<SEC-DOCUMENT>0001140361-19-009912.txt : 20190529
<SEC-HEADER>0001140361-19-009912.hdr.sgml : 20190529
<ACCEPTANCE-DATETIME>20190528201732
ACCESSION NUMBER:		0001140361-19-009912
CONFORMED SUBMISSION TYPE:	DEFA14A
PUBLIC DOCUMENT COUNT:		2
FILED AS OF DATE:		20190529
DATE AS OF CHANGE:		20190528
EFFECTIVENESS DATE:		20190529

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:		DEFA14A
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		19859444

	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>
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<DESCRIPTION>DEFA14A
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      <div style="text-align: center; color: rgb(35, 31, 32); font-family: &quot;Times New Roman&quot;; font-size: 14pt; font-weight: bold;">UNITED STATES</div>
      <div style="text-align: center;"><font style="font-size: 14pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(35, 31, 32);">SECURITIES AND EXCHANGE COMMISSION</font></div>
      <div style="text-align: center; font-size: 12pt;"><font style="font-family: &quot;Times New Roman&quot;; font-weight: bold;">Washington, D.C. 20549</font></div>
      <div><br>
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      <div style="text-align: center;"><font style="font-size: 18pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(35, 31, 32);">SCHEDULE 14A</font></div>
      <div><br>
      </div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(35, 31, 32);">Proxy Statement Pursuant to Section 14(a) of</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(35, 31, 32);">the Securities Exchange Act of 1934 (Amendment No.</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-size: 10pt;
          font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(35, 31, 32);">)</font></div>
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      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Filed by the Registrant &#9746;</font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Filed by a Party other than the Registrant &#9744;</font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Check the appropriate box:</font></div>
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            <td style="width: 96%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Preliminary Proxy Statement</font></div>
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            <td style="width: 4%; vertical-align: top;">&#9744;</td>
            <td style="width: 96%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(35, 31, 32);">Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)(2))</font></div>
            </td>
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            <td style="width: 4%; vertical-align: top;">&#9744;</td>
            <td style="width: 96%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Definitive Proxy Statement</font></div>
            </td>
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            <td style="width: 4%; vertical-align: top;">&#9746;</td>
            <td style="width: 96%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Definitive Additional Materials</font></div>
            </td>
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            <td style="width: 4%; vertical-align: top;">&#9744;</td>
            <td style="width: 96%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Soliciting Material Pursuant to &#167;240.14a-12</font></div>
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              <div style="text-align: center;"><font style="font-family: &quot;Times New Roman&quot;; font-size: 24pt; color: rgb(35, 31, 32);"><font style="font-family: &quot;Times New Roman&quot;; font-size: 24pt;">Ionis Pharmaceuticals, Inc.</font></font></div>
            </td>
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              <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">(Name of Registrant as Specified In Its Charter)</font></div>
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              <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">(Name of Person(s) Filing Proxy Statement, if other than the Registrant)</font></div>
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            <td style="vertical-align: top;" colspan="3">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Payment of Filing Fee (Check the appropriate box):</font></div>
            </td>
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            <td style="width: 4%; vertical-align: top;">&#9746;</td>
            <td style="vertical-align: top;" colspan="2">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">No fee required.</font></div>
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            <td style="width: 4%; vertical-align: top;">&#9744;</td>
            <td style="vertical-align: top;" colspan="2">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Fee computed on table below per Exchange Act Rules 14a-6(i)(1) and 0-11.</font></div>
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            <td style="width: 4%; vertical-align: top;">&#160;</td>
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              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">(1)</font></div>
            </td>
            <td style="width: 92%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Title of each class of securities to which transaction applies:</font></div>
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            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 92%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <td style="width: 4%; vertical-align: top;">&#160;</td>
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              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">(2)</font></div>
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            <td style="width: 92%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Aggregate number of securities to which transaction applies:</font></div>
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            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 92%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <td style="width: 4%; vertical-align: top;">&#160;</td>
            <td style="width: 4%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">(3)</font></div>
            </td>
            <td style="width: 92%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Per unit price or other underlying value of transaction computed pursuant to Exchange Act Rule 0-11 (set forth the
                  amount on which the filing fee is calculated and state how it was determined):</font></div>
            </td>
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            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 92%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <td style="width: 4%; vertical-align: top;">&#160;</td>
            <td style="width: 4%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">(4)</font></div>
            </td>
            <td style="width: 92%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Proposed maximum aggregate value of transaction:</font></div>
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            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
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            <td style="width: 4%; vertical-align: top;">&#160;</td>
            <td style="width: 4%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">(5)</font></div>
            </td>
            <td style="width: 92%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Total fee paid:</font></div>
            </td>
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            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 92%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <td style="width: 4%; vertical-align: top;">&#9744;</td>
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              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Fee paid previously with preliminary materials.</font></div>
            </td>
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            <td style="width: 4%; vertical-align: top;">&#9744;</td>
            <td style="vertical-align: top;" colspan="2">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Check box if any part of the fee is offset as provided by Exchange Act Rule 0-11(a)(2) and identify the filing for
                  which the offsetting fee was paid previously. Identify the previous filing by registration statement number, or the Form or Schedule and the date of its filing.</font></div>
            </td>
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            <td style="width: 4%; vertical-align: top;">&#160;</td>
            <td style="width: 4%; vertical-align: top;">&#160;</td>
            <td style="width: 92%; vertical-align: top;">&#160;</td>
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            <td style="width: 4%; vertical-align: top;">&#160;</td>
            <td style="width: 4%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">(1)</font></div>
            </td>
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              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Amount Previously Paid:</font></div>
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            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 92%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <td style="width: 4%; vertical-align: top;">&#160;</td>
            <td style="width: 4%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">(2)</font></div>
            </td>
            <td style="width: 92%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Form, Schedule or Registration Statement No.:</font></div>
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            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 92%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <td style="width: 4%; vertical-align: top;">&#160;</td>
            <td style="width: 4%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">(3)</font></div>
            </td>
            <td style="width: 92%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Filing Party:</font></div>
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            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
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            <td style="width: 4%; vertical-align: top;">&#160;</td>
            <td style="width: 4%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">(4)</font></div>
            </td>
            <td style="width: 92%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(35, 31, 32);">Date Filed:</font></div>
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            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
            <td style="width: 4%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;</td>
            <td style="width: 92%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
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      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(35, 31, 32);">Persons who are to respond to the collection of information contained in this form are not required to
          respond unless the form displays a currently valid OMB control number</font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(35, 31, 32);"> <br>
        </font></div>
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      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"> Ionis Pharmaceuticals, Inc.<br>
        </font></div>
      <div style="text-align: center;">2019 Annual Meeting of Stockholders</div>
      <div style="text-align: center;">Supplemental Information Regarding Proposal 5<font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><br>
        </font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"> <br>
        </font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">May 28, 2019</font></div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Dear Stockholders:</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">We are writing to ask for your support by voting in accordance with the recommendations of the Board of Directors (the &#8220;Board&#8221;) of Ionis
          Pharmaceuticals, Inc. (the &#8220;Company&#8221; or &#8220;Ionis&#8221;) on all of the Company&#8217;s proxy proposals.&#160; In particular, we are asking for you to vote &#8220;FOR&#8221; Proposal 5: our advisory vote on executive compensation (our &#8220;Say-on-Pay Proposal&#8221;).</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Our compensation philosophy, program and 2018 decisions are described in detail in our 2019 proxy statement (the </font><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">&#8220;Proxy Statement,&#8221;</font> available <font style="font-weight: normal; font-family: &quot;Times New
            Roman&quot;,Times,serif; font-size: 10pt; font-style: normal; font-variant: normal; text-transform: none;"><a href="http://www.sec.gov/Archives/edgar/data/874015/000114036119007625/nc10001158x1_def14a.htm">here</a></font>), but to assist you in
          evaluating our Say-on-Pay Proposal, we would like to provide you with certain additional information and context.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">To understand our executive compensation program, we believe it is important to understand our business and organizational
          strategy:</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" id="zb79a6de6e65f476d95f539f3ea5ed1df" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;">

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                <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">&#8226;</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">Business Strategy</font>: Ionis is a multi-product commercial
                      company with a pipeline of first-in-class and/or best-in-class medicines discovered by Ionis that are designed to treat a broad range of diseases including neurological disease, cardiovascular disease, rare diseases, infectious
                      diseases and cancer.&#160; Ionis has created an efficient, broadly applicable, drug discovery platform called antisense technology with the potential to treat diseases where no other therapeutic approaches have proven effective or ever
                      existed.&#160; <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis is committed to creating long-term value through innovation based on the efficiency of antisense technology.</font>&#160; <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis has been recognized as one of the top innovative companies in the biotechnology industry, based on number of granted patents, scientific
                        strength, industry impact, technology strength and research intensity.</font></font></div>
                </td>
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      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
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                <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">&#8226;</font></td>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">Organizational Strategy</font>: <font style="font-size: 10pt;
                        font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">A key component of our business and organizational strategy is to maintain an optimal size to continue to foster innovation. We are able to maintain an optimal size by
                        licensing our medicines at key value inflection points during development, thus avoiding the need to build the large, complex, inefficient organizations associated with fully integrated pharmaceutical companies.&#160; Ionis has an
                        innovation-focused, science-driven culture that couples with the technology and business model to ensure long-term productivity and a commitment to patients and stockholders.&#160; With more than 1,800 issued patents (over three per
                        employee) that provide substantial control of key elements of the technology for many years to come and </font>a pipeline of more than 40 first-in-class and/or best-in-class medicines (<font style="font-size: 10pt; font-family:
                        &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">one medicine in development per 11 employees</font>), <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">we, by design, demand more of
                        every employee at Ionis, particularly the middle and senior level leaders, and we do not tolerate mediocrity.</font></font></div>
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      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">Ionis delivered significant performance in <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color:
            rgb(0, 0, 0);">2018, with a number of achievements demonstrating the productivity and strength of our business strategy:</font></font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Our TSR outperformed <font style="background-color: rgb(255, 255, 255); font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">the
                        median of the Nasdaq Biotechnology Index over the previous one-, three- and five-year periods.&#160; Outperforming the median of the Nasdaq Biotechnology Index for 2018 was a performance objective and measure set for management at the
                        beginning of 2018. As such, Ionis met the </font><font style="background-color: rgb(255, 255, 255); font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic; color: rgb(0, 0, 0);">pre-defined, objective, stock
                        price performance measure</font><font style="background-color: rgb(255, 255, 255); font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);"> set for the year.&#160; Over the previous one-year period, our TSR also
                        outperformed the Russell 3000 index and the </font><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">peer group of 20 life science companies (the &#8220;Peer Group&#8221;) that the Compensation
                        Committee of our Board (the &#8220;Compensation Committee&#8221;) uses for evaluating Ionis&#8217; compensation</font><font style="background-color: rgb(255, 255, 255); font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">.</font></font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">We obtained approval to market TEGSEDI in the U.S., EU and Canada
                        for the treatment of a devastating disease &#8211; polyneuropathy caused by hereditary TTR amyloidosis.</font></font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">As further described below, we earned an all-time high for
                        revenue, substantially exceeding our 2018 financial guidance and achieving our third consecutive year of non-GAAP<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup> operating income, despite receiving a Complete Response Letter for a medicine we hoped to commercialize in
                        2018.</font></font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">We achieved these financial successes while advancing a diverse
                        pipeline of over 40 potentially transformative medicines, ten of which are advancing toward pivotal studies by the end of 2020, with four of those expected to enter pivotal studies by the end of 2019.</font></font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">While successfully advancing our pipeline and technology, we
                        aggressively invested in commercializing TEGSEDI globally, achieving sales of over $2 million in the first partial quarter of being on the market.</font></font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis and Biogen received the prestigious International Prix Galien Award for the Best Biotechnology Product in 2018 for SPINRAZA.</font></div>
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      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(0, 0, 0);">Additional evidence of our productivity and the benefit of our business strategy is reflected by our
          strong financial position:</font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">We ended 2018 in a very strong financial position, with 2018 revenues of $600 million, an increase of more than 15% from 2017, and <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">Ionis&#8217; seventh consecutive year of revenue growth</font>.</font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">For the third year in a row, we were profitable, with non-GAAP<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;"></sup> operating income in 2018 of $70 million. This success is driven
                      by the strength of our business strategy, which leverages numerous sources of revenue, with multiple opportunities for upside, while reducing risk.</font></div>
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      <div style="text-align: center;"><img src="graphic1.jpg"></div>
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      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">* 2016 and 2017 revised for FASB Topic ASC 606 adjustment.</font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">We ended 2018 with a strong balance sheet with more than $2 billion in cash and short-term investments, making this the <font style="font-size: 10pt;
                        font-family: &quot;Times New Roman&quot;; font-style: italic;">sixth year out of seven that we have been cash accretive</font>. Our strong balance sheet provides us with the financial wherewithal to invest in expanding and advancing
                      our pipeline, in commercializing our medicines through commercial affiliates, and advancing our technology.</font></div>
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      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;"> </sup></font> </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup>&#160;<font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">We use &#8220;non-GAAP&#8221; in place of
            &#8220;pro-forma&#8221; when discussing our financial results that exclude non-cash compensation expense related&#160;to equity awards because we believe that non-GAAP financial results better represent the economics of our business and how we manage&#160;our
            business.</font></font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);"> <br>
          </font></font></div>
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        <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">3</font></div>
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      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">Additionally, we believe it is important to reiterate how our executive compensation strategy is aligned with our business
          and organizational strategy as further context for our 2018 executive compensation decisions:</font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">Simply put, we demand great performance and
                        pay for that performance</font>.&#160; The Compensation Committee has structured the various components of our compensation system to reflect accountability for the successes and failures (both long-term and short-term) of Ionis, which
                      means that a significant proportion of executive officers&#8217; compensation is &#8220;at risk&#8221; <font style="background-color: rgb(255, 255, 255); font-size: 10pt; font-family: &quot;Times New Roman&quot;;">in the form of performance-based cash
                        payments through our annual Performance Management By Objective Program (&#8220;Performance MBO Program&#8221;) and long-term equity awards tied to stock price.&#160; </font>We pay our senior management team for results and their use of judgment in
                      executing the strategies established at the beginning of each year.</font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">Our executive compensation program is designed
                        to align with our strategic focus, organizational strategy and the creation of long-term stockholder value</font>.&#160;&#160; Drug discovery and development across a portfolio of many medicines is a long process that spans many years, where
                      decisions we make today can have a positive or negative consequence five years, ten years, and even further into the future. As such, it is essential we set goals that incentivize our employees to execute our long-term strategy,
                      because we believe our long-term strategy should continue to reward our stockholders into the future.&#160; For us to retain our technology leadership and effectively manage the technical complexity and broad scope of our pipeline, our
                      most senior executives and the members of their teams must advance multiple drug development strategies and collaborative partnerships in parallel and consistently over many years, versus emphasizing one or two at the expense of
                      others that deserve attention.</font></div>
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                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">Our Performance MBO Program includes
                        aggressive results-driven corporate objectives with objective measures, no guaranteed payouts, and maximum payout limits, and the Compensation Committee has negative discretion to reduce payouts after considering one-, three- and
                        five-year total stockholder returns</font>.&#160; At the beginning of each year, the Compensation Committee approves annual performance objectives on which we believe our executive officers should focus during the year in order to
                      achieve our business goals, including financial, operating and/or strategic plans, and we monitor and review progress against these objectives during and after each year.&#160; These objectives are aggressive results-driven corporate
                      objectives and <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">include objective measures for each objective</font>.</font></div>
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      <div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">We typically include a number of objectives that are based on achieving positive data in the clinic.
          For example, in 2018 we had a corporate objective to make our relationship with Novartis successful with one of the objective measures being to achieve positive data from a Phase 2 dose-ranging study, and another corporate objective to advance
          our pipeline with one of the objective measures being to achieve positive proof-of-concept on five or more medicines. These types of objectives only reward our employees if the data are positive&#8212;we do this to encourage the prudent spending of
          stockholder money on development decisions. In other words, we want to structure our objectives to reward success based on good judgment, rather than the making of &#8220;bad bets.&#8221;</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">The Compensation Committee generally believes that a formulaic or purely quantitative approach to our
          Performance MBO Program is not the best way to align executive compensation with our business and organizational strategy and foster long-term success for Ionis and long-term value for stockholders. Other than stock price, budget and our annual
          financial guidance to Wall Street, we currently do not use financial-based metrics as objectives, such as earnings per share, because financial metrics typically overly emphasize two or three annual business metrics and ignore the complexity of
          the tasks we are undertaking. By taking this approach, we avoid the temptation to deviate from creating fundamental long-term value to meet a short-term metric.</font></div>
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        <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">4</font></div>
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      <div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Awards under our Performance MBO Program are not guaranteed (i.e., are 100% at risk) and include a
          multiplier, or performance factor, based on Ionis&#8217; performance (the &#8220;Company Performance Factor</font><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);"><font style="font-size: 10pt; font-family: 'Times
            New Roman', Times, serif; color: #000000;">&#8221;</font>) and the employee&#8217;s performance (the &#8220;Individual Performance Factor&#8221;). Therefore, if <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;"><u>either</u></font><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">&#160;</font>Ionis or the employee performs poorly, the Performance MBO can be, and has been, zero.&#160; We establish rigorous corporate objectives and define
          excellent performance as a year in which we have met most of those objectives.&#160; The Compensation Committee considers our one-, three- and five-year total stockholder returns, and based on these returns has negative discretion to reduce the
          Corporate Performance Factor and Individual Performance Factor for each of our executive officers.&#160; As further described below, although Ionis met nine objectives, exceeded seven objectives, did not meet only one objective and had multiple
          significant unplanned accomplishments, the Company Performance Factor for 2018 was 115%, which reflects <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">a decrease of 20 percentage points from the 2017
            Company Performance Factor of 135%</font>.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; margin-left: 36pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">The Compensation Committee
            measures Ionis&#8217; performance based upon the achievement of the rigorous corporate objectives set at the beginning of the year.&#160; At that time, the Compensation Committee reviews the Company Performance Factor history from the prior ten years to
            form a comparison for our current year&#8217;s successes and/or failures.&#160; The Compensation Committee also approves each executive officer&#8217;s Individual Performance Factor based on the individual&#8217;s performance. We have a maximum Company Performance
            Factor of 200% and a maximum Individual Performance Factor of 160%.&#160; I</font>llustrating the rigor of our performance objectives and culture of high performance and accountability, our CEO&#8217;s 2018 bonus was approximately 25% lower than in 2017.&#160;
        </font></div>
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                <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">The Compensation Committee annually considers
                        the appropriate mix of equity awards and continues to believe that time-vested stock options and restricted stock unit (&#8220;RSU&#8221;) awards are the appropriate mix for the following reasons</font>:</font></div>
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                  <td style="vertical-align: top; width: 18pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">o</font></td>
                  <td style="align: left; vertical-align: top; width: auto;">
                    <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">During the past several years, Ionis has discussed the use of time-vested stock options and RSU awards with
                        our institutional stockholders, many of which acknowledged the prevalence of stock options in the biopharmaceutical industry and agreed that we had the right mix of equity vehicles for our industry and stage.</font></div>
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                <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">o</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Stock options are inherently performance-based compensation.&#160; For the recipient of a stock option to recognize any economic value, the
                      stock price must appreciate following the grant date and prior to vesting and exercise.&#160; Similarly, in the same way our stockholders&#8217; returns increase and decrease based on our stock&#8217;s performance, the value to our employees of RSUs
                      increases and decreases based on our stock&#8217;s performance.</font></div>
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                <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">o</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Time-vested stock options and RSUs facilitate a focus on the totality of Ionis&#8217; ongoing and future activities as potential contributors to
                      stock price appreciation. Performance-based equity awards could promote excessive risk-taking that could adversely impact Ionis or its drug discovery and development efforts.</font></div>
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        <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">5</font></div>
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                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">Our executive compensation program also reflects strong corporate
                        governance attributes</font>. The Compensation Committee, <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">with assistance from our independent compensation consultant, provides
                        comprehensive oversight of our executive compensation program. The Compensation Committee regularly evaluates the economic, strategic and organizational challenges facing Ionis and periodically modifies our executive compensation
                        program to address these and other factors that evolve over time. For example, in response to requests from some of our stockholders who asked that we provide more disclosure around the goal-setting process for our bonus program to
                        demonstrate how the goals translate into measurable results, we recently have been providing more disclosure around our Performance MBO Program.&#160; </font>We also maintain stock ownership and holding guidelines, have a strict policy
                      prohibiting hedging and pledging, maintain a clawback policy, impose minimum vesting requirements for equity awards, do not provide tax gross-up payments other than for relocation, and do not guarantee bonuses or base salary increases
                      or provide perquisites for any employees.</font></div>
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      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">When designing our 2018 executive compensation program, the Compensation Committee remained steadfastly committed to
          aligning our executives&#8217; compensation with the interests of our stockholders and the performance of Ionis.&#160; We strongly believe that our 2018 executive compensation program fostered a culture of high performance and accountability and promoted
          long-term stockholder value creation.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);"><font style="background-color: rgb(255, 255, 255); font-size: 10pt; font-family: &quot;Times New Roman&quot;;">As
            described in the Proxy Statement, </font>the Compensation Committee set the Company Performance Factor for the 2018 Performance MBO Program at 115% due to our strong achievements for the year across drug discovery, development, corporate
          development and financial performance, particularly given:</font></div>
      <div><br>
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                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">SPINRAZA significantly surpassed sales goals, generating 2018 global sales of over $1.7 billion, and is now the standard of care for all
                      patients with spinal muscular atrophy, or SMA;</font></div>
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                <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Regulatory authorities in the U.S., EU and Canada approved marketing applications for TEGSEDI (inotersen) and Akcea launched the product in
                      the U.S. and EU; and</font></div>
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                <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis revenues for 2018 increased by more than 15% compared to 2017, the Company achieved non-GAAP operating income for the third
                      consecutive year, and ended the year with more than $2 billion in cash and short-term investments on its balance sheet.</font></div>
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      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">These positives were offset by a Complete Response Letter we and our affiliate, Akcea Therapeutics, Inc., received for
          WAYLIVRA.&#160; The Company&#8217;s strong performance despite encountering this regulatory setback is a testament to the success of Ionis&#8217; business model, which relies on revenue from a variety of sources.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">The Proxy Statement includes a table with a transparent, detailed and objective evaluation of each performance objective
          that the Board and management set at the beginning of the year, as well as a description of notable unplanned accomplishments that the Compensation Committee considered in evaluating the Company&#8217;s 2018 performance. <font style="background-color:
            rgb(255, 255, 255); font-size: 10pt; font-family: &quot;Times New Roman&quot;;">For reference, at the end of these supplemental materials as </font><font style="background-color: rgb(255, 255, 255); font-size: 10pt; font-family: &quot;Times
            New Roman&quot;;"><u>Schedule I</u></font><font style="background-color: rgb(255, 255, 255); font-size: 10pt; font-family: &quot;Times New Roman&quot;;"> we have included the full table previously published in the Proxy Statement.&#160; </font>The
          Compensation Committee takes great care to ensure that compensation decisions are based on tangible performance in accordance with our pay-for-performance philosophy, as evidenced by the varied decisions related to pay that are reflected in our
          proxy.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic; color: rgb(0, 0, 0);">As described above, although
            we define excellent performance as a year in which we have met most of the objectives, and for 2018, Ionis met nine objectives, exceeded seven objectives, did not meet only one objective and had multiple significant unplanned accomplishments,
            the 2018 Company Performance Factor of 115% reflects a decrease of 20 percentage points from the 2017 Company Performance Factor of 135%</font><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">.&#160; This
            is in large part due to the Complete Response Letter received from the FDA for WAYLIVRA, but nevertheless reflects a strong year of performance against the preset strategic objectives.&#160; Further </font>illustrating the rigor of our performance
          objectives and culture of high performance and accountability, our CEO&#8217;s 2018 bonus was approximately 25% lower than in 2017.&#160; Notably, our CEO&#8217;s target bonus percentage was below the median of our Peer Group and our other named executive
          officers&#8217; target bonuses were either at or below the median of our Peer Group.</font></div>
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        <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">6</font></div>
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      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">Our Board remains committed to an executive compensation program that supports our strategic objectives and aligns with
          stockholders&#8217; interests.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">The Compensation Committee takes into account stockholder feedback (including considering the results of our annual say-on-pay proposals) in
          evaluating and making executive compensation decisions, and is committed to maintaining an active dialogue with our stockholders<font style="background-color: rgb(255, 255, 255); font-size: 10pt; font-family: &quot;Times New Roman&quot;; color:
            rgb(0, 0, 0);"> on topics of particular concern to stockholders, including executive compensation matters.&#160; </font>For the reasons set forth above and in our Proxy Statement, we urge you to vote &#8220;FOR&#8221; our Say-on-Pay Proposal (Proposal 5). Even
          if you have already voted, you can change your vote before the <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">2019 Annual Meeting of Stockholders</font>, as described in more detail in our Proxy
          Statement <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">(under the heading &#8220;</font><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic; color: rgb(0, 0, 0);">Can




            I change my vote after submitting my proxy</font><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">?&#8221;)</font>.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">We appreciate your time and consideration on these matters and ask for your support of the Board&#8217;s recommendation.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(0, 0, 0);"><font style="background-color: rgb(255, 255, 255); font-size: 10pt; font-family: &quot;Times New
            Roman&quot;;">Special Note Regarding Forward-Looking Statements</font></font></div>
      <div><br>
      </div>
      <div style="text-align: left; text-indent: 20pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">These materials include forward-looking statements regarding our business and the therapeutic and
          commercial potential of SPINRAZA (nusinersen), TEGSEDI (inotersen), WAYLIVRA (volanesorsen) and our technologies and products in development, including the business of Akcea Therapeutics, Inc., our majority-owned affiliate. Any statement
          describing our goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly
          those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. Our forward-looking statements also
          involve assumptions that, if they never materialize or prove correct, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Although our forward-looking statements reflect the good faith
          judgment of our management, these statements are based only on facts and factors currently known by us. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning our programs are described in
          additional detail in our Annual Report on Form 10-K for the year ended December 31, 2018, which is on file with the SEC. Copies of the 10-K and other documents are available from the Company.</font></div>
      <div><br>
      </div>
      <div style="text-align: left; text-indent: 20pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">In these materials, unless the context requires otherwise, &#8220;Ionis,&#8221; &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221;
          refers to Ionis Pharmaceuticals, Inc. and its subsidiaries.</font></div>
      <div><br>
      </div>
      <div style="text-align: left; text-indent: 20pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8220;Ionis,&#8221; the Ionis logo, and other trademarks or service marks of Ionis Pharmaceuticals, Inc. appearing in
          these materials are the property of Ionis Pharmaceuticals, Inc. &#8220;Akcea,&#8221; the Akcea logo, and other trademarks or service marks of Akcea Therapeutics, Inc. appearing in these materials are the property of Akcea Therapeutics, Inc. These materials
          contain additional trade names, trademarks and service marks of others, which are the property of their respective owners. Solely for convenience, trademarks and trade names referred to in these materials may appear without the &#174; or TM symbols.</font></div>
      <div><br>
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        <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">7</font></div>
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      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">Schedule I</font></div>
      <div><br>
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      <div>
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                  <div style="text-align: center; color: rgb(0, 0, 0); font-family: &quot;Times New Roman&quot;; font-size: 10pt; font-weight: bold;">Evaluation of 2018 Corporate Objectives</div>
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                  <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(0, 0, 0);">Objective &amp; Pre-Approved Objective Measures</font></div>
                </div>
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                <div>
                  <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; color: rgb(0, 0, 0);">Evaluation</font></div>
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              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
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                  <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">1</font></div>
                </div>
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                  <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">SPINRAZA &#8211; Achieve successful commercialization:</font></div>
                </div>
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              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                        italic;"><u>exceeded</u></font> this objective:</font></div>
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              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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                <div>
                  <div style="text-align: justify; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times
                      New Roman&quot;; color: rgb(0, 0, 0);">2018 sales &#8805;&#160; $1.5 billion</font></div>
                </div>
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                <div>
                  <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;; color: rgb(0, 0, 0);">Ionis and Biogen significantly exceeded this goal, generating 2018 global sales of over $1.7 billion</font></div>
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            </tr>
            <tr>
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              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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                  <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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            </tr>
            <tr>
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            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
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            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                  <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">2</font></div>
                </div>
              </td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                </div>
              </td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                        italic;"><u>did not meet</u></font> this objective, with one exception:</font></div>
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              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                  <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                  <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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                  <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                  <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;; color: rgb(0, 0, 0);">Plan for certain dosage strength agreed with regulators</font></div>
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              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                  <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
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      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">8</font></div>
        <div id="DSPFPageBreak" style="page-break-after:always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zfc4379286f2642889cadb678929b1e0a" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse;">

          <tr>
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              Corporate Objectives</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1"><font style="font-size: 10pt; font-family:
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          <tr>
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          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
              <div>
                <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">3</font></div>
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            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">TEGSEDI (inotersen) &#8211; Approval and successful launch for hATTR polyneuropathy</font></div>
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            </td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                      italic;"><u>met</u></font> this objective:</font></div>
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          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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          </tr>
          <tr>
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            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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          </tr>
          <tr>
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            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Negotiate feasible REMS and RMP and have effective monitoring process in place at launch.</font></div>
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            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Supply chain in place at launch</font></div>
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            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160; &#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Expanded access program rapidly executed in accordance with plan</font></div>
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Ionis licensed to Akcea and is working with Akcea to successfully commercialize TEGSEDI in EU</font></div>
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            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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                    in Brazil and received priority review.</font></div>
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          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
              <div>
                <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">4</font></div>
              </div>
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            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Establish and implement aggressive development plan for AKCEA-TTR-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>:</font></div>
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            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                      italic;"><u>met</u></font> this objective:</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160; &#160; &#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Establish development plan for all forms of TTR amyloidosis with US and EU regulatory support</font></div>
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            </td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Ionis and Akcea established a development plan for hATTR and wtATTR and had constructive meetings with FDA in early 2019 regarding agreement on design of pivotal study for 2019</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Initiate Phase 1 study</font></div>
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            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;;">Ionis initiated a Phase 1/2 study for AKCEA-TTR-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub></font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
              <div>
                <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">5</font></div>
              </div>
            </td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Make Novartis relationship successful:</font></div>
              </div>
            </td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                      italic;"><u>met</u></font> this objective:</font></div>
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            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> dose-ranging study complete with positive data</font></div>
              </div>
              <div>
                <div style="text-indent: -18pt; margin-left: 27pt;">&#160;</div>
              </div>
            </td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Phase 2 dose-ranging study showed statistically significant dose-dependent reductions of Lp(a) compared to placebo at all dose levels and demonstrated favorable safety and tolerability profile</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;;">Positive end of Phase 2 meeting with FDA</font></div>
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            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;;">Ionis and Akcea had a positive end of Phase 2 meeting with FDA</font></div>
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            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Platelet monitoring frequency as per standard Phase 3 studies</font></div>
              </div>
              <div>
                <div style="text-indent: -18pt; margin-left: 27pt;">&#160;</div>
              </div>
            </td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Phase 2 dose-ranging study demonstrated favorable safety and tolerability profile, supporting standard (non-ASO) platelet monitoring frequency</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: justify; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Trigger Novartis option exercise process.</font></div>
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            </td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Completion of Phase 2 dose-ranging study with positive data and end of Phase 2 meeting with FDA triggered process for option decision</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Complete enrollment for dose-ranging study for AKCEA-APOCIII-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub></font></div>
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            </td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Ionis and Akcea continued to conduct the dose-ranging study for AKCEA-APOCIII-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>, with data expected in 2020.</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
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      </table>
      <div><br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">9</font></div>
        <div id="DSPFPageBreak" style="page-break-after:always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z7de22c962af842ffb8b089b77d814198" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse;">

          <tr>
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              Corporate Objectives&#160; </td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1"><font style="font-size: 10pt; font-family:
                &quot;Times New Roman&quot;; font-weight: bold; color: rgb(0, 0, 0);">Objective &amp; Pre-Approved Objective Measures</font></td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1"><font style="font-size: 10pt; font-family:
                &quot;Times New Roman&quot;; font-weight: bold; color: rgb(0, 0, 0);">Evaluation</font></td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
              <div>
                <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">6</font></div>
              </div>
            </td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Complete Biogen strategic transaction:</font></div>
              </div>
            </td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                      italic;"><u>exceeded</u></font> this objective:</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Terms consistent with 2018 budget</font></div>
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              <div>
                <div style="text-indent: -18pt; margin-left: 27pt;">&#160;</div>
              </div>
            </td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Ionis and Biogen entered into a new strategic collaboration to develop novel medicines for a broad range of neurological diseases and received a $1 billion upfront payment, comprised of $625 million
                    stock purchase at 25% premium and $375 million cash, with the potential to receive up to $270 million for each medicine that achieves marketing approval and royalties up to the 20% range.</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Successful collaboration launch and add four new targets to collaboration</font></div>
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            </td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Ionis and Biogen added <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">eleven</font> new targets to this collaboration</font></div>
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            </td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
              <div>
                <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">7</font></div>
              </div>
            </td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Make Biogen relationship successful:</font></div>
              </div>
            </td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                      italic;"><u>met</u></font> this objective:</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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              <div>
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            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
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            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
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            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160; &#160; <font style="font-size: 10pt; font-family: &quot;Times New
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            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
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        <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">10</font></div>
        <div id="DSPFPageBreak" style="page-break-after:always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
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        <table cellspacing="0" cellpadding="0" id="zd9238f767db6488288505859aa20a32f" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse;">

            <tr>
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                Corporate Objectives</td>
            </tr>
            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
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            <tr>
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            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
                <div>
                  <div style="color: rgb(0, 0, 0); font-family: &quot;Times New Roman&quot;; font-size: 10pt;">8</div>
                </div>
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              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                  <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis<font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
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            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            </tr>
            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">9</font></div>
                </div>
              </td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Make AstraZeneca CVMD relationship successful:</font></div>
                </div>
              </td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                        italic;"><u>exceeded</u></font> this objective:</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Achieve one development candidate milestone approval</font></div>
                </div>
              </td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Ionis achieved <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">two</font> development candidate approvals</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Achieve two target sanctions, one involving a novel LICA strategy</font></div>
                </div>
              </td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Ionis achieved two new target sanctions, one of which involved a novel LICA strategy</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            </tr>
            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">10</font></div>
                </div>
              </td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Achieve revenue target across AstraZeneca oncology and CVMD collaborations:</font></div>
                </div>
              </td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                        italic;"><u>exceeded</u></font> this objective:</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Ionis exceeded the revenue target across all AstraZeneca collaborations</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            </tr>
            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            </tr>
            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">11</font></div>
                </div>
              </td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Regulatory:</font></div>
                </div>
              </td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                        italic;"><u>met</u></font> this objective:</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Obtain agreement from FDA and major European regulators on platelet monitoring for frequency similar to standard (non-ASO) clinical studies for LICA programs</font></div>
                </div>
              </td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Regulators acknowledged the favorable safety and tolerability profile of the Phase 2 dose-ranging study for AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> and were supportive of standard (non-ASO) platelet
                      monitoring frequency for LICA programs</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            </tr>
            <tr>
              <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">12</font></div>
                </div>
              </td>
              <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Advance pipeline:</font></div>
                </div>
              </td>
              <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                        italic;"><u>exceeded</u></font> this objective:</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Initiate 1 Phase 3 trial</font></div>
                </div>
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;">&#160;</div>
                </div>
                <br>
              </td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Ionis made substantial progress toward initiating Phase 3 trial for RG6042 (formerly IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>) in patients living with symptoms of Huntington&#8217;s disease, with first patient
                      enrolled in January 2019</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Initiate first Phase 2 trials on &#8805;&#160; 4 medicines</font></div>
                </div>
              </td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Ionis initiated Phase 2 clinical trials for four medicines</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                      Roman&quot;,Times,serif; color: rgb(0, 0, 0);">Positive clinical proof-of-concept on &#8805;&#160; 5 medicines</font></div>
                </div>
              </td>
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            <tr>
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              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
              <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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            <tr>
              <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
              <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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            <tr>
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      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">11</font></div>
        <div style="page-break-after: always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
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              Corporate Objectives</td>
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          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
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            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
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            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
              <div>
                <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">13</font></div>
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              <div>&#160; </div>
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            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
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            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
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            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
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          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
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              <div>
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            </td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Ionis advanced the first Generation 2.5 medicine into clinical testing</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
              <div>
                <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">14</font></div>
              </div>
            </td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Meet budget/projections</font></div>
              </div>
            </td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                      italic;"><u>exceeded</u></font> this objective:</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Ionis significantly exceeded its financial guidance for 2018 and ended 2018 in a very strong financial position</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Ionis improved upon its budget</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
              <div>
                <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">15</font></div>
              </div>
              <div>
                <div>&#160;</div>
              </div>
            </td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Establish a near-, mid- and long-term tax strategy and implementation plan</font></div>
              </div>
            </td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                      italic;"><u>met</u></font> this objective:</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Ionis established a near-, mid- and long-term tax strategy and implementation plan</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
              <div>
                <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">16</font></div>
              </div>
            </td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Increase stock price performance by a percentage greater than or equal to median of the companies
                    listed in the Nasdaq Biotechnology Index</font></div>
              </div>
            </td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                      italic;"><u>exceeded</u></font> this objective:</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left;">
                  <div style="text-align: left; color: rgb(0, 0, 0); font-family: &quot;Times New Roman&quot;; font-size: 10pt; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;,Times,serif;
                      color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis&#8217; stock price outperformed the median stock price change for companies listed in the Nasdaq
                      Biotechnology Index</font></div>
                </div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" rowspan="1">&#160;</td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" rowspan="1">&#160;</td>
          </tr>
          <tr>
            <td style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">
              <div>
                <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">17</font></div>
              </div>
            </td>
            <td style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Achieve successful management transitioning</font></div>
              </div>
            </td>
            <td style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; margin-left: 2pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style:
                      italic;"><u>met</u></font> this objective:</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">New senior leaders contributed meaningfully to Ionis&#8217; and Akcea&#8217;s success in 2018</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0);">
              <div>
                <div style="text-align: left; text-indent: -18pt; margin-left: 27pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">&#8226;</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New
                    Roman&quot;; color: rgb(0, 0, 0);">Ionis successfully established a Translational Medicine group</font></div>
              </div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 3.55%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;">&#160;</td>
            <td rowspan="1" style="width: 42.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 54.27%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>

      </table>
      <div><br>
      </div>
      <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" id="DSPFPageNumberArea"><font style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">12</font></div>
        <div id="DSPFPageBreak" style="page-break-after:always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" border="0" id="z31d797b5f2124a46949af47805c2cd29" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse;">

            <tr>
              <td style="vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);" colspan="2">
                <div>
                  <div style="text-align: center; color: rgb(0, 0, 0); font-family: &quot;Times New Roman&quot;; font-size: 10pt; font-weight: bold;">Unplanned Accomplishments for 2018</div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 4%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">18</font></div>
                </div>
              </td>
              <td style="width: 96%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis licensed the worldwide rights to commercialize TEGSEDI and AKCEA-TTR-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> exclusively to Akcea</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 4%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">19</font></div>
                </div>
              </td>
              <td style="width: 96%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis licensed the worldwide rights to develop and commercialize IONIS-FB-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> for the treatment of
                      complement-mediated diseases exclusively to Roche and received a $75 million upfront payment</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 4%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">20</font></div>
                </div>
              </td>
              <td style="width: 96%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Biogen exercised its option to obtain a worldwide, exclusive royalty-bearing license to develop and commercialize
                      IONIS-SOD1<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> (BIIB067) and paid Ionis a $35 million upfront payment</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 4%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">21</font></div>
                </div>
              </td>
              <td style="width: 96%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis strengthened its clinical development team by completing significant hires</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 4%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">22</font></div>
                </div>
              </td>
              <td style="width: 96%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">IONIS-HTT<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> (RG6042) demonstrated positive correlation between mHTT reduction and clinical outcomes in
                      Phase 1/2 study</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 4%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">23</font></div>
                </div>
              </td>
              <td style="width: 96%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Akcea licensed the rights to commercialize TEGSEDI and WAYLIVRA in Latin America exclusively to PTC Therapeutics</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 4%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">24</font></div>
                </div>
              </td>
              <td style="width: 96%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Phase 1 study of IONIS-SOD1<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> (BIIB067) demonstrated robust clinical benefit in aggressive form of ALS</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 4%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">25</font></div>
                </div>
              </td>
              <td style="width: 96%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis licensed the worldwide rights to develop and commercialize IONIS-RHO-2.5<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> for the treatment of
                      autosomal dominant retinitis pigmentosa exclusively to ProQR Therapeutics</font></div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 4%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); text-align: center;">
                <div>
                  <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">26</font></div>
                </div>
              </td>
              <td style="width: 96%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
                <div>
                  <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; color: rgb(0, 0, 0);">Ionis successfully developed a plan for a new corporate communications brand</font></div>
                </div>
              </td>
            </tr>

        </table>
      </div>
    </div>
    <div><br>
    </div>
    <div><br>
    </div>
    <div style="text-align: center;"><font style="font-family: &quot;Times New Roman&quot;; font-size: 8pt; font-weight: normal; font-style: normal;" id="DSPFPageNumber">13</font></div>
    <div>
      <hr noshade="noshade" align="center" style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;"></div>
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</TEXT>
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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
