Ionis Pharmaceuticals : 1Q23 Earnings Slides

Q1:23 Financial Results and

Business Update

May 3, 2023

Nasdaq: IONS

Every Moment Matters...

in the Discovery, Development & Delivery of Life Transforming Genetic Medicines

On Today's Earnings Call

Brett Monia, Ph.D.	Richard Geary, Ph.D.
Executive Vice President, Development
Chief Executive Officer

Eric Swayze, Ph.D.	Eugene Schneider, M.D.
Executive Vice President, Research	Executive Vice President,
	Chief Clinical Development Officer

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Beth Hougen

Chief Financial Officer

Onaiza Cadoret

Executive Vice President,

Chief Global Product Strategy and

Operations Officer

Forward-Looking Statements

This presentation includes forward-looking statements regarding our business, financial guidance and the therapeutic and commercial potential of QALSODYTM (tofersen), SPINRAZA® (nusinersen), TEGSEDI® (inotersen), WAYLIVRA® (volanesorsen), eplontersen, olezarsen, donidalorsen, ION363, pelacarsen, bepirovirsen, Ionis' technologies, and Ionis' other products in development. 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 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, 2022, which is 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 registered 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. QALSODYTM is a trademark of Biogen. SPINRAZA® is a registered trademark of Biogen.

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Introduction

Brett Monia, Ph.D.

Chief Executive Officer

Every Moment Matters...

in the Discovery, Development & Delivery of Life Transforming Genetic Medicines

2023 Off to Strong Start with Several Important Achievements1

Late-Stage Pipeline

Commercial Readiness

Financial Foundation

• QALSODY: approved by FDA for SOD1-ALS treatment
• Eplontersen: December 2023 PDUFA date; positive Ph3 data reported; on track for oUS submissions
• Olezarsen: Ph3 FCS data planned for H2:23
• Donidalorsen: on track for full enrollment in Phase 3 OASIS-HAE study soon; latest data reinforce potential competitive profile
• On track to launch eplontersen, olezarsen and donidalorsen
• • Co-commercializingeplontersen with AstraZeneca
  • Independently launching olezarsen and donidalorsen
• Key functions in place: global product strategy, market access, in-line commercial teams, etc.
• On track to achieve 2023 financial guidance
• $2.3 billion2 in cash enables continued investment in creating future growth opportunities

Positioned

for Substantial Growth

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1. Timing expectations based on current assumptions and subject to change 2. Cash, cash equivalents and short-term investments at March 31, 2023.