J.P. Morgan

Healthcare

Conference 2021

Brett P. Monia, Ph.D. Chief Executive Officer

January 12, 2021

Forward Looking Language Statement

This presentation includes forward-looking statements regarding our business, financial guidance and the therapeutic and commercial potential of SPINRAZA® (nusinersen), TEGSEDI® (inotersen), WAYLIVRA® (volanesorsen) and Ionis' technologies and products in development, including the business of Akcea Therapeutics, Inc., Ionis' wholly owned subsidiary. 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 related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. 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. 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, 2019 and our most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of this and other documents are available at www.ionispharma.com.

In this presentation, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries.

Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics® is a registered trademark of Akcea Therapeutics, Inc. TEGSEDI® is a trademark of Akcea Therapeutics, Inc. WAYLIVRA® is a registered trademark of Akcea Therapeutics, Inc. SPINRAZA® is a registered trademark of Biogen.

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2020: A New Beginning

New leadership, new vision

Enhanced business model to commercialize Ionis medicines

Advanced late- and mid-stage pipeline towards market

Expanded therapeutic scope through technology advancements

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2021: Positioned for Growth

Commercial

Pipeline

Technology

Expand wholly owned pipeline

Prepare markets for Ionis product launches

Advance and expand Phase 3 pipeline

Deliver multiple Phase 2 readouts

Expand aerosol-delivered clinical pipeline

Advance new LICA chemistry into development

Expand pipeline with novel genetically validated programs

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Ionis Pharmaceuticals Inc. published this content on 12 January 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 12 January 2021 20:45:01 UTC