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;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: #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;(7,093&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;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: #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;" 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 equity securities&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;35,012&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;25,042&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;(15,949&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;44,105&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: 52%; padding-bottom: 4px; 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 debt and equity securities&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;1,949,151&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;27,540&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;(17,675&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;1,959,016&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;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; text-indent: 6.5pt;"&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; padding-bottom: 2px;" 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; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;December 31, 2024&lt;/span&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="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;&lt;span style="text-decoration: underline;"&gt;Available-for-sale debt securities:&lt;/span&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;&#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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; 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;287&lt;/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;(39&lt;/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;143,895&lt;/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: 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;" 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;" valign="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;7,516&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&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;7,524&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: 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;Total debt 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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; 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;723&lt;/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;(2,275&lt;/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;438,009&lt;/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: 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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; 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&lt;/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;(476&lt;/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;148,734&lt;/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: 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;" 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 debt 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;" valign="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;654,600&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;984&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;(3,042&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;652,542&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: 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 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;
          &lt;div style="font-family: 'Times New Roman', Times, 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%;" 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;&lt;span style="text-decoration: underline;"&gt;Equity securities:&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;&#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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 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: 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;" 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;" valign="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;23,115&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;25,001&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;(7,093&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;41,023&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: 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;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;&#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;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;&#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;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;&#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;(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;&#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;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;" 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 debt and equity securities&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;2,091,870&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;27,618&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;(17,194&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;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; 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="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 condensed
            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 three months ended&#160;March 31, 2025, we recorded a $2.2 million net unrealized loss
            in our condensed consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies.&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&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&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;The following is a summary of our investments we consider to be temporarily impaired at March 31, 2025 (in thousands, except for number of investments):&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;&#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; 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;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;" 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;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; 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;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; 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;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; 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;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; 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;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; 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;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;" 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;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;244&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;466,130&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(1,236&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;
          &lt;div style="font-family: 'Times 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;9,945&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(20&lt;/div&gt;
        &lt;/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;476,075&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(1,256&lt;/div&gt;
        &lt;/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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;&#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;45,578&lt;/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;(148&lt;/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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;45,578&lt;/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;(148&lt;/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;" 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;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;271,642&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(266&lt;/div&gt;
        &lt;/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;12,931&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(56&lt;/div&gt;
        &lt;/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;284,573&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(322&lt;/div&gt;
        &lt;/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%; padding-bottom: 2px;" 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;" valign="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;2&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;471&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;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;471&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: 16%; 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 temporarily impaired securities&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;312&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;783,821&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;(1,650&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;22,876&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;(76&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;806,697&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;(1,726&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;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="c20250101to20250331"
      id="Text_0fd547c923744c79bd4f06c68a515bf2">
&lt;div style="display:none;"&gt;&lt;br/&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 March 31, 2025:&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: left; 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;67&lt;/div&gt;
        &lt;/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%;" 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;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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27&lt;/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; 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_f12cc57cfa544d218ac6c26f9aae5797"&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;6&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;
          &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; 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;" 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;100&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;
          &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:InvestmentsClassifiedByContractualMaturityDateTableTextBlock>
    <ions:MaximumContractMaturityPeriodRange1
      contextRef="c20250101to20250331"
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    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage
      contextRef="c20250331"
      decimals="2"
      id="Fact_26a36804df4340729bec0b2f463acda4"
      unitRef="U003">0.67</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage>
    <ions:MaximumContractMaturityPeriodRange1
      contextRef="c20250101to20250331"
      id="Fact_3bd993e525784a5398b297b7856fe228">P1Y</ions:MaximumContractMaturityPeriodRange1>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20250101to20250331"
      id="Fact_beb1ea76eb4a4045aff26b90fc4a4ee3">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage
      contextRef="c20250331"
      decimals="2"
      id="Fact_b3c2ee50dd694d208197df43360458a9"
      unitRef="U003">0.27</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20250101to20250331"
      id="Fact_812c571149d64b329fe4410606d76c7a">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage
      contextRef="c20250331"
      decimals="2"
      id="Fact_8cd01e7f5688446294ec6f1b2d7e38df"
      unitRef="U003">0.06</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage
      contextRef="c20250331"
      decimals="2"
      id="Fact_6217a171f5784696968b178278e97ffa"
      unitRef="U003">1</ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage
      contextRef="c20250331"
      decimals="2"
      id="Fact_ecfa1cb8a4484b48a192e8436b1431fe"
      unitRef="U003">0.94</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20250101to20250331"
      id="Fact_34c87d75876e42c988ffebc06f56b6a3">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20250331"
      decimals="INF"
      id="Fact_b7edbc55e46842cb916a4ced56279788"
      unitRef="U008">7</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20250331"
      decimals="INF"
      id="Fact_8144a98eb4174391a5f3065f3f804da4"
      unitRef="U008">3</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock
      contextRef="c20250101to20250331"
      id="Text_6d9fa3e82c0142dbb746fb5a3a6dc3c0">
&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;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; text-indent: 6.5pt;"&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; padding-bottom: 2px;" 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; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;March 31, 2025&lt;/span&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="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;&lt;span style="text-decoration: underline;"&gt;Available-for-sale debt securities:&lt;/span&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;&#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;516,458&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;299&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(247&lt;/div&gt;
        &lt;/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;516,510&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,961&lt;/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;156&lt;/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;(32&lt;/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;121,085&lt;/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: 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;592,770&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;393&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(270&lt;/div&gt;
        &lt;/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;592,893&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;" 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;" valign="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;3,072&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;2&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;3,074&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: 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;Total debt 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;1,233,261&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;850&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;(549&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;1,233,562&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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;471,479&lt;/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;1,086&lt;/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;(1,009&lt;/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;471,556&lt;/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: 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;61,184&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;188&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(116&lt;/div&gt;
        &lt;/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;61,256&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;145,922&lt;/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;373&lt;/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&lt;/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;146,243&lt;/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: 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 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%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,595&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;1,596&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;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px;" 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&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;698&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;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;698&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: 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;Total debt 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: #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;680,878&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;1,648&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;(1,177&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;681,349&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;" 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 debt securities&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,914,139&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,498&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,726&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;
          &lt;div style="font-family: 'Times New Roman', Times, 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;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,914,911&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: 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;&lt;span style="text-decoration: underline;"&gt;Equity securities:&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;&#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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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: 52%;" 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%;" 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;11,897&lt;/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;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;td colspan="1" style="vertical-align: bottom; width: 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;(8,856&lt;/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;3,082&lt;/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: 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;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: #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;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: #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;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: #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;(7,093&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #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;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: #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;" 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 equity securities&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;35,012&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;25,042&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;(15,949&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;44,105&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: 52%; padding-bottom: 4px; 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 debt and equity securities&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;1,949,151&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;27,540&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;(17,675&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;1,959,016&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;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; text-indent: 6.5pt;"&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; padding-bottom: 2px;" 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; font-weight: bold;"&gt;&lt;span style="text-indent: 0pt;"&gt;December 31, 2024&lt;/span&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="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;&lt;span style="text-decoration: underline;"&gt;Available-for-sale debt securities:&lt;/span&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;&#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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; 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;287&lt;/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;(39&lt;/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;143,895&lt;/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: 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;" 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;" valign="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;7,516&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&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;7,524&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: 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;Total debt 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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; 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;723&lt;/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;(2,275&lt;/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;438,009&lt;/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: 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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" 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%; 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&lt;/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;(476&lt;/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;148,734&lt;/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: 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;" 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 debt 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;" valign="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;654,600&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;984&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;(3,042&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;652,542&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: 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 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;
          &lt;div style="font-family: 'Times New Roman', Times, 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%;" 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;&lt;span style="text-decoration: underline;"&gt;Equity securities:&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;&#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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 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: 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;" 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;" valign="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;23,115&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;25,001&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;(7,093&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;41,023&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: 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;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;&#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;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;&#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;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;&#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;(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;&#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;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;" 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 debt and equity securities&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;2,091,870&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;27,618&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;(17,194&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;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; 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="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 condensed
            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 three months ended&#160;March 31, 2025, we recorded a $2.2 million net unrealized loss
            in our condensed consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies.&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&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&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;The following is a summary of our investments we consider to be temporarily impaired at March 31, 2025 (in thousands, except for number of investments):&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;&#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; 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;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;" 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;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; 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;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; 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;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; 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;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; 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;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; 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;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;" 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;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;244&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;466,130&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(1,236&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;
          &lt;div style="font-family: 'Times 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;9,945&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(20&lt;/div&gt;
        &lt;/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;476,075&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(1,256&lt;/div&gt;
        &lt;/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%;" 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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;&#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;45,578&lt;/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;(148&lt;/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;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;45,578&lt;/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;(148&lt;/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;" 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;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;271,642&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(266&lt;/div&gt;
        &lt;/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;12,931&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(56&lt;/div&gt;
        &lt;/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;284,573&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;(322&lt;/div&gt;
        &lt;/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%; padding-bottom: 2px;" 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;" valign="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;2&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;471&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;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;471&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: 16%; 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 temporarily impaired securities&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;312&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;783,821&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;(1,650&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;22,876&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;(76&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;806,697&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;(1,726&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;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;8.&#160; 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 March 31, 2025 and December 31, 2024 that we regularly measure and
    carry at fair value. 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 security&#x2019;s 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;March 31, 2025&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: left; 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;176,876&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;176,876&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;988,066&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;988,066&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: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,341&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;182,341&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;Debt securities issued by the U.S. Treasury (3)&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;739,136&lt;/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;739,136&lt;/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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,670&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;4,670&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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 (3)&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;698&lt;/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;698&lt;/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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (4)&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;3,082&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;3,082&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;2,094,869&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;919,094&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;1,175,775&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; &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: left; 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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (3)&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: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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: 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 (3)&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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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 (3)&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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (4)&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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following footnotes reference lines in our condensed consolidated balance sheets:&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;(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.&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;$34.0 million was included in cash and cash equivalents, with the difference included in short-term investments.&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 short-term investments.&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;Included in other current assets.&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 $559.0 million and $623.0 million at March 31, 2025, respectively.
    Our 1.75% Notes and 0% Notes had a
    fair value of $569.3 million and $612.8
    million at December 31, 2024, 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="c20250101to20250331"
      id="Text_dacb41a94cdc47da8a6cb9b4a90da3e1">
&lt;div style="display:none;"&gt;&lt;br/&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 March 31, 2025 and December 31, 2024 that we regularly measure and
    carry at fair value. 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 security&#x2019;s 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;March 31, 2025&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: left; 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;176,876&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;176,876&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;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;988,066&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;988,066&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: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,341&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;182,341&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;Debt securities issued by the U.S. Treasury (3)&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;739,136&lt;/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;739,136&lt;/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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,670&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;4,670&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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 (3)&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;698&lt;/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;698&lt;/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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (4)&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;3,082&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;3,082&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;2,094,869&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;919,094&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;1,175,775&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; &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: left; 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: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (3)&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: left; text-indent: -9pt; margin-right: 6pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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: 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 (3)&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 (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-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 (3)&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: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (4)&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;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following footnotes reference lines in our condensed consolidated balance sheets:&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;(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.&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;$34.0 million was included in cash and cash equivalents, with the difference included in short-term investments.&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 short-term investments.&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;Included in other current assets.&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;9. 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;The following table summarizes stock-based compensation expense for the three months ended&#160;March 31, 2025 and 2024 (in thousands):&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;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;Three Months Ended&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 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;2025&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;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: 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;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;100&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;204&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;Research, development and patent expense&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;20,298&lt;/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;22,225&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: 76%; 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;Selling, general and administrative 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;9,320&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;8,911&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: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; 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%; 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;29,718&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;31,340&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: 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;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;491&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: 76%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; 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;30,209&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;31,340&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;As of March 31, 2025, total
    unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $51.9 million, $117.1 million and $17.8 million, respectively.
    Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures, including any PRSUs that do not vest. We expect to recognize the cost of stock-based compensation
    expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.3 years, 1.8 years and 1.9 years, 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;Refer to Part IV, Item 15, 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;, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 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 three months ended&#160;March 31, 2025 and 2024, 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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Options:&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;Three Months Ended&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 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;2025&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;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: 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;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;4.0&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: 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;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;/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;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;41.9&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;44.0&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;" 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;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;/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;ESPP:&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;Three Months Ended&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 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;2025&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;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: 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;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;4.3&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;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;/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;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;/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;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;41.3&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;38.4&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;" 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;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;/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; font-style: italic;"&gt;RSUs:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 grant date fair value of RSUs granted to employees for the three months ended&#160;March 31, 2025 and 2024 was $33.21 and $53.54 per share, 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;PRSUs:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 2025 and 2024, 100 percent of the PRSUs may vest at the end of the three-year performance period based on our relative
    total shareholder return, or 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;The weighted-average grant date fair value of PRSUs we granted to our executive officers for the three months ended&#160;March 31, 2025 and 2024 was $48.81 and $78.41 per share, respectively.&lt;/div&gt;
</us-gaap:DisclosureOfCompensationRelatedCostsShareBasedPaymentsTextBlock>
    <us-gaap:ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock
      contextRef="c20250101to20250331"
      id="Text_41bb03e5346543ff85da32e114653473">
&lt;div style="display:none;"&gt;&lt;br/&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 three months ended&#160;March 31, 2025 and 2024 (in thousands):&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;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;Three Months Ended&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 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;2025&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;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: 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;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;100&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;204&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;Research, development and patent expense&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;20,298&lt;/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;22,225&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: 76%; 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;Selling, general and administrative 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;9,320&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;8,911&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: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; 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%; 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;29,718&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;31,340&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: 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;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;491&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: 76%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; 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;30,209&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;31,340&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: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Options:&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;Three Months Ended&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 31,&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; 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;2025&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;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: 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;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;4.0&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: 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;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;/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;Volatility&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41.9&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;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;44.0&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;" 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;Expected life&lt;/div&gt;
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    &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;
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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;ESPP:&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;
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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 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;2025&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;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: 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;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;4.3&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;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;/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;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;/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;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;41.3&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;38.4&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;" 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;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;/tr&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; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;10.&#160; 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 recorded income tax expense of $0.1
    million for the three months ended March 31, 2025 compared to $0.1 million for the same period in 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;We continue to maintain a full valuation allowance on all of our net deferred tax assets.&lt;/div&gt;
</us-gaap:IncomeTaxDisclosureTextBlock>
    <us-gaap:IncomeTaxExpenseBenefit
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    <us-gaap:IncomeTaxExpenseBenefit
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;11. 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 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. 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, our medicine in
    development to treat patients with elevated lipoprotein(a)-driven cardiovascular disease. 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;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 March 31, 2025 and 2024, the estimated effective interest rate under the agreement was 13.5 percent.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&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 our liability related to sale of future royalties (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: 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;Liability related to sale of future royalties, net as of December 31, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;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;/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;Royalty payments to Royalty Pharma&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;(12,891&lt;/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;Interest expense 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;18,670&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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%; padding-bottom: 2px;" 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;" valign="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;152&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: 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;Liability related to sale of future royalties, net as of March 31, 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;548,143&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Current portion (1)&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;(12,002&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: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Liability related to sale of future royalties, net as of March 31, 2025 &#x2013; Non-current&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;536,141&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;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 other current liabilities in our condensed consolidated balance sheet.&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;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:OtherLiabilitiesDisclosureTextBlock>
    <ions:UpfrontRoyaltyPaymentReceived
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-6"
      id="Fact_378c023c31584e55b0617bdf49309947"
      unitRef="U002">500000000</ions:UpfrontRoyaltyPaymentReceived>
    <ions:MaximumAmountOfPaymentsReceivableForAdditionalMilestones
      contextRef="c20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-6"
      id="Fact_45c4a4d71b5f46aa8fc6a9fd8e84328e"
      unitRef="U002">625000000</ions:MaximumAmountOfPaymentsReceivableForAdditionalMilestones>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20250331_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="2"
      id="Fact_01f145be530749a2b5f41c92469f3150"
      unitRef="U003">0.25</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20250331_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="2"
      id="Fact_4defe32cd3804cbb97e4c7a2e3a297be"
      unitRef="U003">0.45</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid
      contextRef="c20250331_ProductOrServiceAxis_SpinrazaMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-8"
      id="Fact_4af0123d3f9a49d28566cdb7b703162e"
      unitRef="U002">1500000000</ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid>
    <ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine
      contextRef="c20250331_ProductOrServiceAxis_PelacarsenMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="2"
      id="Fact_5ab159c91cd6498eabdc7aec74f5b116"
      unitRef="U003">0.25</ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine>
    <ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack
      contextRef="c20250331_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-6"
      id="Fact_8efbfdbd4aec4c57ba48a38ed1338a40"
      unitRef="U002">475000000</ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack>
    <ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack
      contextRef="c20250331_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-6"
      id="Fact_d8115145c7914c85b8aa1e8af6fd697a"
      unitRef="U002">550000000</ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack>
    <ions:UpfrontRoyaltyPaymentReceived
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-6"
      id="Fact_9289646b66ea4d879d32f2749df14834"
      unitRef="U002">500000000</ions:UpfrontRoyaltyPaymentReceived>
    <ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties
      contextRef="c20230101to20231231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-5"
      id="Fact_8a6642fa98914052a22927c1568c95ba"
      unitRef="U002">10400000</ions:PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20240331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="3"
      id="Fact_c5aa7e1147f648338034fbac9b150014"
      unitRef="U003">0.135</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="3"
      id="Fact_b086ad26f3df4c96a5fb5a381fd3f7e6"
      unitRef="U003">0.135</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:OtherNoncurrentLiabilitiesTableTextBlock
      contextRef="c20250101to20250331"
      id="Text_96e6cdff125b48ec820d34ebadba6671">
&lt;div style="display:none;"&gt;&lt;br/&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 our liability related to sale of future royalties (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: 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;Liability related to sale of future royalties, net as of December 31, 2024&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;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;/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;Royalty payments to Royalty Pharma&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;(12,891&lt;/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;Interest expense 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;18,670&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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%; padding-bottom: 2px;" 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;" valign="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;152&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: 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;Liability related to sale of future royalties, net as of March 31, 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;548,143&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Current portion (1)&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;(12,002&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: top; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Liability related to sale of future royalties, net as of March 31, 2025 &#x2013; Non-current&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;536,141&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;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 other current liabilities in our condensed consolidated balance sheet.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:OtherNoncurrentLiabilitiesTableTextBlock>
    <ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet
      contextRef="c20241231_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_3b7b9d43c6f54a7cacb07fc1a05bb2bc"
      unitRef="U002">542212000</ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet>
    <ions:RoyaltyPayments
      contextRef="c20250101to20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_e9a3ca9fe5b04711b74d0c6a76dde538"
      unitRef="U002">12891000</ions:RoyaltyPayments>
    <ions:InterestExpenseRelatedToSaleOfFutureRoyalties
      contextRef="c20250101to20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_002685b59715478a910f724de61959f1"
      unitRef="U002">18670000</ions:InterestExpenseRelatedToSaleOfFutureRoyalties>
    <ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties
      contextRef="c20250101to20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_619a93a9c8f0480e8113fad674ced5d5"
      unitRef="U002">152000</ions:AmortizationOfIssuanceCostsRelatedToSaleOfFutureRoyalties>
    <ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet
      contextRef="c20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_10d08d4e6c8642349705c72c81e29f3f"
      unitRef="U002">548143000</ions:LiabilityRelatedToSaleOfFutureRoyaltiesNet>
    <ions:LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent
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      id="Fact_b01b2bb503094ea89f3b958f84f5facb"
      unitRef="U002">12002000</ions:LiabilityRelatedToSaleOfFutureRoyaltiesNetCurrent>
    <ions:LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent
      contextRef="c20250331_TypeOfArrangementAxis_RoyaltyPurchaseAgreementMember"
      decimals="-3"
      id="Fact_a207a7fc31024c369b958802e4a63152"
      unitRef="U002">536141000</ions:LiabilityRelatedToSaleOfFutureRoyaltiesNetNoncurrent>
    <us-gaap:DebtDisclosureTextBlock
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      id="Text_932c025cb1a047c69adb81a74fc1d444">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;12. 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; 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 1.75% Notes. We used $532.7
    million of the net proceeds from the issuance of our 1.75% Notes to repurchase and settle our 0.125% Notes, which matured 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;At March 31, 2025, 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;" 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;9.3&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;/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_ac460e99cb6b43a8b64e987880ed0dd5"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.75&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;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.3&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="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: 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 percent 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 March 31, 2025, we had the following &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; 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;3.2&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;&#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_edbb9fb31e834f86ad026d22e567df04"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;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;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&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 &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes by increasing the effective conversion price on our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes. We increased our effective conversion price to $76.39
    with the same number of underlying shares as our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&#160;&lt;/span&gt;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 &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes, our note hedges are subject to adjustment. Additionally, our note hedges
    are exercisable upon conversion of the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes. The note
    hedges will expire upon maturity of the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes, or April
    2026. The warrants will expire in July 2026. The note hedges and warrants are separate transactions and are not part of the terms of our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; Notes. The holders of the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; 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
    condensed consolidated balance sheets. Refer to Part IV, Item 15, 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;, of our audited
    financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2024 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.&lt;/div&gt;
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      decimals="-5"
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      unitRef="U002">575000000</us-gaap:DebtInstrumentFaceAmount>
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      decimals="4"
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      id="Fact_fa4be4826d1d4393908c609847f7c435"
      unitRef="U002">532700000</us-gaap:ProceedsFromConvertibleDebt>
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      decimals="4"
      id="Fact_406d1a1bdf0b4ba1876e7c87768507dd"
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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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 March 31, 2025, 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;" 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;9.3&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;/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_ac460e99cb6b43a8b64e987880ed0dd5"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.75&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;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.3&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;
</us-gaap:ConvertibleDebtTableTextBlock>
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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    <us-gaap:DebtInstrumentConvertibleConversionPrice1
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      id="Fact_2508d5a342a249ecbe2d658f907d3a63"
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      id="Fact_bfa13a09b4f34edabb1b3a7da10b5d07"
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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      decimals="2"
      id="Fact_0e3676949d7c473e97d1d20974f8f44c"
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    <us-gaap:DebtInstrumentFaceAmount
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      decimals="-5"
      id="Fact_a0fd38d74d5c4c09be72aabda7cb2eb5"
      unitRef="U002">632500000</us-gaap:DebtInstrumentFaceAmount>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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      decimals="2"
      id="Fact_730f32942afb4ec58a0cc90a7aa04c99"
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      decimals="-5"
      id="Fact_670c4c4c9cce4c0a8be8b9ce9abe0221"
      unitRef="U002">319000000</us-gaap:ProceedsFromConvertibleDebt>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20250331_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_3466ffd4d4504e1188d0a2b60f294e3c"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:RepaymentsOfConvertibleDebt
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      decimals="-5"
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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      decimals="2"
      id="Fact_0e2006b11da549a3947b9eee3f6cd658"
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    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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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 March 31, 2025, we had the following &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;0%&lt;/span&gt; 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;3.2&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;&#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_edbb9fb31e834f86ad026d22e567df04"&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%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-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;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;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&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;


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    <us-gaap:LegalMattersAndContingenciesTextBlock
      contextRef="c20250101to20250331"
      id="Text_00889d79158c44ab9838be43f7bac562">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;13. 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
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      id="Text_9ea036e338a640e59d659142a871586e">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;14. 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_92f78800150c4bacb3c7033e970a29cb"&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 4, &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="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;Three Months Ended&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 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;2025&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;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: 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&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;131,612&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;119,497&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;&#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: 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;/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: 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;1,363&lt;/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;1,952&lt;/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: -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;26,989&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;28,171&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;112,946&lt;/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;125,751&lt;/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: -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;5,642&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;4,676&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;14,281&lt;/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;11,441&lt;/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: -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;20,553&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;21,946&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;66,980&lt;/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;43,733&lt;/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: 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;29,796&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;24,630&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%;" 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%; 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;(146,938&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;(142,803&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.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:SegmentReportingDisclosureTextBlock>
    <us-gaap:ScheduleOfSegmentReportingInformationBySegmentTextBlock
      contextRef="c20250101to20250331"
      id="Text_b9368ab18c7746ac921c27dcc09b3aaf">
&lt;div style="display:none;"&gt;&lt;br/&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="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;Three Months Ended&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;March 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;2025&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;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: 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&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&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;131,612&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;119,497&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;&#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: 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;/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: 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;1,363&lt;/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;1,952&lt;/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: -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;26,989&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;28,171&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;112,946&lt;/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;125,751&lt;/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: -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;5,642&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;4,676&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;14,281&lt;/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;11,441&lt;/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: -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;20,553&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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;21,946&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="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: 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;66,980&lt;/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;43,733&lt;/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: 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;29,796&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;24,630&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%;" 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%; 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;(146,938&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;

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