<SEC-DOCUMENT>0001140361-20-017840.txt : 20200826
<SEC-HEADER>0001140361-20-017840.hdr.sgml : 20200826
<ACCEPTANCE-DATETIME>20200807174326
ACCESSION NUMBER:		0001140361-20-017840
CONFORMED SUBMISSION TYPE:	S-3ASR
PUBLIC DOCUMENT COUNT:		4
FILED AS OF DATE:		20200807
DATE AS OF CHANGE:		20200807
EFFECTIVENESS DATE:		20200810

FILER:

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

	FILING VALUES:
		FORM TYPE:		S-3ASR
		SEC ACT:		1933 Act
		SEC FILE NUMBER:	333-242382
		FILM NUMBER:		201085648

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

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

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	ISIS PHARMACEUTICALS INC
		DATE OF NAME CHANGE:	19930328
</SEC-HEADER>
<DOCUMENT>
<TYPE>S-3ASR
<SEQUENCE>1
<FILENAME>nt10014191x1_s3asr.htm
<DESCRIPTION>S-3ASR
<TEXT>
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 540pt;"><a name="nt10014191x1_s3asr_100-regcov_pg1"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 540pt; margin-left: 0pt;"><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; text-align: center;">As filed with the Securities and Exchange Commission on August&#160;7, 2020</div><div class="regno" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 4.25pt; text-align: right;">File No. 333-&#8195;&#8195;&#8195;&#8195; </div></div></div><div class="block-frill" style="width: 540pt; margin-left: 0pt;"><div><div class="rule-full" style="height: 0pt; width: 100%; border-bottom: 2pt solid #000000; margin-top: 1pt; margin-bottom: 1pt; margin-left: auto; margin-right: auto;"> </div><div class="rule-full" style="height: 0pt; width: 100%; border-bottom: 1pt solid #000000; margin-bottom: 1pt; margin-left: auto; margin-right: auto; margin-top: 4pt;"> </div></div></div><div class="block-main" style="width: 540pt; margin-left: 0pt;"><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 12pt; font-weight: bold; margin-top: 12pt; text-align: center;">UNITED STATES<br>SECURITIES AND EXCHANGE COMMISSION<br><font style="font-size: 10pt;">Washington, D.C. 20549</font></div><div><div class="rule-partial" style="height: 0pt; width: 96pt; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 10pt;"> </div></div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 14pt; font-weight: bold; margin-top: 8.25pt; text-align: center;">FORM S-3 </div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; font-weight: bold; margin-top: 5.5pt; text-align: center;">REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933</div><div><div class="rule-partial" style="height: 0pt; width: 96pt; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 10.75pt;"> </div></div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 19pt; font-weight: bold; margin-top: 1pt; text-align: center;">IONIS PHARMACEUTICALS, INC.<br><font style="font-size: 9pt; font-weight: normal;">(Exact name of registrant as specified in its charter)</font></div><table cellspacing="0" cellpadding="0" class="txttab" align="center" style="margin-top: 3pt; border-collapse: collapse; width: 540pt; margin-left: 0pt;"><tr><td style="width: 48.89%; text-align: center; vertical-align: top; padding-bottom: 2pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; font-weight: bold; margin-top: 0pt; text-align: center;">Delaware</div></td><td class="gutter" style="width: 1.11%; border-bottom: none; font-size: 2pt; padding-bottom: 2pt;">&#8203;</td><td class="gutter" style="width: 1.11%; border-bottom: none; font-size: 2pt; padding-bottom: 2pt;">&#8203;</td><td style="width: 48.89%; text-align: center; vertical-align: bottom; padding-bottom: 2pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; font-weight: bold; margin-top: 0pt; text-align: center;">33-0336973</div></td></tr><tr><td style="width: 48.89%; text-align: center; vertical-align: top; padding-top: 2pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 0pt; text-align: center;">(State of Incorporation)</div></td><td class="gutter" style="width: 1.11%; border-bottom: none; font-size: 2pt; padding-top: 2pt;">&#8203;</td><td class="gutter" style="width: 1.11%; border-bottom: none; font-size: 2pt; padding-top: 2pt;">&#8203;</td><td style="width: 48.89%; text-align: center; vertical-align: bottom; padding-top: 2pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 0pt; text-align: center;">(I.R.S. Employer Identification No.)</div></td></tr></table><div><div class="rule-partial" style="height: 0pt; width: 96pt; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 4.75pt;"> </div></div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; font-weight: bold; margin-top: 1pt; text-align: center;">2855 Gazelle Court<br>Carlsbad, CA 92010<br><font style="font-weight: normal;">(Address of principal executive offices)</font></div><div><div class="rule-partial" style="height: 0pt; width: 96pt; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 10.75pt;"> </div></div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; font-weight: bold; margin-top: 2pt; text-align: center;">Brett Monia<br>Chief Executive Officer<br>IONIS PHARMACEUTICALS, INC.<br>2855 Gazelle Court<br>Carlsbad, California 92010<br>(760) 931-9200<br><font style="font-weight: normal;">(Name, address, including zip code, and telephone number, including area code, of agent for service)</font></div><div><div class="rule-partial" style="height: 0pt; width: 96pt; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 9.75pt;"> </div></div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 0pt; text-align: center;">Copies to:<br><font style="font-weight: bold;">Patrick R. O&#8217;Neil, Esq.</font><br><font style="font-weight: bold;">Executive Vice President, Legal, General Counsel and Corporate Secretary</font><br><font style="font-weight: bold;">IONIS PHARMACEUTICALS, INC.</font><br><font style="font-weight: bold;">2855 Gazelle Court</font><br><font style="font-weight: bold;">Carlsbad, California 92010</font><br><font style="font-weight: bold;">(760) 931-9200</font></div><div><div class="rule-partial" style="height: 0pt; width: 96pt; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 8.75pt;"> </div></div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; font-weight: bold; margin-top: 6.75pt; text-align: center;">From time to time after the effective date of this Registration Statement.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 4.5pt; text-align: center;">(Approximate date of commencement of proposed sale to the public)</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 3pt; margin-left: 0pt; text-align: left;">If the only securities being registered on this Form are being offered pursuant to dividend or interest reinvestment plans, please check the following box. <font style="font-size: 1pt;">&#8201;</font>&#x2610; </div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 2pt; margin-left: 0pt; text-align: left;">If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, other than securities offered only in connection with dividend or interest reinvestment plans, check the following box.&#x2612; </div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 2pt; margin-left: 0pt; text-align: left;">If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, please check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. <font style="font-size: 1pt;">&#8201;</font>&#x2610; </div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 2pt; margin-left: 0pt; text-align: left;">If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. <font style="font-size: 1pt;">&#8201;</font>&#x2610; </div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 2pt; margin-left: 0pt; text-align: left;">If this Form is a registration statement pursuant to General Instruction I.D. or a post-effective amendment thereto that shall become effective upon filing with the Commission pursuant to Rule 462(e) under the Securities Act, check the following box. &#x2612; </div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 2pt; margin-left: 0pt; text-align: left;">If this Form is a post-effective amendment to a registration statement filed pursuant to General Instruction I.D. filed to register additional securities or additional classes of securities pursuant to Rule 413(b) under the Securities Act, check the following box. <font style="font-size: 1pt;">&#8201;</font>&#x2610; </div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 2pt; margin-left: 0pt; text-align: left;">Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company or an emerging growth company. See the definitions of &#8220;large accelerated filer,&#8221; &#8220;accelerated filer,&#8221; &#8220;smaller reporting company,&#8221; and &#8220;emerging growth company&#8221; in Rule 12b-2 of the Exchange Act. </div><table cellspacing="0" cellpadding="0" class="txttab" align="center" style="margin-top: 3pt; border-collapse: collapse; width: 460pt; margin-left: 40pt;"><tr><td style="width: 36.96%; text-align: left; vertical-align: top; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9.2pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Large accelerated filer </div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 2.61%; text-align: left; vertical-align: bottom; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9.2pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">&#x2612;</div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 10.43%; text-align: left; vertical-align: bottom; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9.2pt;">&#160;</div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 36.96%; text-align: left; vertical-align: bottom; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9.2pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Accelerated filer </div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 2.61%; text-align: left; vertical-align: bottom; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 1pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">&#8201;<font style="font-size: 9.2pt;">&#x2610;</font><font style="font-size: 9.2pt;"> </font></div></td></tr><tr><td style="width: 36.96%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9.2pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Non-accelerated filer </div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 2.61%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 1pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">&#8201;<font style="font-size: 9.2pt;">&#x2610;</font></div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 10.43%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9.2pt;">&#160;</div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 36.96%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9.2pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Smaller reporting company </div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 2.61%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 1pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">&#8201;<font style="font-size: 9.2pt;">&#x2610;</font><font style="font-size: 9.2pt;"> </font></div></td></tr><tr><td style="width: 36.96%; text-align: left; vertical-align: top; padding-top: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9.2pt;">&#160;</div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td style="width: 2.61%; text-align: left; vertical-align: bottom; padding-top: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9.2pt;">&#160;</div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td style="width: 10.43%; text-align: left; vertical-align: bottom; padding-top: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9.2pt;">&#160;</div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td style="width: 36.96%; text-align: left; vertical-align: bottom; padding-top: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9.2pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Emerging growth company </div></td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td class="gutter" style="width: 1.3%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td style="width: 2.61%; text-align: left; vertical-align: bottom; padding-top: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 1pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">&#8201;<font style="font-size: 9.2pt;">&#x2610;</font></div></td></tr></table><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 1pt; margin-left: 0pt; text-align: left;">If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. <font style="font-size: 1pt;">&#8201;</font>&#x2610; </div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; font-weight: bold; margin-top: 7.5pt; text-align: center;">CALCULATION OF REGISTRATION FEE</div><div><div class="rule-full" style="height: 0pt; width: 100%; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 3pt;"> </div></div><table cellspacing="0" cellpadding="0" class="regtab" align="center" style="margin-top: 1.5pt; border-collapse: collapse; width: 540pt; margin-left: 0pt; border-top: 0.5pt solid #000000; border-bottom: 0.5pt solid #000000;"><tr class="header"><td style="width: 44.44%; text-align: center; vertical-align: bottom; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;"><div class="calc" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 7.5pt; font-weight: bold; margin-top: 0pt; text-align: center;">Title of Each Class of Securities to be Registered</div></td><td class="gutter" style="width: 0.56%; font-size: 2pt; border-right: 1pt solid #000000; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;">&#8203;</td><td class="gutter" style="width: 0.56%; font-size: 2pt; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;">&#8203;</td><td style="width: 12.78%; text-align: center; vertical-align: bottom; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;"><div class="calc" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 7.5pt; font-weight: bold; margin-top: 0pt; text-align: center;">Amount to be Registered</div></td><td class="gutter" style="width: 0.56%; font-size: 2pt; border-right: 1pt solid #000000; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;">&#8203;</td><td class="gutter" style="width: 0.56%; font-size: 2pt; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;">&#8203;</td><td style="width: 12.78%; text-align: center; vertical-align: bottom; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;"><div class="calc" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 7.5pt; font-weight: bold; margin-top: 0pt; text-align: center;">Proposed Maximum Offering Per Price Unit</div></td><td class="gutter" style="width: 0.56%; font-size: 2pt; border-right: 1pt solid #000000; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;">&#8203;</td><td class="gutter" style="width: 0.56%; font-size: 2pt; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;">&#8203;</td><td style="width: 12.78%; text-align: center; vertical-align: bottom; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;"><div class="calc" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 7.5pt; font-weight: bold; margin-top: 0pt; text-align: center;">Proposed Maximum Aggregate Offering Price</div></td><td class="gutter" style="width: 0.56%; font-size: 2pt; border-right: 1pt solid #000000; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;">&#8203;</td><td class="gutter" style="width: 0.56%; font-size: 2pt; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;">&#8203;</td><td style="width: 12.78%; text-align: center; vertical-align: bottom; border-bottom: 1pt solid #000000; padding-top: 2px; padding-bottom: 4.25pt;"><div class="calc" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 7.5pt; font-weight: bold; margin-top: 0pt; text-align: center;">Amount of Registration Fee</div></td></tr><tr><td style="width: 44.44%; text-align: left; vertical-align: bottom; padding-top: 4.25pt;"><div class="calc" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Common Stock, par value $0.001 per share<font style="padding-left: 2.34pt;"></font></div></td><td class="gutter" style="width: 0.56%; border-bottom: none; font-size: 2pt; border-right: 1pt solid #000000; padding-top: 4.25pt;">&#8203;</td><td class="gutter" style="width: 0.56%; border-bottom: none; font-size: 2pt; padding-top: 4.25pt;">&#8203;</td><td style="width: 12.78%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 4.25pt;"><div class="calc" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 0pt; margin-left: 29.34pt; text-align: left;">&#8199;<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">(1)</sup></div></td><td class="gutter" style="width: 0.56%; border-bottom: none; font-size: 2pt; border-right: 1pt solid #000000; padding-top: 4.25pt;">&#8203;</td><td class="gutter" style="width: 0.56%; border-bottom: none; font-size: 2pt; padding-top: 4.25pt;">&#8203;</td><td style="width: 12.78%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 4.25pt;"><div class="calc" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 9pt; margin-top: 0pt; margin-left: 29.34pt; text-align: left;">&#8199;<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">(1)</sup></div></td><td class="gutter" style="width: 0.56%; border-bottom: none; font-size: 2pt; border-right: 1pt solid #000000; padding-top: 4.25pt;">&#8203;</td><td class="gutter" style="width: 0.56%; 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line-height: 1; font-size: smaller;">(2)</sup></div></td></tr></table><div><div class="rule-full" style="height: 0pt; width: 100%; border-bottom: 1pt solid #000000; margin-bottom: 1pt; margin-left: auto; margin-right: auto; margin-top: 3pt;"> </div></div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 3pt; margin-left: 0pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; text-align: left;">Omitted pursuant to Form S-3 General Instruction II.E. Such indeterminate number or amount of Common Stock is being registered as may from time to time be offered at indeterminate prices pursuant to this Registration Statement.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 1pt; margin-left: 0pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(2)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; text-align: left;">In accordance with Rules 456(b) and 457(r) under the Securities Act, the registrant is deferring payment of all of the registration fee and is omitting this information.</div></td></tr></table></div><div class="block-frill" style="width: 540pt; margin-top: 12pt; margin-left: 0pt;"><div><div class="rule-full" style="height: 0pt; width: 100%; border-bottom: 1pt solid #000000; margin-top: 1pt; margin-bottom: 1pt; margin-left: auto; margin-right: auto;"> </div><div class="rule-full" style="height: 0pt; width: 100%; border-bottom: 2pt solid #000000; margin-bottom: 1pt; margin-left: auto; margin-right: auto; margin-top: 4pt;"> </div></div></div></div><!--End Page 1-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 456pt;"><a name="nt10014191x1_s3asr_201-cov_pg1"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 456pt; margin-left: 0pt;"><table cellspacing="0" cellpadding="0" class="txttab" align="center" style="margin-top: 4pt; border-collapse: collapse; width: 456pt; margin-left: 0pt;"><tr><td style="width: 48.68%; text-align: left; vertical-align: top;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 0pt; margin-left: 0pt; text-align: left;">PROSPECTUS</div></td><td class="gutter" style="width: 1.32%; border-bottom: none; font-size: 2pt;">&#8203;</td><td class="gutter" style="width: 1.32%; border-bottom: none; font-size: 2pt;">&#8203;</td><td style="width: 48.68%; text-align: right; vertical-align: bottom;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 0pt; text-align: right;">August&#160;7, 2020</div></td></tr></table><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 49.25pt; text-align: center;"><img style="height: 60px; width: 177px;" src="logo_ionis2.jpg"><br>&#8201;</div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 12pt; font-weight: bold; margin-top: 23.75pt; text-align: center;">Common Stock</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 12pt; margin-left: 0pt; text-align: left;">We or selling stockholders may from time to time offer and sell Common Stock in amounts, at prices and on terms described in one or more supplements to this prospectus.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 12pt; margin-left: 0pt; text-align: left;">This prospectus describes some of the general terms that may apply to an offering of our Common Stock. The specific terms and any other information relating to a specific offering, including the names of any selling stockholders, will be set forth in a post-effective amendment to the registration statement of which this prospectus is a part or in a supplement to this prospectus or may be set forth in one or more documents incorporated by reference in this prospectus.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 12pt; margin-left: 0pt; text-align: left;">Our securities may be offered and sold in the same offering or in separate offerings; to or through underwriters, dealers, and agents; or directly to purchasers. The names of any underwriter, dealer or agents involved in the sale of our securities and their compensation will be described in an applicable prospectus supplement. See &#8220;Plan of Distribution.&#8221; You should read this prospectus and the applicable prospectus supplement before you invest in our Common Stock.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 17.75pt; margin-left: 0pt; text-align: left;">Our Common Stock is currently traded on the NASDAQ Global Select Market under the symbol &#8220;IONS.&#8221;</div><div><div class="rule-partial" style="height: 0pt; width: 96pt; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 24.5pt;"> </div></div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 17.75pt; text-align: center;">Investing in our Common Stock involves risks.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; margin-left: 0pt; text-align: left;">See &#8220;Risk Factors&#8221; on page <a href="#tRISK">3</a> of this prospectus, in the applicable prospectus supplement and similar headings in documents incorporated by reference herein and therein before investing in our Common Stock.</div><div><div class="rule-partial" style="height: 0pt; width: 96pt; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 24.5pt;"> </div></div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; margin-left: 0pt; text-align: left;">Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy of this prospectus. Any representation to the contrary is a criminal offense.</div><div><div class="rule-partial" style="height: 0pt; width: 96pt; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 24.5pt;"> </div></div></div></div></div><!--End Page 2-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_202-toc_pg1"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; text-align: center;">TABLE OF CONTENTS</div><a name="TOC"><!--Anchor--></a><table cellspacing="0" cellpadding="0" class="fintab" align="center" style="margin-top: 10.25pt; border-collapse: collapse; width: 468pt; margin-left: 0pt;"><tr class="header"><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-bottom: 4.25pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: bold;">&#160;</div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-bottom: 4.25pt;">&#8203;</td><td class="gutter" style="width: 3.37%; font-size: 2pt; padding-bottom: 4.25pt; border-bottom: 1px solid #ffffff;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; border-bottom: 1pt solid #000000; padding-bottom: 4.25pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: bold; margin-top: 0pt; text-align: center;">Page</div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 4.25pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tATP">About this Prospectus<font style="padding-left: 3.08pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 4.25pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 4.25pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 4.25pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tATP">1</a></div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tSUM">Prospectus Summary<font style="padding-left: 1.97pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tSUM">2</a></div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tRISK">Risk Factors<font style="padding-left: 1.41pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tRISK">3</a></div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tFLS">Forward-Looking Statements<font style="padding-left: 4.2pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tFLS">3</a></div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tUSE">Use of Proceeds<font style="padding-left: 0.87pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tUSE">3</a></div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tSELL">Selling Stockholders<font style="padding-left: 3.63pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tSELL">3</a></div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tPOD">Plan of Distribution<font style="padding-left: 1.41pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tPOD">3</a></div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tDOCS">Description of Capital Stock<font style="padding-left: 0.87pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tDOCS">5</a></div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tLEGAL">Legal Matters<font style="padding-left: 0.86pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tLEGAL">9</a></div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tEXP">Experts<font style="padding-left: 1.95pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tEXP">9</a></div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tINFO">Where You Can Find More Information<font style="padding-left: 4.49pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tINFO">9</a></div></td></tr><tr><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tREF">Incorporation of Certain Documents by Reference<font style="padding-left: 2.59pt;"></font></a></div></td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td class="gutter" style="width: 3.37%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td style="width: 3.51%; text-align: center; vertical-align: bottom; white-space: nowrap; padding-top: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;"><a href="#tREF">9</a></div></td></tr></table></div></div></div><!--End Page 3-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_202-toc_pg2"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; text-align: center;"><a name="tATP"><!--Anchor--></a>ABOUT THIS PROSPECTUS</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">This prospectus is part of a registration statement on Form S-3 that we filed with the Securities and Exchange Commission, or the SEC, using the &#8220;shelf&#8221; registration process as a &#8220;well-known seasoned issuer,&#8221; as defined in Rule 405 under the Securities Act of 1933, as amended, or the Securities Act. By using a shelf registration statement, we and any selling stockholders may offer and sell from time to time in one or more offerings the Common Stock described in this prospectus. No limit exists on the aggregate number of shares of Common Stock we and any selling stockholders may sell pursuant to the registration statement.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Neither we nor any selling stockholders or underwriters named in any prospectus supplement have authorized anyone to provide you with information different from that contained in or incorporated by reference into this prospectus or any applicable prospectus supplement. We take no responsibility for, and can provide no assurance as to the reliability of, any information that others may give you. This document may only be used where it is legal to sell these securities. You should not assume that the information contained in this prospectus, any prospectus supplement or any free writing prospectus prepared by or on behalf of us to which we have referred you, is accurate as of any date other than their respective dates regardless of the time of delivery or any sale of the Common Stock. Our business, financial condition, results of operations and prospects may have changed since that date.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">This prospectus and the information incorporated herein by reference include trademarks, service marks and trade names owned by us or other companies. All trademarks, service marks and trade names included or incorporated by reference in this prospectus are the property of their respective owners.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We urge you to read carefully both this prospectus and any prospectus supplement accompanying this prospectus, together with the information incorporated herein by reference as described under the heading &#8220;Where You Can Find More Information,&#8221; before deciding whether to invest in any of the securities being offered.</div></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">1<br></div></div></div><!--End Page 4-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 492pt;"><a name="nt10014191x1_s3asr_203-sum_pg1"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="border-box" style="border-top: 1pt solid #000000; border-left: 1pt solid #000000; border-right: 1pt solid #000000; border-bottom: 1pt solid #000000; margin-bottom: 12pt; padding-top: 12pt; padding-bottom: 12pt; width: 492pt; margin-left: 0pt;"><div class="block-main" style="width: 468pt; margin-left: 12pt;"><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; text-align: center;"><a name="tSUM"><!--Anchor--></a>PROSPECTUS SUMMARY</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 6pt; margin-left: 0pt; text-align: left;">The following summary does not contain all of the information that may be important to purchasers of our securities. Prospective purchasers of securities should carefully review the detailed information and financial statements, including the notes thereto, appearing elsewhere in or incorporated by reference into this prospectus and any prospectus supplement.</div><div><div class="rule-full" style="height: 0pt; width: 100%; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 11.75pt;"> </div></div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We are a leader in discovering and developing RNA-targeted therapeutics. We have created an efficient and broadly applicable drug discovery platform leveraging our expertise in antisense oligonucleotide therapeutics that we believe has fundamentally changed medicine and transformed the lives of people with devastating diseases. Our large, diverse and advancing pipeline has many potential first-in-class and/or best-in-class medicines designed to address a broad spectrum of therapeutic areas, such as neurodegenerative diseases, cardiometabolic diseases, cancer and others. The medicines in our pipeline address patients with diseases ranging from rare to common. We have commercial medicines approved in major markets around the world. </div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We maintain a website at www.ionispharma.com. The reference to our website does not constitute incorporation by reference into this prospectus of any of the information contained on or accessible through our website.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Our principal executive offices are located at 2855 Gazelle Court, Carlsbad, CA 92010, and our telephone number is (760) 931-9200. We incorporated in California in 1989, and in January 1991, we changed our state of incorporation to Delaware.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 11.75pt; margin-left: 0pt; text-align: left;">In December 2018, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.</div><div><div class="rule-full" style="height: 0pt; width: 100%; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 11.75pt;"> </div></div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">In this prospectus, unless the context requires otherwise, &#8220;Ionis,&#8221; &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221; refers to Ionis Pharmaceuticals, Inc. and its subsidiaries.</div><div><div class="rule-full" style="height: 0pt; width: 100%; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 11.75pt;"> </div></div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">&#8220;Ionis,&#8221; the Ionis logo, and other trademarks or service marks of Ionis Pharmaceuticals, Inc. appearing in this prospectus are the property of Ionis Pharmaceuticals, Inc. &#8220;Akcea,&#8221; the Akcea logo, and other trademarks or service marks of Akcea Therapeutics, Inc. appearing in this report are the property of Akcea Therapeutics, Inc.</div><div><div class="rule-full" style="height: 0pt; width: 100%; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 11.75pt;"> </div></div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 8.5pt; margin-left: 0pt; text-align: left;">SPINRAZA<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">TM</sup> is a trademark of Biogen, Inc.</div><div><div class="rule-full" style="height: 0pt; width: 100%; border-bottom: 1pt solid #000000; margin-bottom: 2pt; margin-left: auto; margin-right: auto; margin-top: 11.75pt;"> </div></div></div></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 12pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">2<br></div></div></div><!--End Page 5-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_204-risk_pg1"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; text-align: center;"><a name="tRISK"><!--Anchor--></a>RISK FACTORS</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Investing in our securities involves risks. Please see the risk factors described under the caption &#8220;Risk Factors&#8221; in our most recent Annual Report on Form 10-K filed with the SEC, our most recent Quarterly Report on Form 10-Q filed with the SEC, as well as any amendments thereto reflected in subsequent filings with the SEC, which are incorporated by reference in this prospectus and in any accompanying prospectus supplement. Before making an investment decision, you should carefully consider these risks as well as information we include or incorporate by reference in this prospectus and in any accompanying prospectus supplement. The risks and uncertainties we have described are not the only ones that we face. Additional risks and uncertainties not presently known to us or that we currently deem immaterial may also affect our business or operations.</div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 21.25pt; text-align: center;"><a name="tFLS"><!--Anchor--></a>FORWARD-LOOKING STATEMENTS</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">This prospectus, each prospectus supplement and the documents incorporated herein and therein by reference contain forward-looking statements regarding our business and the therapeutic and commercial potential of our technologies, products in development and commercial products. Any statement describing our goals, expectations, financial or other projections, intentions or beliefs, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Our forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those discussed in our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. Although our forward-looking statements reflect the good faith judgment of our management, these statements are based only on facts and factors currently known by us. As a result, you are cautioned not to rely on these forward-looking statements.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 for all forward-looking statements.</div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 21.25pt; text-align: center;"><a name="tUSE"><!--Anchor--></a>USE OF PROCEEDS</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Unless otherwise indicated in an applicable prospectus supplement, we will use the net proceeds from the sale of any securities by us for general corporate purposes and to fund our capital expenditures and working capital requirements. Pending the application of the net proceeds, we intend to invest the net proceeds in investment-grade, interest-bearing securities. We will not receive any of the proceeds from the sale of shares of our Common Stock by selling stockholders, if any, pursuant to this prospectus.</div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 21.25pt; text-align: center;"><a name="tSELL"><!--Anchor--></a>SELLING STOCKHOLDERS</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">If the registration statement of which this prospectus is a part is used by any selling stockholder for the resale of any shares of Common Stock registered thereunder, information about such selling stockholder, its beneficial ownership of our securities and its relationship with us will be set forth in a post-effective amendment to the registration statement, in a supplement to this prospectus, or in one or more documents incorporated by reference in this prospectus or the applicable prospectus supplement.</div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 21.25pt; text-align: center;"><a name="tPOD"><!--Anchor--></a>PLAN OF DISTRIBUTION</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We or selling stockholders may sell the offered securities in one or more of the following ways, or any manner specified in a prospectus supplement:</div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">to or through an underwriter or underwriters;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">through dealers;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">through agents;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">directly to one or more purchasers, including affiliates of ours; or</div></td></tr></table></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">3<br></div></div></div><!--End Page 6-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_204-risk_pg2"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">through a combination of any of these methods of sale.</div></td></tr></table><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">The applicable prospectus supplement will contain the terms of the offerings of any securities. The public offering price and any discount or concessions allowed or reallowed to dealers may be changed from time to time. The applicable prospectus supplement will contain the expected time of delivery of the securities for which this prospectus is delivered.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Unless otherwise indicated in the applicable prospectus supplement, if underwriters are used in the sale of the securities, the underwriting agreement will provide that the obligations of the underwriters are subject to certain conditions precedent and that the underwriters will be obligated to purchase all of the securities if any are purchased. In connection with the sale of securities, underwriters may receive compensation from us, selling stockholders or purchasers of securities for whom they may act as agents in the form of discounts, concessions or commissions. Underwriters may sell securities to or through dealers, and dealers may receive compensation in the form of discounts, concessions or commissions from the underwriters and/or commissions from the purchasers for whom they may act as agent.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Underwriters, agents or dealers participating in the distribution of securities may be deemed to be underwriters, and any discounts and commissions received by them and any profit realized by them on resale of the securities may be deemed to be underwriting discounts and commissions under the Securities Act. The securities may be sold in one or more transactions either at a fixed price or at prices which may be changed based on market prices prevailing at the time of sale, at prices related to the prevailing market prices or at negotiated prices. Any underwriter, dealer or agent will be acting on a best efforts basis or, if indicated in the applicable prospectus supplement, on a firm commitment basis.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We or selling stockholders may indemnify the underwriters, agents or dealers who participate in the distribution of securities against certain liabilities, including liabilities under the Securities Act. We or selling stockholders may also contribute to payments that the underwriters, dealers or agents or any of their controlling persons may be required to make in respect of such liabilities. Underwriters, agents or dealers may be customers of, engage in transactions with or perform services for us or our subsidiaries or selling stockholders or their affiliates in the ordinary course of business.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">If so indicated in a prospectus supplement, we or selling stockholders will authorize underwriters, dealers and agents to solicit offers by certain institutions to purchase securities from us or such selling stockholders pursuant to delayed delivery contracts providing for payment and delivery on the date stated in the prospectus supplement. These contracts will be subject only to those conditions contained in the prospectus supplement. The prospectus supplement will also contain the commission payable for solicitation of any of these contracts.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Offers to purchase securities may be solicited directly by us or selling stockholders and sales of securities may be made by us or selling stockholders directly to institutional investors or others who may be deemed to be underwriters within the meaning of the Securities Act, with respect to any resale of the securities. The terms of any such sales will be described in the prospectus supplement relating to the securities. Except as contained in the applicable prospectus supplement, no director, officer or employee of ours will solicit or receive a commission in connection with the direct sales by us of the securities, although these persons may respond to inquiries by potential purchasers and perform ministerial and clerical work in connection with any such direct sales.</div></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">4<br></div></div></div><!--End Page 7-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_205-description_pg1"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; text-align: center;"><a name="tDOCS"><!--Anchor--></a>DESCRIPTION OF CAPITAL STOCK</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 10.25pt; margin-left: 0pt; text-align: left;">Our authorized capital stock consists of:</div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">300,000,000 shares of Common Stock, of which 139,489,405 shares were outstanding as of June&#160;30, 2020; and</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">15,000,000 shares of preferred stock, none of which were outstanding as of June&#160;30, 2020.</div></td></tr></table><div class="h2" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 22.25pt; margin-left: 20pt; text-align: left;">Preferred Stock</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 10.25pt; margin-left: 20pt; text-align: left;">Blank Check Preferred Stock</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We are authorized to issue up to 15,000,000 shares of &#8220;blank check&#8221; preferred stock. Our Board of Directors has the authority to fix the rights and preferences of and issue shares of preferred stock, which may have the effect of delaying or preventing a change in control of our company without action by our stockholders.</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 22.75pt; margin-left: 20pt; text-align: left;">Series C Junior Participating Preferred Stock</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Series C Junior Participating Preferred Stock have been designated but are not outstanding. Each one one-hundredth of a share of the Series C Preferred Stock has designations and powers, preferences and rights, and qualifications, limitations and restrictions that make its value approximately equal to the value of a share of our Common Stock.</div><div class="h2" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 22.75pt; margin-left: 20pt; text-align: left;">Common Stock</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">As of June&#160;30, 2020, we had 300,000,000 shares of Common Stock authorized, of which 139,489,405 were issued and outstanding. As of June&#160;30, 2020, total common shares reserved for future issuance upon the exercise or conversion of outstanding securities that are exercisable or convertible into shares of our Common Stock was approximately 33,181,704. Of these shares reserved for future issuance, approximately 6,590,028 are currently covered by certain convertible note hedge transactions that we entered into in connection with our outstanding 0.125% convertible senior notes due 2024 (the &#8220;2024 notes&#8221;) issued in December 2019, which we expect will reduce dilution to holders of Common Stock upon any conversion of the 2024 notes. As such, those shares covered by the convertible note hedge transactions will likely not increase our total number of shares issued upon any conversion of the 2024 notes. </div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 22.75pt; margin-left: 20pt; text-align: left;">Voting Rights</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Holders of Common Stock are entitled to one vote per share on all matters to be voted upon by the stockholders, including the election of directors. Our Common Stock does not have cumulative voting rights.</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 22.75pt; margin-left: 20pt; text-align: left;">Dividend Rights</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Subject to the preferential rights of outstanding shares of preferred stock, if any, the holders of Common Stock are entitled to receive dividends out of assets legally available at the times and in the amounts that our Board of Directors may determine from time to time in its discretion.</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 22.75pt; margin-left: 20pt; text-align: left;">No Preemptive or Redemption Rights; Right to Receive Liquidation Distributions</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Our Common Stock is not entitled to preemptive rights and is not subject to redemption or sinking fund provisions. Upon our liquidation, dissolution or winding-up, the holders of Common Stock are entitled to share equally in all of our assets remaining after payment of all liabilities and the liquidation preferences of any outstanding preferred stock.</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 22.75pt; margin-left: 20pt; text-align: left;">Classified Board of Directors</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Our Certificate of Incorporation provides for classified terms for the members of our Board of Directors. The Board of Directors is divided into three classes, and each class serves a three-year term. Presently, the Board has twelve members with each class consisting of four directors. </div></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">5<br></div></div></div><!--End Page 8-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_205-description_pg2"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 12pt; margin-left: 20pt; text-align: left;">Size of the Board of Directors; Removal of Directors; Vacancies</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Our Certificate of Incorporation and Bylaws authorize our Board of Directors to fix the number of directors from time to time without stockholder approval. The Board of Directors currently consists of twelve members. Directors may be removed with cause by a majority of the outstanding shares entitled to vote or without cause upon the approval of at least 66-2/3% of the outstanding shares entitled to vote. All vacancies on the Board of Directors are to be filled by the directors then in office.</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 23.25pt; margin-left: 20pt; text-align: left;">Liquidation, Dissolution or Winding Up</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Subject to the preferential rights of outstanding shares of preferred stock, if any, holders of Common Stock will share equally in all assets legally available for distribution, after payment of all liabilities, to our stockholders in the event of liquidation, dissolution or winding up of the Company.</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 23.25pt; margin-left: 20pt; text-align: left;">Other Rights and Preferences</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 10.25pt; margin-left: 0pt; text-align: left;">Our Common Stock has no sinking fund or redemption provisions or preemptive, conversion or exchange rights. </div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 23.25pt; margin-left: 20pt; text-align: left;">Power to Call Special Stockholder Meetings; Stockholder Action by Written Consent; Advance Notice of Stockholder Business and Nominees</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Our Certificate of Incorporation also requires that any action required or permitted to be taken by our stockholders must be taken at a duly called annual or special meeting of stockholders and may not be taken by written consent. Only our Board of Directors, Chairman of the Board or Chief Executive Officer can call special meetings of our stockholders. In addition, our Certificate of Incorporation and Bylaws require advance notice for nominations for election to our Board of Directors or for proposing matters that can be acted upon by stockholders at a stockholder meeting.</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 23.25pt; margin-left: 20pt; text-align: left;">Amendment of Bylaws</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Our Board of Directors is authorized to adopt, alter or repeal our Bylaws, while our Bylaws may be adopted, amended or repealed by stockholders only through the approval of at least 66-2/3% of the outstanding shares entitled to vote.</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 23.25pt; margin-left: 20pt; text-align: left;">Anti-Takeover Effects of Delaware Law</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We are subject to Section 203 of the Delaware General Corporation Law (&#8220;DGCL&#8221;), which prohibits a Delaware corporation from engaging in any business combination with any interested stockholder for a period of three years after the date that such stockholder became an interested stockholder, unless:</div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">the transaction is approved by the Board of Directors before the date the interested stockholder attained that status; </div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">upon consummation of the transaction that resulted in the stockholder becoming an interested stockholder, the interested stockholder owned at least 85% of the voting stock of the corporation outstanding at the time the transaction commenced; or</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">on or after the date the business combination is approved by the Board and authorized at a meeting of stockholders by at least 66-2/3% of the outstanding voting stock that is not owned by the interested stockholder.</div></td></tr></table><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">A &#8220;business combination&#8221; is defined to include any merger or consolidation involving a corporation and the interested stockholder; any sale, transfer, pledge or other disposition involving the interested stockholder of 10% or more of the assets of the corporation; subject to exceptions, any transaction involving the corporation that has the effect of increasing the proportionate share of the stock of any class or series of the corporation beneficially owned by the interested stockholder; subject to exceptions, any transaction that results in the issuance or transfer by the corporation of any stock of the corporation to the interested stockholder; and the receipt by the interested stockholder of the benefit of any loans, advances, guarantees, pledges or other financial benefits provided by or through the corporation.</div></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">6<br></div></div></div><!--End Page 9-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_205-description_pg3"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">In general, an &#8220;interested stockholder&#8221; is an entity or person who, together with affiliates and associates, owns (or within three years prior to the determination of interested stockholder status, did own) 15% or more of a corporation&#8217;s voting stock.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">The fair price provision and Section 203 of the DGCL could prohibit or delay mergers or other takeover or change in control attempts with respect to us and, accordingly, may discourage attempts to acquire us even though such a transaction may offer our stockholders the opportunity to sell their stock at a price above the prevailing market price.</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 23.25pt; margin-left: 20pt; text-align: left;">Anti-Takeover Effects of Our Certificate of Incorporation and Bylaws </div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Our Certificate of Incorporation includes a provision that requires at least 66-2/3% of our voting stockholders to approve a merger or certain other business transactions with, or proposed by, any holder of 15 percent or more of our voting stock, except in cases where certain directors approve the transaction or certain minimum price criteria and other procedural requirements are met.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Provisions of our Certificate of Incorporation and Bylaws may delay or discourage transactions involving an actual or potential change in our control or change in our management, including transactions in which stockholders might otherwise receive a premium for their shares or transactions that our stockholders might otherwise deem to be in their best interests. Therefore, these provisions could adversely affect the price of our Common Stock. Among other things, our Certificate of Incorporation and Bylaws:</div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">permit our Board of Directors to issue up to 15,000,000 shares of preferred stock, with any rights, preferences and privileges as they may designate;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">provide that the authorized number of directors shall be fixed exclusively by the Board of Directors;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">provide that the Board of Directors or any individual director may only be removed with cause by the affirmative vote of the holders of at least a majority of the outstanding Common Stock or without cause by the affirmative vote of the holders of at least 66-2/3% of the voting power of all of our then outstanding Common Stock;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">provide that all vacancies, including newly created directorships, may, except as otherwise required by law or subject to the rights of holders of preferred stock as designated from time to time, be filled by the affirmative vote of a majority of directors then in office, even if less than a quorum, unless the Board of Directors determines by resolution that any such vacancies or newly created directorships shall be filled by stockholders;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">classifies our Board of Directors into three classes;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">require that any action to be taken by our stockholders must be effected at a duly called annual or special meeting of stockholders and not be taken by written consent or electronic transmission;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">provide that stockholders seeking to present proposals before a meeting of stockholders or to nominate candidates for election as directors at a meeting of stockholders must provide notice in writing in a timely manner and also specify requirements as to the form and content of a stockholder&#8217;s notice; </div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">do not provide for cumulative voting rights (therefore allowing the holders of a majority of the shares of Common Stock entitled to vote in any election of directors to elect all of the directors standing for election, if they should so choose); and</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">provide that special meetings of our stockholders may be called only by the Chairman of the Board, our Chief Executive Officer or by the Board of Directors pursuant to a resolution adopted by a majority of the total number of authorized directors (whether or not there exists any vacancies).</div></td></tr></table><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">The foregoing provisions may make it more difficult for our existing stockholders to replace our Board of Directors as well as for another party to obtain control of us by replacing our Board of Directors. Since our Board of Directors has the power to retain and discharge our officers, these provisions could also make it more difficult for existing stockholders or another party to effect a change in management. In addition, the authorization of undesignated preferred stock makes it possible for our Board of Directors to issue preferred stock with voting or other rights or preferences that could impede the success of any attempt to change our control.</div></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">7<br></div></div></div><!--End Page 10-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_205-description_pg4"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">These provisions are intended to enhance the likelihood of continued stability in the composition of our Board of Directors and its policies and to discourage certain types of transactions that may involve an actual or threatened acquisition of us. These provisions are also designed to reduce our vulnerability to an unsolicited acquisition proposal and to discourage certain tactics that may be used in proxy fights. However, such provisions could have the effect of discouraging others from making tender offers for our shares and may have the effect of deterring hostile takeovers or delaying changes in our control or management. As a consequence, these provisions also may inhibit fluctuations in the market price of our stock that could result from actual or rumored takeover attempts.</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 17.25pt; margin-left: 20pt; text-align: left;">Limitation of Liability and Indemnification Matters</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Our Certificate of Incorporation and Bylaws include provisions to eliminate the personal liability of our directors for monetary damages resulting from breaches of their fiduciary duty to the extent permitted under Delaware law. Delaware law provides that directors of a company will not be personally liable for monetary damages for breach of their fiduciary duty as directors, except for liabilities:</div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">for any breach of their duty of loyalty to us or our stockholders; </div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">for acts or omissions not in good faith or which involve intentional misconduct or a knowing violation of law; </div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">for unlawful payment of dividend or unlawful stock repurchase or redemption, as provided under Section 174 of the DGCL; or </div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">for any transaction from which the director derived an improper personal benefit.</div></td></tr></table><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">In addition, our Bylaws provide that we will indemnify our directors and executive officers to the fullest extent not prohibited by Delaware law or any other applicable law, except that we will generally not be required to indemnify a director or executive officer in connection with any proceeding initiated by such director or executive officer. In addition, we have entered into indemnity agreements with each of our executive officers and directors and certain non-executive officers which provide, among other things, that we will indemnify such officer or director, under the circumstances and to the extent provided for therein, for expenses, damages, judgments, fines and settlements he or she may be required to pay in actions or proceedings which he or she is or may be made a party by reason of his or her position as a director, officer or other agent of Ionis, and otherwise to the fullest extent permitted under Delaware law and our Bylaws.</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 17.25pt; margin-left: 20pt; text-align: left;">Listing</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 10.25pt; margin-left: 0pt; text-align: left;">Our Common Stock is listed on the NASDAQ Global Select Market under the symbol &#8220;IONS.&#8221;</div><div class="h4" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; margin-top: 17.25pt; margin-left: 20pt; text-align: left;">Transfer Agent and Registrar</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">The transfer agent and registrar for our Common Stock is American Stock Transfer and Trust. Its address is 59&#160;Maiden Lane, Plaza Level, New York, New York 10038 and its telephone number is (718) 921-8124.</div></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">8<br></div></div></div><!--End Page 11-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_205-description_pg5"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; text-align: center;"><a name="tLEGAL"><!--Anchor--></a>LEGAL MATTERS</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">The validity of the issuance of the Common Stock offered hereby will be passed upon for us by Patrick R. O&#8217;Neil, our Executive Vice President, Legal, General Counsel and Corporate Secretary.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Mr.&#160;O&#8217;Neil holds or has the right to acquire shares of Ionis&#8217; Common Stock in an aggregate amount that is less than 1% of Ionis&#8217; outstanding Common Stock.</div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 22.25pt; text-align: center;"><a name="tEXP"><!--Anchor--></a>EXPERTS</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Ernst &amp; Young LLP, independent registered public accounting firm, has audited our consolidated financial statements included in our <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120004500/form10k.htm">Annual Report on Form 10-K</a> for the year ended December&#160;31, 2019, and the effectiveness of our internal control over financial reporting as of December&#160;31, 2019, as set forth in their reports, which are incorporated by reference in this prospectus and elsewhere in the registration statement. Our financial statements and our management's assessment of the effectiveness of internal control over financial reporting as of December&#160;31, 2019 are incorporated by reference in reliance on Ernst &amp; Young LLP&#8217;s reports, given on their authority as experts in accounting and auditing.</div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 22.25pt; text-align: center;"><a name="tINFO"><!--Anchor--></a>WHERE YOU CAN FIND ADDITIONAL INFORMATION</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We file annual, quarterly and current reports, proxy statements and other information with the SEC. Our SEC filings are available to the public over the Internet at the SEC&#8217;s website at www.sec.gov. The documents referred to below under &#8220;Incorporation by Reference&#8221; are also available on our corporate website, www.ionispharma.com. We have not incorporated by reference into this prospectus the information on our website, and you should not consider it to be a part of this prospectus.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We have filed with the SEC a registration statement under the Securities Act relating to the offering of these securities. The registration statement, including the attached exhibits, contains additional relevant information about us and the securities. This prospectus does not contain all of the information set forth in the registration statement. You can obtain a copy of the registration statement (including the exhibits and schedules thereto), at prescribed rates, from the SEC at www.sec.gov, or our corporate website at www.ionispharma.com.</div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 22.25pt; text-align: center;"><a name="tREF"><!--Anchor--></a>INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">The SEC allows us to &#8220;incorporate by reference&#8221; in this prospectus the information that we file with it. This means that we can disclose important information to you in this document by referring you to other filings we have made with the SEC. The information incorporated by reference is considered to be part of this prospectus. The information incorporated by reference in this prospectus is accurate only as of the date of the information on the front cover of the applicable document, or such earlier date as is expressly stated or otherwise apparent with respect to such incorporated information in the applicable document, regardless of the time of delivery of this prospectus or any sale of securities.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 11.25pt; margin-left: 0pt; text-align: left;">This prospectus incorporates by reference the documents listed below, which we have filed with the SEC:</div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">our Annual Report on Form 10-K for the fiscal year ended December&#160;31, 2019, filed on <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120004500/form10k.htm">March&#160;2, </a><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120004500/form10k.htm">2020</a>; </div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">portions of our Definitive Proxy Statement on Schedule 14A filed on <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120009606/nc10007589x2_def14a.htm">April&#160;24, 2020</a>, incorporated by reference into the Annual Report on Form 10-K for our fiscal year ended December&#160;31, 2019;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">our Quarterly Reports on Form 10-Q for the quarter ended March&#160;31, 2020, filed on <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120010825/form10q.htm">May&#160;6, 2020</a> and the quarter ended June&#160;30, 2020, filed on <a href="https://www.sec.gov/Archives/edgar/data/874015/000087401520000115/form10q.htm">August&#160;5, 2020</a>; </div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">our Current Reports on Form 8-K filed on <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120000641/form8k.htm">January&#160;10, 2020</a>, <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120001081/form8k.htm">January&#160;17, 2020</a>, <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120004102/form8k.htm">February&#160;26, 2020</a>, <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120010790/form8k.htm">May&#160;6, 2020</a>, <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120013453/form8k.htm">June&#160;10, 2020</a> and <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036120017532/brhc10014107_8k.htm">August&#160;5, 2020</a>; and </div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">the description of our Common Stock contained in our Registration Statement on Form 8-A filed with the SEC on April&#160;12, 1991, as updated by our Certificate of Amendment of our Restated Certificate of Incorporation filed with our Definitive Proxy Statement on Schedule 14A filed on <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036114017588/formdef14a.htm">April&#160;25, 2014</a>, and our Certificate of Amendment of our Restated Certificate of Incorporation filed with our current report on Form 8-K filed on <a href="https://www.sec.gov/Archives/edgar/data/874015/000114036115045083/form8k.htm">December&#160;18, 2015</a>.</div></td></tr></table></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">9<br></div></div></div><!--End Page 12-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_205-description_pg6"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We incorporate by reference any additional documents that we may file with the SEC under Section 13(a), 13(c), 14 or 15(d) of the Exchange Act (other than the portions of those made pursuant to Item 2.02 or Item 7.01 of Form 8-K or other information &#8220;furnished&#8221; to the SEC) prior to the termination of the offering of the securities. These documents may include periodic reports, like Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K, as well as Proxy Statements. Any material that we subsequently file with the SEC will automatically update and replace the information previously filed with the SEC.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">This prospectus may contain information that updates, modifies or is contrary to information in one or more of the documents incorporated by reference in this prospectus. You should rely only on the information incorporated by reference or provided in this prospectus. Neither we nor any selling stockholders have authorized anyone else to provide you with different information. You should not assume that the information in this prospectus is accurate as of any date other than the date of this prospectus or the date of the documents incorporated by reference in this prospectus.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">We will provide to each person, including any beneficial owner, to whom this prospectus is delivered, upon written or oral request, at no cost, a copy of any and all of the information that is incorporated by reference in this prospectus.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 11.75pt; margin-left: 0pt; text-align: left;">Requests for such documents should be directed to:</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 20pt; text-align: left;">Ionis Pharmaceuticals, Inc.<br>2855 Gazelle Court<br>Carlsbad, California 92010<br>(760) 931-9200<br>Attention: General Counsel</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">In addition, copies of our filings are available through our corporate website at www.ionispharma.com as soon as reasonably practicable after we electronically file such material with the SEC.</div></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">10<br></div></div></div><!--End Page 13-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_206-part2_pg1"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; text-align: center;"><a name="tP2"><!--Anchor--></a>Part II</div><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 16.25pt; text-align: center;">INFORMATION NOT REQUIRED IN PROSPECTUS</div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 12pt; margin-left: 0pt;"><tr><td style="width: 40pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 14.<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-align: left;">Other Expenses of Issuance and Distribution</div></td></tr></table><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">The following table sets forth all expenses payable by the Registrant in connection with the sale of the securities being registered. All the amounts shown are estimates except for the registration fee.</div><table cellspacing="0" cellpadding="0" class="fintab" align="center" style="margin-top: 11.25pt; border-collapse: collapse; width: 468pt; margin-left: 0pt;"><tr><td style="width: 87.18%; text-align: left; vertical-align: bottom; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">SEC registration fee<font style="padding-left: 2.76pt;"></font></div></td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td style="width: 11.54%; text-align: right; vertical-align: bottom; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 7.5pt; margin-top: 0pt; text-align: right;"><font style="position: relative; top: -4.25pt;">*</font></div></td></tr><tr><td style="width: 87.18%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Printing fees<font style="padding-left: 3.85pt;"></font></div></td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 11.54%; text-align: right; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 7.5pt; margin-top: 0pt; text-align: right;"><font style="position: relative; top: -4.25pt;">**</font></div></td></tr><tr><td style="width: 87.18%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Legal fees and expenses<font style="padding-left: 1.11pt;"></font></div></td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td style="width: 11.54%; text-align: right; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 7.5pt; margin-top: 0pt; text-align: right;"><font style="position: relative; top: -4.25pt;">**</font></div></td></tr><tr><td style="width: 87.18%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Accounting fees and expenses<font style="padding-left: 2.22pt;"></font></div></td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 11.54%; text-align: right; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 7.5pt; margin-top: 0pt; text-align: right;"><font style="position: relative; top: -4.25pt;">**</font></div></td></tr><tr><td style="width: 87.18%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Miscellaneous<font style="padding-left: 2.74pt;"></font></div></td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;">&#8203;</td><td style="width: 11.54%; text-align: right; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt; background-color: #CCEEFF;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 7.5pt; margin-top: 0pt; text-align: right;"><font style="position: relative; top: -4.25pt;">**</font></div></td></tr><tr><td style="width: 87.18%; text-align: left; vertical-align: bottom; padding-top: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 10pt; text-align: left;">Total<font style="padding-left: 0.09pt;"></font></div></td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td class="gutter" style="width: 0.64%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td style="width: 11.54%; text-align: right; vertical-align: bottom; padding-top: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 7.5pt; margin-top: 0pt; text-align: right;"><font style="position: relative; top: -4.25pt;">**</font></div></td></tr></table><div><div class="rule-partial" style="height: 0pt; width: 72pt; border-bottom: 1pt solid #000000; margin-bottom: 1pt; margin-right: auto; margin-left: 0pt; margin-top: 9.75pt;"> </div></div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 3pt; margin-left: 0pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">*<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; text-align: left;">In accordance with Rule 456(b) and 457(r) we are deferring payment of the registration fee for the securities offered by this prospectus.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 3pt; margin-left: 0pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">**<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; text-align: left;">Since an indeterminate amount of securities is covered by this registration statement, the expenses in connection with the issuance and distribution of the securities are not currently determinable.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 12pt; margin-left: 0pt;"><tr><td style="width: 40pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 15.<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-align: left;">Indemnification of Officers and Directors</div></td></tr></table><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Under Section 145 of the DGCL, the Registrant has broad powers to indemnify its directors and officers against liabilities they may incur in such capacities, including liabilities under the Securities Act of 1933.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">The Registrant&#8217;s Certificate of Incorporation and Bylaws include provisions to (i)&#160;eliminate the personal liability of its directors for monetary damages resulting from breaches of their fiduciary duty to the extent permitted by Section 102(b)(7) of the DGCL and (ii)&#160;require the Registrant to indemnify its directors and officers to the fullest extent permitted by Section 145 of the DGCL, including circumstances in which indemnification is otherwise discretionary. Pursuant to Section 145 of the DGCL, a corporation generally has the power to indemnify its present and former directors, officers, employees and agents against expenses incurred by them in connection with any suit to which they are, or are threatened to be made, a party by reason of their serving in such positions so long as they acted in good faith and in a manner they reasonably believed to be in, or not opposed to, the best interest of the corporation, and with respect to any criminal action, they had no reasonable cause to believe their conduct was unlawful. The Registrant believes that these provisions are necessary to attract and retain qualified persons as directors and officers. These provisions do not eliminate the directors&#8217; duty of care, and, in appropriate circumstances, equitable remedies such as injunctive or other forms of non-monetary relief will remain available under the DGCL. In addition, each director will continue to be subject to liability for breach of the directors&#8217; duty of loyalty to the Registrant, for acts or omissions not in good faith or involving intentional misconduct, for knowing violations of law, for acts or omissions that the director believes to be contrary to the best interests of the Registrant or its stockholders, for any transaction from which the director derived an improper personal benefit, for acts or omissions involving a reckless disregard for the directors&#8217; duty to the Registrant or its stockholders when the director was aware or should have been aware of a risk of serious injury to the Registrant or its stockholders, for acts or omissions that constitute an unexcused pattern of inattention that amounts to an abdication of the director&#8217;s duty to the Registrant or its stockholders, for improper transactions between the director and the Registrant and for improper distributions to stockholders and loans to directors and officers. The provision also does not affect a director&#8217;s responsibilities under any other law, such as the federal securities law or state or federal environmental laws.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">The Registrant has entered into indemnity agreements with each of its directors and executive officers that require the Registrant to indemnify such persons against expenses, judgments, fines, settlements and other amounts incurred (including expenses of a derivative action) in connection with any proceeding, whether actual or threatened, to which any such person may be made a party by reason of the fact that such person is or was a director or an executive officer of the Registrant or any of its affiliated enterprises, provided such person acted in good faith and in a manner such persons reasonably believed to be in or not opposed to the best interests of the Registrant and, with respect to any criminal proceeding, has no reasonable cause to believe his conduct was unlawful. The indemnification agreements also set forth certain procedures that will apply in the event of a claim for indemnification thereunder.</div></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">II-1<br></div></div></div><!--End Page 14-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_206-part2_pg2"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">At present, there is no pending litigation or proceeding involving a director or officer of the Registrant as to which indemnification is being sought, nor is the Registrant aware of any threatened litigation that may result in claims for indemnification by any officer or director.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">The Registrant has an insurance policy covering the officers and directors of the Registrant with respect to certain liabilities, including liabilities arising under the Securities Act or otherwise.</div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 12pt; margin-left: 0pt;"><tr><td style="width: 40pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 16.<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-align: left;">Exhibits</div></td></tr></table><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 10.75pt; margin-left: 0pt; text-align: left;">(a) The following exhibits are filed as part of this Registration Statement:</div><table cellspacing="0" cellpadding="0" class="txttab" align="center" style="margin-top: 11.25pt; border-collapse: collapse; width: 468pt; margin-left: 0pt;"><tr class="header"><td style="width: 7.69%; text-align: center; vertical-align: bottom; border-bottom: 1pt solid #000000; padding-bottom: 4.25pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: bold; margin-top: 0pt; text-align: center;">Exhibit<br>Number</div></td><td class="gutter" style="width: 1.28%; font-size: 2pt; padding-bottom: 4.25pt; border-bottom: 1px solid #ffffff;">&#8203;</td><td class="gutter" style="width: 1.28%; font-size: 2pt; padding-bottom: 4.25pt; border-bottom: 1px solid #ffffff;">&#8203;</td><td style="width: 89.74%; text-align: center; vertical-align: bottom; border-bottom: 1pt solid #000000; padding-bottom: 4.25pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: bold; margin-top: 0pt; text-align: center;">Description of Document</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 4.25pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">1.1</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 4.25pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 4.25pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 4.25pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Form of Underwriting Agreement*</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000047/exhibit3_1.htm">3.1</a></div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Amended and Restated Certificate of Incorporation filed June 19, 1991<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">(1)</sup></div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036114017588/formdef14a.htm">3.2</a></div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Certificate of Amendment to Restated Certificate of Incorporation filed April 25, 2014<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">(2)</sup></div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036115045083/ex3_1.htm">3.3</a></div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Certificate of Amendment to Restated Certificate of Incorporation filed December&#160;18, 2015<sup style="vertical-align: text-top; 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margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000114036115045083/ex3_2.htm">3.4</a></div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Amended and Restated Bylaws<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">(3)</sup></div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000047/exhibit4_2.htm">4.1</a></div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Specimen Common Stock Certificate<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">(1)</sup></div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="nt10014191x1_ex5-1.htm">5.1</a></div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Opinion of Patrick R. O&#8217;Neil</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="nt10014191x1_ex23-1.htm">23.1</a></div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Consent of Ernst &amp; Young LLP, Independent Registered Public Accounting Firm</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="nt10014191x1_ex5-1.htm">23.2</a></div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Consent of Patrick R. O&#8217;Neil is contained in Exhibit 5.1 to this Registration Statement</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 7.69%; text-align: left; vertical-align: top; padding-top: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;"><a href="#tSIG">24.1</a></div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt;">&#8203;</td><td style="width: 89.74%; text-align: left; vertical-align: bottom; padding-top: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Power of Attorney is contained on the signature pages hereto</div></td></tr></table><div><div class="rule-partial" style="height: 0pt; width: 72pt; border-bottom: 1pt solid #000000; margin-bottom: 1pt; margin-right: auto; margin-left: 0pt; margin-top: 13.25pt;"> </div></div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 3pt; margin-left: 0pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">*<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; text-align: left;">To be filed by amendment or as an exhibit to a document to be incorporated by reference herein.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 3pt; margin-left: 0pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; text-align: left;">Filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December&#160;31, 2017 and incorporated herein by reference.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 3pt; margin-left: 0pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(2)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; text-align: left;">Filed as an exhibit to the Registrant&#8217;s Definitive Proxy Statement on Schedule 14A filed with the SEC on April&#160;25, 2014 and incorporated herein by reference.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 3pt; margin-left: 0pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(3)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; text-align: left;">Filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed December&#160;18, 2015 and incorporated herein by reference.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 12pt; margin-left: 0pt;"><tr><td style="width: 40pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 17.<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; text-align: left;">Undertakings</div></td></tr></table><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 10.75pt; margin-left: 20pt; text-align: left;">(a) The undersigned Registrant hereby undertakes:</div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 40pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">To file, during any period in which offers or sales are being made, a post-effective amendment to this registration statement;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 60pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(i)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">To include any prospectus required by Section 10(a)(3) of the Securities Act of 1933;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 60pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(ii)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">To reflect in the prospectus any facts or events arising after the effective date of the registration statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in the registration statement. Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value of securities offered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum offering range may be reflected in the form of prospectus filed with the Securities </div></td></tr></table></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">II-2<br></div></div></div><!--End Page 15-->
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<!--Begin Page 16-->
<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_206-part2_pg3"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 80pt; text-align: left;">and Exchange Commission pursuant to Rule 424(b) if, in the aggregate, the changes in volume and price represent no more than a 20 percent change in the maximum aggregate offering price set forth in the &#8220;Calculation of Registration Fee&#8221; table in the effective registration statement; and</div><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 60pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(iii)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">To include any material information with respect to the plan of distribution not previously disclosed in the registration statement or any material change to such information in the registration statement;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 60pt;"><tr><td style="width: 40pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8195;<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">provided, however, that the undertakings set forth in paragraphs (1)(i), (1)(ii)&#160;and (1)(iii)&#160;above do not apply if the information required to be included in a post-effective amendment by those paragraphs is contained in reports filed with or furnished to the Securities and Exchange Commission by the registrant pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 that are incorporated by reference in the registration statement, or is contained in a form of prospectus filed pursuant to Rule 424(b) that is a part of the registration statement.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 40pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">That, for the purpose of determining any liability under the Securities Act of 1933, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered herein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 40pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">To remove from registration by means of a post-effective amendment any of the securities being registered which remain unsold at the termination of the offering.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 40pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">That, for the purpose of determining liability under the Securities Act of 1933 to any purchaser:</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 60pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(A)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">Each prospectus filed by the registrant pursuant to Rule 424(b)(3) shall be deemed to be part of the registration statement as of the date the filed prospectus was deemed part of and included in the registration statement; and</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 60pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(B)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">Each prospectus required to be filed pursuant to Rule 424(b)(2), (b)(5), or (b)(7) as part of a registration statement in reliance on Rule 430B relating to an offering made pursuant to Rule&#160;415(a)(1)(i), (vii), or (x)&#160;for the purpose of providing the information required by Section&#160;10(a) of the Securities Act of 1933 shall be deemed to be part of and included in the registration statement as of the earlier of the date such form of prospectus is first used after effectiveness or the date of the first contract of sale of securities in the offering described in the prospectus. As provided in Rule 430B, for liability purposes of the issuer and any person that is at that date an underwriter, such date shall be deemed to be a new effective date of the registration statement relating to the securities in the registration statement to which that prospectus relates, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof. Provided, however, that no statement made in a registration statement or prospectus that is part of the registration statement or made in a document incorporated or deemed incorporated by reference into the registration statement or prospectus that is part of the registration statement will, as to a purchaser with a time of contract of sale prior to such effective date, supersede or modify any statement that was made in the registration statement or prospectus that was part of the registration statement or made in any such document immediately prior to such effective date.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 40pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">That, for the purpose of determining liability of the registrant under the Securities Act of 1933 to any purchaser in the initial distribution of the securities, the undersigned registrant undertakes that in a primary offering of securities of the undersigned registrant pursuant to this registration statement, regardless of the underwriting method used to sell the securities to the purchaser, if the securities are offered or sold to such purchaser by means of any of the following communications, the undersigned registrant will be a seller to the purchaser and will be considered to offer or sell such securities to such purchaser:</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 60pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(i)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">Any preliminary prospectus or prospectus of the undersigned registrant relating to the offering required to be filed pursuant to Rule 424;</div></td></tr></table></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">II-3<br></div></div></div><!--End Page 16-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_206-part2_pg4"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 60pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(ii)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">Any free writing prospectus relating to the offering prepared by or on behalf of the undersigned registrant or used or referred to by the undersigned registrant;</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 60pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(iii)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">The portion of any other free writing prospectus relating to the offering containing material information about the undersigned registrant or its securities provided by or on behalf of the undersigned registrant; and</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 60pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(iv)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">Any other communication that is an offer in the offering made by the undersigned registrant to the purchaser.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(b)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">The undersigned registrant hereby undertakes that, for purposes of determining any liability under the Securities Act of 1933, each filing of the registrant's annual report pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934 (and, where applicable, each filing of an employee benefit plan's annual report pursuant to Section 15(d) of the Securities Exchange Act of 1934) that is incorporated by reference in the registration statement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(c)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">Insofar as indemnification for liabilities arising under the Securities Act of 1933 may be permitted to directors, officers, and controlling persons of the registrant pursuant to the foregoing provisions, or otherwise, the registrant has been advised that in the opinion of the Securities and Exchange Commission such indemnification is against public policy as expressed in the Securities Act of 1933 and is, therefore, unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the registrant of expenses incurred or paid by a director, officer, or controlling person of the registrant in the successful defense of any action, suit or proceeding) is asserted by such director, officer, or controlling person in connection with the securities being registered, the registrant will, unless in the opinion of its counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 20pt;"><tr><td style="width: 40pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(d)&#8195;(1)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">For purpose of determining any liability under the Securities Act of 1933, the information omitted from the form of prospectus filed as part of this registration statement in reliance upon Rule 430A and contained in a form of prospectus filed by the registrant pursuant to Rule 424(b)(1) or (4) or 497(h) under the Securities Act shall be deemed to be part of this registration statement as of the time it was declared effective.</div></td></tr></table><table border="0" cellpadding="0" cellspacing="0" style="margin-top: 6pt; margin-left: 40pt;"><tr><td style="width: 20pt; text-align: left; vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)<br></div></td><td style="vertical-align: top;"><div style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left;">For purposes of determining any liability under the Securities Act of 1933, each post-effective amendment that contains a form of prospectus shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.</div></td></tr></table></div></div><div class="block-frill" style="width: 468pt; margin-top: 12pt; margin-left: 0pt;"><div class="unknown" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">II-4<br></div></div></div><!--End Page 17-->
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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_207-sig_pg1"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; text-align: center;"><a name="tSIG"><!--Anchor--></a>SIGNATURES</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Pursuant to the requirements of the Securities Act of 1933, the registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-3 and has duly caused this Registration Statement to be signed on its behalf by the undersigned thereunto duly authorized, in the city of Carlsbad, County of San Diego, State of California, on August&#160;7, 2020.</div><table cellspacing="0" cellpadding="0" class="txttab" align="center" style="margin-top: 11.25pt; border-collapse: collapse; width: 468pt; margin-left: 0pt;"><tr><td style="width: 58.97%; text-align: left; vertical-align: top; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 38.46%; text-align: left; vertical-align: bottom; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 0pt; margin-left: 0pt; text-align: left;">IONIS PHARMACEUTICALS, INC.</div></td></tr><tr><td style="width: 58.97%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 3pt;">&#8203;</td><td style="width: 38.46%; text-align: left; vertical-align: bottom; padding-top: 3pt; padding-bottom: 3pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 58.97%; text-align: left; vertical-align: top; padding-top: 3pt; padding-bottom: 4.25pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3pt; padding-bottom: 4.25pt;">&#8203;</td><td class="gutter" style="width: 1.28%; font-size: 2pt; padding-top: 3pt; padding-bottom: 4.25pt; border-bottom: 1px solid #ffffff;">&#8203;</td><td style="width: 38.46%; text-align: center; vertical-align: bottom; border-bottom: 1pt solid #000000; padding-top: 3pt; padding-bottom: 4.25pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">/s/ Brett Monia </div></td></tr><tr><td style="width: 58.97%; text-align: left; vertical-align: top; padding-top: 4.25pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 4.25pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 4.25pt;">&#8203;</td><td style="width: 38.46%; text-align: center; vertical-align: bottom; padding-top: 4.25pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">Brett Monia<br><font style="font-style: italic;">Chief Executive Officer</font></div></td></tr></table><div class="h1" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold; margin-top: 12pt; text-align: center;">POWER OF ATTORNEY</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints BRETT MONIA and ELIZABETH L. HOUGEN, and each of them, as his or her true and lawful attorney-in-fact and agents, with full power of substitution and resubstitution, for the undersigned and in his or her name, place and stead, in any and all capacities, to sign any or all amendments (including post-effective amendments) to this Registration Statement and to sign any Registration Statement that is to be effective on filing pursuant to Rule 462(b) promulgated under the Securities Act of 1933, and all post-effective amendments thereto, and to file the same, with all exhibits thereto, and all documents in connection therewith, with the Securities and Exchange commission, granting unto said attorneys-in-fact and agents, and each of them, full power of authority to do and perform each and every act and thing requisite and necessary to be done in connection therewith, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents, each acting alone, or his or her substitute or substitutes, may lawfully do or cause to be done by virtue hereof.</div><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 6pt; margin-left: 0pt; text-align: left;">Pursuant to the requirements of the Securities Act of 1933, this Registration Statement has been signed below by the following persons in the capacities indicated and on the dates indicated.</div><table cellspacing="0" cellpadding="0" class="txttab" align="center" style="margin-top: 11.25pt; border-collapse: collapse; width: 468pt; margin-left: 0pt;"><tr class="header"><td style="width: 30.77%; text-align: center; vertical-align: bottom; border-bottom: 1pt solid #000000; padding-bottom: 3.75pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: bold; margin-top: 0pt; text-align: center;">Signatures</div></td><td class="gutter" style="width: 1.28%; font-size: 2pt; padding-bottom: 3.75pt; border-bottom: 1px solid #ffffff;">&#8203;</td><td class="gutter" style="width: 1.28%; font-size: 2pt; padding-bottom: 3.75pt; 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Hougen</div></td><td class="gutter" style="width: 1.28%; font-size: 2pt; padding-top: 2.5pt; padding-bottom: 3.75pt; border-bottom: 1px solid #ffffff;">&#8203;</td><td class="gutter" rowspan="2" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 2.5pt; padding-bottom: 3.75pt;">&#8203;</td><td rowspan="2" style="width: 50.63%; text-align: left; vertical-align: top; padding-top: 2.5pt; padding-bottom: 3.75pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">Executive Vice President, Finance and Chief <br>Financial Officer (Principal financial and <br>accounting officer)</div></td><td class="gutter" rowspan="2" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 2.5pt; padding-bottom: 3.75pt;">&#8203;</td><td class="gutter" rowspan="2" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 2.5pt; padding-bottom: 3.75pt;">&#8203;</td><td rowspan="2" style="width: 13.47%; text-align: left; vertical-align: top; padding-top: 2.5pt; padding-bottom: 3.75pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; margin-left: 0pt; text-align: left;">August&#160;7, 2020</div></td></tr><tr><td style="width: 30.77%; text-align: center; vertical-align: top; padding-top: 3.75pt; padding-bottom: 2.5pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">Elizabeth L. Hougen</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 3.75pt; padding-bottom: 2.5pt;">&#8203;</td></tr><tr><td style="width: 30.77%; text-align: center; vertical-align: top; padding-top: 2.5pt; padding-bottom: 2.5pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 2.5pt; padding-bottom: 2.5pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 2.5pt; padding-bottom: 2.5pt;">&#8203;</td><td style="width: 50.63%; text-align: left; vertical-align: top; padding-top: 2.5pt; padding-bottom: 2.5pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 2.5pt; padding-bottom: 2.5pt;">&#8203;</td><td class="gutter" style="width: 1.28%; border-bottom: none; font-size: 2pt; padding-top: 2.5pt; padding-bottom: 2.5pt;">&#8203;</td><td style="width: 13.47%; text-align: left; vertical-align: top; padding-top: 2.5pt; padding-bottom: 2.5pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;</div></td></tr><tr><td style="width: 30.77%; text-align: center; vertical-align: top; border-bottom: 1pt solid #000000; padding-top: 2.5pt; padding-bottom: 3.75pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 10pt; margin-top: 0pt; text-align: center;">/s/ Stanley T. 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<div class="page" style="text-align: left; margin: auto; position: relative; width: 468pt;"><a name="nt10014191x1_s3asr_207-sig_pg2"><!--Anchor--></a><p style="text-align: left; font-family: 'Times New Roman', Times, Serif; font-size: 8pt; font-variant: normal; font-weight: bold"><a href="#TOC">TABLE OF CONTENTS</a></p><div class="page-content"><div class="block-main" style="width: 468pt; margin-left: 0pt;"><table cellspacing="0" cellpadding="0" class="txttab" align="center" style="margin-top: 4pt; border-collapse: collapse; width: 468pt; margin-left: 0pt;"><tr class="header"><td style="width: 30.77%; text-align: center; vertical-align: bottom; border-bottom: 1pt solid #000000; padding-bottom: 3.75pt;"><div class="fpara" style="color: #000000; font-family: 'Times New Roman', Times, serif; font-size: 8pt; font-weight: bold; margin-top: 0pt; text-align: center;">Signatures</div></td><td class="gutter" style="width: 1.28%; font-size: 2pt; padding-bottom: 3.75pt; border-bottom: 1px solid #ffffff;">&#8203;</td><td class="gutter" style="width: 1.28%; 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<DOCUMENT>
<TYPE>EX-5.1
<SEQUENCE>2
<FILENAME>nt10014191x1_ex5-1.htm
<DESCRIPTION>EXHIBIT 5.1
<TEXT>
<html>
  <head>
    <title></title>
    <!-- Licensed to: Broadridge Financial Soultions, Inc.
         Document created using EDGARfilings PROfile 7.1.0.0
         Copyright 1995 - 2020 Broadridge -->
  </head>
<body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000;" bgcolor="#ffffff">
  <div>
    <hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade">
    <div style="text-align: right;"><font style="font-weight: bold;">Exhibit 5.1</font><br>
    </div>
  </div>
  <div><font style="font-weight: bold;"> <br>
    </font></div>
  <div><br>
    <div><br>
    </div>
    <div><br>
    </div>
    <div>OPINION OF PATRICK R. O&#8217;NEIL</div>
    <div><br>
    </div>
    <div>August 7, 2020</div>
    <div>Ionis Pharmaceuticals, Inc.</div>
    <div>2855 Gazelle Court</div>
    <div>Carlsbad, CA 92010</div>
    <div><br>
    </div>
    <div>Ladies and Gentlemen:</div>
    <div><br>
    </div>
    <div>I have acted as counsel to Ionis Pharmaceuticals, Inc., a Delaware corporation (the &#8220;Company&#8221;), in connection with a Registration Statement on Form S-3 (the
      &#8220;Registration Statement&#8221;) to be filed by the Company under the Securities Act of 1933, as amended (the &#8220;Securities Act&#8221;). The Company has provided me with a prospectus (the &#8220;Prospectus&#8221;), which forms part of the Registration Statement. The Prospectus
      provides that it will be supplemented in the future by one or more prospectus supplements (each, a &#8220;Prospectus Supplement&#8221;). The Registration Statement, including the Prospectus as supplemented from time to time by one or more Prospectus Supplements,
      will provide for the registration by the Company of shares of common stock, par value $0.001 per share, of the Company (the &#8220;Common Stock&#8221;).</div>
    <div><br>
    </div>
    <div>The Common Stock is being registered for offer and sale from time to time pursuant to Rule 415 under the Securities Act.</div>
    <div><br>
    </div>
    <div>In connection with this opinion, I have examined and relied upon originals, or copies certified to my satisfaction, of such records, documents, certificates,
      opinions, memoranda and other instruments as in my judgment are necessary or appropriate to enable me to render the opinion expressed below. As to certain factual matters, I have relied upon certificates of officers of the Company and have not
      independently sought to verify such matters.</div>
    <div><br>
    </div>
    <div>In rendering this opinion, I have assumed the genuineness and authenticity of all signatures on original documents; the authenticity of all documents
      submitted to me as originals; the conformity to originals of all documents submitted to me as copies; the accuracy, completeness and authenticity of certificates of public officials; and the due authorization, execution and delivery of all documents
      where authorization, execution and delivery are prerequisites to the effectiveness of such documents. With respect to my opinion as to the Common Stock, I have assumed that, at the time of issuance and sale, a sufficient number of shares of Common
      Stock are authorized and available for issuance and that the consideration for the issuance and sale of the Common Stock is in an amount that is not less than the par value of the Common Stock.</div>
    <div><br>
    </div>
    <div>My opinion herein is expressed solely with respect to the federal laws of the United States and the Delaware General Corporation Law. My opinion is based on
      these laws as in effect on the date hereof. I express no opinion as to whether the laws of any jurisdiction are applicable to the subject matter hereof. I am not rendering any opinion as to compliance with any federal or state law, rule or regulation
      relating to securities, or to the sale or issuance thereof.</div>
    <div><br>
    </div>
    <div>On the basis of the foregoing and in reliance thereon, and subject to the qualifications herein stated, I am of the opinion that, with respect to the Common
      Stock offered under the Registration Statement, provided that (i) the Registration Statement and any required post-effective amendment thereto have all become effective under the Securities Act and the Prospectus and any and all Prospectus
      Supplement(s) required by applicable laws and any and all free-writing prospectus(es) related to the offer and sale of the Common Stock have been delivered and filed as required by such laws; (ii) the issuance of the Common Stock has been duly
      authorized by all necessary corporate action on the part of the Company; (iii) the issuance and sale of the Common Stock do not violate any applicable law, are in conformity with the Company&#8217;s then operative Amended and Restated Certificate of
      Incorporation (the &#8220;Certificate of Incorporation&#8221;) and Bylaws, as amended (the &#8220;Bylaws&#8221;), do not result in a default under or breach of any agreement or instrument binding upon the Company and comply with any applicable requirement or restriction
      imposed by any court or governmental body having jurisdiction over the Company; and (iv) the certificates for the Common Stock have been duly executed by the Company, countersigned by the transfer agent therefor and duly delivered to the purchasers
      thereof against payment therefor, then the Common Stock, when issued and sold as contemplated in the Registration Statement, the Prospectus and the related Prospectus Supplement(s) and any related free-writing prospectus(es) and in accordance with
      any applicable duly authorized, executed and delivered purchase, underwriting or similar agreement, will be duly authorized, validly issued, fully paid and nonassessable.</div>
    <div><br>
    </div>
    <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
      <div id="DSPFPageBreak" style="page-break-after: always;">
        <hr style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;" noshade="noshade"></div>
    </div>
    <div>I am a member of the Bar of the State of California and the foregoing opinion is limited to the laws of the State of California and the General Corporation
      Law of the State of Delaware.</div>
    <div><br>
    </div>
    <div>I hereby consent to the filing of this opinion as an exhibit to the Registration Statement and to the reference to me under the caption &#8220;Legal Matters&#8221; in the
      Prospectus included in the Registration Statement. In giving this consent, I do not admit that I am in the category of persons whose consent is required under Section 7 of the Securities Act. This opinion is expressed as of the date hereof, and I
      disclaim any undertaking to advise you of any subsequent changes in the facts stated or assumed herein or of any subsequent changes in applicable law.</div>
    <div><br>
    </div>
    <div>Sincerely,</div>
    <div><br>
    </div>
    <div><u>/s/ PATRICK R. O&#8217;NEIL</u></div>
    <div><br>
    </div>
    <div>Patrick R. O&#8217;Neil</div>
    <div><br>
    </div>
    <div>Executive Vice President, Legal, General Counsel and Corporate Secretary</div>
    <div><br>
    </div>
    <div><br>
    </div>
    <div><br>
    </div>
    <div>
      <hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"></div>
  </div>
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</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-23.1
<SEQUENCE>3
<FILENAME>nt10014191x1_ex23-1.htm
<DESCRIPTION>EXHIBIT 23.1
<TEXT>
<html>
  <head>
    <title></title>
    <!-- Licensed to: Broadridge Financial Soultions, Inc.
         Document created using EDGARfilings PROfile 7.1.0.0
         Copyright 1995 - 2020 Broadridge -->
  </head>
<body style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000;" bgcolor="#ffffff">
  <div>
    <hr style="height: 4px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade">
    <div style="text-align: right;"><font style="font-weight: bold;">Exhibit 23.1</font><br>
    </div>
  </div>
  <div> <br>
  </div>
  <div>
    <div><br>
    </div>
    <div style="text-align: center;">Consent of Independent Registered Public Accounting Firm</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="text-align: justify;">We consent to the reference to our firm under the caption &#8220;Experts&#8221; in the Registration Statement (Form S-3) and related Prospectus of Ionis
      Pharmaceuticals, Inc. for the registration of its common stock and to the incorporation by reference therein of our reports dated March 2, 2020, with respect to the consolidated financial statements of Ionis Pharmaceuticals, Inc.,&#160;and the
      effectiveness of internal control over financial reporting of Ionis Pharmaceuticals, Inc., included in its Annual Report (Form 10-K) for the year ended December 31, 2019, filed with the Securities and Exchange Commission.</div>
    <div style="text-align: justify;"> <br>
    </div>
    <div style="text-align: center;">&#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;/s/ Ernst &amp; Young LLP</div>
    <div> <br>
    </div>
    <div> <br>
    </div>
    <div> <br>
    </div>
    <div> <br>
    </div>
    <div>San Diego, California</div>
    <div> <br>
    </div>
    <div>August 7, 2020</div>
    <div> <br>
    </div>
    <div> <br>
    </div>
    <div> <br>
    </div>
    <div>
      <hr style="height: 2px; color: #000000; background-color: #000000; text-align: center; margin-left: auto; margin-right: auto; border: none;" align="center" noshade="noshade"> </div>
  </div>
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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
