<SEC-DOCUMENT>0001193125-23-161613.txt : 20230606
<SEC-HEADER>0001193125-23-161613.hdr.sgml : 20230606
<ACCEPTANCE-DATETIME>20230606161201
ACCESSION NUMBER:		0001193125-23-161613
CONFORMED SUBMISSION TYPE:	8-K
PUBLIC DOCUMENT COUNT:		15
CONFORMED PERIOD OF REPORT:	20230606
ITEM INFORMATION:		Other Events
ITEM INFORMATION:		Financial Statements and Exhibits
FILED AS OF DATE:		20230606
DATE AS OF CHANGE:		20230606

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:			CA
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		8-K
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		23996186

	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>
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<td style=" text-align: center;margin:auto; vertical-align:top">&#8220;<ix:nonNumeric name="dei:TradingSymbol" contextRef="duration_2023-06-06_to_2023-06-06">IONS</ix:nonNumeric>&#8221;</td>
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<td style="width:11%;vertical-align:top" align="left"><span style="font-weight:bold">Item&#160;8.01</span></td>
<td align="left" style="vertical-align:top"> <p style=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman;font-weight:bold;text-align:left">Other Events. </p></td></tr></table> <p style="margin-top:6pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">On June 6, 2023, Ionis Pharmaceuticals, Inc. (the &#8220;Company&#8221;) issued a press release announcing the proposed offering of $500.0&#160;million aggregate principal amount of convertible senior notes due 2028 (the &#8220;Notes&#8221;) in a private placement (the &#8220;Offering&#8221;) to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the &#8220;Securities Act&#8221;), and the related grant to the initial purchasers of the Notes of an option to purchase up to an additional $75.0&#160;million aggregate principal amount of Notes in the Offering. The Company expects to use a portion of the net proceeds from the Offering to repurchase for cash certain of its 0.125% Convertible Senior Notes due 2024 (the &#8220;2024 notes&#8221;) in privately negotiated transactions. The Company expects to use the remaining net proceeds from the Offering for additional repurchases of the 2024 notes from time to time following the Offering, including the repayment of any remaining 2024 notes at maturity, and for general corporate purposes. A copy of the press release announcing the Offering is attached hereto as Exhibit 99.1. </p> <p style="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">In connection with the Offering of the Notes, the Company intends to disclose certain information regarding its business to prospective investors in a confidential preliminary offering memorandum dated June 6, 2023. The preliminary offering memorandum includes information that supplements or updates certain prior disclosures of the Company, which information is attached hereto as Exhibit 99.2 and incorporated herein by reference. </p> <p style="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">This Current Report on Form <span style="white-space:nowrap">8-K</span> does not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall it constitute an offer to sell, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful. Any offers of the securities would be made only by means of a confidential offering memorandum. These securities have not been registered under the Securities Act or any state securities laws and, unless so registered, may not be offered or sold in the United States or to U.S. persons except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and applicable state laws. </p> <p style="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman;font-weight:bold">Forward-Looking Statements </p> <p style="margin-top:6pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">This Current Report on Form <span style="white-space:nowrap">8-K</span> contains &#8220;forward-looking statements&#8221; within the meaning of the Private Securities Litigation Reform Act of 1995 that involve risks and uncertainties. All forward-looking statements included in this report, including statements regarding the proposed terms of the Notes, the completion, timing and size of the proposed Offering and the anticipated use of the net proceeds from the Offering, are based upon information available to the Company as of the date of this report, which may change, and the Company assumes no obligation to update any such forward-looking statements. Although the Company&#8217;s forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by the Company. These statements are not guarantees of future performance and actual results could differ materially from the Company&#8217;s current expectations. As a result, you are cautioned not to rely on these forward-looking statements. Factors that could cause or contribute to such differences include the risks and uncertainties discussed in the &#8220;Risk Factors&#8221; section of the Company&#8217;s Quarterly Report on Form <span style="white-space:nowrap">10-Q</span> for the quarter ended March&#160;31, 2023, filed with the Securities and Exchange Commission on May&#160;3, 2023, and other subsequent filings the Company makes with the Securities and Exchange Commission from time to time. The Company assumes no obligation and does not intend to update the forward-looking statements provided, whether as a result of new information, future events or otherwise. </p> <p style="font-size:18pt;margin-top:0pt;margin-bottom:0pt">&#160;</p>
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<td style="width:11%;vertical-align:top" align="left"><span style="font-weight:bold">Item&#160;9.01</span></td>
<td align="left" style="vertical-align:top"> <p style=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman;font-weight:bold;text-align:left">Financial Statements and Exhibits. </p></td></tr></table> <p style="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman;font-weight:bold">(d) Exhibits. </p> <p style="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&#160;</p>
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<td style="vertical-align:bottom;white-space:nowrap"> <p style=" margin-top:0pt ; margin-bottom:0pt; border-bottom:1.00pt solid #000000; display:table-cell; font-size:8pt; font-family:Times New Roman;font-weight:bold">Description</p></td></tr>


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<td style="vertical-align:top;white-space:nowrap">99.1</td>
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<td style="vertical-align:top"><a href="d501696dex991.htm">Press release dated June 6, 2023. </a></td></tr>
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<td style="vertical-align:top"><a href="d501696dex992.htm">Excerpts from Confidential Preliminary Offering Memorandum dated June 6, 2023. </a></td></tr>
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<td style="vertical-align:top">Cover Page Interactive Data File (embedded within the Inline XBRL document).</td></tr>
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 <p style="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman;font-weight:bold;text-align:center">SIGNATURES </p> <p style="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized. </p> <p style="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&#160;</p>
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<td style="vertical-align:bottom" colspan="3"><span style="font-weight:bold">Ionis Pharmaceuticals, Inc.</span></td></tr>
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<td style="vertical-align:bottom">Date: June 6, 2023</td>
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<td style="vertical-align:top">By:</td>
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<td style="vertical-align:bottom"> <p style="margin-top:0pt; margin-bottom:1pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Patrick R. O&#8217;Neil</p></td></tr>
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<td style="vertical-align:bottom"><span style="font-weight:bold">P<small>ATRICK</small> R. O&#8217;N<small>EIL</small></span></td></tr>
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<td style="vertical-align:bottom">Executive Vice President, Legal, General Counsel and Chief Compliance Officer</td></tr>
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<Center><DIV STYLE="width:8.5in" align="left">
 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="right"><B>Exhibit 99.1 </B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<P STYLE="margin-top:0pt;margin-bottom:0pt">


<IMG SRC="g501696g0606111643648.jpg" ALT="LOGO">
 </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Ionis announces proposed private placement </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>of convertible notes </B></P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>CARLSBAD, Calif.,
</B><B>June 6, 2023</B> &#150; Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) announced today that it intends to offer, subject to market conditions and other factors, $500.0&nbsp;million aggregate principal amount of Convertible Senior Notes due 2028
(the &#147;notes&#148;) in a private placement (the &#147;offering&#148;) to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the &#147;Securities Act&#148;). Ionis also intends to grant the initial
purchasers of the notes an option to purchase, within the <FONT STYLE="white-space:nowrap">13-day</FONT> period beginning on, and including, the first date on which the notes are issued, up to an additional $75.0&nbsp;million principal amount of
notes. </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">The notes will be general unsecured obligations of Ionis and will accrue interest payable semiannually in arrears. Upon conversion, Ionis will pay
or deliver, as the case may be, cash, shares of its common stock or a combination of cash and shares of its common stock, at its election. The interest rate, initial conversion rate and other terms of the notes will be determined at the time of
pricing of the offering. </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Ionis expects to use a portion of the net proceeds from the offering to repurchase for cash certain of its 0.125% Convertible
Senior Notes due 2024 (the &#147;2024 notes&#148;) in privately negotiated transactions. Ionis expects to use the remaining net proceeds from the offering for additional repurchases of the 2024 notes from time to time following the offering,
including the repayment of any remaining 2024 notes at maturity, and for general corporate purposes. </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">In connection with any repurchase of the 2024 notes,
Ionis expects that holders of the 2024 notes who agree to have their 2024 notes repurchased and who have hedged their equity price risk with respect to such notes (the &#147;hedged holders&#148;) will unwind all or part of their hedge positions by
buying Ionis&#146; common stock and/or entering into or unwinding various derivative transactions with respect to Ionis&#146; common stock. The amount of Ionis&#146; common stock to be purchased by the hedged holders or in connection with such
derivative transactions may be substantial in relation to the historic average daily trading volume of Ionis&#146; common stock. This activity by the hedged holders could increase (or reduce the size of any decrease in) the market price of
Ionis&#146; common stock, including concurrently with the pricing of the notes, resulting in a higher effective conversion price of the notes. Ionis cannot predict the magnitude of such market activity or the overall effect it will have on the price
of the notes or Ionis&#146; common stock. </P>
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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">The notes and any shares of Ionis&#146; common stock issuable upon conversion of the notes have not been and
will not be registered under the Securities Act, any state securities laws or the securities laws of any other jurisdiction, and unless so registered, may not be offered or sold in the United States absent registration or an applicable exemption
from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws. </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">This press release is
neither an offer to sell nor a solicitation of an offer to buy any of these securities nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to the
registration or qualification thereof under the securities laws of any such state or jurisdiction. </P> <P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>About Ionis Pharmaceuticals </B></P>
<P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">For more than 30 years, Ionis has been a leader in <FONT STYLE="white-space:nowrap">RNA-targeted</FONT> therapy, pioneering new markets and changing standards
of care. Ionis currently has four marketed medicines and a promising late-stage pipeline highlighted by cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which
fuels our vision to become the leader in genetic medicine, utilizing a multi-platform approach to discover, develop and deliver life-transforming therapies. </P>
<P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>Ionis&#146; Forward-looking Statement </B></P> <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">This press release
includes forward-looking statements regarding the proposed offering, including statements regarding the anticipated terms of the proposed offering and Ionis&#146; expected use of proceeds from the proposed offering. Any statement describing
Ionis&#146; expectations, intentions or beliefs is a forward-looking statement and should be considered an <FONT STYLE="white-space:nowrap">at-risk</FONT> statement. Such statements are subject to certain risks and uncertainties, including, without
limitation, changes in market conditions, Ionis&#146; ability to complete the proposed offering on the expected terms, or at all, whether Ionis will be able to satisfy closing conditions related to the proposed offering, whether and on what terms
Ionis may repurchase any of the 2024 notes and unanticipated uses of capital. Ionis&#146; forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those
expressed or implied by such forward-looking statements. Although Ionis&#146; forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result,
you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis&#146; programs are described in additional detail in Ionis&#146; annual report on Form <FONT STYLE="white-space:nowrap">10-K</FONT> for the
year ended December&nbsp;31, 2022 and most recent Form <FONT STYLE="white-space:nowrap">10-Q,</FONT> which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company. </P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">In this press release, unless the context requires otherwise, &#147;Ionis,&#148; &#147;Company,&#148; &#147;we,&#148; &#147;our,&#148; and &#147;us&#148;
refers to Ionis Pharmaceuticals and its subsidiaries. </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Ionis Pharmaceuticals<SUP STYLE="font-size:75%; vertical-align:top">&reg;</SUP> is a trademark of
Ionis Pharmaceuticals, Inc. </P> <P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>Ionis Investor Contact: </B></P>
<P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">D. Wade Walke, Ph.D. </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">info@ionisph.com </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><FONT STYLE="white-space:nowrap"><FONT STYLE="white-space:nowrap">760-603-2331</FONT></FONT> </P>
<P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>Ionis Media Contact: </B></P> <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">David Polk, J.D. </P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">ionis_ca@ionisph.com </P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><FONT STYLE="white-space:nowrap"><FONT
STYLE="white-space:nowrap">760-603-4679</FONT></FONT> </P>
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<Center><DIV STYLE="width:8.5in" align="left">
 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="right"><B>Exhibit 99.2 </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman"><I>In the confidential preliminary offering memorandum to be used in connection with a private placement to qualified institutional buyers
pursuant to Rule 144A of the Securities Act of 1933, as amended, by Ionis Pharmaceuticals, Inc., the Company provided the following overview of the Company&#146;s business as updates or supplements to the information provided in the Company&#146;s
previous periodic filings with the Securities and Exchange Commission. Unless the context requires otherwise, &#147;Ionis,&#148; &#147;Company,&#148; &#147;we,&#148; &#147;our,&#148; and &#147;us&#148; refers to Ionis Pharmaceuticals, Inc. and its
subsidiaries. </I></P> <P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>Overview </B></P> <P STYLE="margin-top:6pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">We were
founded over 30 years ago to deliver innovative medicines for diseases with great medical need. Today, we are building on our advancements in <FONT STYLE="white-space:nowrap">RNA-targeted</FONT> therapeutics to move us closer to achieving our vision
to be the leader in genetic medicines. We believe our medicines have the potential to pioneer new markets, change standards of care and transform the lives of people with devastating diseases. </P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">We currently have four marketed medicines: SPINRAZA, QALSODY, TEGSEDI and WAYLIVRA. Additionally, the U.S. Food and Drug Administration
(&#147;FDA&#148;) accepted our New Drug Application (&#147;NDA&#148;) of eplontersen for polyneuropathy caused by hereditary TTR amyloidosis (&#147;ATTRv-PN&#148;). Eplontersen&#146;s Prescription Drug User Fee Act (&#147;PDUFA&#148;) date is
December&nbsp;22, 2023.&nbsp;We also have a rich innovative late- and <FONT STYLE="white-space:nowrap">mid-stage</FONT> pipeline primarily focused on our leading cardiovascular and neurology franchises. We recently expanded our Phase 3 pipeline to
eight investigational medicines across ten indications following the start of GSK&#146;s Phase 3 program for bepirovirsen in hepatitis B and Roche&#146;s initiation of the Phase 3 study for <FONT STYLE="white-space:nowrap">IONIS-FB-L</FONT><SUB
STYLE="font-size:75%; vertical-align:bottom">Rx</SUB> in IgA nephropathy (&#147;IgAN&#148;). </P> <P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B><I>Marketed Medicines </I></B></P>
<P STYLE="margin-top:6pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">SPINRAZA is the global market leader for the treatment of patients with spinal muscular atrophy, a progressive, debilitating and often fatal
genetic disease. Biogen is our partner responsible for commercializing SPINRAZA worldwide. From inception through March&nbsp;31, 2023, we have earned more than $1.9&nbsp;billion in revenues from our SPINRAZA collaboration, including more than
$1.4&nbsp;billion in royalties on sales of SPINRAZA. </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">QALSODY is an antisense oligonucleotide medicine indicated for the treatment of
amyotrophic lateral sclerosis (&#147;ALS&#148;) in adults who have a mutation in the superoxide dismutase 1 (&#147;<I>SOD1</I>&#148;) gene <FONT STYLE="white-space:nowrap">(&#147;SOD1-ALS&#148;).</FONT> QALSODY was approved under accelerated
approval by the FDA in April 2023. SOD1-ALS is a rare neurodegenerative disorder that causes progressive loss of motor neurons leading to death. The European Medicines Agency (&#147;EMA&#148;) is currently reviewing QALSODY for approval in the
European Union. Biogen is our partner responsible for commercializing QALSODY worldwide. </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">TEGSEDI is a once weekly, self-administered
subcutaneous medicine approved in the United States, Europe, Canada and Brazil for the treatment of patients with polyneuropathy caused by hereditary polyneuropathy (&#147;ATTRv-PN&#148;), a debilitating, progressive, and fatal disease. We launched
TEGSEDI in the United States and the European Union in late 2018. In 2021, we began selling TEGSEDI in Europe through our distribution agreement with Swedish Orphan Biovitrum AB (&#147;Sobi&#148;) and in the second quarter of 2021, Sobi began
distributing TEGSEDI in the United States and Canada. In Latin America, PTC Therapeutics International Limited (&#147;PTC&#148;) is commercializing TEGSEDI in Brazil and is pursuing access in additional Latin American countries through its exclusive
license agreement with us. </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">WAYLIVRA is a once weekly, self-administered, subcutaneous medicine that received conditional marketing
authorization in May 2019 from the European Commission as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome (&#147;FCS&#148;) and at high risk for pancreatitis. We launched WAYLIVRA in the European
Union in the third quarter of 2019. In 2021, we began selling WAYLIVRA in Europe through our distribution agreement with Sobi. In Latin America, PTC is commercializing WAYLIVRA in Brazil for two indications, FCS and familial partial lipodystrophy,
and is pursuing access in additional Latin American countries through its exclusive license agreement with us. </P>
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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B><I>Investigational Medicines in Phase 3 Studies and Registration </I></B></P>
<P STYLE="margin-top:6pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">We currently have eight investigational medicines in Phase 3 studies for ten indications, which are: </P>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">Eplontersen: our investigational medicine in development for transthyretin amyloidosis (&#147;ATTR&#148;)
</P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="10%">&nbsp;</TD>
<TD WIDTH="2%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">We are currently conducting the Phase 3 NEURO-TTRansform study in patients with ATTRv-PN, the Phase 3
CARDIO-TTRansform study in patients with ATTR cardiomyopathy and additional studies supporting our ATTR development program </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="14%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="2%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">In March 2023, the FDA accepted the NDA for eplontersen in the United States for patients with ATTRv-PN with a
PDUFA date of December&nbsp;22, 2023 </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="14%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="2%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">In April 2023, we presented positive <FONT STYLE="white-space:nowrap">week-35</FONT> and <FONT
STYLE="white-space:nowrap">week-66</FONT> data from the Phase 3 NEURO-TTRansform study in patients with ATTRv-PN at the American Academy of Neurology Annual Meeting </P></TD></TR></TABLE>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">Olezarsen: our investigational medicine in development for FCS and severe hypertriglyceridemia (&#147;SHTG&#148;)
</P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="10%">&nbsp;</TD>
<TD WIDTH="2%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">We are currently conducting a broad Phase 3 development program for olezarsen that includes the Phase 3 BALANCE
study in patients with FCS and three Phase 3 studies supporting development for the treatment of SHTG: CORE, CORE2 and ESSENCE </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="14%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
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<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">We remain on track for data from the Phase 3 BALANCE FCS study in the second half of 2023 </P></TD></TR></TABLE>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="14%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
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<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">The FDA granted olezarsen fast track designation for the treatment of patients with FCS </P></TD></TR></TABLE>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="14%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="2%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">In the second half of 2022, we expanded our Phase 3 program for SHTG when we initiated CORE2, a confirmatory
Phase 3 study of olezarsen in patients with SHTG and ESSENCE, a supporting Phase 3 study of olezarsen in patients with SHTG or hypertriglyceridemia and atherosclerotic cardiovascular disease </P></TD></TR></TABLE>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">Donidalorsen: our investigational medicine in development for hereditary angioedema (&#147;HAE&#148;)
</P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="10%">&nbsp;</TD>
<TD WIDTH="2%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">We are currently conducting the Phase 3 <FONT STYLE="white-space:nowrap">OASIS-HAE</FONT> study in patients with
HAE and a Phase 3 study evaluating donidalorsen in HAE patients previously treated with other prophylactic therapies </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="14%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="2%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">We announced the completion of enrollment in the Phase 3 <FONT STYLE="white-space:nowrap">OASIS-HAE</FONT> study
in <FONT STYLE="white-space:nowrap">mid-2023.</FONT> Data from the study is expected in the first half of 2024 </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="14%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="2%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">We reported positive data from the Phase 2 study and Phase 2 open-label extension (&#147;OLE&#148;) study
throughout 2022 and 2023 </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">Ulefnersen (formerly ION363): our investigational medicine in development for ALS with mutations in the fused in
sarcoma gene (&#147;FUS&#148;) </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="10%">&nbsp;</TD>
<TD WIDTH="2%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">We are currently conducting a Phase 3 study of ulefnersen in juvenile and adult patients with <FONT
STYLE="white-space:nowrap">FUS-ALS</FONT> </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">QALSODY: an antisense oligonucleotide medicine that is approved in the United States for the treatment of
SOD1-ALS </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="10%">&nbsp;</TD>
<TD WIDTH="2%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">Biogen is responsible for commercializing QALSODY worldwide </P></TD></TR></TABLE>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="10%">&nbsp;</TD>
<TD WIDTH="2%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">The EMA is currently reviewing QALSODY&#146;s Marketing Authorization Application (&#147;MAA&#148;) in the
European Union </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="10%">&nbsp;</TD>
<TD WIDTH="2%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">In June 2022, Biogen presented new positive data from the ongoing VALOR OLE study at the European Network to Cure
ALS meeting. These data were included in the NDA filing in the United States and MAA filing in the European Union </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="10%">&nbsp;</TD>
<TD WIDTH="2%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">Biogen is also conducting an ongoing Phase 3 study (ATLAS) in presymptomatic SOD1 patients </P></TD></TR></TABLE>
</DIV></Center>


<p style="margin-top:1em; margin-bottom:0em; page-break-before:always">
<HR SIZE="3" style="COLOR:#999999" WIDTH="100%" ALIGN="CENTER">

<Center><DIV STYLE="width:8.5in" align="left">

<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">Pelacarsen: our investigational medicine in development to treat patients with elevated lipoprotein(a)
(&#147;Lp(a)&#148;) and cardiovascular disease </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="10%">&nbsp;</TD>
<TD WIDTH="2%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">Novartis is developing pelacarsen, including conducting the ongoing Lp(a) HORIZON Phase 3 cardiovascular outcome
study in patients with established cardiovascular disease and elevated Lp(a) </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="14%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="2%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">In July 2022, Novartis achieved full enrollment in the Lp(a) HORIZON study </P></TD></TR></TABLE>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="14%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="2%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">In the first quarter of 2021, pelacarsen was granted fast track designation in the United States
</P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">Bepirovirsen: our investigational medicine in development for hepatitis B virus (&#147;HBV&#148;)
</P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="10%">&nbsp;</TD>
<TD WIDTH="2%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">GSK is developing bepirovirsen, including conducting the ongoing <FONT STYLE="white-space:nowrap">B-Well</FONT>
Phase 3 program in patients with HBV </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="14%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="2%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">In 2022, GSK presented positive data from the Phase 2b <FONT STYLE="white-space:nowrap">B-Clear</FONT> study of
bepirovirsen demonstrating potential for functional cures in patients with chronic HBV </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt"><FONT STYLE="white-space:nowrap">IONIS-FB-L</FONT><SUB STYLE="font-size:75%; vertical-align:bottom">Rx</SUB>: our
investigational medicine in development for IgAN and geographic atrophy (&#147;GA&#148;) </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="10%">&nbsp;</TD>
<TD WIDTH="2%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">Roche has initiated a Phase 3 study in IgAN. Additionally, we are currently conducting a Phase 2 study in GA
</P></TD></TR></TABLE> <P STYLE="margin-top:18pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>Special Note Regarding Forward-Looking Statements </B></P>
<P STYLE="margin-top:6pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">This document contains forward-looking statements regarding our business and the therapeutic and commercial potential of our technologies,
products in development and commercial products, including anticipated timing of data from ongoing Phase 3 studies. Any statement describing our goals, expectations, financial or other projections, intentions or beliefs is a forward-looking
statement and should be considered an <FONT STYLE="white-space:nowrap">at-risk</FONT> statement that is subject to change. 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 the section titled &#147;Risk Factors&#148; in our Annual Report on Form <FONT STYLE="white-space:nowrap">10-K</FONT> for the year ended
December&nbsp;31, 2022 and our Quarterly Report on Form <FONT STYLE="white-space:nowrap">10-Q</FONT> for the three months ended March&nbsp;31, 2023. 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. </P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">The forward-looking statements made herein relate only to events as of the date on which such statements are made. We undertake no obligation
to update any forward-looking statements after the date hereof or to conform such statements to actual results or revised expectations, except as required by law. </P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">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. </P>
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      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="ions-20230606_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:title="Presentation Links, all" xlink:type="simple" />
      <link:roleType roleURI="http://ionispharma.com//20230606/taxonomy/role/DocumentDocumentAndEntityInformation" id="Role_DocumentDocumentAndEntityInformation">
        <link:definition>100000 - Document - Document and Entity Information</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </xsd:appinfo>
  </xsd:annotation>
</xsd:schema>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.LAB
<SEQUENCE>5
<FILENAME>ions-20230606_lab.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii" standalone="yes"?>
<!-- DFIN - https://www.dfinsolutions.com/ -->
<!-- CTU Version: Release master Build:20221108.6 -->
<!-- Creation date: 6/7/2023 12:06:51 AM Eastern Time -->
<!-- Copyright (c) 2023 Donnelley Financial Solutions, Inc. All Rights Reserved. -->
<link:linkbase
  xmlns:link="http://www.xbrl.org/2003/linkbase"
  xmlns:xlink="http://www.w3.org/1999/xlink"
  xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"
  xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:labelLink xlink:role="http://www.xbrl.org/2003/role/link" xlink:type="extended">
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_CoverAbstract" xlink:type="locator" xlink:label="dei_CoverAbstract" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_CoverAbstract" xlink:to="dei_CoverAbstract_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_CoverAbstract_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Cover [Abstract]</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_CoverAbstract_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Cover [Abstract]</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityRegistrantName" xlink:type="locator" xlink:label="dei_EntityRegistrantName" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_EntityRegistrantName" xlink:to="dei_EntityRegistrantName_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_EntityRegistrantName_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Entity Registrant Name</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_EntityRegistrantName_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Entity Registrant Name</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_AmendmentFlag" xlink:type="locator" xlink:label="dei_AmendmentFlag" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_AmendmentFlag" xlink:to="dei_AmendmentFlag_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_AmendmentFlag_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Amendment Flag</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_AmendmentFlag_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Amendment Flag</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityCentralIndexKey" xlink:type="locator" xlink:label="dei_EntityCentralIndexKey" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_EntityCentralIndexKey" xlink:to="dei_EntityCentralIndexKey_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_EntityCentralIndexKey_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Entity Central Index Key</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_EntityCentralIndexKey_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Entity Central Index Key</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentType" xlink:type="locator" xlink:label="dei_DocumentType" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_DocumentType" xlink:to="dei_DocumentType_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_DocumentType_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Document Type</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_DocumentType_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Document Type</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentPeriodEndDate" xlink:type="locator" xlink:label="dei_DocumentPeriodEndDate" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_DocumentPeriodEndDate" xlink:to="dei_DocumentPeriodEndDate_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_DocumentPeriodEndDate_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Document Period End Date</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_DocumentPeriodEndDate_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Document Period End Date</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityIncorporationStateCountryCode" xlink:type="locator" xlink:label="dei_EntityIncorporationStateCountryCode" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_EntityIncorporationStateCountryCode" xlink:to="dei_EntityIncorporationStateCountryCode_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_EntityIncorporationStateCountryCode_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Entity Incorporation State Country Code</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_EntityIncorporationStateCountryCode_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Entity Incorporation State Country Code</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityFileNumber" xlink:type="locator" xlink:label="dei_EntityFileNumber" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_EntityFileNumber" xlink:to="dei_EntityFileNumber_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_EntityFileNumber_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Entity File Number</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_EntityFileNumber_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Entity File Number</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityTaxIdentificationNumber" xlink:type="locator" xlink:label="dei_EntityTaxIdentificationNumber" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_EntityTaxIdentificationNumber" xlink:to="dei_EntityTaxIdentificationNumber_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_EntityTaxIdentificationNumber_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Entity Tax Identification Number</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_EntityTaxIdentificationNumber_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Entity Tax Identification Number</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressAddressLine1" xlink:type="locator" xlink:label="dei_EntityAddressAddressLine1" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_EntityAddressAddressLine1" xlink:to="dei_EntityAddressAddressLine1_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_EntityAddressAddressLine1_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Entity Address, Address Line One</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_EntityAddressAddressLine1_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Entity Address, Address Line One</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressCityOrTown" xlink:type="locator" xlink:label="dei_EntityAddressCityOrTown" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_EntityAddressCityOrTown" xlink:to="dei_EntityAddressCityOrTown_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_EntityAddressCityOrTown_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Entity Address, City or Town</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_EntityAddressCityOrTown_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Entity Address, City or Town</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressStateOrProvince" xlink:type="locator" xlink:label="dei_EntityAddressStateOrProvince" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_EntityAddressStateOrProvince" xlink:to="dei_EntityAddressStateOrProvince_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_EntityAddressStateOrProvince_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Entity Address, State or Province</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_EntityAddressStateOrProvince_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Entity Address, State or Province</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressPostalZipCode" xlink:type="locator" xlink:label="dei_EntityAddressPostalZipCode" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_EntityAddressPostalZipCode" xlink:to="dei_EntityAddressPostalZipCode_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_EntityAddressPostalZipCode_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Entity Address, Postal Zip Code</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_EntityAddressPostalZipCode_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Entity Address, Postal Zip Code</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_CityAreaCode" xlink:type="locator" xlink:label="dei_CityAreaCode" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_CityAreaCode" xlink:to="dei_CityAreaCode_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_CityAreaCode_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">City Area Code</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_CityAreaCode_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">City Area Code</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_LocalPhoneNumber" xlink:type="locator" xlink:label="dei_LocalPhoneNumber" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_LocalPhoneNumber" xlink:to="dei_LocalPhoneNumber_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_LocalPhoneNumber_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Local Phone Number</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_LocalPhoneNumber_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Local Phone Number</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_WrittenCommunications" xlink:type="locator" xlink:label="dei_WrittenCommunications" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_WrittenCommunications" xlink:to="dei_WrittenCommunications_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_WrittenCommunications_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Written Communications</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_WrittenCommunications_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Written Communications</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_SolicitingMaterial" xlink:type="locator" xlink:label="dei_SolicitingMaterial" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_SolicitingMaterial" xlink:to="dei_SolicitingMaterial_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_SolicitingMaterial_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Soliciting Material</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_SolicitingMaterial_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Soliciting Material</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_PreCommencementTenderOffer" xlink:type="locator" xlink:label="dei_PreCommencementTenderOffer" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_PreCommencementTenderOffer" xlink:to="dei_PreCommencementTenderOffer_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_PreCommencementTenderOffer_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Pre Commencement Tender Offer</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_PreCommencementTenderOffer_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Pre Commencement Tender Offer</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_PreCommencementIssuerTenderOffer" xlink:type="locator" xlink:label="dei_PreCommencementIssuerTenderOffer" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_PreCommencementIssuerTenderOffer" xlink:to="dei_PreCommencementIssuerTenderOffer_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_PreCommencementIssuerTenderOffer_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Pre Commencement Issuer Tender Offer</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_PreCommencementIssuerTenderOffer_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Pre Commencement Issuer Tender Offer</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_Security12bTitle" xlink:type="locator" xlink:label="dei_Security12bTitle" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_Security12bTitle" xlink:to="dei_Security12bTitle_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_Security12bTitle_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Security 12b Title</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_Security12bTitle_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Security 12b Title</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_TradingSymbol" xlink:type="locator" xlink:label="dei_TradingSymbol" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_TradingSymbol" xlink:to="dei_TradingSymbol_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_TradingSymbol_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Trading Symbol</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_TradingSymbol_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Trading Symbol</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_SecurityExchangeName" xlink:type="locator" xlink:label="dei_SecurityExchangeName" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_SecurityExchangeName" xlink:to="dei_SecurityExchangeName_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_SecurityExchangeName_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Security Exchange Name</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_SecurityExchangeName_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Security Exchange Name</link:label>
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityEmergingGrowthCompany" xlink:type="locator" xlink:label="dei_EntityEmergingGrowthCompany" />
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="dei_EntityEmergingGrowthCompany" xlink:to="dei_EntityEmergingGrowthCompany_lbl" />
    <link:label xml:lang="en-US" xlink:label="dei_EntityEmergingGrowthCompany_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/label">Entity Emerging Growth Company</link:label>
    <link:label xml:lang="en-US" xlink:label="dei_EntityEmergingGrowthCompany_lbl" xlink:type="resource" xlink:role="http://www.xbrl.org/2003/role/terseLabel">Entity Emerging Growth Company</link:label>
  </link:labelLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.PRE
<SEQUENCE>6
<FILENAME>ions-20230606_pre.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii" standalone="yes"?>
<!-- DFIN - https://www.dfinsolutions.com/ -->
<!-- CTU Version: Release master Build:20221108.6 -->
<!-- Creation date: 6/7/2023 12:06:51 AM Eastern Time -->
<!-- Copyright (c) 2023 Donnelley Financial Solutions, Inc. All Rights Reserved. -->
<link:linkbase
    xmlns:link="http://www.xbrl.org/2003/linkbase"
    xmlns:xlink="http://www.w3.org/1999/xlink"
    xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"
    xmlns:xbrldt="http://xbrl.org/2005/xbrldt"
    xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:roleRef roleURI="http://ionispharma.com//20230606/taxonomy/role/DocumentDocumentAndEntityInformation" xlink:href="ions-20230606.xsd#Role_DocumentDocumentAndEntityInformation" xlink:type="simple" />
  <link:presentationLink xlink:type="extended" xlink:role="http://ionispharma.com//20230606/taxonomy/role/DocumentDocumentAndEntityInformation">
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_CoverAbstract" xlink:type="locator" xlink:label="dei_CoverAbstract" />
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityRegistrantName" xlink:type="locator" xlink:label="dei_EntityRegistrantName" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="dei_CoverAbstract" xlink:to="dei_EntityRegistrantName" order="22.001" priority="2" use="optional" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_AmendmentFlag" xlink:type="locator" xlink:label="dei_AmendmentFlag" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="dei_CoverAbstract" xlink:to="dei_AmendmentFlag" order="23.001" priority="2" use="optional" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityCentralIndexKey" xlink:type="locator" xlink:label="dei_EntityCentralIndexKey" />
    <link:presentationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/parent-child" xlink:from="dei_CoverAbstract" xlink:to="dei_EntityCentralIndexKey" order="24.001" priority="2" use="optional" preferredLabel="http://www.xbrl.org/2003/role/terseLabel" />
    <link:loc xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentType" xlink:type="locator" xlink:label="dei_DocumentType" />
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<span style="display: none;">v3.23.1</span><table class="report" border="0" cellspacing="2" id="idm140150311550416">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Document and Entity Information<br></strong></div></th>
<th class="th"><div>Jun. 06, 2023</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_CoverAbstract', window );"><strong>Cover [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityRegistrantName', window );">Entity Registrant Name</a></td>
<td class="text">IONIS PHARMACEUTICALS INC<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_AmendmentFlag', window );">Amendment Flag</a></td>
<td class="text">false<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityCentralIndexKey', window );">Entity Central Index Key</a></td>
<td class="text">0000874015<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentType', window );">Document Type</a></td>
<td class="text">8-K<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentPeriodEndDate', window );">Document Period End Date</a></td>
<td class="text">Jun.  06,  2023<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityIncorporationStateCountryCode', window );">Entity Incorporation State Country Code</a></td>
<td class="text">DE<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityFileNumber', window );">Entity File Number</a></td>
<td class="text">000-19125<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityTaxIdentificationNumber', window );">Entity Tax Identification Number</a></td>
<td class="text">33-0336973<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressAddressLine1', window );">Entity Address, Address Line One</a></td>
<td class="text">2855 Gazelle Court<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressCityOrTown', window );">Entity Address, City or Town</a></td>
<td class="text">Carlsbad<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressStateOrProvince', window );">Entity Address, State or Province</a></td>
<td class="text">CA<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressPostalZipCode', window );">Entity Address, Postal Zip Code</a></td>
<td class="text">92010<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_CityAreaCode', window );">City Area Code</a></td>
<td class="text">(760)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_LocalPhoneNumber', window );">Local Phone Number</a></td>
<td class="text">931-9200<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_WrittenCommunications', window );">Written Communications</a></td>
<td class="text">false<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_SolicitingMaterial', window );">Soliciting Material</a></td>
<td class="text">false<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_PreCommencementTenderOffer', window );">Pre Commencement Tender Offer</a></td>
<td class="text">false<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_PreCommencementIssuerTenderOffer', window );">Pre Commencement Issuer Tender Offer</a></td>
<td class="text">false<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_Security12bTitle', window );">Security 12b Title</a></td>
<td class="text">Common Stock, $.001 Par Value<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_TradingSymbol', window );">Trading Symbol</a></td>
<td class="text">IONS<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_SecurityExchangeName', window );">Security Exchange Name</a></td>
<td class="text">NASDAQ<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityEmergingGrowthCompany', window );">Entity Emerging Growth Company</a></td>
<td class="text">false<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AmendmentFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the XBRL content amends previously-filed or accepted submission.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AmendmentFlag</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CityAreaCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Area code of city</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CityAreaCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CoverAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cover page.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CoverAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentPeriodEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For the EDGAR submission types of Form 8-K: the date of the report, the date of the earliest event reported; for the EDGAR submission types of Form N-1A: the filing date; for all other submission types: the end of the reporting or transition period.  The format of the date is YYYY-MM-DD.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentPeriodEndDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:dateItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentType">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The type of document being provided (such as 10-K, 10-Q, 485BPOS, etc). The document type is limited to the same value as the supporting SEC submission type, or the word 'Other'.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentType</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:submissionTypeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressAddressLine1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Address Line 1 such as Attn, Building Name, Street Name</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressAddressLine1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressCityOrTown">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the City or Town</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressCityOrTown</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressPostalZipCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Code for the postal or zip code</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressPostalZipCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressStateOrProvince">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the state or province.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressStateOrProvince</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:stateOrProvinceItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCentralIndexKey">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A unique 10-digit SEC-issued value to identify entities that have filed disclosures with the SEC. It is commonly abbreviated as CIK.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCentralIndexKey</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:centralIndexKeyItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityEmergingGrowthCompany">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate if registrant meets the emerging growth company criteria.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityEmergingGrowthCompany</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityFileNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Commission file number. The field allows up to 17 characters. The prefix may contain 1-3 digits, the sequence number may contain 1-8 digits, the optional suffix may contain 1-4 characters, and the fields are separated with a hyphen.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityFileNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:fileNumberItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityIncorporationStateCountryCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Two-character EDGAR code representing the state or country of incorporation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityIncorporationStateCountryCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarStateCountryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityRegistrantName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The exact name of the entity filing the report as specified in its charter, which is required by forms filed with the SEC.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityRegistrantName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityTaxIdentificationNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The Tax Identification Number (TIN), also known as an Employer Identification Number (EIN), is a unique 9-digit value assigned by the IRS.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityTaxIdentificationNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:employerIdItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_LocalPhoneNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Local phone number for entity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_LocalPhoneNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_PreCommencementIssuerTenderOffer">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 13e<br> -Subsection 4c<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_PreCommencementIssuerTenderOffer</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_PreCommencementTenderOffer">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 14d<br> -Subsection 2b<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_PreCommencementTenderOffer</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_Security12bTitle">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Title of a 12(b) registered security.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_Security12bTitle</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:securityTitleItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_SecurityExchangeName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the Exchange on which a security is registered.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection d1-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_SecurityExchangeName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarExchangeCodeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_SolicitingMaterial">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as soliciting material pursuant to Rule 14a-12 under the Exchange Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Section 14a<br> -Number 240<br> -Subsection 12<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_SolicitingMaterial</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_TradingSymbol">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Trading symbol of an instrument as listed on an exchange.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_TradingSymbol</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td>dei:tradingSymbolItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_WrittenCommunications">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as written communications pursuant to Rule 425 under the Securities Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Securities Act<br> -Number 230<br> -Section 425<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_WrittenCommunications</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
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<td>xbrli:booleanItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
