<SEC-DOCUMENT>0001140361-20-017841.txt : 20200826
<SEC-HEADER>0001140361-20-017841.hdr.sgml : 20200826
<ACCEPTANCE-DATETIME>20200807175032
ACCESSION NUMBER:		0001140361-20-017841
CONFORMED SUBMISSION TYPE:	S-8
PUBLIC DOCUMENT COUNT:		5
FILED AS OF DATE:		20200807
DATE AS OF CHANGE:		20200807
EFFECTIVENESS DATE:		20200810

FILER:

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

	FILING VALUES:
		FORM TYPE:		S-8
		SEC ACT:		1933 Act
		SEC FILE NUMBER:	333-242386
		FILM NUMBER:		201085677

	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>S-8
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<FILENAME>nt10014191x2_s8.htm
<DESCRIPTION>S-8
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        <div style="font-weight: bold;">As filed with the Securities and Exchange Commission on August 7, 2020</div>
        <div style="text-align: right; font-weight: bold;">Registration No. 333-</div>
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      <font style="font-size: 14pt;">UNITED STATES</font></div>
    <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-size: 14pt; font-weight: bold;">SECURITIES AND EXCHANGE COMMISSION</div>
    <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-size: 12pt;">Washington, D.C. 20549</div>
    <div>
      <hr style="height: 2px; width: 10%; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"></div>
    <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-size: 18pt; font-weight: bold;">FORM S-8</div>
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    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933</div>
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      <hr style="height: 2px; width: 10%; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"></div>
    <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-size: 24pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">(Exact name of registrant as specified in its charter)</div>
    <div><br>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z342b3fcfcea44c2ead51abc3ab036545" border="0" cellpadding="0" cellspacing="0">

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            <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Delaware</div>
          </td>
          <td style="width: 20%; vertical-align: top;">&#160;</td>
          <td style="width: 40%; vertical-align: top;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">33-0336973</div>
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            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">(State of Incorporation)</div>
          </td>
          <td style="width: 20%; vertical-align: top;">&#160;</td>
          <td style="width: 40%; vertical-align: top;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">(I.R.S. Employer Identification No.)</div>
          </td>
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      <hr style="height: 2px; width: 10%; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"></div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2855 Gazelle Court</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Carlsbad, CA&#160; 92010</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">(Address of principal executive offices)</div>
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      <hr style="height: 2px; width: 10%; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"></div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors&#8217; Stock Option Plan</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">(Full title of the plan)</div>
    <div><br>
    </div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Brett Monia</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Chief Executive Officer</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2855 Gazelle Court</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Carlsbad, California&#160; 92010</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(760) 931-9200</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">(Name, address, and telephone number, including area code, of agent for service)</div>
    <div>
      <hr style="height: 2px; width: 10%; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"></div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Copies to:</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Patrick R. O&#8217;Neil, Esq.</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Executive Vice President, Legal, General Counsel and Corporate Secretary</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">2855 Gazelle Court</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Carlsbad, California&#160; 92010</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(760) 931-9200</div>
    <div><br>
    </div>
    <div style="text-align: justify; margin-left: 13.5pt; font-family: 'Times New Roman', Times, serif;">Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company
      or an emerging growth company. See the definitions of &#8220;large accelerated filer,&#8221; &#8220;accelerated filer,&#8221; &#8220;smaller reporting company,&#8221; and &#8220;emerging growth company&#8221; in Rule 12b-2 of the Exchange Act.</div>
    <div><br>
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          <td style="width: 50%; vertical-align: top;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Large accelerated filer&#160; &#9746;</div>
          </td>
          <td style="width: 50%; vertical-align: top;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Accelerated filer&#160; &#9744;</div>
          </td>
        </tr>
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          <td style="width: 50%; vertical-align: top;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Non-accelerated filer&#160; &#9744;</div>
          </td>
          <td style="width: 50%; vertical-align: top;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Smaller reporting company&#160; &#9744;</div>
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Emerging growth company&#160; &#9744;</div>
          </td>
        </tr>

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    <div style="margin-left: 13.5pt; font-family: 'Times New Roman', Times, serif;"> <br>
    </div>
    <div style="margin-left: 13.5pt; font-family: 'Times New Roman',Times,serif; text-align: justify;">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 7(a)(2)(B) of the Securities Act.&#160; &#160; &#9744;</div>
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      <hr style="height: 2px; width: 10%; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"></div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">CALCULATION OF REGISTRATION FEE</div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z4ffd0bd729dc479ca80647f31787e3c5" cellpadding="0" cellspacing="0">

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            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Title of Securities</div>
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">to be Registered</div>
          </td>
          <td style="width: 21.24%; vertical-align: bottom; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 4px double;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Amount to be Registered (1,2)</div>
          </td>
          <td style="width: 21.24%; vertical-align: bottom; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 4px double;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Proposed Maximum</div>
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Offering</div>
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Price per Share (3)</div>
          </td>
          <td style="width: 21.24%; vertical-align: bottom; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 4px double;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Proposed Maximum</div>
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Aggregate</div>
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Offering Price (3)</div>
          </td>
          <td style="width: 15.04%; vertical-align: bottom; border-left: #000000 2px solid; border-top: #000000 4px double;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Amount of</div>
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Registration Fee</div>
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            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">Common Stock, par value $.001 per share</div>
          </td>
          <td style="width: 21.24%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 4px double;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">800,000 shares</div>
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          <td style="width: 21.24%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 4px double;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">$56.95</div>
          </td>
          <td style="width: 21.24%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 4px double;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">$45,560,000</div>
          </td>
          <td style="width: 15.04%; vertical-align: top; border-left: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 4px double;">
            <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">$5,913.69</div>
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    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z4767e006250a4d63919a184cb3025a87" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif;">(1)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-family: 'Times New Roman', Times, serif;">In accordance with Rule 416 under the Securities Act of 1933, as amended (the &#8220;Securities Act&#8221;),&#160;this Registration Statement on Form S-8 (this &#8220;Registration Statement&#8221;) shall be deemed
              to cover any additional securities that may from time to time be offered or issued by Ionis Pharmaceuticals, Inc. (&#8220;Ionis&#8221; or the &#8220;Registrant&#8221;) to prevent dilution resulting from stock splits, stock dividends or similar transactions.</div>
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    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="ze95dc8807248441f912b565b91bf53ff" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif;">(2)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-family: 'Times New Roman', Times, serif;">Includes 800,000 shares issuable pursuant to the Registrant&#8217;s Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors&#8217; Stock Option Plan (the &#8220;2002 NED Plan&#8221;).</div>
          </td>
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    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z26bf63f3682e467aa4fdd17154711c49" cellpadding="0" cellspacing="0">

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          <td style="width: 36pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif;">(3)</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-family: 'Times New Roman', Times, serif;">Estimated solely for the purpose of calculating the amount of the registration fee pursuant to Rule 457(c) and Rule 457(h) of the Securities Act.&#160; The price per share and the aggregate
              offering price are calculated on the basis of $56.95, the average of the high and low sales prices of Registrant&#8217;s Common Stock on August 6, 2020, as reported on the NASDAQ Global Market for the shares subject to the 2002 NED Plan.</div>
          </td>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">EXPLANATORY NOTE</div>
      <div><br>
      </div>
    </div>
    <div>
      <div style="text-indent: 36pt; font-family: 'Times New Roman',Times,serif; text-align: justify;">Pursuant to General Instruction E of Form S-8, this Registration Statement is being filed in order to register an additional 800,000<font style="font-weight: bold;">&#160;</font>shares of Common Stock of the Registrant issuable under the 2002 NED Plan, which are securities of the same class and relate to the same employee benefit plan as those shares of Common Stock registered on the
        Registrant&#8217;s registration statements on Form S-8 previously filed with the Securities and Exchange Commission (the &#8220;Commission&#8221;) on <a href="http://www.sec.gov/Archives/edgar/data/874015/000114036115040249/forms8.htm">November 9, 2015
          (Registration No. 333-207900)</a>, <a href="http://www.sec.gov/Archives/edgar/data/874015/000110465912074771/a12-26127_1s8.htm">November 6, 2012 (Registration No. 333-184788)</a>, <a href="http://www.sec.gov/Archives/edgar/data/874015/000110465910043194/a10-15434_1s8.htm">August 9, 2010 (Registration No. 333-168674)</a>, <a href="http://www.sec.gov/Archives/edgar/data/874015/000110465906031585/a06-10506_1s8.htm">May 5, 2006
          (Registration No. 333-133853)</a> and <a href="http://www.sec.gov/Archives/edgar/data/874015/000091205702025900/a2083343zs-8.htm">June 28, 2002 (Registration No. 333-91572)</a>, all of which are hereby incorporated by reference.</div>
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    <div>
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Part II</div>
      <div><br>
      </div>
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">INFORMATION REQUIRED IN THE REGISTRATION STATEMENT</div>
      <div><br>
      </div>
    </div>
    <div>
      <div style="font-family: 'Times New Roman', Times, serif; font-weight: bold;">Item 3. Incorporation of Documents by Reference.</div>
      <div><br>
      </div>
    </div>
    <div>
      <div style="text-indent: 36pt; font-family: 'Times New Roman',Times,serif; text-align: justify;">The following documents filed with the Commission by the Registrant are hereby incorporated by reference into this Registration Statement:</div>
      <div><br>
      </div>
    </div>
    <div>
      <div><br>
      </div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z2387f6a1df6748deb4162a4a0c175f97" cellpadding="0" cellspacing="0">

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          <td style="width: 4%; vertical-align: middle;">&#160;</td>
          <td style="width: 5%; vertical-align: top;">
            <div style="font-family: 'Times New Roman', Times, serif;">(a)</div>
          </td>
          <td style="width: 91%; vertical-align: top;">
            <div style="font-family: 'Times New Roman',Times,serif; text-align: justify;">the Registrant&#8217;s Annual Report on <a href="http://www.sec.gov/Archives/edgar/data/874015/000114036120004500/form10k.htm">Form 10-K</a> for the year ended
              December 31, 2019, as filed with the Commission on March 2, 2020;</div>
          </td>
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      <div><br>
      </div>
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    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zedf809d4c19d4d68b18fe209af33c605" cellpadding="0" cellspacing="0">

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          <td style="width: 4%; vertical-align: middle;">&#160;</td>
          <td style="width: 5%; vertical-align: top;">
            <div style="font-family: 'Times New Roman', Times, serif;">(b)</div>
          </td>
          <td style="width: 91%; vertical-align: top;">
            <div style="font-family: 'Times New Roman',Times,serif; text-align: justify;">the Registrant&#8217;s Quarterly Report on <a href="http://www.sec.gov/Archives/edgar/data/874015/000114036120010825/form10q.htm">Form 10-Q for the quarterly
                period ended March 31, 2020</a>, as filed with the Commission on May 6, 2020 and Quarterly Report on <a href="http://www.sec.gov/Archives/edgar/data/874015/000087401520000115/form10q.htm">Form 10-Q for the quarterly period ended June 30,
                2020</a>, as filed with the Commission on August 5, 2020;</div>
          </td>
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      <div><br>
      </div>
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    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zdd26910faba64e05abce7c1da6a7944e" cellpadding="0" cellspacing="0">

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          <td style="width: 4%; vertical-align: middle;">&#160;</td>
          <td style="width: 5%; vertical-align: top;">
            <div style="font-family: 'Times New Roman', Times, serif;">(c)</div>
          </td>
          <td style="width: 91%; vertical-align: top;">
            <div style="font-family: 'Times New Roman',Times,serif; text-align: justify;">the Registrant&#8217;s Current Reports on Form 8-K filed with the Commission on <a href="http://www.sec.gov/Archives/edgar/data/874015/000114036120000641/form8k.htm">January 10, 2020</a>, <a href="http://www.sec.gov/Archives/edgar/data/874015/000114036120001081/form8k.htm">January 17, 2020</a>, <a href="http://www.sec.gov/Archives/edgar/data/874015/000114036120004102/form8k.htm">February 26, 2020</a>, <a href="http://www.sec.gov/Archives/edgar/data/874015/000114036120010790/form8k.htm">May 6, 2020</a>, <a href="http://www.sec.gov/Archives/edgar/data/874015/000114036120013453/form8k.htm">June 10, 2020</a> and <a href="http://www.sec.gov/Archives/edgar/data/874015/000114036120017532/brhc10014107_8k.htm">August 5, 2020</a>; and</div>
          </td>
        </tr>

    </table>
    <div>
      <div><br>
      </div>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z39e0a332faab473cb341edc701445bfd" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 4%; vertical-align: middle;">&#160;</td>
          <td style="width: 5%; vertical-align: top;">
            <div style="font-family: 'Times New Roman', Times, serif;">(d)</div>
          </td>
          <td style="width: 91%; vertical-align: top;">
            <div style="font-family: 'Times New Roman',Times,serif; text-align: justify;">the sections of the Registrant&#8217;s Definitive Proxy Statement on <a href="http://www.sec.gov/Archives/edgar/data/874015/000114036120009606/nc10007589x2_def14a.htm">Schedule 14A</a> for the 2020 Annual Meeting of Shareholders incorporated by reference in the Annual Report.</div>
          </td>
        </tr>

    </table>
    <div>
      <div><br>
      </div>
    </div>
    <div>
      <div style="text-indent: 36pt; font-family: 'Times New Roman',Times,serif; text-align: justify;">All documents filed by the Registrant with the Commission pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Securities Exchange Act of
        1934, as amended (the &#8220;Exchange Act&#8221;), after the date hereof and prior to the filing of a post-effective amendment which indicates that all securities offered pursuant to this Registration Statement have been sold or which deregisters all
        securities then remaining unsold, shall be deemed to be incorporated by reference herein and to be a part hereof from the date of filing of such documents.</div>
    </div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Item 5. Interests of Named Experts and Counsel.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif;">The validity of the issuance of the common stock offered in this Registration Statement will be passed upon for the Registrant by Patrick R. O&#8217;Neil,
      Executive Vice President, Legal, General Counsel and Corporate Secretary of Ionis.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif;">Mr. O&#8217;Neil holds or has the right to acquire shares of Ionis&#8217; Common Stock in an aggregate amount that is less than 1% of Ionis&#8217; outstanding Common
      Stock.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Item 6. Indemnification of Directors and Officers.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif;">Under Section 145 of the Delaware General Corporation Law (the &#8220;DGCL&#8221;), we have broad powers to indemnify our directors and officers against liabilities
      they may incur in such capacities, including liabilities under the Securities Act.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif;">Our certificate of incorporation and bylaws include provisions to (i) eliminate the personal liability of its directors for monetary damages resulting
      from breaches of their fiduciary duty to the extent permitted by Section 102(b)(7) of the DGCL and (ii) require us to indemnify our directors and officers to the fullest extent permitted by Section 145 of the DGCL, including circumstances in which
      indemnification is otherwise discretionary. Pursuant to Section 145 of the DGCL, a corporation generally has the power to indemnify its present and former directors, officers, employees and agents against expenses incurred by them in connection with
      any suit to which they are, or are threatened to be made, a party by reason of their serving in such positions so long as they acted in good faith and in a manner they reasonably believed to be in, or not opposed to, the best interest of the
      corporation, and with respect to any criminal action, they had no reasonable cause to believe their conduct was unlawful.&#160; We believe that these provisions are necessary to attract and retain qualified persons as directors and officers. These
      provisions do not eliminate the directors&#8217; duty of care, and, in appropriate circumstances, equitable remedies such as injunctive or other forms of non-monetary relief will remain available under Delaware law.&#160; In addition, each director will
      continue to be subject to liability for breach of the director&#8217;s duty of loyalty to us, for acts or omissions not in good faith or involving intentional misconduct, for knowing violations of law, for acts or omissions that the director believes to be
      contrary to the best interests of Ionis or our stockholders, for any transaction from which the director derived an improper personal benefit, for acts or omissions involving a reckless disregard for the director&#8217;s duty to Ionis or our stockholders
      when the director was aware or should have been aware of a risk of serious injury to Ionis or our stockholders, for acts or omissions that constitute an unexcused pattern of inattention that amounts to an abdication of the director&#8217;s duty to Ionis or
      our stockholders, for improper transactions between the director and us and for improper distributions to stockholders and loans to directors and officers.&#160; The provision also does not affect a director&#8217;s responsibilities under any other law, such as
      the federal securities law or state or federal environmental laws.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif;">We have entered into indemnity agreements with each of our directors and executive officers that require us to indemnify such persons against expenses,
      judgments, fines, settlements and other amounts incurred (including expenses of a derivative action) in connection with any proceeding, whether actual or threatened, to which any such person may be made a party by reason of the fact that such person
      is or was a director or an executive officer of Ionis or any of our affiliated enterprises, provided such person acted in good faith and in a manner such persons reasonably believed to be in, or not opposed to, the best interests of Ionis and, with
      respect to any criminal proceeding, has no reasonable cause to believe his conduct was unlawful. The indemnification agreements also set forth procedures that will apply in the event of a claim for indemnification thereunder.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif;">We have an insurance policy covering our officers and directors with respect to certain liabilities, including liabilities arising under the Securities
      Act or otherwise.</div>
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    </div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Item 8. Exhibits.</div>
    <div><br>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="ze08a7bc15d0e40638927d14083f12b9f" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 10.55%; vertical-align: bottom;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Exhibit</div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Number</div>
          </td>
          <td style="width: 89.45%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Description</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10.55%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;"><a href="nt10014191x2_ex5-1.htm">5.1</a></div>
          </td>
          <td style="width: 89.45%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Opinion of Patrick R. O&#8217;Neil</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10.55%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;"><a href="nt10014191x2_ex23-1.htm">23.1</a></div>
          </td>
          <td style="width: 89.45%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Consent of Independent Registered Public Accounting Firm</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10.55%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;"><a href="nt10014191x2_ex5-1.htm">23.2</a></div>
          </td>
          <td style="width: 89.45%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Consent of Patrick R. O&#8217;Neil. <font style="font-variant: small-caps;">&#160;</font>Reference is made to Exhibit 5.1</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10.55%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;"><a href="#SIGNATURES">24.1</a></div>
          </td>
          <td style="width: 89.45%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Power of Attorney is contained on the signature pages</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10.55%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;"><a href="http://www.sec.gov/Archives/edgar/data/874015/000114036120009606/nc10007589x2_def14a.htm">99.1</a></div>
          </td>
          <td style="width: 89.45%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors&#8217; Stock Option Plan (1)</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10.55%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;"><a href="nt10014191x2_ex99-2.htm">99.2</a></div>
          </td>
          <td style="width: 89.45%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Form of Option Agreement for options granted under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors&#8217; Stock Option Plan (2)</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10.55%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;"><a href="nt10014191x2_ex99-3.htm">99.3</a></div>
          </td>
          <td style="width: 89.45%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Form of Restricted Stock Unit Agreement for restricted stock units granted under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors&#8217;
              Stock Option Plan (3)</div>
          </td>
        </tr>

    </table>
    <div style="text-align: justify;"><br>
    </div>
    <div style="text-align: justify;"><font style="font-family: 'Times New Roman', Times, serif;">(1)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">Filed as an appendix to the Registrant&#8217;s <a href="http://www.sec.gov/Archives/edgar/data/874015/000114036120009606/nc10007589x2_def14a.htm">Notice of 2020 Annual Meeting of Stockholders and Proxy Statement</a> filed with the SEC on April 24, 2020, and incorporated herein by reference.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-family: 'Times New Roman', Times, serif;">(2)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">Filed herewith.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify;"><font style="font-family: 'Times New Roman', Times, serif;">(3)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">Filed herewith.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Item 9. Undertakings.</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif;">(a) The undersigned Registrant hereby undertakes:</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-family: 'Times New Roman', Times, serif;">(1)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">To file, during any period in which offers or sales are
        being made, a post-effective amendment to this Registration Statement:</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-family: 'Times New Roman', Times, serif;">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">To include any prospectus required by section 10(a)(3) of
        the Securities Act;</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-family: 'Times New Roman', Times, serif;">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">To reflect in the prospectus any facts or events arising
        after the effective date of the Registration Statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in the Registration Statement.&#160;
        Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value of securities offered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum
        offering range may be reflected in the form of prospectus filed with the Commission pursuant to Rule 424(b) if, in the aggregate, the changes in volume and price represent no more than a 20% change in the maximum aggregate offering price set forth
        in the &#8220;Calculation of Registration Fee&#8221; table in the effective Registration Statement;</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-family: 'Times New Roman', Times, serif;">(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">To include any material information with respect to the
        plan of distribution not previously disclosed in the Registration Statement or any material change to such information in the Registration Statement;</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif;"><font style="font-style: italic;">Provided, however,</font> that paragraphs (a)(1)(i) and (a)(1)(ii) of this section do not apply if
      the information required to be included in a post-effective amendment by those paragraphs is contained in reports filed with or furnished to the Commission by the Registrant pursuant to section 13 or section 15(d) of the Securities Exchange Act of
      1934 (the &#8220;Exchange Act&#8221;) that are incorporated by reference in the Registration Statement; and</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt;"><font style="font-family: 'Times New Roman', Times, serif;">(2)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">That, for the purpose of determining any liability under
        the Securities Act, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered herein, and the offering of such securities at that time shall be deemed to be the initial <font style="font-style: italic;">bona fide</font> offering thereof.</font></div>
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    <div style="text-align: justify; text-indent: 36pt;"><font style="font-family: 'Times New Roman', Times, serif;">(3)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">To remove from registration by means of a post-effective
        amendment any of the securities being registered which remain unsold at the termination of the offering.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif;">(4)&#160; &#160; &#160;&#160; That, for the purpose of determining liability of the Registrant under the Securities Act to any purchaser in the initial distribution of the
      securities: The undersigned Registrant undertakes that in a primary offering of securities of the undersigned Registrant pursuant to this Registration Statement, regardless of the underwriting method used to sell the securities to the purchaser, if
      the securities are offered or sold to such purchaser by means of any of the following communications, the undersigned Registrant will be a seller to the purchaser and will be considered to offer or sell such securities to such purchaser:</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-family: 'Times New Roman', Times, serif;">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">Any preliminary prospectus or prospectus of the undersigned
        Registrant relating to the offering required to be filed pursuant to Rule 424;</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-family: 'Times New Roman', Times, serif;">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">Any free writing prospectus relating to the offering
        prepared by or on behalf of the undersigned Registrant or used or referred to by the undersigned Registrant;</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-family: 'Times New Roman', Times, serif;">(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">The portion of any other free writing prospectus relating
        to the offering containing material information about the undersigned Registrant or its securities provided by or on behalf of the undersigned Registrant; and</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 72pt;"><font style="font-family: 'Times New Roman', Times, serif;">(iv)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-family: 'Times New Roman', Times, serif;">Any other communication that is an offer in the offering
        made by the undersigned Registrant to the purchaser.</font></div>
    <div><br>
    </div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">(b) The undersigned Registrant hereby undertakes that, for purposes of determining any liability under the Securities Act, each filing of the Registrant&#8217;s annual report
      pursuant to Section 13(a) or Section 15(d) of the Exchange Act (and, where applicable, each filing of an employee benefit plan&#8217;s annual report pursuant to Section 15(d) of the Exchange Act) that is incorporated by reference in the Registration
      Statement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial <font style="font-style: italic;">bona fide</font> offering
      thereof.</div>
    <div><br>
    </div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">(c) Insofar as indemnification for liabilities arising under the Securities Act may be permitted to directors, officers and controlling persons of the Registrant pursuant
      to the foregoing provisions, or otherwise, the Registrant has been advised that in the opinion of the Securities and Exchange Commission such indemnification is against public policy as expressed in the Securities Act and is, therefore,
      unenforceable.&#160; In the event that a claim for indemnification against such liabilities (other than the payment by the Registrant of expenses incurred or paid by a director, officer or controlling person of the Registrant in the successful defense of
      any action, suit or proceeding) is asserted by such director, officer or controlling person in connection with the securities being registered, the Registrant will, unless in the opinion of its counsel the matter has been settled by controlling
      precedent, submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue.</div>
    <div><br>
    </div>
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    </div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;"><a name="SIGNATURES"><!--Anchor--></a>SIGNATURES</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif;">Pursuant to the requirements of the Securities Act of 1933, as amended, the Registrant certifies that it has reasonable grounds to believe that it meets
      all of the requirements for filing on Form S&#8209;8 and has duly caused this Registration Statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Carlsbad, State of California, on August 7, 2020.</div>
    <div><br>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zf356e171573c4430a7dd601c8735e276" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td colspan="2" style="vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td style="width: 44%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td style="width: 6%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">By:</div>
          </td>
          <td style="width: 44%; vertical-align: top; border-bottom: 2px solid black;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">&#160;/s/ Brett Monia</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td colspan="2" style="vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Brett Monia</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td colspan="2" style="vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Chief Executive Officer</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-weight: bold;">POWER OF ATTORNEY</div>
    <div><br>
    </div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif;"><font style="font-weight: bold; font-variant: small-caps;">Know All Persons By These Presents</font><font style="font-variant: small-caps;">,</font> that
      each person whose signature appears below constitutes and Brett Monia and Elizabeth Hougen, and each or any one of them, his or her true and lawful attorney-in-fact and agent, with full power of substitution and resubstitution, for him or her and in
      his or her name, place and stead, in any and all capacities, to sign any and all amendments (including post-effective amendments) to this Registration Statement, and to file the same, with all exhibits thereto, and other documents in connection
      therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection
      therewith, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents, or any of them, or their or his or her substitutes or substitute, may lawfully do or
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          <td style="width: 40%; vertical-align: top;">&#160;</td>
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          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 35%; vertical-align: top;">&#160;</td>
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            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">August 7, 2020</div>
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          <td style="width: 40%; vertical-align: top;">&#160;</td>
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        <tr>
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          <td style="width: 35%; vertical-align: top;">&#160;</td>
          <td style="width: 25%; vertical-align: top;">&#160;</td>
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        <tr>
          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 35%; vertical-align: top;">&#160;</td>
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          <td style="width: 25%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">August 7, 2020</div>
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          <td style="width: 35%; vertical-align: top;">&#160;</td>
          <td style="width: 25%; vertical-align: top;">&#160;</td>
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          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 35%; vertical-align: top;">&#160;</td>
          <td style="width: 25%; vertical-align: top;">&#160;</td>
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            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">August 7, 2020</div>
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          <td style="width: 35%; vertical-align: top;">&#160;</td>
          <td style="width: 25%; vertical-align: top;">&#160;</td>
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          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 35%; vertical-align: top;">&#160;</td>
          <td style="width: 25%; vertical-align: top;">&#160;</td>
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          <td style="width: 25%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">August 7, 2020</div>
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          <td style="width: 25%; vertical-align: top;">&#160;</td>
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          <td style="width: 40%; vertical-align: top;">&#160;</td>
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          <td style="width: 25%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">August 7, 2020</div>
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        <tr>
          <td style="width: 40%; vertical-align: top;">
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          <td style="width: 35%; vertical-align: top;">&#160;</td>
          <td style="width: 25%; vertical-align: top;">&#160;</td>
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          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 35%; vertical-align: top;">&#160;</td>
          <td style="width: 25%; vertical-align: top;">&#160;</td>
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        <tr>
          <td style="width: 40%; vertical-align: top; border-bottom: 2px solid black;">
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          <td style="width: 35%; vertical-align: top;">
            <div style="margin-left: 9pt; font-family: 'Times New Roman', Times, serif;">Director</div>
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          <td style="width: 25%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">August 7, 2020</div>
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        <tr>
          <td style="width: 40%; vertical-align: top;">
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          <td style="width: 35%; vertical-align: top;">&#160;</td>
          <td style="width: 25%; vertical-align: top;">&#160;</td>
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          <td style="width: 40%; vertical-align: top;">&#160;</td>
          <td style="width: 35%; vertical-align: top;">&#160;</td>
          <td style="width: 25%; vertical-align: top;">&#160;</td>
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          <td style="width: 25%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">August 7, 2020</div>
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          <td style="width: 35%; vertical-align: top;">&#160;</td>
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          <td style="width: 25%; vertical-align: top;">
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<DOCUMENT>
<TYPE>EX-5.1
<SEQUENCE>2
<FILENAME>nt10014191x2_ex5-1.htm
<DESCRIPTION>EXHIBIT 5.1
<TEXT>
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      <hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade">Exhibit 5.1</div>
    <div><br>
    </div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">August 7, 2020</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">&#160;</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Ionis Pharmaceuticals, Inc.</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">2855 Gazelle Court</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Carlsbad, CA 92010</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">&#160;</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Ladies and Gentlemen:</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">&#160;</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">You have requested my opinion with respect to certain matters in connection with the filing by Ionis Pharmaceuticals, Inc.&#160; (the &#8220;Company&#8221;) of a
      Registration Statement on Form S-8 (the &#8220;Registration Statement&#8221;) with the Securities and Exchange Commission, covering the offering of an additional 800,000 shares of the Company&#8217;s Common Stock, $.001 par value (the &#8220;Shares&#8221;), of which, 2,800,000
      Shares are issuable pursuant to its Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors&#8217; Stock Option Plan (the &#8220;2002 NED Plan&#8221;) as described in the Registration Statement.</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">&#160;</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">In connection with this opinion, I have examined and relied upon the Registration Statement, the Company&#8217;s Restated Certificate of Incorporation, as
      amended, and Bylaws and the originals or copies certified to my satisfaction, of such records, documents, certificates, memoranda and other instruments as in my judgment are necessary or appropriate to enable me to render the opinion expressed below.</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">&#160;</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">On the basis of the foregoing, and in reliance thereon, I am of the opinion that the Shares, when issued and sold in accordance with the 2002 NED Plan and
      related prospectuses, will be validly issued, fully paid and nonassessable.</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">&#160;</div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">I consent to the reference to myself under the caption &#8220;Interests of Named Experts and Counsel&#8221; in the Registration Statement and to the filing of this
      opinion as an exhibit to the Registration Statement.</div>
    <div style="text-align: center; font-family: 'Times New Roman', Times, serif;">&#160;</div>
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        <tr>
          <td style="width: 50.16%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Very truly yours,</div>
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            <div style="text-align: justify; font-family: 'Times New Roman', serif; font-size: 1pt;">&#160;</div>
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          <td style="width: 49.84%; vertical-align: top;">
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        </tr>
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          <td style="width: 50.16%; vertical-align: top; border-bottom: #000000 2px solid;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">/s/ Patrick R. O&#8217;Neil</div>
          </td>
          <td style="width: 49.84%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', serif; font-size: 1pt;">&#160;</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50.16%; vertical-align: top; border-top: #000000 2px solid;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">&#160;</div>
          </td>
          <td style="width: 49.84%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">&#160;</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50.16%; vertical-align: top;">
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          <td style="width: 49.84%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', serif; font-size: 1pt;">&#160;</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50.16%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">Executive Vice President, Legal, General Counsel and Corporate Secretary</div>
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          </td>
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        <tr>
          <td style="width: 50.16%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">&#160;</div>
          </td>
          <td style="width: 49.84%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">&#160;</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div>
      <hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"></div>
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<DOCUMENT>
<TYPE>EX-23.1
<SEQUENCE>3
<FILENAME>nt10014191x2_ex23-1.htm
<DESCRIPTION>EXHIBIT 23.1
<TEXT>
<html>
  <head>
    <title></title>
    <!-- Licensed to: Broadridge
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<body style="font-family: 'Times New Roman'; font-size: 10pt; text-align: left; color: #000000;" bgcolor="#ffffff">
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    <div id="DSPFPageHeader">
      <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-weight: bold;">
        <hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade">Exhibit 23.1</div>
      <div><br>
      </div>
    </div>
    <div style="text-align: center; font-family: 'Times New Roman',Times,serif;">Consent of Independent Registered Public Accounting Firm</div>
    <div><br>
    </div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;">We consent to the incorporation by reference in the Registration Statement (Form S-8) pertaining to the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee
      Directors&#8217; Stock Option Plan of Ionis Pharmaceuticals, Inc. of our reports dated March 2, 2020, with respect to the consolidated financial statements of Ionis Pharmaceuticals, Inc. and the effectiveness of internal control over financial reporting of
      Ionis Pharmaceuticals, Inc. included in its Annual Report (Form 10-K) for the year ended December 31, 2019, filed with the Securities and Exchange Commission.</div>
    <div><br>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z670cdf789f3a4378b33c0966f627dd62" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
          <td style="width: 50%; vertical-align: top;">
            <div style="font-family: 'Times New Roman', Times, serif;">/s/ Ernst &amp; Young LLP</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="font-family: 'Times New Roman', Times, serif;">San Diego, California</div>
          </td>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top;">
            <div style="font-family: 'Times New Roman', Times, serif;">August 7, 2020</div>
          </td>
          <td style="width: 50%; vertical-align: top;">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <div>
      <hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"> </div>
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<DOCUMENT>
<TYPE>EX-99.2
<SEQUENCE>4
<FILENAME>nt10014191x2_ex99-2.htm
<DESCRIPTION>EXHIBIT 99.2
<TEXT>
<html>
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    <title></title>
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<body style="font-family: 'Times New Roman'; font-size: 10pt; text-align: left; color: #000000;" bgcolor="#ffffff">
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="text-align: right;">
    <hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"><font style="font-weight: bold; font-family: 'Times New Roman',Times,serif;">Exhibit



      99.2</font><font style="font-family: 'Times New Roman',Times,serif;"><br>
    </font> </div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div>
    <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-variant: small-caps; font-weight: bold;">Amended and Restated</div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="text-align: center; margin-bottom: 6pt; font-family: 'Times New Roman',Times,serif; font-variant: small-caps; font-weight: bold;">2002 Non-Employee Directors&#8217; Stock Option Plan</div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-variant: small-caps; font-weight: bold;">Grant Notice</div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="font-family: 'Times New Roman',Times,serif;"><br>
    </div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="font-family: 'Times New Roman',Times,serif;"><br>
    </div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z433e092025f0449b8961d1550d2c2d53" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 10%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify;">Optionee:</div>
          </td>
          <td style="width: 40%; vertical-align: top; border-bottom: 2px solid black; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify; font-weight: bold;">&#171;Name&#187;</div>
          </td>
          <td style="width: 15%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 10%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify;">Date of Grant:</div>
          </td>
          <td style="width: 25%; vertical-align: top; border-bottom: 2px solid black;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;">&#160;</font><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif; font-weight: bold;">&#171;Date&#187;</font></div>
          </td>
        </tr>

    </table>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="font-family: 'Times New Roman',Times,serif;"><br>
    </div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-weight: bold;"><u>Non-Statutory</u> Stock Option Agreement</div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="font-family: 'Times New Roman',Times,serif;"><br>
    </div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif;"><font style="font-variant: small-caps; font-family: 'Times New Roman',Times,serif;">Ionis Pharmaceuticals, Inc.</font><font style="font-family: 'Times New Roman',Times,serif;"> (the &#8220;Company&#8221;), pursuant to its Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan (the &#8220;Plan&#8221;), hereby grants to Optionholder an option to purchase the number of shares of the Company&#8217;s Common Stock set
        forth below.&#160; This option is subject to all of the terms and conditions as set forth herein and in the Stock Option Agreement (Attachment I hereto), the Plan and the Notice of Exercise, all of which are attached hereto and incorporated herein in
        their entirety.</font></div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="font-family: 'Times New Roman',Times,serif;"><br>
    </div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="text-align: center; font-family: 'Times New Roman',Times,serif;">Number of Shares Subject to Option: <font style="font-weight: bold; font-style: italic;"><u>12,000</u></font></div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="font-family: 'Times New Roman',Times,serif;"><br>
    </div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="text-align: justify; font-family: 'Times New Roman',Times,serif; font-weight: bold;">Vesting Schedule:</div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="font-family: 'Times New Roman',Times,serif;"><br>
    </div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zed410988988147a6b5e0c19047386466" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 7%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 36%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify;"><u>Number of Shares</u></div>
          </td>
          <td style="width: 57%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify;"><u>Date of Earliest Exercise (vesting)</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 7%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td rowspan="4" style="width: 36%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify; font-weight: bold;">12,000</div>
          </td>
          <td rowspan="4" style="width: 57%; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt; font-style: italic; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;">Either</font><font style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;"> (1) the annual anniversary of the Date of Grant,</font></div>
            <div style="text-align: justify; font-family: 'Times New Roman',Times,serif; font-style: italic; font-weight: bold;">or (2) the next regularly scheduled annual meeting of</div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt; font-style: italic; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;">stockholders of the Company</font><font style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">, whichever occurs&#160;earlier</font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 7%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 7%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 7%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
        </tr>

    </table>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="font-family: 'Times New Roman',Times,serif;"><br>
    </div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z2a23f0e363fb4cf799cde9665ee9c5c6" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 15%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify;">Exercise Price Per Share: </div>
          </td>
          <td style="width: 30%; vertical-align: top; border-bottom: 2px solid black;">
            <div style="text-align: justify; font-family: 'Times New Roman',Times,serif;">&#160;<font style="font-weight: bold;">$&#171;Price&#187; </font><sup style="font-family: 'Times New Roman', serif; font-weight: bold; vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup></div>
          </td>
          <td style="width: 8%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 12%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify;">Expiration Date:</div>
          </td>
          <td style="width: 35%; vertical-align: top; border-bottom: 2px solid black;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-weight: bold;"><font style="font-family: 'Times New Roman',Times,serif;">&#171;Date&#187; </font><font style="font-family: 'Times New Roman',Times,serif;"><sup style="font-family: 'Times New Roman', serif; vertical-align: text-top; line-height: 1; font-size: smaller;">2</sup></font></div>
          </td>
        </tr>
        <tr>
          <td style="width: 15%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 30%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 8%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 12%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 35%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
        </tr>
        <tr>
          <td colspan="2" style="vertical-align: top; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify;">Ionis Pharmaceuticals, Inc.</div>
          </td>
          <td style="width: 8%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 12%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 35%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 15%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 30%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 8%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 12%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 35%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 15%; vertical-align: top; font-family: 'Times New Roman',Times,serif; padding-bottom: 2px;">
            <div style="text-align: justify;">By:</div>
          </td>
          <td style="width: 30%; vertical-align: top; font-family: 'Times New Roman',Times,serif; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          <td style="width: 8%; vertical-align: top; font-family: 'Times New Roman',Times,serif; padding-bottom: 2px;">&#160;</td>
          <td style="width: 12%; vertical-align: top; font-family: 'Times New Roman',Times,serif; padding-bottom: 2px;">
            <div style="text-align: justify;">Optionee:</div>
          </td>
          <td style="width: 35%; vertical-align: top; font-family: 'Times New Roman',Times,serif; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
        </tr>
        <tr>
          <td colspan="2" rowspan="2" style="vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman',Times,serif;">Duly authorized on behalf of</div>
            <div style="text-align: justify; font-family: 'Times New Roman',Times,serif;">&#160;&#160;the Board of Directors</div>
          </td>
          <td style="width: 8%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 12%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify;">Address:</div>
          </td>
          <td style="width: 35%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify; font-weight: bold;">&#171;Address_1&#187;</div>
          </td>
        </tr>
        <tr>
          <td style="width: 8%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 12%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">&#160;</td>
          <td style="width: 35%; vertical-align: top; font-family: 'Times New Roman',Times,serif;">
            <div style="text-align: justify; font-weight: bold;">&#171;Address_2&#187;</div>
          </td>
        </tr>

    </table>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="font-family: 'Times New Roman',Times,serif;"><br>
    </div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="text-align: justify; font-family: 'Times New Roman',Times,serif; font-weight: bold;">Optionee:</div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="font-family: 'Times New Roman',Times,serif;"><br>
    </div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="text-align: justify; margin-bottom: 6pt; font-family: 'Times New Roman', Times, serif;"><font style="font-weight: bold; font-family: 'Times New Roman',Times,serif;">Additional Terms/Acknowledgements:</font><font style="font-family: 'Times New Roman',Times,serif;">&#160; The undersigned Optionholder acknowledges receipt of, and understands and agrees to, this Grant Notice, the Stock Option Agreement and the Plan.&#160; Optionholder further acknowledges that as of the Date of Grant, this Grant
        Notice, the Stock Option Agreement and the Plan set forth the entire understanding between Optionholder and the Company regarding the acquisition of stock in the Company and supersede all prior oral and written agreements on that subject with the
        exception of (i) options previously granted and delivered to Optionholder under the Plan, and (ii)&#160;the following agreements only:</font></div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <table style="border-collapse: collapse; width: 70%; color: #000000; font-family: 'Times New Roman'; font-size: 10pt; text-align: left;" id="z3c0be351c07c45e982aeceab594a90c8" align="center" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="vertical-align: top; font-family: 'Times New Roman',Times,serif; padding-bottom: 2px;">
            <div style="text-align: justify; font-variant: small-caps; font-weight: bold;">Other Agreements:</div>
          </td>
          <td style="width: 75%; vertical-align: top; font-family: 'Times New Roman',Times,serif; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; font-family: 'Times New Roman',Times,serif; padding-bottom: 2px;">&#160;</td>
          <td style="width: 75%; vertical-align: top; font-family: 'Times New Roman',Times,serif; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
        </tr>

    </table>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <div style="font-family: 'Times New Roman',Times,serif;"><br>
    </div>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z366ca33b2035446d9a69c82ce6d069e4" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 13.5pt; vertical-align: top; font-family: 'Times New Roman',Times,serif; font-style: italic;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup></td>
          <td style="width: auto; vertical-align: top; text-align: justify; font-family: 'Times New Roman',Times,serif;">
            <div style="font-style: italic;">Not less than 100% of the fair market value of the Common Stock on the Date of Grant of this option.</div>
          </td>
        </tr>

    </table>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z54dd36ebb454477d951cc0a1f124cfb7" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 13.5pt; vertical-align: top; font-family: 'Times New Roman',Times,serif; font-style: italic;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">2</sup></td>
          <td style="width: auto; vertical-align: top; text-align: justify; font-family: 'Times New Roman',Times,serif;">
            <div style="font-style: italic;">Less than 10 years from the Date of Grant of this option.</div>
          </td>
        </tr>

    </table>
    <font style="font-family: 'Times New Roman',Times,serif;"> </font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> <br>
    <br>
  </font>
  <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div id="DSPFPageBreak" style="page-break-after: always;">
      <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
    <div id="DSPFPageHeader"></div>
  </div>
  <div style="text-align: center; margin-bottom: 6pt; font-family: 'Times New Roman',Times,serif; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.<br>
    Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan<br>
    Stock Option Agreement<br>
    (Nonstatutory Stock Option)</div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="font-family: 'Times New Roman',Times,serif;"><br>
  </div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="text-align: justify; text-indent: 36pt; margin-bottom: 12pt; font-family: 'Times New Roman',Times,serif;">Pursuant to your Stock Option Grant Notice (&#8220;Grant Notice&#8221;) and this Stock Option Agreement, Ionis Pharmaceuticals, Inc. (the &#8220;Company&#8221;)
    has granted you an option under its Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan (the &#8220;Plan&#8221;) to purchase the number of shares of the Company&#8217;s Common Stock indicated in your Grant Notice at the exercise price indicated in your
    Grant Notice.&#160; Defined terms not explicitly defined in this Stock Option Agreement but defined in the Plan shall have the same definitions as in the Plan.</div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="text-align: justify; text-indent: 36pt; margin-bottom: 6pt; font-family: 'Times New Roman',Times,serif;">The details of your option are as follows:</div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">1.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Vesting.&#160;



      </font>Subject to the limitations contained herein, your option will vest as provided in your Grant Notice, provided that vesting will cease upon the termination of your Continuous Service.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">2.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Number
        of Shares and Exercise Price.</font>&#160; The number of shares of Common Stock subject to your option and your exercise price per share referenced in your Grant Notice may be adjusted from time to time for Capitalization Adjustments, as provided in the
      Plan.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">3.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Method
        of Payment.</font>&#160; Payment of the exercise price is due in full upon exercise of all or any part of your option.&#160; You may make payment of the exercise price in cash or by check&#160;or pursuant to a &#8220;same-day-sale&#8221; under Regulation T.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">4.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Whole
        Shares.</font>&#160; You may exercise your option only for whole shares of Common Stock.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">5.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Securities



        Law Compliance.</font>&#160; Notwithstanding anything to the contrary contained herein, you may not exercise your option unless the shares of Common Stock issuable upon such exercise are then registered under the Securities Act or, if such shares of
      Common Stock are not then so registered, the Company has determined that such exercise and issuance would be exempt from the registration requirements of the Securities Act.&#160; The exercise of your option must also comply with other applicable laws and
      regulations governing your option, and you may not exercise your option if the Company determines that such exercise would not be in material compliance with such laws and regulations.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">6.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Term.</font>&#160;
      You may not exercise your option before the commencement of its term or after its term expires.&#160; Unless otherwise provided in Section 11(d) of the Plan, the term of your option commences on the Date of Grant and expires upon the <font style="font-weight: bold; font-style: italic;">earliest</font> of the following:</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif;">(a)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;3 months after the termination of your Continuous Service for any
      reason other than your Disability or death, provided that if during any part of such 3 month period your option is not exercisable solely because of the condition set forth in the preceding paragraph relating to &#8220;Securities Law Compliance,&#8221; your
      option shall not expire until the earlier of the Expiration Date or until it shall have been exercisable for an aggregate period of 3 months after the termination of your Continuous Service;</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif;">(b)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;12 months after the termination of your Continuous Service due to
      your Disability;</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif;">(c)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;18 months after your death if you die either during your
      Continuous Service or within 3 months after your Continuous Service terminates; or</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif;">(d)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;18&#160;months after the termination of your Continuous Service due to
      your retirement, where (i)&#160;you were over the age of 55 at the time of such retirement; and (ii)&#160;you had been an employee, director or consultant (or any combination thereof) of the Company for a continuous and uninterrupted period of at least 5&#160;years
      prior to such retirement (having satisfied all of the conditions set forth in clauses&#160;(i) and (ii) above, &#8220;Qualified Retirement&#8221;); or</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif;">(e)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;the day before the 10th anniversary of the Date of Grant.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
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    <div id="DSPFPageBreak" style="page-break-after: always;">
      <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
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  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">7.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Exercise.</font></font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif;">(a)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;You may exercise the vested portion of your option during its
      term by delivering a Notice of Exercise (in a form designated by the Company) together with the exercise price to the Secretary of the Company, or to such other person as the Company may designate, during regular business hours, together with such
      additional documents as the Company may then require.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif;">(b)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The minimum number of shares with respect to which this option
      may be exercised at any one time is 1,000, unless the number of shares available for exercise (that is, the remaining vested shares) equals less than 1,000 shares, in which case the minimum number of shares exercised must equal the number of shares
      then vested.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif;">(c)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;By exercising your option you agree that, as a condition to any
      exercise of your option, the Company may require you to enter into an arrangement providing for the payment by you to the Company of any tax withholding obligation of the Company arising by reason of (1) the exercise of your option, (2) the lapse of
      any substantial risk of forfeiture to which the shares of Common Stock are subject at the time of exercise, or (3) the disposition of shares of Common Stock acquired upon such exercise.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">8.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Transferability.</font>&#160;
      This option is not transferable except by will or by the laws of descent and distribution, and is exercisable during your lifetime only by you; notwithstanding the foregoing, you may transfer part or all of this option to any of the following:</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="text-align: justify; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif;">(i)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;your spouse, children (by birth or adoption), stepchildren,
      grandchildren, or parents;</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="font-family: 'Times New Roman',Times,serif;"><br>
  </div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="text-align: justify; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif;">(ii)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;a trust or other entity established solely for your benefit or
      the benefit of your spouse, children (by birth or adoption), stepchildren, grandchildren, or parents for estate planning purposes; or,</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="font-family: 'Times New Roman',Times,serif;"><br>
  </div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="text-align: justify; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif;">(iii)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; an organization which is exempt from taxation under Section
      501(c)(3) of the Code or to which tax-deductible charitable contributions may be made under Section 170 of the Code.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="font-family: 'Times New Roman',Times,serif;"><br>
  </div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="text-align: justify; text-indent: 36pt; margin-bottom: 12pt; font-family: 'Times New Roman',Times,serif;">Furthermore, you may, by delivering written notice to the Company, in a form satisfactory to the Company, designate a third party who,
    in the event of your death, will thereafter be entitled to exercise the option.</div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">9.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Right
        of Repurchase.</font>&#160; To the extent provided in the Company&#8217;s bylaws as amended from time to time, the Company shall have the right to repurchase all or any part of the shares of Common Stock you acquire pursuant to the exercise of your option.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">10.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Option
        not a Service Contract.</font>&#160; Your option is not an employment or service contract, and nothing in your option shall be deemed to create in any way whatsoever any obligation on your part to continue in the employ of the Company or an Affiliate,
      or of the Company or an Affiliate to continue your employment.&#160; In addition, nothing in your option shall obligate the Company or an Affiliate, their respective stockholders, Boards of Directors, Officers or Employees to continue any relationship
      that you might have as a Director or Consultant for the Company or an Affiliate.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">11.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Withholding



        Obligations.&#160; </font>You may not exercise your option unless the tax withholding obligations of the Company and/or any Affiliate are satisfied.&#160; Accordingly, you may not be able to exercise your option when desired even though your option is
      vested, and the Company shall have no obligation to issue a certificate for such shares of Common Stock or release such shares of Common Stock from any escrow provided for herein.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">12.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Notices.</font>&#160;
      Any notices provided for in your option or the Plan shall be given in writing and shall be deemed effectively given upon receipt or, in the case of notices delivered by mail by the Company to you, 5 days after deposit in the United States mail,
      postage prepaid, addressed to you at the last address you provided to the Company.</font></div>
  <font style="font-family: 'Times New Roman',Times,serif;"> </font>
  <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif;">13.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Governing



        Plan Document.</font>&#160; Your option is subject to all the provisions of the Plan, the provisions of which are hereby made a part of your option, and is further subject to all interpretations, amendments, rules and regulations which may from time to
      time be promulgated and adopted pursuant to the Plan.&#160; In the event of any conflict between the provisions of your option and those of the Plan, the provisions of the Plan shall control.</font>
    <hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"></div>
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<DOCUMENT>
<TYPE>EX-99.3
<SEQUENCE>5
<FILENAME>nt10014191x2_ex99-3.htm
<DESCRIPTION>EXHIBIT 99.3
<TEXT>
<html>
  <head>
    <title></title>
    <!-- Licensed to: Broadridge
         Document created using EDGARfilings PROfile 7.1.0.0
         Copyright 1995 - 2020 Broadridge -->
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  <div>
    <div style="text-align: center; margin-bottom: 24pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt;"> </font>
      <hr style="height: 4px; color: #000000; background-color: #000000; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade">
      <div style="text-align: right;"><font style="font-family: 'Times New Roman',Times,serif; font-size: 10pt;">Exhibit 99.3</font></div>
    </div>
    <div style="text-align: center; margin-bottom: 24pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif; font-variant: small-caps;">Ionis
        Pharmaceuticals, Inc.</font><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;"><br>
      </font><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif; font-variant: small-caps;">Restricted Stock Unit</font><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif; font-variant: small-caps;"> Grant Notice</font><font style="font-size: 10pt; font-family: 'Times New Roman',Times,serif;"><br>
      </font><font style="font-size: 10pt;">(<font style="font-family: 'Times New Roman',Times,serif; font-variant: small-caps;">Amended &amp; Restated 2002 Non-Employee Directors&#8217; Stock Option Plan)</font></font></div>
    <div style="text-align: justify; margin-bottom: 12pt; font-family: 'Times New Roman', Times, serif;">Ionis Pharmaceuticals, Inc. (the <font style="font-family: 'Times New Roman',Times,serif; font-weight: bold; font-style: italic;">&#8220;Company&#8221;</font>),
      pursuant to its Amended &amp; Restated 2002 Non-Employee Directors&#8217; Stock Option Plan (the <font style="font-family: 'Times New Roman',Times,serif; font-weight: bold; font-style: italic;">&#8220;Plan&#8221;</font>), hereby awards to Participant a Restricted
      Stock Unit Award for the number of stock units set forth below (the <font style="font-family: 'Times New Roman',Times,serif; font-weight: bold; font-style: italic;">&#8220;Award&#8221;</font>).&#160; The Award is subject to all of the terms and conditions as set
      forth herein; and in the Plan and the Restricted Stock Unit Agreement, both of which are attached hereto and incorporated herein in their entirety.&#160; Capitalized terms not otherwise defined herein shall have the meanings set forth in the Plan or the
      Restricted Stock Unit Agreement.&#160; In the event of any conflict between the terms in the Award and the Plan, the terms of the Plan shall control.</div>
    <table style="border-collapse: collapse; width: 90%; color: #000000; font-family: 'Times New Roman'; font-size: 10pt; text-align: left;" id="zd419e8b801bb4e8b9062a34d9ac63370" align="center" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 40%; vertical-align: top;">
            <div style="font-family: 'Times New Roman',Times,serif;">Participant:</div>
          </td>
          <td style="width: 60%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: top;">
            <div style="font-family: 'Times New Roman',Times,serif;">Date of Grant:</div>
          </td>
          <td style="width: 60%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: top;">
            <div style="font-family: 'Times New Roman',Times,serif;">Delivery Date:</div>
          </td>
          <td style="width: 60%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: top;">
            <div style="font-family: 'Times New Roman',Times,serif;">Number of Stock Units Subject to Award:</div>
          </td>
          <td style="width: 60%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 40%; vertical-align: top;">
            <div style="font-family: 'Times New Roman',Times,serif;">Consideration:</div>
          </td>
          <td style="width: 60%; vertical-align: top; border-bottom: 2px solid black;">
            <div style="font-family: 'Times New Roman',Times,serif;">Participant&#8217;s Services</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z85e2f7c6c0354791a53a5d877e005b30" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 0.9pt;"><br>
          </td>
          <td style="width: 107.1pt; vertical-align: top; align: right;"><font style="font-family: 'Times New Roman', Times, serif; font-weight: bold;">Vesting Schedule</font><font style="font-family: 'Times New Roman', Times, serif;">:</font></td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-family: 'Times New Roman',Times,serif;">100% of the Stock Units subject to this Award will vest either on (1) the annual anniversary of the Date of Grant, or (2) the next regularly scheduled annual meeting of stockholders of
              the Company, whichever occurs earlier.&#160; Notwithstanding the foregoing, vesting shall terminate upon the Participant&#8217;s termination of Continuous Service.</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000; margin-bottom: 12pt;" class="DSPFListTable" id="z3e19572987ca48ec9b5d890db29623d7" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 108pt; vertical-align: top; align: right; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Issuance Schedule:</td>
          <td style="width: auto; vertical-align: top; text-align: justify;">
            <div style="font-family: 'Times New Roman',Times,serif;">The shares of Common Stock to be issued in respect of the Award will be issued in accordance with the issuance schedule set forth in Section 6 of the Restricted Stock Unit Agreement.</div>
          </td>
        </tr>

    </table>
    <div style="text-align: justify; text-indent: -90pt; margin-left: 90pt; font-family: 'Times New Roman', Times, serif;"><font style="font-weight: bold;">Additional Terms/Acknowledgements:</font>&#160; The undersigned Participant acknowledges receipt of, and
      understands and agrees to, this Restricted Stock Unit Grant Notice, the Restricted Stock Unit Agreement and the Plan.&#160; Participant further acknowledges that as of the Date of Grant, this Restricted Stock Unit Grant Notice, the Restricted Stock Unit
      Agreement and the Plan set forth the entire understanding between Participant and the Company regarding the Award and supersedes all prior oral and written agreements on that subject.</div>
    <div style="margin-top: 18pt; margin-bottom: 18pt;"><br>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="zcc00ecfcea054b9c9976fb8f3223c20e" border="0" cellpadding="0" cellspacing="0">

        <tr>
          <td colspan="2" style="vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman',Times,serif; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
          </td>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td colspan="2" style="vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman',Times,serif; font-variant: small-caps; font-weight: bold;">Participant:</div>
          </td>
        </tr>
        <tr>
          <td style="width: 7%; vertical-align: top; padding-bottom: 2px;">
            <div style="text-align: justify; font-family: 'Times New Roman',Times,serif;">By:</div>
          </td>
          <td style="width: 40%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          <td style="width: 6%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
          <td colspan="2" rowspan="1" style="vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;&#160;</td>
        </tr>
        <tr>
          <td style="width: 7%; vertical-align: top;">&#160;</td>
          <td style="width: 40%; vertical-align: top;">
            <div style="text-align: center; font-family: 'Times New Roman',Times,serif;">Signature</div>
          </td>
          <td style="width: 6%; vertical-align: top;">&#160;</td>
          <td colspan="2" rowspan="1" style="vertical-align: top; text-align: center;">
            <div style="font-family: 'Times New Roman',Times,serif;">Signature</div>
          </td>
        </tr>
        <tr>
          <td style="width: 7%; vertical-align: top; padding-bottom: 2px;">
            <div style="text-align: justify; font-family: 'Times New Roman',Times,serif;">Title:</div>
          </td>
          <td style="width: 40%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          <td style="width: 6%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
          <td style="width: 7%; vertical-align: top; padding-bottom: 2px;">
            <div style="text-align: justify; font-family: 'Times New Roman',Times,serif;">Date:</div>
          </td>
          <td style="width: 40%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
        </tr>
        <tr>
          <td style="width: 7%; vertical-align: top; padding-bottom: 2px;">
            <div style="text-align: justify; font-family: 'Times New Roman',Times,serif;">Date:</div>
          </td>
          <td style="width: 40%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          <td style="width: 6%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
          <td style="width: 7%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
          <td style="width: 40%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
        </tr>

    </table>
    <div><br>
    </div>
    <table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" id="z97dbca7e3dbc4f768e82e537293a2fed" cellpadding="0" cellspacing="0">

        <tr>
          <td style="width: 144pt; vertical-align: top; align: right;"><font style="font-family: 'Times New Roman', Times, serif; font-weight: bold; font-variant: small-caps;">Attachments</font><font style="font-family: 'Times New Roman', Times, serif;">:</font></td>
          <td style="width: auto; vertical-align: top;">
            <div style="font-family: 'Times New Roman',Times,serif;">Restricted Stock Unit Agreement, Amended &amp; Restated 2002 Non-Employee Directors&#8217; Stock Option Plan</div>
          </td>
        </tr>

    </table>
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    <div style="text-align: center; font-family: 'Times New Roman',Times,serif; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
    <div style="text-align: center; margin-bottom: 12pt; font-family: 'Times New Roman',Times,serif; font-variant: small-caps; font-weight: bold;">Amended &amp; Restated 2002 Non-Employee Directors&#8217;<br>
      Stock Option Plan</div>
    <div style="text-align: center; margin-bottom: 24pt; font-family: 'Times New Roman',Times,serif; font-variant: small-caps; font-weight: bold;">Restricted Stock Unit Agreement</div>
    <div style="text-align: justify; text-indent: 36pt; margin-bottom: 12pt; font-family: 'Times New Roman',Times,serif;">Pursuant to the Restricted Stock Unit Grant Notice (&#8220;<font style="font-weight: bold; font-style: italic;">Grant Notice</font>&#8221;) and
      this Restricted Stock Unit Agreement and in consideration of your services, Ionis Pharmaceuticals, Inc. (the&#160;&#8220;<font style="font-weight: bold; font-style: italic;">Company</font>&#8221;) has awarded you a Restricted Stock Unit Award (the &#8220;<font style="font-weight: bold; font-style: italic;">Award</font>&#8221;) under its Amended &amp; Restated 2002 Non-Employee Director&#8217;s Stock Option Plan (the &#8220;<font style="font-weight: bold; font-style: italic;">Plan</font>&#8221;). Your Award is granted to you
      effective as of the Date of Grant set forth in the Grant Notice for this Award.&#160; This Restricted Stock Unit Award Agreement shall be deemed to be agreed to by the Company and you upon the earlier of (i) signing (or electronic acceptance) by you of
      the Restricted Stock Unit Grant Notice to which it is attached, and (ii) your receipt of shares of Common Stock under this Restricted Stock Unit Agreement.&#160; Capitalized terms not explicitly defined in this Restricted Stock Unit Agreement shall have
      the same meanings given to them in the Plan or the Grant Notice, as applicable.&#160; In the event of any conflict between the terms in this Restricted Stock Unit Agreement and the Plan, the terms of the Plan shall control.&#160; The details of your Award, in
      addition to those set forth in the Grant Notice and the Plan, are as follows.</div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">1.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Grant of the Award.&#160; &#160; </font>This Award represents the right to be issued on a future date the number of shares of the Company&#8217;s Common Stock that is equal to the number of stock units indicated in the Grant Notice (the &#8220;<font style="font-weight: bold; font-style: italic;">Stock Units</font>&#8221;).&#160; As of the Date of Grant, the Company will credit to a bookkeeping account maintained by the Company for your benefit (the &#8220;<font style="font-weight: bold; font-style: italic;">Account</font>&#8221;)


        the number of Stock Units subject to the Award.&#160; This Award was granted in consideration of your services to the Company.&#160; Except as otherwise provided herein, you will not be required to make any payment to the Company (other than past and future
        services to the Company) with respect to your receipt of the Award, the vesting of the Stock Units or the delivery of the Common Stock to be issued in respect of the Award.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">2.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Vesting</font><font style="font-weight: bold;">.</font></font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(a)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">In General.</font>&#160;
        Subject to the limitations contained herein, your Award will vest, if at all, in accordance with the vesting schedule provided in the Grant Notice, provided that vesting will cease upon the termination of your Continuous Service.&#160; Upon such
        termination of your Continuous Service, the Stock Units credited to the Account that were not vested on the date of such termination will be forfeited at no cost to the Company and you will have no further right, title or interest in the Stock
        Units or the shares of Common Stock to be issued in respect of the Award.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">3.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Number of Shares</font><font style="font-weight: bold;">.</font></font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(a)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The number of Stock Units subject to your
        Award may be adjusted from time to time for Capitalization Adjustments, as provided in the Plan.</font></div>
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    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(b)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Any additional Stock Units that become
        subject to the Award pursuant to this Section 3 and Section 7, if any, shall be subject, in a manner determined by the Board, to the same forfeiture restrictions, restrictions on transferability, and time and manner of delivery as applicable to the
        other Stock Units covered by your Award.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(c)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Notwithstanding the provisions of this
        Section 3, no fractional shares or rights for fractional shares of Common Stock shall be created pursuant to this Section 3.&#160; The Board shall, in its discretion, determine an equivalent benefit for any fractional shares or fractional shares that
        might be created by the adjustments referred to in this Section 3.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">4.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Securities Law Compliance</font><font style="font-weight: bold;">.</font>&#160; You may not be issued any shares in respect of your Award unless either (i) the shares are registered under the Securities Act; or (ii) the Company has
        determined that such issuance would be exempt from the registration requirements of the Securities Act. Your Award also must comply with other applicable laws and regulations governing the Award, and you will not receive such shares if the Company
        determines that such receipt would not be in material compliance with such laws and regulations.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">5.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Transfer Restrictions.</font>&#160; Prior to the time that shares of Common Stock have been delivered to you, you may not transfer, pledge, sell or otherwise dispose of this Award or the shares issuable in respect of your Award, except as
        expressly provided in this Section 5.&#160; For example, you may not use shares that may be issued in respect of your Award as security for a loan.&#160; The restrictions on transfer set forth herein will lapse upon delivery to you of shares in respect of
        your vested Award.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(a)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Death</font>.&#160;


        Your Award is transferable by will and by the laws of descent and distribution.&#160; In addition, upon receiving written permission from the Board or its duly authorized designee, you may, by delivering written notice to the Company, in a form provided
        by or otherwise satisfactory to the Company and any broker designated by the Company to effect transactions under the Plan, designate a third party who, in the event of your death, shall thereafter be entitled to receive any distribution of Common
        Stock or other consideration to which you were entitled at the time of your death pursuant to this Agreement.&#160; In the absence of such a designation, your executor or administrator of your estate shall be entitled to receive, on behalf of your
        estate, such Common Stock or other consideration.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(b)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Certain
          Trusts.</font>&#160; Upon receiving written permission from the Board or its duly authorized designee, you may transfer your Award to a trust if you are considered to be the sole beneficial owner (determined under Section 671 of the Code and
        applicable state law) while the Award is held in the trust, provided that you and the trustee enter into transfer and other agreements required by the Company.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(c)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;">Domestic
          Relations Orders.</font>&#160; Upon receiving written permission from the Board or its duly authorized designee, and provided that you and the designated transferee enter into transfer and other agreements required by the Company, you may transfer
        your Award or your right to receive the distribution of Common Stock or other consideration thereunder, pursuant to a domestic relations order that contains the information required by the Company to effectuate the transfer.&#160; You are encouraged to
        discuss the proposed terms of any division of this Award with the Company prior to finalizing the domestic relations order to help ensure the required information is contained within the domestic relations order.</font></div>
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    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">6.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Date of Issuance.</font></font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(a)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If the Award is exempt from application of
        Section 409A of the Code and the regulations and other guidance thereunder and any state law of similar effect (collectively <font style="font-weight: bold;">&#8220;</font><font style="font-weight: bold; font-style: italic;">Section</font>&#160;<font style="font-weight: bold; font-style: italic;">409A</font><font style="font-weight: bold;">&#8221;</font>), the Company will deliver to you a number of shares of the Company&#8217;s Common Stock equal to the number of vested Stock Units subject to your
        Award, including any additional Stock Units received pursuant to Section 3 above that relate to those vested Stock Units on the applicable delivery date.&#160; However, if a scheduled delivery date falls on a date that is not a business day, such
        delivery date shall instead fall on the next following business day.&#160; Notwithstanding the foregoing, in the event that (i) you are subject to the Company&#8217;s policy permitting officers and directors to sell shares only during certain &#8220;window&#8221;
        periods, in effect from time to time (the &#8220;<font style="font-weight: bold; font-style: italic;">Policy</font>&#8221;) or you are otherwise prohibited from selling shares of the Company&#8217;s Common Stock in the public market and any shares covered by your
        Award are scheduled to be delivered on a day (the &#8220;<font style="font-weight: bold; font-style: italic;">Original Distribution Date</font>&#8221;) that does not occur during an open &#8220;window period&#8221; applicable to you or a day on which you are permitted to
        sell shares of the Company&#8217;s common stock pursuant to a written plan that meets the requirements of Rule 10b5-1 under the Exchange Act, in each case as determined by the Company in accordance with the Policy, or does not occur on a date when you
        are otherwise permitted to sell shares of the Company&#8217;s common stock on the open market, and (ii) the Company elects not to satisfy its tax withholding obligations (if any) by withholding shares from your distribution, then such shares shall not be
        delivered on such Original Distribution Date and shall instead be delivered on the first business day of the next occurring open &#8220;window period&#8221; applicable to you pursuant to such policy (regardless of whether you are still providing continuous
        services at such time) or the next business day when you are not prohibited from selling shares of the Company&#8217;s Common Stock in the open market, but in no event later than the fifteenth day of the third calendar month of the calendar year
        following the calendar year in which the shares covered by the Award vest.&#160; Delivery of the shares pursuant to the provisions of this Section 6(a) is intended to comply with the requirements for the short-term deferral exemption available under
        Treasury Regulation 1.409A-1(b)(4) and shall be construed and administered in such manner.&#160; The form of such delivery of the shares (<font style="font-style: italic;">e.g.</font>, a stock certificate or electronic entry evidencing such shares)
        shall be determined by the Company.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(b)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The provisions of this Section 6(b) are
        intended to apply if the Award is subject to Section 409A because of the terms of a severance arrangement or other agreement between you and the Company, if any, that provides for acceleration of vesting of the Award upon your separation from
        service (as such term is defined in section 409A(a)(2)(A)(i) of the Code and applicable guidance thereunder (&#8220;<font style="font-weight: bold; font-style: italic;">Separation From Service</font>&#8221;) and such severance benefit does not satisfy the
        requirements for an exemption from application of Section 409A provided under Treasury Regulations Sections 1.409A-1(b)(4) or 1.409A-1(b)(9) (&#8220;<font style="font-weight: bold; font-style: italic;">Non-Exempt Severance Arrangement</font>&#8221;).&#160; If the
        Award is subject to and not exempt from application of Section 409A due to application of a Non-Exempt Severance Arrangement, the following provisions in this Section 6(b) shall supersede anything to the contrary in Section 6(a).</font></div>
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    <div style="margin-bottom: 12pt; text-indent: 108pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(i)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If the Award vests in ordinary course
        during your Continuous Service in accordance with the vesting schedule set forth in the Grant Notice, in no event will the shares to be issued in respect of your Award be issued any later than the later of: (i) December 31<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">st</sup> of the calendar year that includes the applicable vesting date, or (ii) the 60<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> day
        that follows the applicable vesting date.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 108pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(ii)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If the Award accelerates vesting under the
        terms of your Non-Exempt Severance Arrangement in connection with your Separation From Service, and such vesting acceleration provisions of your Non-Exempt Severance Arrangement were in effect as of the date of grant of the Award and therefore part
        of the terms of the Award as of the date of grant, then the shares will be earlier issued in respect of your Award upon your Separation From Service in accordance with the terms of the Non-Exempt Severance Arrangement, but in no event later than
        the 60<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> day that follows the date of your Separation From Service.&#160; However, if at the time the shares would otherwise be issued you are subject to the distribution
        limitations contained in section 409A of the Code applicable to &#8220;specified employees&#8221; as defined in section 409A(a)(2)(B)(i) of the Code and applicable guidance thereunder, such share issuances shall not be made before the date which is six months
        following the date of your Separation From Service, or, if earlier, the date of your death that occurs within such six month period.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 108pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(iii)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If the Award accelerates vesting under
        the terms of your Non-Exempt Severance Arrangement in connection with your Separation From Service, and such vesting acceleration provisions of your Non-Exempt Severance Arrangement were not in effect as of the date of grant of the Award and
        therefore not a part of the terms of the Award on the date of grant, then such acceleration of vesting of the Award shall not accelerate the issuance date of the shares, but the shares shall instead be issued on the same schedule as set forth on
        the Grant Notice as if they had vested in ordinary course during your Continuous Service, notwithstanding the vesting acceleration of the Award.&#160; Such issuance schedule is intended to satisfy the requirements of payment on a specified date or
        pursuant to a fixed schedule, as provided under Treas. Reg. 1.409A-3(a)(4).</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(c)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The provisions in this Agreement for
        delivery of the shares in respect of the Award are intended either to comply with the requirements of Section 409A or to provide a basis for exemption from such requirements so that the delivery of the shares will not trigger the additional tax
        imposed under Section 409A, and any ambiguities herein will be so interpreted.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">7.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Dividends.</font><font style="font-weight: bold;">&#160; </font>You shall be entitled to receive payments equal to any cash dividends and other distributions paid with respect to&#160; a corresponding number of shares to be issued in respect
        of the Stock Units covered by your Award, provided that if any such dividends or distributions are paid in shares, the Fair Market Value of such shares shall be converted into additional Stock Units covered by the Award, and further provided that
        such additional Stock Units shall be subject to the same forfeiture restrictions and restrictions on transferability as apply to the Stock Units subject to the Award with respect to which they relate.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">8.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Restrictive Legends.</font>&#160; The shares issued in respect of your Award shall be endorsed with appropriate legends determined by the Company.</font></div>
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    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">9.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Award not a Service Contract</font><font style="font-weight: bold;">.</font></font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(a)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Your Continuous Service with the Company or
        an Affiliate is not for any specified term and may be terminated by you or by the Company or an Affiliate at any time, for any reason, with or without cause and with or without notice.&#160; Nothing in this Restricted Stock Unit Agreement (including,
        but not limited to, the vesting of your Award pursuant to the schedule set forth in Section 2 herein or the issuance of the shares in respect of your Award), the Plan or any covenant of good faith and fair dealing that may be found implicit in this
        Restricted Stock Unit Agreement or the Plan shall:&#160; (i) confer upon you any right to continue in the employ of, or affiliation with, the Company or an Affiliate; (ii) constitute any promise or commitment by the Company or an Affiliate regarding the
        fact or nature of future positions, future work assignments, future compensation or any other term or condition of employment or affiliation; (iii) confer any right or benefit under this Restricted Stock Unit Agreement or the Plan unless such right
        or benefit has specifically accrued under the terms of this Agreement or Plan; or (iv) deprive the Company of the right to terminate you at will and without regard to any future vesting opportunity that you may have.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(b)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;By accepting this Award, you acknowledge and
        agree that the right to continue vesting in the Award pursuant to the schedule set forth in Section 2 is earned only by continuing as an employee, director or consultant at the will of the Company (not through the act of being hired, being granted
        this Award or any other award or benefit) and that the Company has the right to reorganize, sell, spin-out or otherwise restructure one or more of its businesses or Affiliates at any time or from time to time, as it deems appropriate (a
        &#8220;reorganization&#8221;).&#160; You further acknowledge and agree that such a reorganization could result in the termination of your Continuous Service, or the termination of Affiliate status of your employer and the loss of benefits available to you under
        this Restricted Stock Unit Agreement, including but not limited to, the termination of the right to continue vesting in the Award.&#160; You further acknowledge and agree that this Restricted Stock Unit Agreement, the Plan, the transactions contemplated
        hereunder and the vesting schedule set forth herein or any covenant of good faith and fair dealing that may be found implicit in any of them do not constitute an express or implied promise of continued engagement as an employee or consultant for
        the term of this Agreement, for any period, or at all, and shall not interfere in any way with your right or the Company&#8217;s right to terminate your Continuous Service at any time, with or without cause and with or without notice.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">10.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Withholding Obligations.</font></font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(a)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;On or before the time you receive a
        distribution of the shares subject to your Award, or at any time thereafter as requested by the Company, you hereby authorize any required withholding (if any) from the Common Stock issuable to you and/or otherwise agree to make adequate provision
        in cash for any sums required to satisfy the federal, state, local and foreign tax withholding obligations (if any) of the Company or any Affiliate which arise in connection with your Award (the &#8220;<font style="font-weight: bold; font-style: italic;">Withholding


          Taxes</font>&#8221;).&#160; Additionally, the Company may, in its sole discretion, satisfy all or any portion of the Withholding Taxes obligation relating to your Award by any of the following means or by a combination of such means: (i) withholding from
        any compensation otherwise payable to you by the Company; (ii) causing you to tender a cash payment; or (iii) withholding shares of Common Stock from the shares of Common Stock issued or otherwise issuable to you in connection with the Award with a
        Fair Market Value (measured as of the date shares of Common Stock are issued to pursuant to Section 6) equal to the amount of such Withholding Taxes; provided, however, that the number of such shares of Common Stock so withheld shall not exceed the
        amount necessary to satisfy the Company&#8217;s required tax withholding obligations using the minimum statutory withholding rates for federal, state, local and foreign tax purposes, including payroll taxes, that are applicable to supplemental taxable
        income.</font></div>
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    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(b)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Unless the tax withholding obligations of
        the Company and/or any Affiliate are satisfied, the Company shall have no obligation to deliver to you any Common Stock.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(c)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;In the event the Company&#8217;s obligation to
        withhold arises prior to the delivery to you of Common Stock or it is determined after the delivery of Common Stock to you that the amount of the Company&#8217;s withholding obligation was greater than the amount withheld by the Company, you agree to
        indemnify and hold the Company harmless from any failure by the Company to withhold the proper amount.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(d)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If specified in your Grant Notice and
        permitted by the Company, you may direct the Company to withhold shares of Common Stock with a Fair Market Value (measured as of the date shares of Common Stock are issued pursuant to Section 6) equal to the amount of such Withholding Taxes;
        provided, however, that the number of such shares of Common Stock so withheld shall not exceed the amount necessary to satisfy the Company&#8217;s required tax withholding obligations using the minimum statutory withholding rates for federal, state,
        local and foreign tax purposes, including payroll taxes, that are applicable to supplemental taxable income.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">11.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Unsecured Obligation.</font>&#160; Your Award is unfunded, and as a holder of a vested Award, you shall be considered an unsecured creditor of the Company with respect to the Company&#8217;s obligation, if any, to issue shares
        pursuant to this Agreement.&#160; You shall not have voting or any other rights as a stockholder of the Company with respect to the shares to be issued pursuant to this Agreement until such shares are issued to you pursuant to Section 6 of this
        Agreement.&#160;&#160; Upon such issuance, you will obtain full voting and other rights as a stockholder of the Company.&#160; Nothing contained in this Agreement, and no action taken pursuant to its provisions, shall create or be construed to create a trust of
        any kind or a fiduciary relationship between you and the Company or any other person.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">12.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Other Documents</font><font style="font-variant: small-caps;">.</font>&#160; You hereby acknowledge receipt or the right to receive a document providing the information required by Rule 428(b)(1) promulgated under the
        Securities Act, which includes the Plan prospectus.&#160; In addition, you acknowledge receipt of the Company&#8217;s insider-trading policy and agree that you may sell shares only in compliance with such policy, in effect from time to time.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">13.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Notices</font><font style="font-weight: bold;">.</font>&#160; Any notices provided for in your Award or the Plan shall be given in writing and shall be deemed effectively given upon receipt or, in the case of notices
        delivered by the Company to you, five days after deposit in the United States mail, postage prepaid, addressed to you at the last address you provided to the Company.&#160; Notwithstanding the foregoing, the Company may, in its sole discretion, decide
        to deliver any documents related to participation in the Plan and this Award by electronic means or to request your consent to participate in the Plan by electronic means.&#160; You hereby consent to receive such documents by electronic delivery and, if
        requested, to agree to participate in the Plan through an on-line or electronic system established and maintained by the Company or another third party designated by the Company.</font></div>
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    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">14.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold;"><font style="font-variant: small-caps;">Miscellaneous</font>.</font></font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(a)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The rights and obligations of the Company
        under your Award shall be transferable to any one or more persons or entities, and all covenants and agreements hereunder shall inure to the benefit of, and be enforceable by the Company&#8217;s successors and assigns. Your rights and obligations under
        your Award may only be assigned with the prior written consent of the Company.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(b)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;You agree upon request to execute any
        further documents or instruments necessary or desirable in the sole determination of the Company to carry out the purposes or intent of your Award.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(c)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;You acknowledge and agree that you have
        reviewed your Award in its entirety, have had an opportunity to obtain the advice of counsel prior to executing and accepting your Award, and fully understand all provisions of your Award.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(d)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;This Agreement shall be subject to all
        applicable laws, rules, and regulations, and to such approvals by any governmental agencies or national securities exchanges as may be required.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 72pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">(e)</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;All obligations of the Company under the
        Plan and this Agreement shall be binding on any successor to the Company, whether the existence of such successor is the result of a direct or indirect purchase, merger, consolidation, or otherwise, of all or substantially all of the business
        and/or assets of the Company.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">15.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Governing Plan Document</font><font style="font-weight: bold;">.</font>&#160; Your Award is subject to all the provisions of the Plan, the provisions of which are hereby made a part of your Award, and is further subject to
        all interpretations, amendments, rules and regulations which may from time to time be promulgated and adopted pursuant to the Plan.&#160; Except as expressly provided herein, in the event of any conflict between the provisions of your Award and those of
        the Plan, the provisions of the Plan shall control.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">16.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Severability.</font>&#160; If all or any part of this Agreement or the Plan is declared by any court or governmental authority to be unlawful or invalid, such unlawfulness or invalidity shall not invalidate any portion of
        this Agreement or the Plan not declared to be unlawful or invalid. Any Section of this Agreement (or part of such a Section) so declared to be unlawful or invalid shall, if possible, be construed in a manner which will give effect to the terms of
        such Section or part of a Section to the fullest extent possible while remaining lawful and valid.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">17.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Choice of Law</font><font style="font-weight: bold;">.</font>&#160; The interpretation, performance and enforcement of this Agreement will be governed by the law of the state of California without regard to such state&#8217;s
        conflicts of laws rules.</font></div>
    <div style="margin-bottom: 12pt; text-indent: 36pt;"><font style="font-family: 'Times New Roman',Times,serif; font-weight: bold;">18.</font><font style="font-family: 'Times New Roman',Times,serif;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-weight: bold; font-variant: small-caps;">Amendment.</font>&#160; This Agreement may not be modified, amended or terminated except by an instrument in writing, signed by you and by a duly authorized representative of the Company. Notwithstanding the foregoing, this
        Agreement may be amended solely by the Board by a writing which specifically states that it is amending this Agreement, so long as a copy of such amendment is delivered to you, and provided that no such amendment adversely affecting your rights
        hereunder may be made without your written consent. Without limiting the foregoing, the Board reserves the right to change, by written notice to you, the provisions of this Agreement in any way it may deem necessary or advisable to carry out the
        purpose of the grant as a result of any change in applicable laws or regulations or any future law, regulation, ruling, or judicial decision, provided that any such change shall be applicable only to rights relating to that portion of the Award
        which is then subject to restrictions as provided herein.</font></div>
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