<SEC-DOCUMENT>0001104659-19-074467.txt : 20191220
<SEC-HEADER>0001104659-19-074467.hdr.sgml : 20191220
<ACCEPTANCE-DATETIME>20191219175541
ACCESSION NUMBER:		0001104659-19-074467
CONFORMED SUBMISSION TYPE:	SC 13D/A
PUBLIC DOCUMENT COUNT:		1
FILED AS OF DATE:		20191220
DATE AS OF CHANGE:		20191219

SUBJECT COMPANY:	

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			AKCEA THERAPEUTICS, INC.
		CENTRAL INDEX KEY:			0001662524
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		IRS NUMBER:				472608175
		STATE OF INCORPORATION:			DE
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		SC 13D/A
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	005-90051
		FILM NUMBER:		191297232

	BUSINESS ADDRESS:	
		STREET 1:		22 BOSTON WHARF RD
		STREET 2:		9TH FLOOR
		CITY:			BOSTON
		STATE:			MA
		ZIP:			02210
		BUSINESS PHONE:		617-207-0202

	MAIL ADDRESS:	
		STREET 1:		22 BOSTON WHARF RD
		STREET 2:		9TH FLOOR
		CITY:			BOSTON
		STATE:			MA
		ZIP:			02210

FILED BY:		

	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:		SC 13D/A

	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>SC 13D/A
<SEQUENCE>1
<FILENAME>a19-26706_1sc13da.htm
<DESCRIPTION>SC 13D/A
<TEXT>


<html>
<head>






  </head>
<body link=blue bgcolor="white" lang="EN-US">
<div style="font-family:Times New Roman;">
<p style="margin:0in 0in .0001pt;"><font size="3" face="Times New Roman" style="font-size:12.0pt;">&nbsp;</font></p>
<table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;">
<tr>
<td width="23%" valign="top" style="padding:0in .7pt .7pt .7pt;width:23.0%;">
<p align="center" style="margin:0in 0in .0001pt 10.0pt;text-align:center;text-indent:-10.0pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="54%" valign="top" style="padding:0in .7pt .7pt .7pt;width:54.02%;">
<p align="center" style="margin:0in 0in .0001pt 10.0pt;text-align:center;text-indent:-10.0pt;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">SECURITIES AND   EXCHANGE COMMISSION</font></b></p>    </td>
<td width="22%" valign="top" style="padding:0in .7pt .7pt .7pt;width:22.98%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="23%" valign="top" style="padding:0in .7pt .7pt .7pt;width:23.0%;">
<p align="center" style="margin:0in 0in .0001pt 10.0pt;text-align:center;text-indent:-10.0pt;"><b><font size="2" face="Times New Roman" style="font-size:1.0pt;font-weight:bold;">&nbsp;</font></b></p>    </td>
<td width="54%" valign="top" style="padding:0in .7pt .7pt .7pt;width:54.02%;">
<p align="center" style="margin:0in 0in .0001pt 10.0pt;text-align:center;text-indent:-10.0pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Washington, DC 20549</font></b></p>    </td>
<td width="22%" valign="bottom" style="padding:0in .7pt .7pt .7pt;width:22.98%;">
<p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:1.0pt;font-weight:bold;">&nbsp;</font></b></p>    </td>   </tr>
<tr>
<td width="23%" valign="top" style="padding:0in .7pt .7pt .7pt;width:23.0%;">
<p align="center" style="margin:0in 0in .0001pt 10.0pt;text-align:center;text-indent:-10.0pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">&nbsp;</font></b></p>    </td>
<td width="54%" valign="top" style="padding:0in .7pt .7pt .7pt;width:54.02%;">
<p align="center" style="margin:0in 0in .0001pt 10.0pt;text-align:center;text-indent:-10.0pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">&nbsp;</font></b></p>    </td>
<td width="22%" valign="bottom" style="padding:0in .7pt .7pt .7pt;width:22.98%;">
<p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">&nbsp;</font></b></p>    </td>   </tr>
<tr height="19" style="height:.2in;">
<td width="23%" height="19" valign="top" style="height:.2in;padding:0in .7pt .7pt .7pt;width:23.0%;">
<p align="center" style="margin:0in 0in .0001pt 10.0pt;text-align:center;text-indent:-10.0pt;"><b><font size="2" face="Times New Roman" style="font-size:1.0pt;font-weight:bold;">&nbsp;</font></b></p>    </td>
<td width="54%" height="19" valign="top" style="height:.2in;padding:0in .7pt .7pt .7pt;width:54.02%;">
<p align="center" style="margin:0in 0in .0001pt 10.0pt;text-align:center;text-indent:-10.0pt;"><b><font size="3" face="Times New Roman" style="font-size:12.0pt;font-weight:bold;">SCHEDULE 13D</font></b></p>    </td>
<td width="22%" height="19" valign="bottom" style="height:.2in;padding:0in .7pt .7pt .7pt;width:22.98%;">
<p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:1.0pt;font-weight:bold;">&nbsp;</font></b></p>    </td>   </tr>  </table>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Under the Securities Exchange Act of 1934 <br> (Amendment No. 5)*</font></b></p>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="3" face="Times New Roman" style="font-size:12.0pt;">&nbsp;</font></p>
<div style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 1.0pt 0in;">
<p align="center" style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:center;"><b><font size="5" face="Times New Roman" style="font-size:18.0pt;font-weight:bold;">Akcea Therapeutics, Inc.</font></b></p>
</div>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(Name of Issuer)</font></p>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="3" face="Times New Roman" style="font-size:12.0pt;">&nbsp;</font></p>
<div style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 1.0pt 0in;">
<p align="center" style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Common Stock</font></b></p>
</div>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(Title of Class of Securities)</font></p>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="3" face="Times New Roman" style="font-size:12.0pt;">&nbsp;</font></p>
<div style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 1.0pt 0in;">
<p align="center" style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">00972L 107</font></b></p>
</div>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(CUSIP Number)</font></p>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<div style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 1.0pt 0in;">
<p align="center" style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Elizabeth L. Hougen</font></b></p>
<p align="center" style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Ionis Pharmaceuticals, Inc.</font></b></p>
<p align="center" style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">2855 Gazelle Court</font></b></p>
<p align="center" style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Carlsbad, CA 92010</font></b></p>
<p align="center" style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">(760) 931-9200</font></b></p>
</div>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(Name, Address and Telephone Number of Person<br> Authorized to Receive Notices and Communications)</font></p>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="3" face="Times New Roman" style="font-size:12.0pt;">&nbsp;</font></p>
<div style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 1.0pt 0in;">
<p align="center" style="border:none;margin:0in 0in .0001pt;padding:0in;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">December 17, 2019</font></b></p>
</div>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(Date of Event Which Requires Filing of this Statement)<br><br></font></p>
<p style="margin:0in .5in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">If the filing person has previously filed a statement on Schedule 13G to report the acquisition that is the subject of this Schedule 13D, and is filing this schedule because of &#167;&#167;240.13d-1(e), 240.13d-1(f)&nbsp;or 240.13d-1(g), check the following box.</font><font size="2" style="font-size:10.0pt;">  </font><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font></p>
<p style="margin:5.0pt .5in;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Note</font></b><font size="2" style="font-size:10.0pt;">: Schedules filed in paper format shall include a signed original and five copies of the schedule, including all exhibits. See Rule&nbsp;13d-7 for other parties to whom copies are to be sent.</font><font size="2" style="font-size:10.0pt;">  </font></p>
<p style="margin:5.0pt .5in;"><font size="1" face="Times New Roman" style="font-size:6.5pt;position:relative;top:-3.0pt;">*</font><font size="2" style="font-size:10.0pt;">&#160;</font><font size="2" style="font-size:10.0pt;">The remainder of this cover page&nbsp;shall be filled out for a reporting person&#146;s initial filing on this form with respect to the subject class of securities, and for any subsequent amendment containing information which would alter disclosures provided in a prior cover page.</font><font size="2" style="font-size:10.0pt;">  </font></p>
<p style="margin:0in .5in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">The information required on the remainder of this cover page shall not be deemed to be &quot;filed&quot; for the purpose of Section 18 of the Securities Exchange Act of 1934 (&quot;Act&quot;) or otherwise subject to the liabilities of that section of the Act but shall be subject to all other provisions of the Act (however, see the Notes).</font></p>
<p style="margin:0in .5in .0001pt;"><font size="3" face="Times New Roman" style="font-size:12.0pt;">&nbsp;</font></p>
<div style="margin:0in 0in .0001pt;"><hr size="3" width="100%" noshade align="left" style="color:#010101;"></div>
</div>
<!-- SEQ.=1,FOLIO='',FILE='C:\JMS\109764\19-26706-1\task9565404\26706-1-ba.htm',USER='109764',CD='Dec 20 03:47 2019' -->


<div style="page-break-before:always;"></div>
<div style="font-family:Times New Roman;">
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<div align="center">
<table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;">
<tr>
<td width="33%" colspan="6" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:33.32%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">CUSIP No.   00972L 107</font></p>    </td>
<td width="33%" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:33.34%;">
<p align="center" style="margin:4.0pt 0in;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">13D</font></b></p>    </td>
<td width="33%" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:33.34%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="100%" colspan="8" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:100.0%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">1.</font></p>    </td>
<td width="91%" colspan="6" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:91.1%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Name of Reporting Persons<br>   Ionis Pharmaceuticals, Inc. (&#147;Ionis&#148;)</font></p>    </td>   </tr>
<tr>
<td width="100%" colspan="8" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:100.0%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">2.</font></p>    </td>
<td width="91%" colspan="6" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:91.1%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Check the   Appropriate Box if a Member of a Group (See Instructions)</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="8%" colspan="3" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:8.36%;">
<p style="margin:4.0pt 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(a)</font></p>    </td>
<td width="82%" colspan="3" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:82.74%;">
<p style="margin:4.0pt 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="8%" colspan="3" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:8.36%;">
<p style="margin:4.0pt 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(b)</font></p>    </td>
<td width="82%" colspan="3" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:82.74%;">
<p style="margin:4.0pt 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font></p>    </td>   </tr>
<tr>
<td width="100%" colspan="8" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:100.0%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">3.</font></p>    </td>
<td width="91%" colspan="6" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:91.1%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">SEC Use   Only </font></p>    </td>   </tr>
<tr>
<td width="100%" colspan="8" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:100.0%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">4.</font></p>    </td>
<td width="91%" colspan="6" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:91.1%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Source of   Funds (See Instructions)<br>    </font><font size="2" style="font-size:10.0pt;">WC</font></p>    </td>   </tr>
<tr>
<td width="100%" colspan="8" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:100.0%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">5.</font></p>    </td>
<td width="91%" colspan="6" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:91.1%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Check if Disclosure of Legal   Proceedings Is Required Pursuant to Items 2(d) or 2(e)&nbsp; </font><font size="2" style="font-size:10.0pt;">&nbsp;&nbsp;&nbsp;</font><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font></p>    </td>   </tr>
<tr>
<td width="100%" colspan="8" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:100.0%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">6.</font></p>    </td>
<td width="91%" colspan="6" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:91.1%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Citizenship or Place of   Organization<br>    </font><font size="2" style="font-size:10.0pt;">Delaware</font></p>    </td>   </tr>
<tr>
<td width="100%" colspan="8" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:100.0%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr style="page-break-inside:avoid;">
<td width="12%" colspan="3" rowspan="7" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:12.04%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Number of<br>   Shares<br>   Beneficially<br>   Owned by<br>   Each<br>   Reporting<br>   Person With</font></p>    </td>
<td width="4%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:4.46%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">7.</font></p>    </td>
<td width="83%" colspan="4" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:83.5%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Sole   Voting Power <br>    </font><font size="2" style="font-size:10.0pt;">77,094,682</font></p>    </td>   </tr>
<tr style="page-break-inside:avoid;">
<td width="87%" colspan="5" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:87.96%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr style="page-break-inside:avoid;">
<td width="4%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:4.46%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">8.</font></p>    </td>
<td width="83%" colspan="4" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:83.5%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Shared   Voting Power</font><font size="2" style="font-size:10.0pt;">  <br><br></font></p>    </td>   </tr>
<tr style="page-break-inside:avoid;">
<td width="87%" colspan="5" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:87.96%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr style="page-break-inside:avoid;">
<td width="4%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:4.46%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">9.</font></p>    </td>
<td width="83%" colspan="4" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:83.5%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Sole   Dispositive Power</font><font size="2" style="font-size:10.0pt;">  <br>   77,094,682</font></p>    </td>   </tr>
<tr style="page-break-inside:avoid;">
<td width="87%" colspan="5" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:87.96%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr style="page-break-inside:avoid;">
<td width="4%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:4.46%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">10.</font></p>    </td>
<td width="83%" colspan="4" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:83.5%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Shared Dispositive Power</font><font size="2" style="font-size:10.0pt;">  <br><br></font></p>    </td>   </tr>
<tr>
<td width="100%" colspan="8" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:100.0%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">11.</font></p>    </td>
<td width="91%" colspan="6" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:91.1%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Aggregate   Amount Beneficially Owned by Each Reporting Person</font><font size="2" style="font-size:10.0pt;">  <br>   77,094,682</font></p>    </td>   </tr>
<tr>
<td width="100%" colspan="8" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:100.0%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">12.</font></p>    </td>
<td width="91%" colspan="6" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:91.1%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Check if   the Aggregate Amount in Row (11) Excludes Certain Shares (See Instructions)</font><font size="2" style="font-size:10.0pt;">&nbsp;&nbsp; </font><font size="2" face="Wingdings" style="font-size:10.0pt;">o</font></p>    </td>   </tr>
<tr>
<td width="100%" colspan="8" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:100.0%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">13.</font></p>    </td>
<td width="91%" colspan="6" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:91.1%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Percent   of Class Represented by Amount in Row 11</font><font size="2" style="font-size:10.0pt;">  <br>   76.5%</font></p>    </td>   </tr>
<tr>
<td width="100%" colspan="8" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:100.0%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="3%" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:3.32%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:3.0pt 3.0pt 3.0pt 3.0pt;width:5.58%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">14.</font></p>    </td>
<td width="91%" colspan="6" style="border:none;border-bottom:solid windowtext 1.0pt;padding:3.0pt 3.0pt 3.0pt 3.0pt;width:91.1%;">
<p style="margin:4.0pt 0in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Type of   Reporting Person (See Instructions)</font><font size="2" style="font-size:10.0pt;"><br>   CO</font></p>    </td>   </tr>
<tr height="0">
<td width="23" style="border:none;"></td>
<td width="39" style="border:none;"></td>
<td width="22" style="border:none;"></td>
<td width="32" style="border:none;"></td>
<td width="5" style="border:none;"></td>
<td width="114" style="border:none;"></td>
<td width="236" style="border:none;"></td>
<td width="236" style="border:none;"></td>   </tr> </table>
</div>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" style="font-size:10.0pt;">2</font><font size="2"><a name="PB_2_034228_2306"></a></font></p>
<div style="margin:0in 0in .0001pt;"><hr size="3" width="100%" noshade align="left" style="color:#010101;"></div>
</div>
<!-- SEQ.=1,FOLIO='2',FILE='C:\JMS\109764\19-26706-1\task9565404\26706-1-bc.htm',USER='109764',CD='Dec 20 03:47 2019' -->


<div style="page-break-before:always;"></div>
<div style="font-family:Times New Roman;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt .75in;text-indent:-.75in;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Item 1.</font></b><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><b>Security and Issuer.</b></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">This Amendment No.&nbsp;5 to Schedule 13D is being filed as an amendment to the initial statement on Schedule 13D relating to the Common Stock, $0.001 par value per share (&#147;Common Stock&#148;) of Akcea Therapeutics,&nbsp;Inc., a Delaware corporation (the &#147;Issuer&#148;) as filed with the Securities and Exchange Commission (the &#147;SEC&#148;) on July&nbsp;27, 2017 (the &#147;Original Schedule 13D&#148;) as amended by Amendment No.&nbsp;1 filed April&nbsp;26, 2018,&#160; Amendment No.&nbsp;2 filed August&nbsp;7, 2018, Amendment No.&nbsp;3 filed October&nbsp;22, 2018 and Amendment No.&nbsp;4 filed April&nbsp;2, 2019.&#160; The principal executive offices of the Issuer are located at 22 Boston Wharf Road, 9</font><font size="1" style="font-size:6.5pt;position:relative;top:-3.0pt;">th</font>&#160;Floor, Boston, Massachusetts 02210.&#160; This Amendment is being filed to report the acquisition of an aggregate of 6,873,344 shares of the Issuer&#146;s Common Stock by Ionis Pharmaceuticals,&nbsp;Inc., a Delaware corporation (&#147;Ionis&#148; or the &#147;Reporting Person&#148;), on December&nbsp;17,&nbsp;2019.</p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Items 2(c), 4 and 5 of the Original Schedule 13D are hereby amended and supplemented to the extent hereinafter expressly set forth and, except as amended and supplemented hereby, the Original Schedule 13D remains in full force and effect.&#160; All capitalized terms used in this Amendment No.&nbsp;5 but not defined herein shall have the meanings ascribed thereto in the Original Schedule 13D.</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt .75in;text-indent:-.75in;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Item 2.</font></b><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><b>Identity and Background.</b></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt .75in;text-indent:-.75in;"><i><font size="2" face="Times New Roman" style="font-size:10.0pt;font-style:italic;">Schedule A to Item 2(c)&nbsp;is hereby amended.</font></i></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt .75in;text-indent:-.75in;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Item 4.</font></b><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><b>Purpose of Transaction.</b></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt;"><i><font size="2" face="Times New Roman" style="font-size:10.0pt;font-style:italic;">Item 4 of the Original Schedule 13D is hereby amended and supplemented by adding the following paragraph at the end of Item 4:</font></i></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">On December&nbsp;17, 2019, the Reporting Person received 6,873,344 shares of the Issuer&#146;s Common Stock in satisfaction of the Issuer&#146;s obligations to the Reporting Person pursuant to that certain Development, Commercialization and License Agreement, dated December&nbsp;18, 2015, between the Issuer and the Reporting Person.</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt .75in;text-indent:-.75in;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Item 5.</font></b><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><b>Interest in Securities of the Issuer.</b></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt .75in;text-indent:-.75in;"><i><font size="2" face="Times New Roman" style="font-size:10.0pt;font-style:italic;">Item 5 of the Original Schedule 13D is hereby amended and restated in its entirety as follows:</font></i></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">The following information with respect to the ownership of the Common Stock of the Issuer by the Reporting Person filing this Schedule 13D is provided as of December&nbsp;17, 2019:</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt .5in;text-indent:-.25in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(a)</font><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The Reporting Person beneficially owns 77,094,682 shares of the Common Stock of the Issuer, or approximately 76.5% of the Issuer&#146;s outstanding Common Stock.</p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt .5in;text-indent:-.25in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(b)</font><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Ionis has sole power to vote and dispose of the securities of the Issuer held by it.</p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt .5in;text-indent:-.25in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(c)</font><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The Reporting Person has not effected any other transactions in the Issuer&#146;s Common Stock within the past sixty days, except as provided herein.</p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt .5in;text-indent:-.25in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(d)</font><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Not applicable.</p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt .5in;text-indent:-.25in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">(e)</font><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Not applicable.</p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt .75in;text-indent:-.75in;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Item 6.</font></b><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><b>Contracts, Arrangements, Understandings or Relationships with Respect to Securities of the Issuer.</b></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">None.</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p align="center" style="font-size:10.0pt;margin:0in 0in .0001pt;text-align:center;">3<a name="PB_3_033701_9825"></a></p>
<div style="margin:0in 0in .0001pt;"><hr size="3" width="100%" noshade align="left" style="color:#010101;"></div>
</div>
<!-- SEQ.=1,FOLIO='3',FILE='C:\JMS\111407\19-26706-1\task9565394\26706-1-be.htm',USER='111407',CD='Dec 20 03:37 2019' -->

<div style="page-break-before:always;"></div>
<div style="font-family:Times New Roman;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="font-size:10.0pt;margin:0in 0in .0001pt .75in;text-indent:-.75in;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Item 7.</font></b><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><b>Material to Be Filed as Exhibits.</b></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">None.</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p align="center" style="font-size:10.0pt;margin:0in 0in .0001pt;text-align:center;">4<a name="PB_4_033705_7056"></a></p>
<div style="margin:0in 0in .0001pt;"><hr size="3" width="100%" noshade align="left" style="color:#010101;"></div>
</div>
<!-- SEQ.=1,FOLIO='4',FILE='C:\JMS\111407\19-26706-1\task9565394\26706-1-be.htm',USER='111407',CD='Dec 20 03:37 2019' -->


<div style="page-break-before:always;"></div>
<div style="font-family:Times New Roman;">
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">SIGNATURE</font></b></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">After reasonable inquiry and to the best of my knowledge and belief,&nbsp;I certify that the information set forth in this statement is true, complete and correct.</font></p>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;">
<tr>
<td width="50%" valign="top" style="padding:0in 0in 0in 0in;width:50.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Date: December&nbsp;19, 2019</font></p>    </td>
<td width="50%" colspan="2" valign="top" style="padding:0in 0in 0in 0in;width:50.0%;">
<p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">IONIS   PHARMACEUTICALS,&nbsp;INC.</font></b></p>    </td>   </tr>
<tr>
<td width="50%" valign="top" style="padding:0in 0in 0in 0in;width:50.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="50%" colspan="2" valign="top" style="padding:0in 0in 0in 0in;width:50.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="50%" valign="top" style="padding:0in 0in 0in 0in;width:50.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:0in 0in 0in 0in;width:5.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">By:</font></p>    </td>
<td width="45%" valign="top" style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;width:45.0%;">
<p style="margin:0in 0in .0001pt;"><i><font size="2" face="Times New Roman" style="font-size:10.0pt;font-style:italic;">/s/ Elizabeth L. Hougen</font></i></p>    </td>   </tr>
<tr>
<td width="50%" valign="top" style="padding:0in 0in 0in 0in;width:50.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:0in 0in 0in 0in;width:5.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="45%" valign="top" style="padding:0in 0in 0in 0in;width:45.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Elizabeth L.   Hougen</font></p>    </td>   </tr>
<tr>
<td width="50%" valign="top" style="padding:0in 0in 0in 0in;width:50.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:0in 0in 0in 0in;width:5.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="45%" valign="top" style="padding:0in 0in 0in 0in;width:45.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Sr. Vice   President, Finance and</font></p>    </td>   </tr>
<tr>
<td width="50%" valign="top" style="padding:0in 0in 0in 0in;width:50.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="5%" valign="top" style="padding:0in 0in 0in 0in;width:5.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="45%" valign="top" style="padding:0in 0in 0in 0in;width:45.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Chief   Financial Officer</font></p>    </td>   </tr>  </table>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">The original statement shall be signed by each person on whose behalf the statement is filed or his authorized representative. If the statement is signed on behalf of a person by his authorized representative (other than an executive officer or general partner of the filing person), evidence of the representative&#146;s authority to sign on behalf of such person shall be filed with the statement:&#160; provided, however, that a power of attorney for this purpose which is already on file with the Commission may be incorporated by reference. The name and any title of each person who signs the statement shall be typed or printed beneath his signature.</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p align="center" style="font-size:10.0pt;margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">Attention:</font></b><font size="1" style="font-size:3.0pt;">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><b>Intentional misstatements or omissions of fact<br> constitute Federal criminal violations (See 18 U.S.C. 1001)</b></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p align="center" style="font-size:10.0pt;margin:0in 0in .0001pt;text-align:center;">5<a name="PB_5_033902_7086"></a></p>
<div style="margin:0in 0in .0001pt;"><hr size="3" width="100%" noshade align="left" style="color:#010101;"></div>
</div>
<!-- SEQ.=1,FOLIO='5',FILE='C:\JMS\C605009\19-26706-1\task9565392\26706-1-bg.htm',USER='C605009',CD='Dec 20 03:39 2019' -->


<div style="page-break-before:always;"></div>
<div style="font-family:Times New Roman;">
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">&nbsp;</font></b></p>
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">SCHEDULE A<br> DIRECTORS AND EXECUTIVE OFFICERS OF IONIS</font></b></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt;text-indent:.5in;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">The following table sets forth the name, business address, present principal occupation or employment and material occupations, positions, offices or employment of each of the directors and executive officers of Ionis.&#160; All directors and executive officers listed below are citizens of the United States unless otherwise noted herein.</font></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">DIRECTORS</font></b></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<div align="center">
<table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;">
<tr>
<td width="32%" valign="bottom" style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><b><font size="1" face="Times New Roman" style="font-size:8.0pt;font-weight:bold;">Name</font></b></p>    </td>
<td width="2%" valign="bottom" style="padding:0in 0in 0in 0in;width:2.0%;">
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="1" face="Times New Roman" style="font-size:1.0pt;font-weight:bold;">&nbsp;</font></b></p>    </td>
<td width="32%" valign="bottom" style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;width:32.0%;">
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="1" face="Times New Roman" style="font-size:8.0pt;font-weight:bold;">Current&nbsp;Principal&nbsp;Affiliation</font></b></p>    </td>
<td width="2%" valign="bottom" style="padding:0in 0in 0in 0in;width:2.0%;">
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="1" face="Times New Roman" style="font-size:1.0pt;font-weight:bold;">&nbsp;</font></b></p>    </td>
<td width="32%" valign="bottom" style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;width:32.0%;">
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="1" face="Times New Roman" style="font-size:8.0pt;font-weight:bold;">Business&nbsp;Address</font></b></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Stanley T. Crooke, M.D., Ph.D.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Chairman of the Board and Chief Executive   Officer,&nbsp;Ionis Pharmaceuticals,&nbsp;Inc.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">B. Lynne Parshall,&nbsp;Esq.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Senior Strategic Advisor to Ionis   Pharmaceuticals,&nbsp;Inc.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Spencer R. Berthelsen, M.D.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Chairman and Managing Director, Kelsey-Seybold   Clinic</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Breaux Castleman</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">President and Chief Executive Officer, Syntiro   Healthcare Services,&nbsp;Inc.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Joseph Klein,&nbsp;III</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Managing Director, Gauss Capital Advisors, LLC</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Joseph Loscalzo, M.D., Ph.D.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Head of Department of Medicine and   Physician-in-Chief, Brigham&nbsp;&amp; Woman&#146;s Hospital, Harvard Medical   School</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Brett P. Monia, Ph.D.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Chief Operating Officer and Senior Vice President,   Translational Medicine,&nbsp;Ionis Pharmaceuticals,&nbsp;Inc.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Frederick T. Muto,&nbsp;Esq.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Partner, Cooley LLP</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Joseph H. Wender</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Senior Consultant, Goldman Sachs&nbsp;&amp; Co.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Michael Hayden</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Killam Professor at the University of British   Columbia and the Director of the Translational Laboratory in Genetic Medicine</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Peter N. Reikes</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Vice Chairman,&nbsp;Investment Banking Division,   Stifel, Nicolaus&nbsp;&amp; Company,&nbsp;Inc.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Joan E. Herman</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">President&nbsp;&amp; CEO of Herman and Associates</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>  </table>
</div>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p align="center" style="font-size:10.0pt;margin:0in 0in .0001pt;text-align:center;">6<a name="PB_6_033738_5156"></a></p>
<div style="margin:0in 0in .0001pt;"><hr size="3" width="100%" noshade align="left" style="color:#010101;"></div>
</div>
<!-- SEQ.=1,FOLIO='6',FILE='C:\jms\111408\19-26706-1\task9565401\26706-1-bi.htm',USER='111408',CD='Dec 20 03:42 2019' -->

<div style="page-break-before:always;"></div>
<div style="font-family:Times New Roman;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p style="margin:0in 0in .0001pt 1.0in;text-indent:-1.0in;"><b><font size="2" face="Times New Roman" style="font-size:10.0pt;font-weight:bold;">OFFICERS</font></b></p>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<div align="center">
<table border="0" cellspacing="0" cellpadding="0" width="100%" style="border-collapse:collapse;">
<tr>
<td width="32%" valign="bottom" style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><b><font size="1" face="Times New Roman" style="font-size:8.0pt;font-weight:bold;">Name</font></b></p>    </td>
<td width="2%" valign="bottom" style="padding:0in 0in 0in 0in;width:2.0%;">
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="1" face="Times New Roman" style="font-size:1.0pt;font-weight:bold;">&nbsp;</font></b></p>    </td>
<td width="32%" valign="bottom" style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;width:32.0%;">
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="1" face="Times New Roman" style="font-size:8.0pt;font-weight:bold;">Position</font></b></p>    </td>
<td width="2%" valign="bottom" style="padding:0in 0in 0in 0in;width:2.0%;">
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="1" face="Times New Roman" style="font-size:1.0pt;font-weight:bold;">&nbsp;</font></b></p>    </td>
<td width="32%" valign="bottom" style="border:none;border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;width:32.0%;">
<p align="center" style="margin:0in 0in .0001pt;text-align:center;"><b><font size="1" face="Times New Roman" style="font-size:8.0pt;font-weight:bold;">Business&nbsp;Address</font></b></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Stanley T. Crooke, M.D., Ph.D.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Chief Executive Officer</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Brett P. Monia, Ph.D.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Chief Operating Officer and Senior Vice President,   Translational Medicine</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Elizabeth Hougen</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Senior Vice President, Finance and Chief Financial   Officer</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">C Frank Bennett</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Senior Vice President, Research</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Richard S. Geary, Ph.D.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Senior Vice President, Development</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="2%" valign="top" style="padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" style="padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>    </td>   </tr>
<tr>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Patrick R. O&#146;Neil,&nbsp;Esq.</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">Senior Vice President, Legal and General Counsel</font></p>    </td>
<td width="2%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:2.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:1.0pt;">&nbsp;</font></p>    </td>
<td width="32%" valign="top" bgcolor="#CCEEFF" style="background:#CCEEFF;padding:0in 0in 0in 0in;width:32.0%;">
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">c/o Ionis Pharmaceuticals,&nbsp;Inc.<br>   2855 Gazelle Court<br>   Carlsbad, CA 92010</font></p>    </td>   </tr>  </table>
</div>
<p style="margin:0in 0in .0001pt;"><font size="2" face="Times New Roman" style="font-size:10.0pt;">&nbsp;</font></p>
<p align="center" style="font-size:10.0pt;margin:0in 0in .0001pt;text-align:center;">7<a name="PB_7_033810_7056"></a></p>
<div style="margin:0in 0in .0001pt;"><hr size="3" width="100%" noshade align="left" style="color:#010101;"></div>
</div>
<!-- SEQ.=1,FOLIO='7',FILE='C:\jms\111408\19-26706-1\task9565401\26706-1-bi.htm',USER='111408',CD='Dec 20 03:42 2019' -->

</body>
</html>
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
