<SEC-DOCUMENT>0001140361-26-015801.txt : 20260421
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<ACCEPTANCE-DATETIME>20260421070040
ACCESSION NUMBER:		0001140361-26-015801
CONFORMED SUBMISSION TYPE:	8-K
PUBLIC DOCUMENT COUNT:		13
CONFORMED PERIOD OF REPORT:	20260421
ITEM INFORMATION:		Regulation FD Disclosure
ITEM INFORMATION:		Other Events
ITEM INFORMATION:		Financial Statements and Exhibits
FILED AS OF DATE:		20260421
DATE AS OF CHANGE:		20260421

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			IONIS PHARMACEUTICALS INC
		CENTRAL INDEX KEY:			0000874015
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		ORGANIZATION NAME:           	03 Life Sciences
		EIN:				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:		26876704

	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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      <div style="text-align: center; font-family: 'Times New Roman'; font-size: 14pt; font-weight: bold;">UNITED STATES SECURITIES AND EXCHANGE COMMISSION</div>

      <div style="text-align: center; font-family: 'Times New Roman'; font-size: 12pt; font-weight: bold;">Washington, D.C.&#160; 20549</div>

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      <div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">CURRENT REPORT</div>

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      <div style="font-size: 10pt;">&#160;</div>

      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following
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              <div style="font-family: 'Times New Roman';">Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)</div>
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              <div style="font-family: 'Times New Roman';">Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))</div>
            </td>

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      <div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman';"> </span><span style="font-size: 10pt;"><br/>
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    <td style="width: auto; vertical-align: top; text-align: left; font-size: 10pt;">
              <div style="font-family: 'Times New Roman';">Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))</div>
            </td>

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      <div style="font-size: 10pt;">&#160;</div>

      <div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Securities registered pursuant to Section 12(b) of the Act:</div>

      <div style="font-size: 10pt;"><br/>
      </div>

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              <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman';">Title of each class</div>
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              <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman';">Trading symbol</div>
            </td>

    <td style="width: 2%; vertical-align: top; font-size: 10pt;"><br/>
            </td>

    <td style="width: 42.41%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); font-size: 10pt;">
              <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman';">Name of each exchange on which </div>
              <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman';">registered</div>
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    <td style="width: 2%; vertical-align: top; font-size: 10pt;">&#160;</td>

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              <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman';">&#8220;<ix:nonNumeric name="dei:TradingSymbol" id="Fact_5715c0b7926447679f9a7db1f2eb69de" contextRef="c20260421to20260421">IONS</ix:nonNumeric>&#8221;<br/>
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    <td style="width: 2%; vertical-align: top; font-size: 10pt;">&#160;</td>

    <td style="width: 42.41%; vertical-align: top; text-align: center;"><ix:nonNumeric name="dei:SecurityExchangeName" id="Fact_a19c607e4a2246289b72c1d6f680cedf" contextRef="c20260421to20260421" format="ixt-sec:exchnameen">The Nasdaq Stock Market, LLC</ix:nonNumeric><br/>
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      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (Section 230.405 of this chapter) or
        Rule 12b-2 of the Securities Exchange Act of 1934 (Section 240.12b-2 of this chapter).</div>

      <div style="text-align: center; text-indent: 288pt; font-family: 'Times New Roman'; font-size: 10pt;">&#160;&#160;Emerging growth company <ix:nonNumeric name="dei:EntityEmergingGrowthCompany" id="Fact_5b4e3aa341aa4ab78518bb5a7b242ad9" contextRef="c20260421to20260421" format="ixt-sec:boolballotbox">&#9744;</ix:nonNumeric>
        &#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160; &#160; <a id="z_Hlk11148519"></a></div>

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      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised
        financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. &#9744;</div>

      <div style="font-size: 10pt;">
<div>&#160;
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    <td style="width: 45pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Item 7.01</td>

    <td style="width: auto; vertical-align: top; text-align: justify; font-size: 10pt;">
              <div style="font-family: 'Times New Roman'; font-weight: bold;">Regulation FD Disclosure.</div>
            </td>

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      <div style="font-size: 10pt;">&#160;</div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">On April 21, 2026, Ionis Pharmaceuticals, Inc.&#160; (&#8220;<span style="font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Ionis</span>,&#8221; &#8220;<span style="font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">we</span>,&#8221; &#8220;<span style="font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">us</span>&#8221; or &#8220;<span style="font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">our company</span>&#8221;) issued a press release announcing additional positive results from the pivotal study of zilganersen in children and adults living with Alexander disease (&#8220;<span style="font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">AxD</span>&#8221;). A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.</div>

      <div style="font-size: 10pt;">&#160;</div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">The information in this Item 7.01 and the exhibit attached hereto shall not be deemed &#8220;filed&#8221; for purposes of Section 18 of the Securities Exchange Act of 1934, as
        amended (the &#8220;<span style="font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">Exchange Act</span>&#8221;), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under
        the Securities Act of 1933, as amended, or the Exchange Act, regardless of any general incorporation language in such filing.</div>

      <div style="font-size: 10pt;">&#160;</div>

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    <td style="width: 45pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Item 8.01</td>

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

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      <div style="font-size: 10pt;">&#160;</div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;"><a id="z_Hlk206488672"></a>On April 21, 2026, we announced additional positive results from the pivotal study of zilganersen in children and adults living with AxD,
        a rare, progressive and often fatal neurological condition with no approved disease-modifying treatments. These findings, which will be presented today at the 2026 American Academy of Neurology annual meeting, build on previously reported positive
        topline data and provide a more comprehensive view of treatment effect across multiple clinically meaningful domains.</div>

      <div style="font-size: 10pt;"><br/>
      </div>

      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">The study met its primary endpoint in individuals &#8805;5 years of age, with zilganersen 50 mg demonstrating statistically significant and clinically meaningful stabilization
        of gait speed as assessed by the 10-Meter Walk Test (10MWT), compared to control at Week 61. The 10MWT is a commonly used measure of gross motor function in neurologic disease. New data from the Gross Motor Function Measure-88 (GMFM-88), a
        well-established motor endpoint, supports the primary outcome of the study by demonstrating that treatment with zilganersen may improve gross motor function in younger children (2-4 years of age), compared to control. Key secondary endpoint results
        from patient/caregiver-and clinician-reported outcome assessments consistently favored zilganersen. Zilganersen demonstrated favorable safety and tolerability.</div>

      <div style="font-size: 10pt;"><br/>
      </div>

      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">AxD is a rare, genetic, progressive and often fatal neurological condition that is primarily associated with toxic over-production of glial fibrillary acidic protein (&#8220;<span style="font-family: 'Times New Roman'; font-weight: bold; font-style: italic;">GFAP</span>&#8221;). It is estimated to occur in approximately 1 per 1 to 3 million people worldwide. Although symptoms vary depending on age of onset, individuals may
        experience progressive motor and cognitive dysfunction, a loss of independence and the inability to control muscles for swallowing, airway protection and purposeful movements. Zilganersen is an investigational RNA-targeted medicine designed to
        reduce overproduction of GFAP, the underlying cause of AxD.</div>

      <div style="font-size: 10pt;"><br/>
      </div>

      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Zilganersen Pivotal Study Results</div>

      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">The pivotal Phase 1-3 study of zilganersen included 53 people with AxD aged 2 to 53 years. Results presented today are from the 60-week double-blind, randomized
        controlled treatment period of the ongoing trial.<span style="font-family: 'Times New Roman'; font-weight: bold;">&#160;</span>Zilganersen met the primary endpoint in patients &#8805;5 years, resulting in statistically significant and clinically meaningful
        stabilization of gait speed on the 10MWT at Week 61 compared to control (least square mean difference 33.3%, p=0.041). Additionally, results from the GMFM-88 in children 2-4 years of age support that zilganersen may improve gross motor function at
        Week 61 compared to control (least square mean difference 22.9 points, nominal<sup>1</sup> p=0.034).</div>

      <div style="font-size: 10pt;"><br/>
      </div>

      <div style="font-size: 10pt;">
        <hr style="height: 2px; width: 23%; color: #000000; background-color: #000000; text-align: left; border: none; margin-left: 0px; margin-right: auto;"/>
        <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;"><sup>1</sup> Nominal p-value; statistical analysis was not controlled for multiplicity</div>

        <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;"><br/>
        </div>

      </div>

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      </div>

      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Key secondary endpoints favored zilganersen over control:</div>

      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Key secondary endpoints evaluated the disease&#8217;s heterogeneous presentation through assessments focused on the individual&#8217;s most bothersome AxD symptom and their overall
        health. Across these measures, outcomes favored zilganersen-treated individuals, with more reporting improvement or no change and fewer reporting worsening compared to control.</div>

      <div style="font-size: 10pt;"><br/>
      </div>

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    <td style="width: 18pt; font-size: 10pt;"><br/>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt;">&#8226;</td>

    <td style="width: auto; vertical-align: top; text-align: left; font-size: 10pt;">
              <div style="font-family: 'Times New Roman'; font-weight: bold;">Most Bothersome Symptom:</div>
            </td>

  </tr>


</table>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; margin-left: 36pt;">In the zilganersen group, 32% of patients rated their most bothersome symptom as &#8220;much better&#8221; compared to 0% on control. Only 5% of patients receiving
        zilganersen rated their most bothersome symptom as &#8220;much worse&#8221; compared to 31% on control.</div>

      <div style="font-size: 10pt;"><br/>
      </div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt;">&#8226;</td>

    <td style="width: auto; vertical-align: top; text-align: left; font-size: 10pt;">
              <div style="font-family: 'Times New Roman'; font-weight: bold;">Patient Global Impression of Severity:</div>
            </td>

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</table>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; margin-left: 36pt;">In the zilganersen group, 83% of patients reported improvement or no change in overall disease severity compared to 76% on control. Only 17% of
        patients receiving zilganersen reported worsening compared to 24% on control.</div>

      <div style="font-size: 10pt;"><br/>
      </div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt;">&#8226;</td>

    <td style="width: auto; vertical-align: top; text-align: left; font-size: 10pt;">
              <div style="font-family: 'Times New Roman'; font-weight: bold;">Patient Global Impression of Change:</div>
            </td>

  </tr>


</table>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; margin-left: 36pt;">In the zilganersen group, 21% of patients reported feeling &#8220;much better&#8221; overall compared to 0% on control. Only 4% of patients receiving zilganersen
        reported feeling &#8220;much worse&#8221; compared to 18% on control.</div>

      <div style="font-size: 10pt;"><br/>
      </div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt;">&#8226;</td>

    <td style="width: auto; vertical-align: top; text-align: left; font-size: 10pt;">
              <div style="font-family: 'Times New Roman'; font-weight: bold;">Clinical Global Impression of Change:</div>
            </td>

  </tr>


</table>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; margin-left: 36pt;">Clinicians rated 75% of patients receiving zilganersen as improved (&#8220;a little better&#8221;) or &#8220;no change&#8221; compared to 47% on control.<span style="font-family: 'Times New Roman'; font-weight: bold;">&#160;</span>Clinicians rated 25% of patients receiving zilganersen as &#8220;a little worse&#8221; and 0% as &#8220;much worse&#8221; compared to 41% as &#8220;a little worse&#8221; and 12% as &#8220;much worse&#8221; on control.</div>

      <div style="font-size: 10pt;"><br/>
      </div>

      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Results from additional secondary and exploratory endpoints assessing communication, swallowing, gastrointestinal and autonomic symptoms, support that zilganersen may
        have a positive impact across AxD symptoms.</div>

      <div style="font-size: 10pt;">&#160;</div>

      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">In an exploratory analysis, zilganersen reduced plasma GFAP levels by 33.6% at Week 61 compared to control (nominal<sup>1</sup> p=0.003)<sup>2</sup>, consistent with its
        mechanism of targeting <span style="font-family: 'Times New Roman'; font-style: italic;">GFAP</span> RNA in the central nervous system.</div>

      <div style="font-size: 10pt;">&#160;</div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">Zilganersen demonstrated a favorable safety and tolerability profile, with most adverse events mild or moderate in severity. Serious treatment-emergent adverse events
        occurred less frequently in the zilganersen group compared to control (37.5% zilganersen 25 mg or 50 mg; 47.1% pooled control).</div>

      <div style="font-size: 10pt;"><br/>
      </div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">Zilganersen is currently under Priority Review by the U.S. Food and Drug Administration with a Prescription Drug User Fee Act action date of September 22, 2026.</div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;"> <br/>
      </div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">
        <hr style="height: 2px; width: 23%; color: #000000; background-color: #000000; text-align: left; border: none; margin-left: 0px; margin-right: auto;"/></div>

      <div style="font-size: 10pt;"><sup>2</sup> Ratio (zilganersen vs. pooled control) of least-squares geometric mean ratio to baseline 0.664</div>

      <div style="font-size: 10pt;"> <br/>
      </div>

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      </div>

      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Forward-Looking Statements</div>

      <div style="font-size: 10pt;">&#160;</div>

      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">This report includes forward-looking statements regarding Ionis&#8217; business and the therapeutic and commercial potential of zilganersen, our commercial medicines,
        additional medicines in development and technologies and our expectations regarding development and regulatory milestones. Any statement describing Ionis&#8217; goals, expectations, financial or other projections, intentions or beliefs is a
        forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including 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. Ionis&#8217; 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&#8217; forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known
        by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis&#8217;
        programs are described in additional detail in Ionis&#8217; annual report on Form 10-K for the year ended December 31, 2025, which is on file with the Securities and Exchange Commission. Copies of these and other documents are available from Ionis.</div>

      <div style="font-size: 10pt;">&#160;</div>

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    <td style="width: 45pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Item 9.01</td>

    <td style="width: auto; vertical-align: top; text-align: left; font-size: 10pt;">
              <div style="font-family: 'Times New Roman'; font-weight: bold;">Financial Statements and Exhibits.</div>
            </td>

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      <div style="font-size: 10pt;">&#160;</div>

      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">(d) Exhibits.</div>

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              <div style="text-align: center; font-family: 'Times New Roman'; font-weight: bold;"><span style="text-decoration: underline;">Exhibit No.</span></div>
            </td>

    <td style="width: 88%; vertical-align: bottom; font-size: 10pt;">
              <div style="text-align: left; font-family: 'Times New Roman'; font-weight: bold;"><span style="text-decoration: underline;">Description</span></div>
            </td>

  </tr>

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    <td style="width: 12%; vertical-align: top;">
              <div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt;"><a href="ef20071051_ex99-1.htm">99.1</a></div>
            </td>

    <td style="width: 88%; vertical-align: top;">
              <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Press Release dated April 21, 2026.</div>
            </td>

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    <td rowspan="1" style="width: 88%; vertical-align: top;">&#160;</td>

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    <td rowspan="1" style="width: 12%; vertical-align: top; text-align: center;">104</td>

    <td rowspan="1" style="width: 88%; vertical-align: top;">
              <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Cover Page Interactive Data File (embedded within the Inline XBRL document).</div>
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      <div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt; font-variant: small-caps; font-weight: bold;">SIGNATURE</div>

      <div style="font-size: 10pt;">&#160;</div>

      <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman'; font-size: 10pt;">Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its
        behalf by the undersigned, thereunto duly authorized.</div>

      <div style="font-size: 10pt;">
<div>&#160;
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                <div>&#160;</div>
              </td>

    <td colspan="2" rowspan="1">
                <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
              </td>

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    <td style="width: 50%;">
                <div>&#160;</div>
              </td>

    <td style="width: 3%;">
                <div>&#160;</div>
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              </td>

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    <td style="width: 50%; padding-bottom: 2px;">
                <div><span style="font-size: 10pt; font-family: 'Times New Roman';">Dated:&#160; April 21, 2026</span></div>
              </td>

    <td style="width: 3%; padding-bottom: 2px;"><span style="font-size: 10pt;"><span style="font-family: 'Times New Roman';"><span style="font-family: 'Times New Roman';">By:</span></span></span></td>

    <td style="width: 47%; border-bottom: 2px solid rgb(0, 0, 0);"><span style="font-size: 10pt;"><span style="font-family: 'Times New Roman';"><span style="font-family: 'Times New Roman';">/s/ Patrick R. O&#8217;Neil</span></span></span></td>

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    <td style="width: 47%;">
                <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt; font-variant: small-caps; font-weight: bold;">Patrick R. O&#8217;Neil</div>
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    <td style="width: 3%;"><br/>
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    <td style="width: 47%;">
                <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">Executive Vice President, Chief Legal Officer and General Counsel</div>
              </td>

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<DOCUMENT>
<TYPE>EX-99.1
<SEQUENCE>2
<FILENAME>ef20071051_ex99-1.htm
<DESCRIPTION>EXHIBIT 99.1
<TEXT>
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    <div style="text-align: right;"> <font style="font-size: 10pt; font-weight: bold;">Exhibit 99.1<br>
      </font></div>
    <font style="font-size: 10pt;"><br>
    </font>
    <table cellspacing="0" cellpadding="0" border="0" id="z1479f2870d07412c8f20cbe0363319e7" style="font-family: 'Times New Roman'; font-size: 10pt; color: #000000; width: 100%;">

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          <td style="width: 50%; text-align: right; vertical-align: middle; font-size: 10pt;">
            <div style="font-family: 'Times New Roman'; font-style: italic;">FINAL: April 20, 2026</div>
          </td>
        </tr>

    </table>
    <div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Ionis presents new data from pivotal study of zilganersen in Alexander disease (AxD) at AAN 2026 Annual Meeting</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div>
        <div style="font-family: 'Times New Roman'; font-weight: bold; text-align: center; font-size: 10pt;">&#8211; New data highlight potential treatment benefit across multiple AxD symptom domains, </div>
        <div style="font-family: 'Times New Roman'; font-weight: bold; text-align: center; font-size: 10pt;">reinforcing zilganersen&#8217;s positive impact on people living with this rare, often fatal </div>
        <div style="font-family: 'Times New Roman'; font-weight: bold; text-align: center; font-size: 10pt;">neurological disease &#8211;</div>
      </div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">&#8211; PDUFA date set for September 22, 2026 &#8211;</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman'; font-weight: bold;">CARLSBAD, Calif., April 21, 2026 </font><font style="font-size: 10pt;">-- <u><font style="font-family: 'Times New Roman';">Ionis Pharmaceuticals, Inc.</font></u> (Nasdaq: IONS) today announced additional positive results from the pivotal study of zilganersen in children and adults living with
          Alexander disease (AxD), a rare, progressive and often fatal neurological condition with no approved disease-modifying treatments. These findings, which will be presented today at the 2026 American Academy of Neurology (AAN) annual meeting, build
          on <u><font style="font-family: 'Times New Roman';">previously reported positive topline data</font></u> and provide a more comprehensive view of treatment effect across multiple clinically meaningful domains.</font></div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">The study met its primary endpoint in individuals &#8805;5 years of age, with zilganersen 50 mg demonstrating statistically significant and clinically meaningful
        stabilization of gait speed as assessed by the 10-Meter Walk Test (10MWT), compared to control at Week 61. The 10MWT is a commonly used measure of gross motor function in neurologic disease. New data from the Gross Motor Function Measure-88
        (GMFM-88), a well-established motor endpoint, supports the primary outcome of the study by demonstrating that treatment with zilganersen may improve gross motor function in younger children (2-4 years of age), compared to control. Key secondary
        endpoint results from patient/caregiver-and clinician-reported outcome assessments consistently favored zilganersen. Zilganersen demonstrated favorable safety and tolerability.</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">&#8220;As a clinician who cares for people living with Alexander disease, I see firsthand the profound and progressive impact this disease has on individuals and
        their families, particularly given the lack of disease modifying treatment options available today,&#8221; said Amy Waldman, M.D., pediatric neurologist and lead investigator for the zilganersen study at Children&#8217;s Hospital of Philadelphia. &#8220;These
        results mark a meaningful step forward for families who have waited so long for innovation in Alexander disease. Taken together, the consistent pattern across multiple clinically meaningful measures demonstrates that zilganersen has the potential
        to change the trajectory of this devastating disease.&#8221;</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">AxD is a rare, genetic, progressive and often fatal neurological condition that is primarily associated with toxic over-production of glial fibrillary acidic
        protein (GFAP). It is estimated to occur in approximately 1 per 1 to 3 million people worldwide. Although symptoms vary depending on age of onset, individuals may experience progressive motor and cognitive dysfunction, a loss of independence and
        the inability to control muscles for swallowing, airway protection and purposeful movements. Zilganersen is an investigational RNA-targeted medicine designed to reduce overproduction of GFAP, the underlying cause of AxD.</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Zilganersen Pivotal Study Results</div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">The pivotal Phase 1-3 study of zilganersen included 53 people with AxD aged 2 to 53 years. Results presented today are from the 60-week double-blind,
        randomized controlled treatment period of the ongoing trial.<font style="font-family: 'Times New Roman'; font-weight: bold;">&#160;</font>Zilganersen met the primary endpoint in patients &#8805;5 years, resulting in statistically significant and
        clinically meaningful stabilization of gait speed on the 10MWT at Week 61 compared to control (least square mean difference 33.3%, p=0.041). Additionally, results from the GMFM-88 in children 2-4 years of age support that zilganersen may improve
        gross motor function at Week 61 compared to control (least square mean difference 22.9 points, nominal<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup> p=0.034).</div>
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                    <div style="font-family: 'Times New Roman'; font-style: italic;">FINAL: April 20, 2026</div>
                  </td>
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          </div>
        </div>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Key secondary endpoints favored zilganersen over control:</div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">Key secondary endpoints evaluated the disease&#8217;s heterogeneous presentation through assessments focused on the individual&#8217;s most bothersome AxD symptom and
        their overall health. Across these measures, outcomes favored zilganersen-treated individuals, with more reporting improvement or no change and fewer reporting worsening compared to control.</div>
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          <tr>
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              <div style="font-family: 'Times New Roman'; font-weight: bold;">Most Bothersome Symptom (MBS):</div>
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      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt; margin-left: 36pt;">In the zilganersen group, 32% of patients rated their most bothersome symptom as &#8220;much better&#8221; compared to 0% on control. Only 5% of
        patients receiving zilganersen rated their most bothersome symptom as &#8220;much worse&#8221; compared to 31% on control.</div>
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            <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt;">&#8226;</td>
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              <div style="font-family: 'Times New Roman'; font-weight: bold;">Patient Global Impression of Severity (PGIS):</div>
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      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt; margin-left: 36pt;">In the zilganersen group, 83% of patients reported improvement or no change in overall disease severity compared to 76% on control. Only
        17% of patients receiving zilganersen reported worsening compared to 24% on control.</div>
      <div style="font-size: 10pt;"><br>
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            <td style="width: 18pt; font-size: 10pt;"><br>
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            <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: left; font-size: 10pt;">
              <div style="font-family: 'Times New Roman'; font-weight: bold;">Patient Global Impression of Change (PGIC):</div>
            </td>
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      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt; margin-left: 36pt;">In the zilganersen group, 21% of patients reported feeling &#8220;much better&#8221; overall compared to 0% on control. Only 4% of patients receiving
        zilganersen reported feeling &#8220;much worse&#8221; compared to 18% on control.</div>
      <div style="font-size: 10pt;"><br>
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            <td style="width: 18pt; font-size: 10pt;"><br>
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            <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt;">&#8226;</td>
            <td style="width: auto; vertical-align: top; text-align: left; font-size: 10pt;">
              <div style="font-family: 'Times New Roman'; font-weight: bold;">Clinical Global Impression of Change (CGIC):</div>
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      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt; margin-left: 36pt;">Clinicians rated 75% of patients receiving zilganersen as improved (&#8220;a little better&#8221;) or &#8220;no change&#8221; compared to 47% on control.<font style="font-family: 'Times New Roman'; font-weight: bold;">&#160;</font>Clinicians rated 25% of patients receiving zilganersen as &#8220;a little worse&#8221; and 0% as &#8220;much worse&#8221; compared to 41% as &#8220;a little worse&#8221; and 12% as &#8220;much worse&#8221; on control.</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">Results from additional secondary and exploratory endpoints assessing communication, swallowing, gastrointestinal and autonomic symptoms, consistently
        support that zilganersen may have a positive impact across AxD symptoms.</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">In an exploratory analysis, zilganersen reduced plasma GFAP levels by 33.6% at Week 61 compared to control (nominal<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup> p=0.003)<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">2</sup>,
        consistent with its mechanism of targeting <font style="font-family: 'Times New Roman'; font-style: italic;">GFAP</font> RNA in the central nervous system.</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">&#8220;These data further build on the promise of zilganersen and reinforce its potential to help transform the treatment landscape for people living with
        Alexander disease,&#8221; said Holly Kordasiewicz, Ph.D., executive vice president, chief development officer, Ionis. &#8220;The zilganersen results underscore the strength of our technology in targeting the underlying cause of disease, even in complex and
        heterogenous neurological conditions such as Alexander disease. We are deeply grateful to the patients, families, investigators and broader community who made this research possible. As we look ahead to the FDA action date in September, we remain
        focused on bringing this potential new treatment to a community that has long been underserved.&#8221;</div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"> <br>
      </div>
      <div style="font-size: 10pt;">
        <hr noshade="noshade" align="left" style="height: 2px; width: 23%; color: #000000; background-color: #000000; text-align: left; margin-left: 0px; margin-right: auto; border: none;"></div>
      <div style="font-size: 10pt;">
        <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup> Nominal p-value; statistical analysis was not controlled for multiplicity</div>
        <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">2</sup> Ratio (zilganersen vs. pooled control) of least-squares geometric mean ratio to baseline 0.664</div>
        <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;"> <br>
        </div>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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        <div class="BRPFPageHeader" style="width: 100%;">
          <div>
            <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; color: #000000; width: 100%;">

                <tr>
                  <td style="width: 50%; font-size: 10pt;"><img src="image00001.jpg"></td>
                  <td style="width: 50%; text-align: right; vertical-align: middle; font-size: 10pt;">
                    <div style="font-family: 'Times New Roman'; font-style: italic;">FINAL: April 20, 2026</div>
                  </td>
                </tr>

            </table>
          </div>
        </div>
      </div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">Zilganersen demonstrated a favorable safety and tolerability profile, with most adverse events (AE) mild or moderate in severity. Serious treatment-emergent
        adverse events (TEAEs) occurred less frequently in the zilganersen group compared to control (37.5% zilganersen 25 mg or 50 mg; 47.1% pooled control).</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">Zilganersen is currently under Priority Review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) action date of
        September 22, 2026.</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">About the Zilganersen Study</div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;"><font style="font-size: 10pt; font-family: 'Times New Roman';">The global, multicenter, randomized, double-blind, controlled, multiple-ascending
          dose (MAD) Phase 1-3 study (</font><u><font style="font-size: 10pt; font-family: 'Times New Roman';">NCT04849741</font></u><font style="font-size: 10pt; font-family: 'Times New Roman';">) enrolled 54 participants with
          Alexander disease (AxD) between the ages of 1.5 and 53 years across 13 sites in eight countries. Most participants in the study were children, reflecting the early onset and severe progression of AxD in pediatric populations. Participants were
          randomized in a 2:1 ratio to receive zilganersen or control for a 60-week double-blind treatment period. The study included two dose cohorts, 25 mg and 50 mg, with the 50 mg dose cohort analyzed as the pivotal dose cohort, with dosing every 12
          weeks. At 60 weeks, all eligible participants transitioned into an open-label treatment period, followed by a 120-week open-label, long-term extension treatment period, during which participants in the 25 mg dose cohort moved to the 50 mg dose
          cohort, and finally a 28-week post-treatment follow-up period. The primary endpoint is percent change from baseline in gait speed as assessed by the 10-Meter Walk Test (10MWT), an assessment of functional mobility, at the end of the double-blind
          treatment period. Key secondary endpoints include patients' self-identified Most Bothersome Symptom (MBS) Score, change from baseline in Patient Global Impression of Severity (PGIS) Score and Patient Global Impression of Change (PGIC) Score and
          Clinician Global Impression of Change (CGIC) Score at the end of the double-blind treatment period.</font></div>
      <div style="font-size: 10pt;"><br>
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      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">About Zilganersen</div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">Zilganersen is an investigational RNA-targeted medicine being evaluated as a treatment for people with Alexander disease (AxD). Zilganersen is designed to
        inhibit production of excess glial fibrillary acidic protein (GFAP) that accumulates because of disease-causing variants in the <font style="font-family: 'Times New Roman'; font-style: italic;">GFAP</font> gene. The U.S. Food and Drug
        Administration (FDA) granted zilganersen <u><font style="font-family: 'Times New Roman';">Breakthrough Therapy</font></u>, <u><font style="font-family: 'Times New Roman';">Orphan Drug</font></u> and Rare Pediatric Disease
        designations. In addition, the European Medicines Agency (EMA) granted zilganersen <u><font style="font-family: 'Times New Roman';">Orphan Drug designation</font></u>.</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">About Alexander Disease (AxD)</div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">AxD is a rare, progressive and often fatal neurological disease that occurs in approximately 1 per 1 to 3 million people worldwide and affects a type of cell
        in the brain called astrocytes. Astrocytes have multiple roles in the brain to support neurons and oligodendrocytes, including maintenance of the myelin sheath that protects nerve fibers. AxD is caused by disease-causing variants in the glial
        fibrillary acidic protein (<font style="font-family: 'Times New Roman'; font-style: italic;">GFAP</font>) gene and is generally characterized by progressive neurological deterioration resulting in loss of functional mobility, loss of
        independence and the inability to control muscles for large movements, swallowing and airway protection, though symptoms can vary depending on age of onset. AxD usually leads to death within 14-25 years after symptom onset. There are no approved
        disease-modifying medicines.</div>
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      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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          <div>
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                <tr>
                  <td style="width: 50%; font-size: 10pt;"><img src="image00001.jpg"></td>
                  <td style="width: 50%; text-align: right; vertical-align: middle; font-size: 10pt;">
                    <div style="font-family: 'Times New Roman'; font-style: italic;">FINAL: April 20, 2026</div>
                  </td>
                </tr>

            </table>
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      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">About Ionis Neurology</div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">Ionis has been at the forefront of discovering and developing leading neurological disease medicines, including SPINRAZA<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#174;</sup> (nusinersen), the first
        approved treatment for spinal muscular atrophy, WAINUA<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#174;</sup> (eplontersen), a medicine to treat hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN), and QALSODY<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#174;</sup> (tofersen) for SOD1-ALS. The clinical-stage portfolio
        includes 12 investigational medicines, of which six are wholly owned by Ionis. Ionis' investigational portfolio includes medicines for which there are few or no disease modifying treatments, such as rare diseases including Angelman syndrome, prion
        disease, multiple system atrophy, Huntington&#8217;s disease and Alexander disease, as well as more common conditions such as Alzheimer's disease.</div>
      <div style="font-size: 10pt;"><br>
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      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">About Ionis Pharmaceuticals, Inc.</div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has marketed medicines and a
        leading pipeline in neurology, cardiometabolic disease and select areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A
        deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit <u><font style="font-family: 'Times New Roman';">Ionis.com</font> </u>and follow us on <u><font style="font-family: 'Times New Roman';">X (Twitter)</font></u>, <u><font style="font-family: 'Times New Roman';">LinkedIn</font></u> and <u><font style="font-family: 'Times New Roman';">Instagram</font></u>.</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Ionis Forward-looking Statements</div>
      <div style="text-align: justify; font-family: 'Times New Roman'; font-size: 10pt;">This press release includes forward-looking statements regarding Ionis' business and the therapeutic and commercial potential of zilganersen, our commercial
        medicines, additional medicines in development and technologies and our expectations regarding development and regulatory milestones. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a
        forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including 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. Ionis' 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' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known
        by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis'
        programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2025, which is on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company.</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its subsidiaries.</div>
      <div style="font-size: 10pt;"><br>
      </div>
      <div style="text-align: justify;">Ionis Pharmaceuticals<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#174;</sup> is a trademark of Ionis Pharmaceuticals, Inc. SPINRAZA<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#174;</sup> and QALSODY<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#174; </sup>are registered trademarks of Biogen. WAINUA&#8482;<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#160;</sup>is a registered trademark of the
        AstraZeneca group of companies.</div>
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  <link:roleRef roleURI="http://www.xbrl.org/2009/role/negatedLabel" xlink:type="simple" xlink:href="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd#negatedLabel" />
  <link:labelLink xlink:type="extended" xlink:role="http://www.xbrl.org/2003/role/link">
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    <link:label xlink:type="resource" xlink:label="dei_CoverAbstract" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CoverAbstract" xml:lang="en-US" id="dei_CoverAbstract">Cover [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="dei_DocumentType" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentType" xml:lang="en-US" id="dei_DocumentType">Document Type</link:label>
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    <link:label xlink:type="resource" xlink:label="dei_WrittenCommunications" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_WrittenCommunications" xml:lang="en-US" id="dei_WrittenCommunications">Written Communications</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WrittenCommunications" xlink:to="dei_WrittenCommunications" xlink:title="label: WrittenCommunications to dei_WrittenCommunications" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_SolicitingMaterial" xlink:label="SolicitingMaterial" xlink:title="SolicitingMaterial" />
    <link:label xlink:type="resource" xlink:label="dei_SolicitingMaterial" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_SolicitingMaterial" xml:lang="en-US" id="dei_SolicitingMaterial">Soliciting Material</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SolicitingMaterial" xlink:to="dei_SolicitingMaterial" xlink:title="label: SolicitingMaterial to dei_SolicitingMaterial" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_PreCommencementTenderOffer" xlink:label="PreCommencementTenderOffer" xlink:title="PreCommencementTenderOffer" />
    <link:label xlink:type="resource" xlink:label="dei_PreCommencementTenderOffer" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_PreCommencementTenderOffer" xml:lang="en-US" id="dei_PreCommencementTenderOffer">Pre-commencement Tender Offer</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PreCommencementTenderOffer" xlink:to="dei_PreCommencementTenderOffer" xlink:title="label: PreCommencementTenderOffer to dei_PreCommencementTenderOffer" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_PreCommencementIssuerTenderOffer" xlink:label="PreCommencementIssuerTenderOffer" xlink:title="PreCommencementIssuerTenderOffer" />
    <link:label xlink:type="resource" xlink:label="dei_PreCommencementIssuerTenderOffer" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_PreCommencementIssuerTenderOffer" xml:lang="en-US" id="dei_PreCommencementIssuerTenderOffer">Pre-commencement Issuer Tender Offer</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PreCommencementIssuerTenderOffer" xlink:to="dei_PreCommencementIssuerTenderOffer" xlink:title="label: PreCommencementIssuerTenderOffer to dei_PreCommencementIssuerTenderOffer" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_AmendmentFlag" xlink:label="AmendmentFlag" xlink:title="AmendmentFlag" />
    <link:label xlink:type="resource" xlink:label="dei_AmendmentFlag" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AmendmentFlag" xml:lang="en-US" id="dei_AmendmentFlag">Amendment Flag</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AmendmentFlag" xlink:to="dei_AmendmentFlag" xlink:title="label: AmendmentFlag to dei_AmendmentFlag" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentFiscalYearFocus" xlink:label="DocumentFiscalYearFocus" xlink:title="DocumentFiscalYearFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalYearFocus" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalYearFocus" xml:lang="en-US" id="dei_DocumentFiscalYearFocus">Document Fiscal Year Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalYearFocus" xlink:to="dei_DocumentFiscalYearFocus" xlink:title="label: DocumentFiscalYearFocus to dei_DocumentFiscalYearFocus" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentFiscalPeriodFocus" xlink:label="DocumentFiscalPeriodFocus" xlink:title="DocumentFiscalPeriodFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalPeriodFocus" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalPeriodFocus" xml:lang="en-US" id="dei_DocumentFiscalPeriodFocus">Document Fiscal Period Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalPeriodFocus" xlink:to="dei_DocumentFiscalPeriodFocus" xlink:title="label: DocumentFiscalPeriodFocus to dei_DocumentFiscalPeriodFocus" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_DocumentPeriodEndDate" xlink:label="DocumentPeriodEndDate" xlink:title="DocumentPeriodEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentPeriodEndDate" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentPeriodEndDate" xml:lang="en-US" id="dei_DocumentPeriodEndDate">Document Period End Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentPeriodEndDate" xlink:to="dei_DocumentPeriodEndDate" xlink:title="label: DocumentPeriodEndDate to dei_DocumentPeriodEndDate" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityRegistrantName" xlink:label="EntityRegistrantName" xlink:title="EntityRegistrantName" />
    <link:label xlink:type="resource" xlink:label="dei_EntityRegistrantName" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityRegistrantName" xml:lang="en-US" id="dei_EntityRegistrantName">Entity Registrant Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityRegistrantName" xlink:to="dei_EntityRegistrantName" xlink:title="label: EntityRegistrantName to dei_EntityRegistrantName" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityCentralIndexKey" xlink:label="EntityCentralIndexKey" xlink:title="EntityCentralIndexKey" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCentralIndexKey" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCentralIndexKey" xml:lang="en-US" id="dei_EntityCentralIndexKey">Entity Central Index Key</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCentralIndexKey" xlink:to="dei_EntityCentralIndexKey" xlink:title="label: EntityCentralIndexKey to dei_EntityCentralIndexKey" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityFileNumber" xlink:label="EntityFileNumber" xlink:title="EntityFileNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFileNumber" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFileNumber" xml:lang="en-US" id="dei_EntityFileNumber">Entity File Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityFileNumber" xlink:to="dei_EntityFileNumber" xlink:title="label: EntityFileNumber to dei_EntityFileNumber" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityTaxIdentificationNumber" xlink:label="EntityTaxIdentificationNumber" xlink:title="EntityTaxIdentificationNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityTaxIdentificationNumber" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityTaxIdentificationNumber" xml:lang="en-US" id="dei_EntityTaxIdentificationNumber">Entity Tax Identification Number</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityIncorporationStateCountryCode" xlink:label="EntityIncorporationStateCountryCode" xlink:title="EntityIncorporationStateCountryCode" />
    <link:label xlink:type="resource" xlink:label="dei_EntityIncorporationStateCountryCode" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityIncorporationStateCountryCode" xml:lang="en-US" id="dei_EntityIncorporationStateCountryCode">Entity Incorporation, State or Country Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityIncorporationStateCountryCode" xlink:to="dei_EntityIncorporationStateCountryCode" xlink:title="label: EntityIncorporationStateCountryCode to dei_EntityIncorporationStateCountryCode" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityEmergingGrowthCompany" xlink:label="EntityEmergingGrowthCompany" xlink:title="EntityEmergingGrowthCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityEmergingGrowthCompany" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityEmergingGrowthCompany" xml:lang="en-US" id="dei_EntityEmergingGrowthCompany">Entity Emerging Growth Company</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressAddressLine1" xlink:label="EntityAddressAddressLine1" xlink:title="EntityAddressAddressLine1" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressAddressLine1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressAddressLine1" xml:lang="en-US" id="dei_EntityAddressAddressLine1">Entity Address, Address Line One</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressAddressLine2" xlink:label="EntityAddressAddressLine2" xlink:title="EntityAddressAddressLine2" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressAddressLine2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressAddressLine2" xml:lang="en-US" id="dei_EntityAddressAddressLine2">Entity Address, Address Line Two</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_EntityAddressPostalZipCode" xlink:label="EntityAddressPostalZipCode" xlink:title="EntityAddressPostalZipCode" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_CityAreaCode" xlink:label="CityAreaCode" xlink:title="CityAreaCode" />
    <link:label xlink:type="resource" xlink:label="dei_CityAreaCode" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CityAreaCode" xml:lang="en-US" id="dei_CityAreaCode">City Area Code</link:label>
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    <link:label xlink:type="resource" xlink:label="dei_LocalPhoneNumber" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_LocalPhoneNumber" xml:lang="en-US" id="dei_LocalPhoneNumber">Local Phone Number</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_TradingSymbol" xlink:label="TradingSymbol" xlink:title="TradingSymbol" />
    <link:label xlink:type="resource" xlink:label="dei_TradingSymbol" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_TradingSymbol" xml:lang="en-US" id="dei_TradingSymbol">Trading Symbol</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2025/dei-2025.xsd#dei_SecurityExchangeName" xlink:label="SecurityExchangeName" xlink:title="SecurityExchangeName" />
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  </link:labelLink>
</link:linkbase>
</XBRL>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>EX-101.PRE
<SEQUENCE>5
<FILENAME>ions-20260421_pre.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION PRESENTATION LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.26.1</span><table class="report" border="0" cellspacing="2" id="id2">
<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>Apr. 21, 2026</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_DocumentType', window );">Document Type</a></td>
<td class="text">8-K<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_DocumentPeriodEndDate', window );">Document Period End Date</a></td>
<td class="text">Apr. 21,  2026<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_EntityFileNumber', window );">Entity File Number</a></td>
<td class="text">000-19125<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_EntityCentralIndexKey', window );">Entity Central Index Key</a></td>
<td class="text">0000874015<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_EntityIncorporationStateCountryCode', window );">Entity Incorporation, State or Country Code</a></td>
<td class="text">DE<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_Security12bTitle', window );">Title of 12(b) Security</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>
<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>
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<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>
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<div style="display: none;">
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<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><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_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>
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<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:normalizedStringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td>duration</td>
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<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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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<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>
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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:dateItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<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>
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<td>dei_</td>
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<td><strong> Data Type:</strong></td>
<td>dei:submissionTypeItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<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_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>
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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:normalizedStringItemType</td>
</tr>
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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>
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<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>
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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>xbrli:normalizedStringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<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_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>
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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:normalizedStringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<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>
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<td>dei:centralIndexKeyItemType</td>
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<td><strong> Period Type:</strong></td>
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<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>
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<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">
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<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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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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>
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<td>xbrli:normalizedStringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<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>
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<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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<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>
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<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>
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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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<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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>dei:securityTitleItemType</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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<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>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></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>
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<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> -Number 240<br> -Section 14a<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>
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<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>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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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>
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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>
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      id="Fact_f879425189c14148aed336cbc89441aa">2026-04-21</dei:DocumentPeriodEndDate>
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      id="Fact_968994bb07f742fb9a623b688bbfe012">IONIS PHARMACEUTICALS, INC.</dei:EntityRegistrantName>
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