<SEC-DOCUMENT>0001140361-19-005627.txt : 20190326
<SEC-HEADER>0001140361-19-005627.hdr.sgml : 20190326
<ACCEPTANCE-DATETIME>20190326144950
ACCESSION NUMBER:		0001140361-19-005627
CONFORMED SUBMISSION TYPE:	8-K
PUBLIC DOCUMENT COUNT:		6
CONFORMED PERIOD OF REPORT:	20190322
ITEM INFORMATION:		Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers: Compensatory Arrangements of Certain Officers
ITEM INFORMATION:		Financial Statements and Exhibits
FILED AS OF DATE:		20190326
DATE AS OF CHANGE:		20190326

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:		8-K
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		19705076

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

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

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	ISIS PHARMACEUTICALS INC
		DATE OF NAME CHANGE:	19930328
</SEC-HEADER>
<DOCUMENT>
<TYPE>8-K
<SEQUENCE>1
<FILENAME>form8k.htm
<DESCRIPTION>8-K
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      <div style="text-align: center; font-family: &quot;Times New Roman&quot;; font-size: 14pt; font-weight: bold;">SECURITIES AND EXCHANGE COMMISSION</div>
      <div style="text-align: center; font-size: 12pt;"><font style="font-family: &quot;Times New Roman&quot;; font-weight: bold;">Washington, D.C.&#160; 20549</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;"> <br>
        </font></div>
      <div style="text-align: center; font-size: 18pt;"><font style="font-family: &quot;Times New Roman&quot;; font-weight: bold;">FORM 8-K</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;"> <br>
        </font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">CURRENT REPORT</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">PURSUANT TO SECTION 13 OR 15(d) OF THE</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">SECURITIES EXCHANGE ACT OF 1934</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;"> <br>
        </font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Date of report (Date of earliest event reported):&#160; March 22, 2019</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"> <br>
        </font></div>
      <div style="text-align: center; font-size: 24pt;"><font style="font-family: &quot;Times New Roman&quot;; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">(Exact Name of Registrant as Specified in Charter)</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"> <br>
        </font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">Delaware</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">(State or Other Jurisdiction of Incorporation)</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"> <br>
        </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;">000-19125</font></div>
            </td>
            <td colspan="1" style="width: 2%; vertical-align: top;">&#160;</td>
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              <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">33-0336973</font></div>
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              <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">(Commission File No.)</font></div>
            </td>
            <td colspan="1" style="width: 2%; vertical-align: top;">&#160;</td>
            <td style="width: 49%; vertical-align: top;">
              <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">(IRS Employer Identification No.)</font></div>
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      <div><br>
      </div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">2855 Gazelle Court</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Carlsbad, CA 92010</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(Address of Principal Executive Offices and Zip Code)</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
        </font></div>
      <div>
        <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Registrant&#8217;s telephone number, including area code: <font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(760) 931-9200</font></font></div>
        <div><br>
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      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the
          following provisions:</font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> </font><br>
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                    <div><font style="font-size: 10pt; font-family: 'Times New Roman';"><font style="font-size: 10pt; font-family: 'Times New Roman';">Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)</font></font></div>
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                    <div><font style="font-size: 10pt; font-family: 'Times New Roman';"><font style="font-size: 10pt; font-family: 'Times New Roman';">Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)</font></font></div>
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                  <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">&#9744;</font></td>
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                    <div><font style="font-size: 10pt; font-family: 'Times New Roman';"><font style="font-size: 10pt; font-family: 'Times New Roman';">Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))</font></font></div>
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                    <div><font style="font-size: 10pt; font-family: 'Times New Roman';"><font style="font-size: 10pt; font-family: 'Times New Roman';">Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))</font></font></div>
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      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> </font><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (Section 230.405 of this
          chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (Section 240.12b-2 of this chapter).</font></div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';"><br>
          Emerging growth company</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#9744;</div>
      <div style="text-align: justify;"> <br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new
          or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#9744;</font></div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
          </font></font></div>
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                <td style="width: 54pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Item 5.02</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers.</font></div>
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      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
        </font></div>
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                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(d)</font></div>
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              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Appointment of Dr. Brett Monia to Board of Directors</font></div>
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      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
        </font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">On March 22, 2019, the Board of Directors (the &#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Board</font>&#8221;)



          of Ionis Pharmaceuticals, Inc. (the &#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Company</font>&#8221;) increased the size of the Board from ten directors to eleven directors and appointed Brett
          Monia, Ph.D, the Company&#8217;s Chief Operating Officer, to the Board to fill the resulting vacancy.&#160; Dr. Monia will serve on the Board&#8217;s Agenda Committee, effective immediately.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Since the beginning of the Company&#8217;s last fiscal year through the present, there have been no related person transactions between Dr. Monia and the Company,
          and there are currently no proposed related person transactions between Dr. Monia and the Company, within the meaning of Item 404(a) of Regulation S-K.&#160; There are no arrangements or understandings between Dr. Monia and any other persons pursuant
          to which Dr. Monia was appointed as a director of the Company.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">A copy of the press release announcing the appointment of Dr. Monia is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated
          herein by reference.</font></div>
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                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(e)</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Amended and Restated Advisory Services Agreement between the Company and B. Lynne Parshall</font></div>
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      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">As the Company previously reported on its Current Report on Form 8-K filed on January 16, 2018, B. Lynne Parshall, who was with the Company for 27 years and
          was the Company&#8217;s former Chief Operating Officer, became a Senior Strategic Advisor to the Company effective January 2018.&#160; The Company and Ms. Parshall entered into a Strategic Advisory Services Agreement on January 15, 2018 to reflect her new
          role (the &#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Advisory Services Agreement</font>&#8221;). In 2018, Ms. Parshall performed significantly more services than originally expected. The
          Company thus agreed, with the approval of the Compensation Committee, to increase the amount of fees to be paid to Ms. Parshall commensurate with the amount of additional work performed and agreed that Ms. Parshall would be eligible for a bonus
          with a target of 30% of her fees with a personal performance factor and final bonus amount to be approved by the Compensation Committee.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">On March 22, 2019, the Company and Ms. Parshall entered into an amendment and restatement of the Advisory Services Agreement (the &#8220;<font style="font-size:
            10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Amended and Restated Advisory Services Agreement</font>&#8221;).&#160; Pursuant to the Amended and Restated Advisory Services Agreement, Ms. Parshall will receive compensation
          of $500,000 for services we expect Ms. Parshall to provide in the fiscal year ending December 31, 2019, which amount may be increased (but will not exceed $750,000 for the year) if Ms. Parshall renders more services than currently expected.&#160; In
          addition, at the conclusion of each fiscal year, Ms. Parshall will be eligible for a bonus with a target of 35% of her fees with a personal performance factor to be approved by the Compensation Committee.&#160; Payment for services after 2019 will be
          set by mutual written agreement between the Company and Ms. Parshall.</font></div>
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      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Ms. Parshall will continue to serve on the board of directors of the Company and Akcea Therapeutics, Inc. (&#8220;<font style="font-weight: bold; font-style:
            italic;">Akcea</font>&#8221;).&#160; Ms. Parshall will receive for her board service the same compensation as the Company and Akcea provide their other nonemployee directors.&#160; If in the future Ms. Parshall ends her board of director service for the
          Company, for 18 months following such date, the Company will pay Ms. Parshall&#8217;s COBRA premium payments, or if COBRA is not available, an amount equal to the cost of comparable health insurance coverage.&#160; The Amended and Restated Advisory Services
          Agreement will continue until terminated by the Company or Ms. Parshall upon 120 days&#8217; advance written notice.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">The foregoing summary of the Amended and Restated Advisory Services Agreement does not purport to be complete and is qualified in its entirety by reference
          to the Amended and Restated Advisory Services Agreement, a copy of which is attached hereto as Exhibit 10.1 to this Current Report on Form 8-K and incorporated herein by reference.</font></div>
      <div><br>
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                <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(e)</font></div>
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                <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Amendment and Restatement of Employee Stock Purchase Plan</font></div>
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      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">On March 22, 2019, the Board adopted and approved an amendment and restatement of the Company&#8217;s 2000 Employee Stock Purchase Plan (the &#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">ESPP</font>&#8221;) to extend the ESPP so that it will terminate on March 21, 2029.&#160; No additional shares were added to the ESPP.</font></div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
        </font></div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">The foregoing description of the amended and restated ESPP does not purport to be complete and is qualified in its entirety by reference to the amended
          and restated ESPP, a copy of which is attached hereto as Exhibit 10.2 to this Current Report on Form 8-K and incorporated herein by reference.</font></div>
      <div><br>
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                <td style="width: 54pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Item 9.01</font></td>
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                  <div><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Financial Statements and Exhibits.</font></div>
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                  <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(d)</font></div>
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                  <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Exhibits</font></div>
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            <td style="width: 6%; vertical-align: top;">&#160;</td>
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              <div style="text-align: left;"><a href="ex10_1.htm"><font style="font-size: 10pt; font-family: 'Times New Roman';">10.1</font></a></div>
            </td>
            <td style="width: 90%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Amended and Restated Advisory Services Agreement dated March 22, 2019</font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;">&#160;</td>
            <td style="width: 4%; vertical-align: top;">
              <div style="text-align: left;"><a href="ex10_2.htm"><font style="font-size: 10pt; font-family: 'Times New Roman';">10.2</font></a></div>
            </td>
            <td style="width: 90%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan</font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 6%; vertical-align: top;">&#160;</td>
            <td style="width: 4%; vertical-align: top;">
              <div style="text-align: left;"><a href="ex99_1.htm"><font style="font-size: 10pt; font-family: 'Times New Roman';">99.1</font></a></div>
            </td>
            <td style="width: 90%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Press Release dated March 25, 2019</font></div>
            </td>
          </tr>

      </table>
      <div> <br>
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      </div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-variant: small-caps;">SIGNATURE</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-variant: small-caps;"> <br>
        </font></div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be
          signed on its behalf by the undersigned, thereunto duly authorized.</font></div>
      <div style="text-align: justify; text-indent: 36pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
        </font></div>
      <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse;" id="z0cef066b5454435cbd9dcd46df363950">

          <tr>
            <td style="width: 52%; vertical-align: top;"> <br>
            </td>
            <td colspan="2" style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-variant: small-caps;">Ionis Pharmaceuticals, Inc</font></div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 52%; vertical-align: top;">&#160;</td>
            <td rowspan="1" colspan="2" style="vertical-align: top;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 52%; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Dated:&#160; March 26, 2019</font></div>
            </td>
            <td style="width: 3%; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">By:</font></div>
            </td>
            <td style="width: 45%; vertical-align: top; border-bottom: 2px solid black;">
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';"><font style="font-size: 10pt; font-family: 'Times New Roman';">/s/ Patrick R. O&#8217;Neil</font></font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 52%; vertical-align: top;">&#160;</td>
            <td style="width: 3%; vertical-align: top;">&#160;</td>
            <td style="width: 45%; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-variant: small-caps;">Patrick R. O&#8217;Neil</font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 52%; vertical-align: top;">&#160;</td>
            <td style="width: 3%; vertical-align: top;">&#160;</td>
            <td style="width: 45%; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Senior Vice President, Legal, General </font></div>
              <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Counsel and Chief Compliance Officer</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div><br>
      </div>
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<DOCUMENT>
<TYPE>EX-10.1
<SEQUENCE>2
<FILENAME>ex10_1.htm
<DESCRIPTION>EXHIBIT 10.1
<TEXT>
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    <div>
      <div style="text-align: right;"><font style="font-weight: bold;">Exhibit 10.1</font><br>
      </div>
      <br>
      <div style="text-align: center;"><img src="image00001.jpg"><br>
        <br>
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      <div style="text-align: center; font-family: &quot;Times New Roman&quot;; font-size: 10pt; font-weight: bold;">AMENDED AND RESTATED IONIS PHARMACEUTICALS, INC.</div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">STRATEGIC ADVISORY SERVICES AGREEMENT</font></div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(&#8220;<font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-style: italic;">SUMMARY PAGE</font>&#8221;)</font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">This Amended and Restated Strategic Advisory Services Agreement is entered into and made effective as of March 22, 2019, and amends and restates the
          Strategic Advisory Service Agreement dated January 15, 2018, by and between B. Lynne Parshall and Ionis Pharmaceuticals, Inc. (&#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Ionis</font>&#8221;)</font></div>
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            <td style="width: 40%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Date of Strategic Advisory Services Agreement: (&#8220;<font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight:
                    bold; font-style: italic;">Agreement</font>&#8221;)</font></div>
            </td>
            <td colspan="1" style="width: 2%; vertical-align: bottom;">&#160;</td>
            <td style="width: 58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">January 15, 2018 (&#8220;<font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; font-style: italic;">Effective





                    Date</font>&#8221;).&#160; Effective Date of Amendment and Restatement March 22, 2019.</font></div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 40%; vertical-align: bottom;">&#160;</td>
            <td colspan="1" rowspan="1" style="width: 2%; vertical-align: bottom;">&#160;</td>
            <td rowspan="1" style="width: 58%; vertical-align: bottom;">&#160;</td>
          </tr>
          <tr>
            <td style="width: 40%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Name of Strategic Advisor:</font></div>
            </td>
            <td colspan="1" style="width: 2%; vertical-align: bottom;">&#160;</td>
            <td style="width: 58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">B. Lynne Parshall (hereinafter &#8220;<font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold; font-style:
                    italic;">Strategic Advisor</font>&#8221;).</font></div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 40%; vertical-align: bottom;">&#160;</td>
            <td colspan="1" rowspan="1" style="width: 2%; vertical-align: bottom;">&#160;</td>
            <td rowspan="1" style="width: 58%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 40%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Scope of Strategic Advisory Services:</font></div>
            </td>
            <td colspan="1" style="width: 2%; vertical-align: bottom;">&#160;</td>
            <td style="width: 58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">As set forth on Schedule A attached hereto.</font></div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 40%; vertical-align: bottom;">&#160;</td>
            <td colspan="1" rowspan="1" style="width: 2%; vertical-align: bottom;">&#160;</td>
            <td rowspan="1" style="width: 58%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 40%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Duration of Strategic Advisory Services (the &#8220;<font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;
                    font-style: italic;">Strategic Advisory Period</font>&#8221;):</font></div>
            </td>
            <td colspan="1" style="width: 2%; vertical-align: bottom;">&#160;</td>
            <td style="width: 58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Until termination by Ionis or Strategic Advisor in accordance with Section 8 of Exhibit A below.</font></div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 40%; vertical-align: bottom;">&#160;</td>
            <td colspan="1" rowspan="1" style="width: 2%; vertical-align: bottom;">&#160;</td>
            <td rowspan="1" style="width: 58%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 40%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Consideration for Strategic Advisory Services:</font></div>
            </td>
            <td colspan="1" style="width: 2%; vertical-align: bottom;">&#160;</td>
            <td style="width: 58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">As set forth on Schedule B attached hereto.</font></div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 40%; vertical-align: bottom;">&#160;</td>
            <td colspan="1" rowspan="1" style="width: 2%; vertical-align: bottom;">&#160;</td>
            <td rowspan="1" style="width: 58%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 40%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">Time Provided by Strategic Advisor:</font></div>
            </td>
            <td colspan="1" style="width: 2%; vertical-align: bottom;">&#160;</td>
            <td style="width: 58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">As set forth on Schedule A attached hereto.</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">In addition to such compensation, Ionis will reimburse Strategic Advisor for Ionis approved travel and other out-of-pocket costs reasonably
          incurred in the course of performing Strategic Advisory Services under this Agreement as further described on Schedule B attached hereto.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Strategic Advisor agrees to provide Ionis with Strategic Advisory Services on the terms described above and according to the additional terms attached
          hereto as Exhibit A.&#160; In this Agreement references to Ionis, including but not limited to Sections 3-6 of Exhibit A, will include Ionis&#8217; affiliate companies where applicable.</font></div>
      <div><br>
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            <td style="width: 12%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td style="width: 43%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Strategic Advisor</font></div>
            </td>
            <td style="width: 1.89%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid;">&#160;</td>
            <td style="width: 43%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Ionis Pharmaceuticals, Inc.</font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 12%; vertical-align: top;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">By (Signature):</font></div>
            </td>
            <td style="width: 43%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">/s/ B. Lynne Parshall</font></div>
            </td>
            <td style="width: 1.89%; vertical-align: top;">&#160;</td>
            <td style="width: 43%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">/s/ Stanley T. Crooke</font></div>
            </td>
          </tr>
          <tr>
            <td rowspan="1" style="width: 12%; vertical-align: top;">&#160;</td>
            <td rowspan="1" style="width: 43%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
            <td rowspan="1" style="width: 1.89%; vertical-align: top;">&#160;</td>
            <td rowspan="1" style="width: 43%; vertical-align: top; border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 12%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Date:</font></div>
            </td>
            <td style="width: 43%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);"><br>
            </td>
            <td style="width: 1.89%; vertical-align: bottom;">&#160;</td>
            <td style="width: 43%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">3/21/19</font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 12%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Printed Name:</font></div>
            </td>
            <td style="width: 43%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">B. Lynne Parshall</font></div>
            </td>
            <td style="width: 1.89%; vertical-align: bottom;">&#160;</td>
            <td style="width: 43%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">Stanley T. Crooke<br>
            </td>
          </tr>
          <tr>
            <td style="width: 12%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Title:</font></div>
            </td>
            <td style="width: 43%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Individual</font></div>
            </td>
            <td style="width: 1.89%; vertical-align: bottom;">&#160;</td>
            <td style="width: 43%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>
          <tr>
            <td style="width: 12%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Address:</font></div>
            </td>
            <td style="width: 43%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Provided Separately</font></div>
            </td>
            <td style="width: 1.89%; vertical-align: bottom;">&#160;</td>
            <td style="width: 43%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">2855 Gazelle Court,</font></div>
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Carlsbad, CA 92010</font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 12%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Telephone:</font></div>
            </td>
            <td style="width: 43%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Provided Separately</font></div>
            </td>
            <td style="width: 1.89%; vertical-align: bottom;">&#160;</td>
            <td style="width: 43%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">760-931-9200</font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 12%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Fax:</font></div>
            </td>
            <td style="width: 43%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Provided Separately</font></div>
            </td>
            <td style="width: 1.89%; vertical-align: bottom;">&#160;</td>
            <td style="width: 43%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">760-603-3820</font></div>
            </td>
          </tr>
          <tr>
            <td style="width: 12%; vertical-align: bottom;">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">e-mail:</font></div>
            </td>
            <td style="width: 43%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Provided Separately</font></div>
            </td>
            <td style="width: 1.89%; vertical-align: bottom;">&#160;</td>
            <td style="width: 43%; vertical-align: bottom; border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">&#160;</td>
          </tr>

      </table>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"> <br>
        </font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Social Security or Employer Tax ID Number to be provided separately via W-9 form or foreign equivalent.</font></div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">1 of 12</font></div>
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      </div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">EXHIBIT A</font></div>
      <div><br>
      </div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">TERMS OF STRATEGIC ADVISORY AGREEMENT</font></div>
      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="z5d024aa72dbb4e3bb574507efacfa6e1" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

            <tr style="vertical-align: top;">
              <td style="vertical-align: top; width: 36pt;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">1.</font></div>
              </td>
              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"><u>Engagement of Services</u></font></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Strategic Advisor is retained to perform certain services, as needed and requested by Ionis, which services are specifically described on Schedule A
          attached hereto (&#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Strategic Advisory Services</font>&#8221;).&#160; Strategic Advisor will perform such Strategic Advisory Services to the best of
          Strategic Advisor&#8217;s talent and ability.</font></div>
      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="z110940aa49994e6283d04595dc037fc9" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

            <tr style="vertical-align: top;">
              <td style="vertical-align: top; width: 36pt;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">2.</font></div>
              </td>
              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"><u>Compensation</u></font></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">As full and complete compensation for Strategic Advisory Services and for the discharge of all of Strategic Advisor&#8217;s obligations hereunder, Ionis will
          pay Strategic Advisor at the rate set forth on Schedule B attached hereto. Strategic Advisor will invoice Ionis on a quarterly basis for Strategic Advisor fees and reimbursable expenses, and Ionis, upon its approval, will pay all undisputed fees
          and expenses within 30 days after Ionis&#8217; receipt of the invoice.</font></div>
      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="zcaf1f7a4fc40450b8d4abb8768b73537" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

            <tr style="vertical-align: top;">
              <td style="vertical-align: top; width: 36pt;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">3.</font></div>
              </td>
              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"><u>Independent Contractor</u></font></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Strategic Advisor is an independent contractor and not an employee of Ionis.&#160; Strategic Advisor has no authority to obligate Ionis by contract or
          otherwise.&#160; Strategic Advisor will not be eligible for any employee benefits.&#160; Taxes will be the sole responsibility of Strategic Advisor.</font></div>
      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="zec18bdc829a6427aa23c3fe50f5e7d9c" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

            <tr style="vertical-align: top;">
              <td style="vertical-align: top; width: 36pt;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">4.</font></div>
              </td>
              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"><u>Additional Activities</u></font></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z9c2935f4f8bf49adaaf0cb32a3702670">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(a)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Strategic Advisor agrees that during the Strategic Advisory Period and for one year thereafter, Strategic Advisor will not attempt to induce any employee or employees of
                      Ionis to terminate their employment with, or otherwise cease their relationship with Ionis.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z2d20b3e6b51545718113ecedbf118256">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(b)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Strategic Advisor acknowledges that Ionis has developed, through an extensive acquisition process, valuable information regarding actual or prospective partners,
                      licensors, licensees, clients, customers and accounts of Ionis (&#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Trade Secret Information</font>&#8221;). Strategic Advisor acknowledges
                      that Strategic Advisor&#8217;s use of such Trade Secret Information after the termination of the Strategic Advisory Period would cause Ionis irreparable harm. Therefore, Strategic Advisor also agrees that Strategic Advisor will not utilize
                      any Trade Secret Information to solicit the business relationship or patronage of any of the actual or prospective partners, licensors, licensees, clients, customers or accounts of Ionis.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z9286be78f7cd48db8e0026bfc06f77e7">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(c)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">The restrictions set forth in this Section 4 are considered by the parties to be reasonable for the purposes of protecting Ionis&#8217; business.&#160; However, if any such
                      restriction is found by a court of competent jurisdiction to be unenforceable because it extends for too long a period of time or over too great a range of activities or in too broad a geographic area, it will be interpreted to extend
                      only over the maximum period of time, range of activities or geographic areas as to which it may be enforceable.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">2 of 12</font></div>
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      </div>
      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="z5d01e76486d344b9822c8fdd85a0ad3c" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

            <tr style="vertical-align: top;">
              <td style="vertical-align: top; width: 36pt;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">5.</font></div>
              </td>
              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"><u>Confidential Information</u></font></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zab52aee651f145f493bf04ed92b6d437">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(a)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Ionis possesses confidential information that has been created, discovered, developed by, or otherwise become known to Ionis (including, without limitation, information
                      created, discovered, developed or made known by Strategic Advisor arising from the Strategic Advisory Services).</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z5806f540df2c4e1bac65ebf682ff40de">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(i)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">All such information is hereinafter referred to as &#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Confidential
                        Information</font>.&#8221;&#160; By way of illustration, but not limitation, Confidential Information includes:&#160; (A) inventions, developments, designs, improvements, trade secrets, ideas, formulas, source and object codes, programs, other
                      works of authorship, organisms, plasmids, expression vectors, know-how, processes, cell lines, discoveries, techniques, data and documentation systems (hereinafter collectively referred to as &#8220;<font style="font-size: 10pt;
                        font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Inventions</font>&#8221;); and (B) information regarding plans for research, development, new products, clinical data, pre-clinical product data, clinical trial
                      patient data, marketing and selling, business plans, budgets and unpublished financial statements, licenses, prices and costs, as well as information regarding the skills and compensation of employees of Ionis.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zcaf7a58fdcff48719e9ac512c2096e89">

              <tr>
                <td style="width: 36pt;"><br>
                </td>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(ii)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">All Confidential Information will be the sole property of Ionis and its assigns, and Ionis and its assigns will be the sole owner of all patents, copyrights and other
                      rights in connection with such Confidential Information.&#160; At all times, both during the term of this Agreement and for five years after its termination, Strategic Advisor will keep in confidence and trust all Confidential Information
                      and will not use, disclose, lecture upon or publish any Confidential Information or anything related to such information without Ionis&#8217; prior written consent.&#160; Any permitted disclosures will be made in strict compliance with the Ionis
                      publication and presentation clearance policy.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z5241885f5c7e4cd1a7442acb2b62b79f">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(b)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Strategic Advisor also understands that Ionis has received and in the future, will receive valuable information from third parties that is confidential or proprietary (&#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Third-Party Information</font>&#8221;) subject to a duty on the part of Ionis to maintain the confidentiality of such information and to use
                      it only for certain limited purposes.&#160; During the term of this Agreement and for five years thereafter, Strategic Advisor will hold Third-Party Information in the strictest confidence and will not disclose or use Third-Party
                      Information except as permitted by the agreement between Ionis and such third party, unless expressly authorized to act otherwise by an officer of Ionis in writing.&#160; Any permitted disclosures will be made in strict compliance with
                      Ionis publication and presentation clearance policy.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zb48d5d5af56d4d5da597ee4039dcb470">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(c)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">The obligations of Section 5 will not apply to information that Strategic Advisor can establish by written records: (i) was known by Strategic Advisor prior to the
                      receipt of Confidential Information; (ii) was disclosed to Strategic Advisor by a third party having the right to do so; (iii) was, or subsequently became, in the public domain through no fault of Strategic Advisor, its officers,
                      directors, affiliates employees or agents; (iv) was independently developed by Strategic Advisor without use of Confidential Information; or (v) was disclosed by Strategic Advisor pursuant to any judicial, governmental or stock
                      exchange request, requirement or order, so long as Strategic Advisor provided Ionis with sufficient prior notice in order to allow Ionis to contest such request, requirement or order.</font></div>
                </td>
              </tr>

          </table>
          <div> <br>
          </div>
        </div>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">3 of 12</font></div>
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      </div>
      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="z855e0917222f494db1217a3392b0c58d" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

            <tr style="vertical-align: top;">
              <td style="vertical-align: top; width: 36pt;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">6.</font></div>
              </td>
              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"><u>Inventions</u></font></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">In the course of performing Strategic Advisory Services for Ionis, Strategic Advisor may develop new ideas or Inventions or make other contributions of
          value to Ionis.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zf0f52fb981e2456398578eeedf3dfc70">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(a)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Strategic Advisor hereby assigns to Ionis Strategic Advisor&#8217;s entire right, title and interest in and to any and all Inventions (and all patent rights, copyrights, and
                      all other rights in connection therewith, hereinafter referred to as &#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Proprietary Rights</font>&#8221;) whether or not patentable or
                      registrable under patent, copyright or similar statutes, made or conceived of or reduced to practice or learned by Strategic Advisor, either alone or jointly with others, as a result of performing Strategic Advisory Services
                      hereunder.&#160; All Inventions assigned to Ionis pursuant to this section will be known as &#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Company Inventions</font>&#8221;.&#160; Strategic
                      Advisor agrees that all Proprietary Rights and Company Inventions are Ionis&#8217; sole property.&#160; Strategic Advisor agrees, upon request, to execute, verify and deliver assignments of such Proprietary Rights to Ionis or its designee.&#160;
                      Strategic Advisor understands that, to the extent this Agreement will be construed in accordance with the laws of any state which precludes a requirement in an agreement to assign certain classes of inventions made by an individual
                      acting as a Strategic Advisor, this section will be interpreted not to apply to any inventions that a court rules and/or Ionis agrees falls within such classes.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z9ae870ab61664107a11a7da62cd112ae">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(b)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Strategic Advisor further agrees to assist Ionis in every proper way to obtain, from time to time, and to enforce United States and foreign Proprietary Rights relating to
                      Company Inventions in any and all countries.&#160; To that end Strategic Advisor will execute, verify and deliver such documents and perform such other acts (including appearances as a witness) as Ionis may reasonably request for use in
                      applying for, obtaining, sustaining and enforcing such Proprietary Rights relating to Company Inventions.&#160; Strategic Advisor&#8217;s obligation to assist Ionis in obtaining and enforcing Proprietary Rights relating to Company Inventions in
                      any and all countries will continue beyond the termination of this Agreement, but Ionis will compensate Strategic Advisor at a reasonable rate after such termination for the time actually spent by Strategic Advisor at Ionis&#8217; request
                      in connection with such assistance.&#160; If Ionis is unable, after reasonable effort, to secure Strategic Advisor&#8217;s signature on any document needed to apply for or prosecute any Proprietary Rights relating to a Company Invention,
                      Strategic Advisor hereby irrevocably designates and appoints Ionis and its duly authorized officers and agents as&#160; her agent and attorney in fact, to act for and on Strategic Advisor&#8217;s behalf to execute, verify and file any such
                      applications and to do all other lawfully permitted acts to further the prosecution and issuance of any such Proprietary Rights with the same legal force and effect as if executed by Strategic Advisor.</font></div>
                </td>
              </tr>

          </table>
          <div> <br>
          </div>
        </div>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">4 of 12</font></div>
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      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z10c434efc5c448eca2acfb2b9e682fcf">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(d)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">During the term of this Agreement, Strategic Advisor will promptly disclose to Ionis, or any persons designated by it, fully and in writing and will hold in trust for the
                      sole right and benefit of Ionis any and all Company Inventions, whether or not patentable or protectable by copyright.&#160; At the time of each such disclosure, Strategic Advisor will advise Ionis in writing of any Inventions that
                      Strategic Advisor believes are not subject to the assignment provisions of Section 6(a) above, and Strategic Advisor will at that time provide to Ionis in writing all evidence necessary to substantiate that belief.&#160; Strategic Advisor
                      will not be obligated to disclose information received by Strategic Advisor from others under a contract of confidentiality.&#160; In addition, after termination of this Agreement, Strategic Advisor will disclose to Ionis all patent
                      applications filed by Strategic Advisor relating to any Company Inventions or relating to any work performed by Strategic Advisor on behalf of Ionis.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="z9aa39127b7fd47f998a42bd91306ea92" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

            <tr style="vertical-align: top;">
              <td style="vertical-align: top; width: 36pt;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">7.</font></div>
              </td>
              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"><u>Previous Strategic Advisory Relationships</u></font></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Strategic Advisor represents that Strategic Advisor&#8217;s performance of Strategic Advisory Services, as well as Strategic Advisor&#8217;s performance of the rest
          of Strategic Advisor&#8217;s obligations under the terms of this Agreement, will not breach any agreement to keep in confidence any proprietary information acquired by Strategic Advisor in confidence or in trust from another entity prior to the date of
          this Agreement.&#160; Strategic Advisor agrees not to bring to Ionis or to use in the performance of Strategic Advisory Services for Ionis any materials or documents of a present or former employer or client of Strategic Advisor, or any materials or
          documents obtained by Strategic Advisor under a confidentiality agreement imposed by reason of another of Strategic Advisor&#8217;s Strategic Advisory relationships, unless such materials or documents are generally available to the public or Strategic
          Advisor has authorization from such present or former employer or client for the possession and unrestricted use of such materials.</font></div>
      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="z0adf1efecfb04e4dbec3ecd3c8e0a613" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

            <tr style="vertical-align: top;">
              <td style="vertical-align: top; width: 36pt;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">8.</font></div>
              </td>
              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"><u>Termination; Survival</u></font></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<font style="font-size: 10pt; font-family: 'Times New Roman';">The term of this Agreement will begin on January 15, 2018 and will end
          when terminated by either Ionis or Strategic Advisor.&#160; Ionis may terminate this Agreement at any time for any reason by providing Strategic Advisor at least 120 days advance written notice.&#160; Strategic Advisor may terminate this Agreement at any
          time for any reason by providing Ionis at least 120 days advance written notice; <font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">provided</font>, once Strategic Advisor delivers such a termination notice, Ionis
          may elect to accelerate the effective date of such termination.&#160; Upon any termination, Ionis will pay Strategic Advisor for any Strategic Advisory Services appropriately rendered and for any out of pocket expenses reasonably incurred on behalf of
          Ionis, up to and including the termination date.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">Sections 9 and 10, the last sentence of the second paragraph of
          Schedule B and the last paragraph of Schedule B will survive termination of this Agreement.&#160; In addition, upon expiration or termination of this Agreement, each party will be released from all obligations and liabilities to the other occurring or
          arising after the date of such expiration or termination, except that any termination or expiration of this Agreement will not relieve Strategic Advisor of Strategic Advisor&#8217;s obligations under Sections 4, 5, 6, 7, 9, 10 and 11 hereof, nor will
          any such expiration or termination relieve Strategic Advisor or Ionis from any liability arising from any breach of this Agreement.&#160; Upon expiration or termination of this Agreement for any reason whatsoever, Strategic Advisor will promptly
          surrender and deliver to Ionis any and all notes, business records, memoranda, specifications, devices, formulas, molecules, cells, storage media, including calculations, sequences, data and other materials of any nature pertaining to Strategic
          Advisory Services for Ionis, as well as any documents or data of any description (or any reproduction of any documents or data) containing or pertaining to any Trade Secret Information, Ionis&#8217; Confidential Information or Third Party Information.</font></div>
      <div><br>
      </div>
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      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="zd6f55ba12f774def8260b47094d967b1" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

            <tr style="vertical-align: top;">
              <td style="vertical-align: top; width: 36pt;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">9.</font></div>
              </td>
              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"><u>Arbitration</u></font></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z32670d297c404cc1b8ad795b7eac7506">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(a)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Ionis and Strategic Advisor agree to resolve by arbitration all disputes, claims or controversies (&#8220;<font style="font-size: 10pt; font-family: 'Times New Roman';
                        font-weight: bold; font-style: italic;">Claims</font>&#8221;), past, present or future, whether or not arising out of this Agreement or its termination, that Ionis may have against Strategic Advisor or that Strategic Advisor may have
                      against any of the following (i) Ionis; (ii) Ionis officers, directors; employees or agents; (iii) Ionis&#8217; subsidiary or affiliated entities, joint ventures, or joint employers; (iv) Ionis&#8217; benefit plans or the plans&#8217; sponsors,
                      fiduciaries, administrators, affiliates and agents; and/or (v) all successors and assigns of any of the foregoing.&#160; The Claims covered by this Agreement include all disputes that Ionis or Strategic Advisor could otherwise pursue in
                      state or federal court including, but not limited to, Claims based on any state, federal, or local statute, regulation or ordinance (including Claims for discrimination, retaliation, harassment, unpaid wages or violation of state or
                      federal wage and hour laws), as well as common law Claims (including Claims for breach of contract, breach of the implied covenant of good faith and fair dealing, wrongful discharge, defamation, misrepresentation, fraud, or infliction
                      of emotional distress).&#160; Ionis and Strategic Advisor anticipates that this Section 9 provides the benefits of a speedy, less formal, impartial, final and binding dispute resolution procedure.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z22ee8e3e86fd4a9fa2b6db1d0595add6">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(b)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">To the maximum extent permitted by law, Strategic Advisor hereby waives any right to bring on behalf of persons other than Strategic Advisor, or to otherwise participate
                      with other persons in, any class, collective or representative action (i.e. a type of lawsuit in which one or several persons sue on behalf of a larger group of persons).</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z495687b3e49d49a0b85f2a24102879b2">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(c)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">The arbitration will be conducted by a single neutral arbitrator in accordance with the then-current Commercial Arbitration and Mediation Procedures of the American
                      Arbitration Association (&#8220;<font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">AAA</font>&#8221;).&#160; The arbitration will take place in San Diego, California.&#160; Ionis will pay the arbitrator&#8217;s
                      fee and will bear all administrative charges by AAA.&#160; All parties will be entitled to engage in reasonable pre-hearing discovery to obtain information to prosecute or defend the asserted claims.&#160; Any disputes between the parties
                      regarding the nature or scope of discovery will be decided by the arbitrator.&#160; The arbitrator will hear and issue a written ruling upon any dispositive motions brought by either party, including but not limited to, motions for summary
                      judgment or summary adjudication of issues.&#160; After the hearing, the arbitrator will issue a written decision setting forth the award, if any, and explaining the basis therefore.&#160; The arbitrator will have the power to award any type of
                      relief that would be available in court.&#160; The arbitrator&#8217;s award will be final and binding upon the parties and may be entered as a judgment in any court of competent jurisdiction.&#160; If there is conflict in the arbitration procedures
                      set forth in this Agreement and the AAA rules specified above, the AAA rules will control.&#160; Notwithstanding the foregoing, and regardless of what is provided by the AAA rules, the arbitrator will not have authority or jurisdiction to
                      consolidate claims of different individuals or entities into one proceeding, nor will the arbitrator have authority or jurisdiction to hear the arbitration as a class action.&#160; As noted above, Strategic Advisor has agreed to waive any
                      right to bring any class, collective or representative action.&#160; To the extent that the class, collective or representative action waiver described above is not enforceable, the issue of whether to certify any alleged or putative class
                      for a class action proceeding must be decided by a court of competent jurisdiction.&#160; The arbitrator will not have authority or jurisdiction to decide class certification, collective or representative action issues.&#160; Until any class
                      certification, collective, or representative action issues are decided by the court, all arbitration proceedings will be stayed, and the arbitrator will take no action with respect to the matter.&#160; However, once any issues regarding
                      class certification, collective, or representative action have been decided by the court, the arbitrator will have authority to decide the substantive claims.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
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      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="zcb3d29591b9741319746e2936223c158" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

            <tr style="vertical-align: top;">
              <td style="vertical-align: top; width: 36pt;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">10.</font></div>
              </td>
              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"><u>Indemnification</u></font></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zd14e83907b1349aebe1fa4bba566745a">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(a)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Ionis will indemnify, defend and hold Strategic Advisor harmless against any and all losses, costs, expenses and damages (including reasonable attorney&#8217;s fees)
                      (&#8220;Loss(es)&#8221;) incurred as a result of any third party claims, suits, actions, demands or proceedings resulting or arising&#160; from the performance of Strategic Advisory Services as specifically directed by Ionis in accordance with the
                      Agreement to the extent such Loss(es) are not the result of Strategic Advisor&#8217;s gross negligence, intentional misconduct or material breach of this Agreement.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z485b24f36b2b4ec5b20534f38a784207">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(b)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Ionis&#8217; agreement to indemnify, defend and hold&#160; Strategic Advisor harmless is conditioned upon the Strategic Advisor (i) providing written notice to Ionis of any claim,
                      demand or action arising out of the indemnified activities within thirty (30) days after Strategic Advisor has knowledge of such claim, demand or action, <font style="font-size: 10pt; font-family: 'Times New Roman'; font-style:
                        italic;">provided</font> that the failure to so notify Ionis shall not relieve Ionis of its obligations hereunder except to the extent such failure shall have actually materially prejudiced Ionis; (ii) permitting Ionis to assume
                      full responsibility to investigate, prepare for and defend against any such claim or demand; (iii) assisting Ionis, at Ionis&#8217; reasonable expense, in the investigation of, preparation of and defense of any such claim or demand; (iv)
                      undertaking reasonable steps to mitigate any loss, damage or expense with respect to the applicable claim or demand; and (v) not settling such claim or demand without Ionis&#8217; prior written consent.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z6aecf306ca244309a7e32ff809aedf4f">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(c)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Ionis will endeavor to include Strategic Advisor as a covered attorney on its insurance policy for attorneys who advise Ionis.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" id="z526538e215a44ef59c839ebd0982f2a2" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;">

            <tr style="vertical-align: top;">
              <td style="vertical-align: top; width: 36pt;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman';">11.</font></div>
              </td>
              <td style="align: left; vertical-align: top; width: auto;">
                <div style="text-align: justify;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"><u>Miscellaneous</u></font></div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
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      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z4ecc60a60eb24ba78cbbb309bf05f7cf">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(a)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">The rights and liabilities of the parties hereto will bind and inure to the benefit of their respective successors, heirs, executors and administrators, as the case may
                      be; <font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">provided that</font>, as Ionis has specifically contracted for Strategic Advisor&#8217;s services, Strategic Advisor may not assign or delegate
                      Strategic Advisor&#8217;s obligations under this Agreement either in whole or in part without Ionis&#8217; prior written consent.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z08c215068faa4a528d36dfa308842cd8">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(b)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Because Strategic Advisor&#8217;s services are personal and unique and because Strategic Advisor has access to and become acquainted with Ionis&#8217; Confidential Information, the
                      parties agree that in the event of a threatened or actual material breach of this Agreement by Strategic Advisor injunctive relief would be appropriate.&#160; As such, Ionis has the right to enforce this Agreement and any of its provisions
                      by injunction, specific performance or other equitable relief without prejudice to any other rights and remedies that Ionis may have for a breach of this Agreement.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="ze475d548b23d4039ba97c302ccef4b15">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(c)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">This Agreement will be governed by and construed according to the laws of the State of California as such laws are applied to contracts entered into and performed
                      entirely within such State.&#160; If any provision of this Agreement is held to be or becomes invalid, illegal or unenforceable, such provision will be validly reformed to approximate as nearly as possible the intent of the parties and the
                      remainder of this Agreement will not be affected thereby and will remain valid and enforceable to the greatest extent permitted by law.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zdf9644ba3ff2405aa7d64a99db18cba8">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(d)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">This Agreement, and all other documents mentioned herein, constitute the final, exclusive and complete understanding and agreement of the parties hereto and supersedes
                      all prior understandings and agreements.&#160; Any waiver, modification or amendment of any provision of this Agreement will be effective only if in writing and signed by the parties hereto.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zd3851729f5684fd2b0a8ef4affbbb79e">

              <tr>
                <td style="width: 36pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman';">(e)</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Any notices required or permitted hereunder will be given to the appropriate party at the address specified on the Summary Page or at such other address as the party will
                      specify in writing.&#160; Such notice will be deemed given upon personal delivery to the appropriate address, or by facsimile transmission (receipt verified and with confirmation copy followed by another permitted method), sent by express
                      courier service, or, if sent by certified or registered mail, three (3) days after the date of mailing.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse;" id="z09bda95bfae343fea0081383caaa9afa">

          <tr>
            <td style="width: 100%; vertical-align: top;">
              <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">[END OF EXHIBIT A]</font></div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
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      <!--PROfilePageNumberReset%Num%1%%%-->
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">SCHEDULE&#160; A</font></div>
      <div><br>
      </div>
      <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Strategic Advisory Services</font></div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">Ionis Board of Directors</font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">You will serve on the Ionis board of directors as a nonemployee director until your resignation or removal in accordance with Ionis&#8217; corporate charter.&#160;
          Ionis will recommend that you serve on the Agenda committee of the Board, and periodically evaluate your ability to serve on other Board committees to the extent permitted by applicable SEC and Nasdaq rules. You will participate in other Board
          Committee meetings as requested as a non-member.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">Akcea Board of Directors</font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Ionis will recommend that you serve on the Akcea board of directors as a nonemployee director until your resignation or removal in accordance with Akcea&#8217;s
          corporate charter. You will serve on the Audit Committee during Akcea&#8217;s first year as a public company and as permitted by applicable SEC and Nasdaq rules, and participate in other committees as a member or non-member as requested.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">Strategic Neurology/Rare Disease Subsidiary Board of Directors</font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">When Ionis forms a strategic neurological/rare disease focused&#160; subsidiary, you will serve on the board of directors of such subsidiary as a non employee
          director on the same terms as other non employee directors until your resignation or removal in accordance with the subsidiary&#8217;s corporate charter.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">Additional Strategic Advisory Services</font></div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">You will provide Ionis strategic advice regarding Ionis&#8217; business, including but not limited to the following:</font></div>
      <div><br>
      </div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Through July 1, 2018, you will provide approximately forty hours per week of strategic advice.&#160; After July 1, 2018 and continuing through the end of 2018 it
          is anticipated you will provide approximately five business days of strategic advice each month.&#160; For each year following 2018, you and Ionis will mutually agree on the approximate number of business days each month you will provide strategic
          advice during such year.&#160; You will make yourself generally available for conference calls and in person meetings Ionis invites you to attend.&#160; You will travel to locations as reasonably requested by Ionis, including to Ionis, Akcea, Ionis&#8217;
          partners, or other locations where Ionis is conducting corporate development activities (e.g. JP Morgan conference or strategic off-site meetings).&#160; You and Ionis expect that, you will participate in Ionis&#8217; development management committee (DMC)
          meetings, Ionis&#8217; affiliate&#8217;s and Biogen joint steering committee meetings, and through July 1, 2018 and thereafter when requested, Ionis&#8217; strategic management meetings (e.g. G8 meetings).&#160; As requested by Ionis, you will facilitate Ionis&#8217;
          strategic partnerships and help develop Ionis&#8217; subsidiaries&#8217; and affiliates&#8217; senior management teams.&#160; You will help Ionis&#8217; new CBO be trained and assimilated into Ionis&#8217; business team.&#160; You will help Ionis&#8217; new COO as requested be trained and
          assimilated into Ionis&#8217; business team.&#160; You will work with the CEO, COO and others on strategic planning and direction for the Company.&#160; You will participate in major corporate communication initiatives, including business/financial messaging and
          rebranding project.&#160;&#160; You will participate in structuring and negotiating as requested new strategic alliances.&#160; Your advisory services may include providing Ionis legal advice.</font></div>
      <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
        </font></div>
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                    <div style="text-align: left; font-family: &amp;quot;">Schedule A</div>
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        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">You and Ionis will reasonably coordinate to have you present on site for board of directors meetings, and a few days before and/or after such meetings to
            perform strategic advisory services.&#160; The time you spend preparing for or attending board of directors or board committee meetings for Ionis, Akcea or any subsidiary will not count towards your commitment to perform additional strategic
            advisory services outlined above, except if you attend Akcea Board committee meetings as an observer on Ionis&#8217; behalf (and Akcea does not compensate you for such attendance), such attendance will count as strategic advisory services.</font></div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> </font><br>
        </div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">While you are providing such services, Ionis will make an appropriate level of administrative and technical personnel available to facilitate your
            performance of Advisory Services at no cost to you, including, without limitation IT support and access to Ionis&#8217; electronic calendar and IT systems that are necessary to perform your duties.</font></div>
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                    <div style="text-align: left; font-family: &amp;quot;">Schedule A</div>
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        <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">SCHEDULE&#160; B</font></div>
        <div><br>
        </div>
        <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Compensation for Strategic Advisory Services</font></div>
        <div><br>
        </div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">Ionis Board of Directors</font></div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">For your service on the Ionis board of directors, starting with the first quarter of 2018, you will receive the same compensation as Ionis provides its
            other nonemployee directors.&#160; You will not receive an initial nonemployee director award. Starting in 2018, you will receive the same annual equity awards as Ionis&#8217; other nonemployee directors.&#160; You will also be eligible for any benefits
            (including any applicable health benefits) Ionis provides to its nonemployee directors.</font></div>
        <div><br>
        </div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">Akcea Board of Directors</font></div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">For your service on the Akcea board of directors, you will receive the same compensation as Akcea provides its other nonemployee directors.&#160; On January
            15, 2018, you will receive an initial nonemployee director stock option award of 52,837 shares with an option exercise price equal to the fair market value of Akcea&#8217;s stock on that day. Thereafter, you will receive the same annual equity awards
            as Akcea&#8217;s other nonemployee /outside directors.</font></div>
        <div><br>
        </div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">Strategic Neurology/Rare Disease Subsidiary Board of Directors</font></div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">For your service on the board of directors of Ionis&#8217; strategic neurological/rare disease subsidiary (if formed), you will receive the same compensation
            (including equity awards) as such subsidiary provides its other nonemployee /outside directors.</font></div>
        <div><br>
        </div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">Additional Strategic Advisory Services</font></div>
        <div><br>
        </div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">For your other strategic advisory services, starting in the fiscal year ending in 2018, Ionis will pay you as follows:</font></div>
        <div style="text-align: left;">
          <div>
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                  <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: Symbol, serif;">&#183;</font></td>
                  <td style="width: auto; vertical-align: top; text-align: left;">
                    <div><font style="font-size: 10pt; font-family: 'Times New Roman';">$375,000 for services rendered through June 30, 2018 to be paid in two installments.</font></div>
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          </div>
        </div>
        <div style="text-align: left;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="ze13a6f37e293413fb18706660cb539ed">

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                  <td style="width: 18pt;"><br>
                  </td>
                  <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: Symbol, serif;">&#183;</font></td>
                  <td style="width: auto; vertical-align: top; text-align: left;">
                    <div><font style="font-size: 10pt; font-family: 'Times New Roman';">$125,000 for services rendered July 1, 2018 through December 31, 2018 paid in quarterly installments; <font style="font-size: 10pt; font-family: 'Times New Roman';
                          font-style: italic;">provided, however</font>, that if you provide more than thirty-seven full days during the aforementioned period, then payment for additional days will be made on a pro-rata basis, such compensation to be
                        confirmed by the Ionis Compensation Committee and not to exceed $750,000 for any year.</font></div>
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          </div>
        </div>
        <div style="text-align: left;">
          <div>
            <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zb706a7e9ed614b33bfc1fc36e5005739">

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                  <td style="width: 18pt;"><br>
                  </td>
                  <td style="width: 18pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: Symbol, serif;">&#183;</font></td>
                  <td style="width: auto; vertical-align: top; text-align: left;">
                    <div><font style="font-size: 10pt; font-family: 'Times New Roman';">Upon the conclusion of each fiscal year, you will be eligible to receive a bonus at the 35% bonus level of Ionis&#8217; MBO Plan with the personal performance factor
                        recommended by the Ionis CEO and approved by the Ionis Compensation Committee and the corporate performance factor determined and approved by the Ionis Board of Directors pro-rated by the total number of full days of service you
                        provided in the applicable fiscal year.&#160; For purposes of the Ionis MBO Plan 220 days constitutes full-time employment.</font></div>
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            </table>
          </div>
        </div>
        <div><br>
        </div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Since you are transitioning seamlessly from an Ionis employee to a nonemployee director, the stock options and RSUs you received for your previous service
            as an Ionis employee will continue to vest so long as your Continuous Service (as defined in the applicable equity plan) continues.&#160; Once you are no longer serving on the Ionis board and no longer providing strategic advisory services, to the
            extent permitted by the terms of the applicable stock option agreement, your vested stock options will not terminate until the earlier of 18 months following your retirement or the expiration of the original term of such stock option.</font></div>
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                    <div style="text-align: left; font-family: &amp;quot;">Schedule B<br>
                    </div>
                  </td>
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        </div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">For Ionis-directed travel and lodging Ionis will reimburse you for such travel, lodging and related expenses or <font style="font-size: 10pt;
              font-family: 'Times New Roman';">reasonable rate equivalents for lodging, car and meals you provide</font>.&#160; All such reimbursements will be in accordance with Ionis&#8217; travel policy and you will provide Ionis reasonably acceptable supporting
            documentation.</font></div>
        <div><br>
        </div>
        <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">For the 18 months following the end of your Ionis board of directors services, if you are eligible for continued health coverage under COBRA, Ionis will
            pay your COBRA premium payments sufficient to continue your coverage at your then current level, or if COBRA is not available, Ionis will pay you an amount equal to the cost of comparable replacement coverage.</font></div>
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                    <div style="text-align: left; font-family: &quot;Times New Roman&quot;;">Schedule B<br>
                    </div>
                  </td>
                  <td style="width: 50%; vertical-align: top; font-size: 8pt;">
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<DOCUMENT>
<TYPE>EX-10.2
<SEQUENCE>3
<FILENAME>ex10_2.htm
<DESCRIPTION>EXHIBIT 10.2
<TEXT>
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      <div style="text-align: right;"><font style="font-weight: bold;">Exhibit 10.2</font><br>
      </div>
      <div style="text-align: center; margin-right: 0.75pt; font-family: 'Times New Roman'; font-size: 10pt;"> <br>
      </div>
      <div style="text-align: center; margin-right: 0.75pt; font-family: 'Times New Roman'; font-size: 10pt;">IONIS PHARMACEUTICALS, INC.</div>
      <div><br>
      </div>
      <div style="text-align: center; margin-right: 0.75pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">2000 EMPLOYEE STOCK PURCHASE PLAN</font></div>
      <div><br>
      </div>
      <div style="text-align: center; margin-right: 0.75pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Approved by the Board of Directors on January 6, 2000</font></div>
      <div style="text-align: center; margin-right: 0.75pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Approved by Stockholders on June 8, 2000</font></div>
      <div style="text-align: center; margin-right: 0.75pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Amended on September 23, 2003</font></div>
      <div style="text-align: center; margin-right: 0.75pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Amended and Restated by the Board of Directors on February 27, 2009</font></div>
      <div style="text-align: center; margin-right: 0.75pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Amended and Restated by the Stockholders on June 2, 2009</font></div>
      <div style="text-align: center; margin-right: 0.75pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Amended and Restated by the Board of Directors on March 22, 2019</font></div>
      <div style="text-align: center; margin-right: 0.75pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
        </font></div>
      <div style="text-align: left;">
        <div>
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                <td style="width: 35.3pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">1.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">PURPOSE.</font></div>
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        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.2pt; margin-right: 5.75pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(a)</font>&#160;&#160; &#160; &#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">The
          purpose of this Amended and Restated 2000 Employee Stock Purchase Plan (the "Plan") is to provide a means by which employees of Ionis Pharmaceuticals, Inc. (the "Company") and its Affiliates, as defined in Subsection 1(b), which are designated as
          provided in Subsection 2(b), may be given an opportunity to purchase common stock of the Company (the "Common Stock"). Effective March 22, 2019 (the &#8220;A&amp;R Effective Date&#8221;) this Plan supersedes and replaces the 2000 Employee Stock Purchase Plan
          adopted by the Company's stockholders on June 2, 2009, as amended.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.2pt; margin-right: 5.35pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">The
          word "Affiliate" as used in the Plan means any parent corporation or subsidiary corporation of the Company, as those terms are defined in Sections 424(e) and (f), respectively, of the Internal Revenue Code of 1986, as amended (the "Code").</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 6.05pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New
          Roman';">The Company, by means of the Plan, seeks to retain the services of its employees, to secure and retain the services of new employees, and to provide incentives for such persons to exert maximum efforts for the success of the Company.</font></div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: &quot;Times New Roman&quot;; font-size: 10pt; text-indent: 36pt;"><font style="font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160; &#160;&#160; The Company intends that the rights to purchase stock of the Company granted under the
        Plan be considered options issued under an "employee stock purchase plan" as that term is defined in Section 423(b) of the Code.</div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z3f061ece338f462587fdb80d1234a81b">

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                <td style="width: 35.75pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">2.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman';"><font style="font-weight: bold;">ADMINISTRATION</font>.</font></div>
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      <div style="text-align: justify; text-indent: 36.2pt; margin-right: 5.75pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">The
          Plan shall be administered by the Board of Directors (the "Board") of the Company unless and until the Board delegates administration to a Committee, as provided in Subsection 2(c). Whether or not the Board has delegated administration, the Board
          shall have the final power to determine all questions of policy and expediency that may arise in the administration of the Plan.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; margin-right: 6pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">The
          Board shall have the power, subject to, and within the limitations of, the express provisions of the Plan:</font></div>
      <div><br>
      </div>
      <div style="text-align: left; text-indent: 72.45pt; margin-right: 5.85pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">To
          determine when and how rights to purchase stock of the Company shall be granted and the provisions of each offering of such rights (which need not be identical).</font></div>
      <div style="text-align: left; text-indent: 72.45pt; margin-right: 5.85pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
        </font></div>
      <div style="text-align: justify; text-indent: 72pt; margin-right: 7.15pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">To
          designate from time to time which Affiliates of the Company shall be eligible to participate in the Plan.</font></div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">1.</font></div>
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      <div style="text-align: justify; text-indent: 72pt; margin-right: 7pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(iii)</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">To construe
          and interpret the Plan and rights granted under it, and to establish, amend and revoke rules and regulations for its administration. The Board, in the exercise of this power, may correct any defect, omission or inconsistency in the Plan, in a
          manner and to the extent it shall deem necessary or expedient to make the Plan fully effective.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div style="text-indent: 72pt;">
          <div>
            <div><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(iv)&#160;&#160;&#160;&#160;&#160; </font><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">To amend the Plan as provided in Section 13.</font></div>
          </div>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: left; text-indent: 72pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(v)</font>&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">To terminate or
          suspend the Plan as provided in Section 15.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72.45pt; margin-right: 7pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(vi)</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">Generally,
          to exercise such powers and to perform such acts as the Board deems necessary or expedient to promote the best interests of the Company and its Affiliates and to carry out the intent that the Plan be treated as an "employee stock purchase plan"
          within the meaning of Section 423 of the Code.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 6.55pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';"><font style="font-weight: bold;">(c)</font>&#160; &#160; &#160;&#160;&#160; The Board may delegate administration of the Plan to a
          Committee composed of not fewer than two (2) members of the Board (the "Committee"). If administration is delegated to a Committee, the Committee shall have, in connection with the administration of the Plan, the powers theretofore possessed by
          the Board, subject, however, to such resolutions, not inconsistent with the provisions of the Plan, as may be adopted from time to time by the Board. The Board may abolish the Committee at any time and revest in the Board the administration of
          the Plan.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zaa4aca3501274c8f88b121ae49992bb0">

              <tr>
                <td style="width: 36.5pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">3.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">SHARES SUBJECT TO THE PLAN.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.65pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New
          Roman';">The Company&#8217;s board of directors and stockholders have previously approved reserving a number of shares for purchase under this plan (the &#8220;Reserved Shares&#8221;).&#160; As of the A&amp;R Effective Date, and subject to the provisions of Section 12
          relating to the adjustments upon changes in stock, there were 749,699 shares available for future sale under the Plan. If any right granted under the Plan shall for any reason terminate without having been exercised, the Common Stock not
          purchased under such right shall again become available for the Plan.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; margin-right: 8.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">The stock
          subject to the Plan may be unissued shares or reacquired shares, bought on the market or otherwise.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zdf4ddd4ebe9d4082af25acd993591d4a">

              <tr>
                <td style="width: 36pt; vertical-align: top;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">4.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">GRANT OF RIGHTS; OFFERING.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 6.55pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">The Board or the Committee may from time to time grant or provide for the grant of rights to purchase Common
          Stock of the Company under the Plan to eligible employees (an "Offering") on a date or dates (the "Offering Date(s)") selected by the Board or the Committee. Each Offering shall be in such form and shall contain such terms and conditions as the
          Board or the Committee shall deem appropriate, which shall comply with the requirements of Section 423(b)(5) of the Code that all employees granted rights to purchase stock under the Plan shall have the same rights and privileges.&#160; &#160; </font></div>
      <font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
      </font>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">2.</font></div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: justify;">
        <div>
          <div>
            <div style="text-align: justify; margin-right: 5.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">The terms and conditions of an Offering shall be incorporated by reference into the Plan and treated as part of the Plan. The
                provisions of separate Offerings need not be identical, but each Offering shall include (through incorporation of the provisions of this Plan by reference in the document comprising the Offering or otherwise) the period during which the
                Offering shall be effective, which period shall not exceed six (6) months beginning with the Offering Date (except the first offering following the A&amp;R Effective Date may be nine (9) months, and the substance of the provisions contained
                in Sections 5 through 8, inclusive.</font></div>
          </div>
          <div> <br>
          </div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z037d55f49fd94a028ea404f27bd69d4f">

              <tr>
                <td style="width: 35.8pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">5.</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">ELIGIBILITY.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">Rights
          may be granted only to employees of the Company or, as the Board or the Committee may designate as provided in Subsection 2(c), to employees of any Affiliate of the Company. Except as provided in Subsection 5(b), an employee of the Company or any
          Affiliate shall not be eligible to be granted rights under the Plan unless, on the Offering Date, such employee has been in the employ of the Company or any Affiliate for such continuous period preceding such grant as the Board or the Committee
          may require, but in no event shall the required period of continuous employment be greater than two (2) years. In addition, unless otherwise determined by the Board or the Committee and set forth in the terms of the applicable Offering, no
          employee of the Company or any Affiliate shall be eligible to be granted rights under the Plan, unless, on the Offering Date, such employee's customary employment with the Company or such Affiliate is for at least twenty (20) hours per week and
          at least five (5) months per calendar year. The Company, in its sole discretion, may exclude from participation in the Plan employees of the Company or any Affiliate of the Company who reside and/or perform services in certain specific
          jurisdictions if the laws of those jurisdictions make participation in the Plan impractical.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.75pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160; &#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">The
          Board or the Committee may provide that each person who, during the course of an Offering, first becomes an eligible employee of the Company or designated Affiliate will, on a date or dates specified&#160; in the Offering which coincides with the day
          on which such person becomes an eligible employee or occurs thereafter, receive a right under that Offering, which right shall thereafter be deemed to be a part of that Offering. Such right shall have the same characteristics as any rights
          originally granted under that Offering, as described herein, except that:</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72.2pt; margin-right: 5.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(i)</font>&#160;&#160;&#160;&#160; &#160; &#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">the date
          on which such right is granted shall be the "Offering Date" of such right for all purposes, including determination of the exercise price of such right;</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt; margin-right: 5.6pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">the period
          of the Offering with respect to such right shall begin on its Offering Date and end coincident with the end of such Offering; and</font></div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: &quot;Times New Roman&quot;; font-size: 10pt; text-indent: 72pt;"><font style="font-weight: bold;">(iii)</font> &#160; &#160; &#160; the Board or the Committee may provide that if such person first becomes an eligible
        employee within a specified period of time before the end of the Offering, he or she will not receive any right under that Offering.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.2pt; margin-right: 5.95pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">No
          employee shall be eligible for the grant of any rights under the Plan if, immediately after any such rights are granted, such employee owns stock possessing five percent (5%) or more of the total combined voting power or value of all classes of
          stock of the Company or of any Affiliate. For purposes of this Subsection 5(c), the rules of Section 424(d) of the Code shall apply in determining the stock ownership of any employee, and stock which such employee </font><font style="font-size:
          10pt; font-family: &quot;Times New Roman&quot;;">may purchase under all outstanding rights and options shall be treated as stock owned by such employee.</font></div>
      <div style="text-align: justify; text-indent: 36.2pt; margin-right: 5.95pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"> <br>
        </font></div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">3.</font></div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 6.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">An
          eligible employee may be granted rights under the Plan only if such rights, together with any other rights granted under "employee stock purchase plans" of the Company and any Affiliates, as specified by Section 423(b)(8) of the Code, do not
          permit such employee's rights to purchase stock of the Company or any Affiliate to accrue at a rate which exceeds twenty-five thousand dollars ($25,000) of fair market value of such stock (determined at the time such rights are granted) for each
          calendar year in which such rights are outstanding at any time.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.2pt; margin-right: 6pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">Officers of
          the Company and any designated Affiliate shall be eligible to participate in Offerings under the Plan; <font style="font-size: 10pt; font-family: 'Times New Roman'; font-style: italic;">provided, however, </font>that the Board may provide in an
          Offering that certain employees who are highly compensated employees within the meaning of Section 423(b)(4)(D) of the Code shall not be eligible to participate.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z00e3132eb2fe4aa6becf0db0655972c7">

              <tr>
                <td style="width: 35.8pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">6.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">RIGHTS; PURCHASE PRICE.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">On each
          Offering Date, each eligible employee, pursuant to an Offering made under the Plan, shall be granted the right to purchase up to the number of shares of Common Stock of the Company purchasable with a percentage designated by the Board or the
          Committee not exceeding ten percent (10%)&#160; of such employee's Earnings (as defined in Subsection 7(a)) during the period which begins on the Offering Date (or such later date as the Board or the Committee determines for a particular Offering) and
          ends on the date stated in the Offering, which date shall be no later than the end of the Offering. In addition, the Board or the Committee may specify a maximum dollar amount that each employee may use to purchase shares during any Offering made
          under the Plan. The Board or the Committee&#160; shall establish one or more dates during an Offering (the "Exercise Date(s)") on which rights granted under the Plan shall be exercised and purchases of Common Stock carried out in accordance with such
          Offering.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.55pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">In
          connection with each Offering made under the Plan, the Board or the Committee may specify a maximum number of shares that may be purchased by any employee as well as a maximum aggregate number of shares that may be purchased by all eligible
          employees pursuant to such Offering. In addition, in connection with each Offering that contains more than one Exercise Date, the Board or the Committee may specify a maximum aggregate number of shares which may be purchased by all eligible
          employees on any given Exercise Date under the Offering. If the aggregate purchase of shares upon exercise of rights granted under the Offering would exceed any such maximum aggregate number, the Board or the Committee shall make a pro rata
          allocation of the shares available in as nearly a uniform manner as shall be practicable and as it shall deem to be equitable.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 35.75pt; margin-right: 6.2pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">The
          purchase price of stock acquired pursuant to rights granted under the Plan shall be not less than the lesser of:</font></div>
      <div><br>
      </div>
      <div style="text-align: left; text-indent: 72.45pt; margin-right: 5.55pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">an amount
          equal to eighty-five percent (85%) of the fair market value of the stock on the Offering Date; or</font></div>
      <div><br>
      </div>
      <div style="text-align: left; text-indent: 72.45pt; margin-right: 5.55pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">an amount
          equal to eighty-five percent (85%) of the fair market value of the stock on the Exercise Date.</font></div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">4.</font></div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zd5b9beea73ec4098bd2065493203d6fd">

              <tr>
                <td style="width: 35.8pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">7.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">PARTICIPATION; WITHDRAWAL; TERMINATION.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.5pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">An
          eligible employee may become a participant in the Plan pursuant to an Offering by delivering a participation agreement to the Company within the time specified in the Offering, in such form as the Company provides. Each such agreement shall
          authorize payroll deductions of up to the maximum percentage specified by the Board or the Committee of such employee's Earnings during the Offering. "Earnings" is defined as the total compensation paid to an employee including all salary, wages
          (including amounts thereof elected to be deferred by the employee, that would otherwise have been paid, under any arrangement established by the Company that is intended to comply with Section 125, Section 40l(k), Section 402(h) or Section 403(b)
          of the Code or that provides non-qualified deferred compensation), which shall include overtime pay, commissions, bonuses and other remuneration paid directly to the employee, but shall exclude profit sharing, the cost of employee benefits paid
          for by the Company or an Affiliate, education or tuition reimbursements, imputed income arising under any group insurance or benefit program, traveling expenses, business and moving expense reimbursements, income received in connection with stock
          awards, contributions made by the Company or an Affiliate under any employee benefit plan, and similar items of compensation, as determined by the Board or the Committee. The payroll deductions made for each participant shall be credited to an
          account for such participant under the Plan and shall be deposited with the general funds of the Company. A participant may reduce (including to zero) or increase such payroll deductions, and an eligible employee may begin such payroll
          deductions, after the beginning of any Offering only as provided for in the Offering. A participant may make additional payments into his or her account only if specifically provided for in the Offering and only if the participant has not had the
          maximum permitted amount withheld during the Offering.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.65pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New
          Roman';">At any time during an Offering, a participant may terminate his or her payroll deductions under the Plan and withdraw from the Offering by delivering to the Company a notice of withdrawal in such form as the Company provides. Such
          withdrawal may be elected at any time prior to the end of the Offering except as provided by the Board or the Committee in the Offering. Upon such withdrawal from the Offering by a participant, the Company shall distribute to such participant all
          of his or her accumulated payroll deductions (reduced to the extent, if any, such deductions have been used to acquire stock for the participant) under the Offering, without interest, and such participant's interest in that Offering shall be
          automatically terminated. A participant's withdrawal from an Offering will have no effect upon such participant's eligibility to re-enroll in the Offering or to participate in any other Offerings under the Plan but such participant will be
          required to deliver&#160; a new participation agreement&#160; in order to participate in subsequent Offerings under the Plan.</font></div>
      <div><font style="font-weight: bold;"><br>
        </font> </div>
      <font style="font-weight: bold;"> </font>
      <div style="text-align: left; font-family: &quot;Times New Roman&quot;; font-size: 10pt; text-indent: 36pt;"><font style="font-weight: bold;">(c) </font>&#160; &#160;&#160;&#160;&#160; Rights granted pursuant to any Offering under the Plan shall terminate immediately upon
        cessation of any participating employee's employment with the Company and any designated Affiliate, for any reason, and the Company shall distribute to such terminated employee all of his or her accumulated payroll deductions (reduced to the
        extent, if any, such deductions have been used to acquire&#160; stock for the terminated employee), under the Offering, without interest.</div>
      <div style="text-align: left; font-family: &quot;Times New Roman&quot;; font-size: 10pt; text-indent: 72pt;"> <br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">5.</font></div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.8pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">Rights
          granted under the Plan shall not be transferable by a participant otherwise than by will or the laws of descent and distribution, or by a beneficiary designation as provided in Section 14 and, otherwise during his or her lifetime, shall be
          exercisable only by the person to whom such rights are granted.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zd64bbec736b74e439f01b895740321bb">

              <tr>
                <td style="width: 35.8pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">8.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">EXERCISE; MINIMUM HOLDING PERIOD.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.6pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(a)</font>&#160;&#160;&#160; &#160; &#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">On
          each Exercise Date specified therefor in the relevant Offering, each participant's accumulated payroll deductions and other additional payments specifically provided for in the Offering (without any increase for interest) will be applied to the
          purchase of whole shares of stock of the Company, up to the maximum number of shares permitted pursuant to the terms of the Plan and the applicable Offering, at the purchase price specified in the Offering. No fractional shares shall be issued
          upon the exercise of rights granted under the Plan. The amount, if any, of accumulated payroll deductions remaining in each participant's account after the purchase of shares which is less than the amount required to purchase one share of stock
          on the final Exercise Date of an Offering shall be held in each such participant's account for the purchase of shares under the next Offering under the Plan, unless such participant withdraws from such next Offering, as provided in Subsection
          7(b), or is no longer eligible to be granted rights under the Plan, as provided in Section 5, in which case such amount shall be distributed to the participant after such final Exercise Date, without interest. The amount, if any, of accumulated
          payroll deductions remaining in any participant's account after the purchase of shares which is equal to the amount required to purchase whole shares of stock on the final Exercise Date of an Offering shall be distributed in full to the
          participant after such Exercise Date, without interest.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.75pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(b)</font>&#160;&#160;&#160; &#160; &#160; <font style="font-size: 10pt; font-family: 'Times New
          Roman';">No rights granted under the Plan may be exercised to any extent unless the shares to be issued upon such exercise under the Plan (including rights granted thereunder) are covered by an effective registration statement pursuant to the
          Securities Act of 1933, as amended (the "Securities Act") and the Plan is in material compliance with all applicable state, foreign and other securities and other laws applicable to the Plan. If on an Exercise Date in any Offering hereunder the
          Plan is not so registered or in such compliance, no rights granted under the Plan or any Offering shall be exercised and all payroll deductions accumulated during the Offering (reduced to the extent, if any, such deductions have been used to
          acquire stock) shall be distributed to the participants, without interest.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.55pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160; &#160; <font style="font-size: 10pt; font-family: 'Times New
          Roman';">With respect to any Common Stock of the Company purchased under any Offering initiated after the Effective Date, as a condition to participating in, and purchasing shares of Common Stock under this Plan, each participant irrevocably
          agrees that, without the prior written consent of the Company, such participant will not, directly or indirectly, (1) offer for sale, sell, pledge, or otherwise dispose of (or enter into any transaction or device that is designed to, or could be
          expected to, result in the disposition by any person at any time in the future of) any shares of Common Stock of the Company (the "Held Shares") purchased by such participant in an Offering that was initiated after the Effective Date, or (2)
          enter into any swap or other derivatives transaction that transfers to another, in whole or in part, any of the economic benefits or risks of ownership of the Held Shares, in each case before the passage of the six-month anniversary of the date
          the participant purchased the applicable Held Shares (the "Holding Period"). The Company may impose stop-transfer instructions with respect to the shares of Common Stock subject to the foregoing restriction until the end of the applicable Holding
          Period.</font></div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"> <br>
        </font></div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">6.</font></div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: justify; text-indent: 35.75pt; margin-right: 6pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(d)</font>&#160;&#160;&#160;&#160; &#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">Each
          participant understands and agrees that on any certificates evidencing&#160; the shares of Common Stock purchased under the Plan, the Company may place a legend, substantially in the form of the following:</font></div>
      <div><br>
      </div>
      <div style="text-align: left; margin-left: 36pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;">THE SHARES EVIDENCED BY THIS CERTIFICATE CANNOT BE SOLD UNTIL [INSERT DATE THAT IS 6 MONTHS FROM DATE OF PURCHASE].</font></div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z746b0e72910b441ca772a0152bf3cc9f">

              <tr>
                <td style="width: 36pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">9.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">COVENANTS OF THE COMPANY.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36pt; margin-right: 6.4pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160; &#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">During
          the terms of the rights granted under the Plan, the Company shall keep available at all times the number of shares of stock required to satisfy such rights.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.2pt; margin-right: 5.85pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">The
          Company shall seek to obtain from each federal, state, foreign or other regulatory commission or agency having jurisdiction over the Plan such authority as may be required to issue and sell shares of stock upon exercise of the rights granted
          under the Plan.&#160; If, after reasonable efforts, the Company is unable to obtain from any such regulatory commission or agency the authority which counsel for the Company deems necessary for the lawful issuance and sale of stock under the Plan, the
          Company shall be relieved from any liability for failure to issue and sell stock upon exercise of such rights unless and until such authority is obtained.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="zb708dd9256c44599a6f2a150bd161a56">

              <tr>
                <td style="width: 35.3pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">10.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">USE OF PROCEEDS FROM STOCK.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 35.75pt; margin-right: 6.3pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Proceeds from the sale of stock pursuant to rights granted under the Plan shall constitute general funds of
          the Company.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="ze8a8dcd5d61f497fbeda8aed8bed0eb1">

              <tr>
                <td style="width: 35.3pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">11.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">RIGHTS AS A STOCKHOLDER.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.2pt; margin-right: 5.65pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">A participant shall not be deemed to be the holder of, or to have any of the rights of a holder with respect
          to, any shares subject to rights granted under the Plan unless and until the participant's shareholdings acquired upon exercise of rights under the Plan are recorded in the books of the Company.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z7ed3c1f738d44e749e70675590648c54">

              <tr>
                <td style="width: 35pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">12.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">ADJUSTMENTS UPON CHANGES IN STOCK.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: &quot;Times New Roman&quot;; font-size: 10pt; text-indent: 36pt;">(a)&#160; &#160; &#160;&#160;&#160; If any change is made in the stock subject to the Plan, or subject to any rights granted under the Plan, due to a change in
        corporate capitalization and without the receipt of consideration by the Company (through reincorporation, stock dividend, stock split, reverse stock split, combination or reclassification of shares), the Plan will be appropriately adjusted in the
        class(es) and maximum number of securities subject to the Plan pursuant to subsection 3(a), and the outstanding rights will be appropriately adjusted in the class(es) and number of securities and price per share of stock subject to such outstanding
        rights. Such adjustments shall be made by the Board, the determination of which shall be final, binding and conclusive.</div>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">7.</font></div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: justify; margin-right: 5.9pt;">
        <div style="text-align: justify; text-indent: 36pt; margin-right: 5.8pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">In
            the event of: (1) a dissolution, liquidation or sale of all or substantially all of the assets of the Company, (2) a merger or consolidation in which the Company is not the surviving corporation, or (3) a reverse merger in which the Company is
            the surviving corporation but the shares of Common Stock outstanding immediately preceding the merger are converted by virtue of the merger into other property, whether in the form of securities, cash or otherwise or (4) any</font><font style="font-size: 10pt; font-family: 'Times New Roman';"> other capital reorganization in&#160; which more than fifty percent (50%) of the secunt1es of the Company entitled to vote are sold or otherwise exchanged, then any surviving corporation may
            assume outstanding rights or substitute similar rights for those under the Plan. In the event that no surviving corporation assumes such outstanding rights or substitutes similar rights therefor, participants' accumulated payroll deductions
            will be used to purchase Common Stock immediately prior to the transaction described above and the participants' rights under the ongoing Offering terminated immediately following such purchase.</font></div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="za557dfb1cd074a6a8c4f39bf3ee8e7c4">

              <tr>
                <td style="width: 35.05pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">13.</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">AMENDMENT OF THE PLAN.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 6.35pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New
          Roman';">The Board at any time, and from time to time, may amend the Plan. However, except as provided in Section 12 relating to adjustments upon changes in stock, no amendment shall be effective unless approved by the stockholders of the Company
          within twelve (12) months before or after the adoption of the amendment, where the amendment will:</font></div>
      <div><br>
      </div>
      <div style="text-align: left; text-indent: 72pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">Increase the number of shares
          reserved for rights under the Plan;</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72pt; margin-right: 5.1pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(ii)</font>&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">Modify the
          provisions as to eligibility for participation in the Plan (to the extent such modification requires stockholder approval in order for the Plan to obtain employee stock purchase plan treatment under Section 423 of the Code or to comply with the
          requirements of Rule 16b-3 promulgated under the Securities Exchange Act of 1934, as amended ("Rule 16b-3")); or</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 72.2pt; margin-right: 6pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(iii)</font>&#160;&#160; &#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">Modify the
          Plan in any other way if such modification requires stockholder approval in order for the Plan to obtain employee stock purchase plan treatment under Section 423 of the Code or to comply with the requirements of Rule 16b-3.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; margin-right: 6pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">It is expressly contemplated that the Board may amend the Plan in any respect the Board deems necessary or advisable to provide
          eligible employees with the maximum benefits provided or to be provided under the provisions of the Code and the regulations promulgated thereunder relating to employee stock purchase plans and/or to bring the Plan and/or rights granted under it
          into compliance therewith.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.2pt; margin-right: 5.8pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Rights and
          obligations under any rights granted before amendment of the Plan shall not be impaired by any amendment of the Plan, except with the consent of the person to whom such rights were granted, or except as necessary to comply with any laws or
          governmental regulations, or except as necessary to ensure that the Plan and/or rights granted under the Plan comply with the requirements of Section 423 of the Code.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z313338fb1cb142269cb260fefea2cbb6">

              <tr>
                <td style="width: 35.3pt; vertical-align: top; align: right;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">14.</font></td>
                <td style="width: auto; vertical-align: top; text-align: justify;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">DESIGNATION OF BENEFICIARY.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.2pt; margin-right: 5.55pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">A
          participant may file a written designation of a beneficiary who is to receive any shares and cash, if any, from the participant's account under the Plan in the event of such participant's death subsequent to the end of an Offering but prior to
          delivery to the participant of such shares and cash. In addition, a participant may file a written designation of a beneficiary who is to receive any cash from the participant's account under the Plan in the event of such participant's death
          during an Offering.</font></div>
      <div style="text-align: justify;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;;"> <br>
        </font></div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">8.</font></div>
        <div style="page-break-after:always;" id="DSPFPageBreak">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.8pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">Such
          designation of beneficiary may be changed by the participant at any time by written notice. In the event of the death of a participant and in the absence of a beneficiary validly designated under the Plan who is living at the time of such
          participant's death, the Company shall deliver such shares and/or cash to the executor or administrator of the estate of the participant, or if no such executor or administrator has been appointed (to the knowledge of the Company), the Company,
          in its sole discretion, may deliver such shares and/or cash to the spouse or to any one or more dependents or relatives of the participant, or if no spouse, dependent or relative is known to the Company, then to such other person as the Company
          may designate.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z48cce718449d414cb72e20920ab92f74">

              <tr>
                <td style="width: 35.55pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">15.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">TERMINATION OR SUSPENSION OF THE PLAN.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: left; font-family: &quot;Times New Roman&quot;; font-size: 10pt; text-indent: 36pt;"><font style="font-weight: bold;">(a)</font>&#160;&#160;&#160;&#160;&#160; &#160; The Board in its discretion may suspend or terminate the Plan at any time. No rights may
        be granted under the Plan while the Plan is suspended or after it is terminated.</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.45pt; margin-right: 5.55pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New
          Roman';">Rights and obligations under any rights granted while the Plan is in effect shall not be altered or impaired by suspension or termination of the Plan, except as expressly provided in the Plan or with the consent of the person to whom
          such rights were granted, or except as necessary to comply with any laws or governmental regulation, or except as necessary to ensure that the Plan and/or rights granted under the Plan comply with the requirements of Section 423 of the Code.</font></div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 36.2pt; margin-right: 6.25pt;"><font style="font-size: 10pt; font-family: &quot;Times New Roman&quot;; font-weight: bold;">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-size: 10pt; font-family: 'Times New Roman';">Notwithstanding
          the foregoing, the Plan shall terminate on March 21, 2029 and no rights may be granted under the Plan after such termination.</font></div>
      <div><br>
      </div>
      <div style="text-align: left;">
        <div>
          <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%;" class="DSPFListTable" id="z626698464dea40008a3a7af83d586615">

              <tr>
                <td style="width: 35.3pt; vertical-align: top; font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">16.</font></td>
                <td style="width: auto; vertical-align: top; text-align: left;">
                  <div style="font-weight: bold;"><font style="font-size: 10pt; font-family: 'Times New Roman';">EFFECTIVE DATE OF PLAN.</font></div>
                </td>
              </tr>

          </table>
        </div>
      </div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 35.75pt; margin-right: 6pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">The Plan shall become effective on the date on which it is first approved by the stockholders of the Company
          (the "Effective Date").</font></div>
      <div><br>
      </div>
      <div><br>
      </div>
      <div>
        <div id="DSPFPageNumberArea" style="text-align: center;"><font id="DSPFPageNumber" style="font-family: 'Times New Roman'; font-size: 8pt; font-weight: normal; font-style: normal;">9.</font></div>
      </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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</DOCUMENT>
<DOCUMENT>
<TYPE>EX-99.1
<SEQUENCE>4
<FILENAME>ex99_1.htm
<DESCRIPTION>EXHIBIT 99.1
<TEXT>
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  <div style="text-align: left;"><font style="font-weight: bold;"> </font>
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  <div style="text-align: right;"><font style="font-weight: bold;">Exhibit 99.1</font><br>
  </div>
  <div> <br>
  </div>
  <div>
    <div style="text-align: left;"><img src="image00003.jpg"></div>
    <div><br>
    </div>
    <div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Ionis announces appointment of Brett P. Monia Ph.D. to its board of directors</div>
    <div><br>
    </div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">CARLSBAD, Calif., March 25, 2019</font> &#8211; Ionis Pharmaceuticals, Inc<font style="font-size: 10pt; font-family: 'Times New Roman';">.</font> (NASDAQ: IONS), the leader in RNA-targeted therapeutics, today announced that Brett P. Monia, Ph.D., has been appointed to the company&#8217;s board of directors. Dr. Monia currently
        serves as Ionis&#8217; chief operating officer and, as was previously announced, will be appointed chief executive officer of the company in January 2020, succeeding current CEO Stanley T. Crooke, M.D., Ph.D., who will become executive chairman of the
        Ionis board of directors. With the addition of Dr. Monia, the Ionis board now has a total of 11 members.<br>
        <br>
      </font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">&#8220;I am pleased to welcome Brett to the board. His business leadership, expertise in developing antisense medicines for nearly 30 years, commitment to the Ionis
        business model and culture and bringing transformational therapies to patients make him an ideal addition to our board,&#8221; said Dr. Crooke.</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
      </font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Dr. Monia is a founding member of Ionis and has been an executive officer of the company since 2012. Prior to becoming COO in 2018, he was senior vice
        president of translational medicine and the franchise leader for programs in oncology and rare diseases. Dr. Monia has also served as Ionis&#8217; head of drug discovery where he supervised the discovery of more than 40 antisense-based medicines reaching
        clinical development, resulting in several market approvals, including TEGSEDI&#8482;.</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
      </font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Dr. Monia has published more than 200 primary research manuscripts, reviews and book chapters, and he is an inventor on more than 100 issued patents. He is a
        senior editor for the journal Nucleic Acid Therapeutics, a member of the Board of Directors of Dynacure Therapeutics and a past president of the Oligonucleotide Therapeutics Society. Dr. Monia is also an adjunct professor of biology at San Diego
        State University where he lectures at the graduate level on pharmacology.</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"> <br>
      </font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">About Ionis Pharmaceuticals</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"> <br>
      </font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">As the leader in RNA-targeted drug discovery and development, Ionis has created an efficient, broadly applicable, drug discovery platform called antisense
        technology that can treat diseases where no other therapeutic approaches have proven effective. Our drug discovery platform has served as a springboard for actionable promise and realized hope for patients with unmet needs. We created the first and
        only approved treatment for children and adults with spinal muscular atrophy as well as the world&#8217;s first RNA-targeted therapeutic approved for the treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis. Our sights are set
        on all the patients we have yet to reach with a pipeline of more than 40 novel medicines designed to treat a broad range of diseases including cardiovascular diseases, neurological diseases, infectious diseases, pulmonary diseases and cancer.</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
      </font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">To learn more about Ionis follow us on twitter @ionispharma or visit <font style="font-size: 10pt; font-family: 'Times New Roman';"><u>www.ionispharma.com</u></font>.</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
      </font></div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" id="DSPFPageBreakArea">
      <div style="page-break-after: always;" id="DSPFPageBreak">
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    </div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Ionis Pharmaceuticals Investor Contact:</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"> <br>
      </font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">D. Wade Walke, Ph.D.</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Vice President, Investor Relations</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">760-603-2741</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';"> <br>
      </font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">Ionis Pharmaceuticals Media Contact:</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;"> <br>
      </font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Roslyn Patterson</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">Vice President, Corporate Communications</font></div>
    <div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman';">760-603-2681</font></div>
    <div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">###</font></div>
    <div><br>
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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
