Ionis Pharmaceuticals : 2Q23 Earnings Slides

Q2:23 Financial Results and Business Update

August 9, 2023

Nasdaq: IONS

On Today's Earnings Call

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

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

Beth Hougen

Chief Financial Officer

Onaiza Cadoret

Executive Vice President,

Chief Global Product Strategy and

Operations Officer

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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, ulefnersen, pelacarsen, bepirovirsen, IONIS-FB-LRx, 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, and most recent Form 10-Q, which are on file with the SEC. Copies of these 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.

3

Introduction

Brett Monia, Ph.D. Chief Executive Officer

Important Achievements in the First Half of 20231

	•	QALSODY: approved by FDA for SOD1-ALS2
Late-Stage	•	Eplontersen:
	- PN: December 2023 PDUFA date; on track for oUS submissions
Pipeline	•	- CM: largest study in ATTR-CM now fully enrolled; data as early as H1:2025
	Olezarsen: Ph3 FCS data expected H2:23
	•	Donidalorsen: Ph3 study fully enrolled; data expected H1:24

Commercial Readiness

Financial Foundation

• On track to launch eplontersen, olezarsen and donidalorsen
• • Co-commercializingeplontersen with AstraZeneca in the US
  • Independently launching olezarsen and donidalorsen
• Key functions in place: global product strategy, market access, brand teams, etc.
• On track to achieve 2023 financial guidance
• $2.4 billion3 in cash enables investment to drive increasing value
• Successfully refinanced 2024 convertible notes to further strengthen balance sheet

Positioned

For

Substantial

Revenue

Growth

5 1. Timing expectations based on current assumptions and subject to change 2. For important prescribing and safety information, please refer to: www.qalsody.com3. Cash, cash equivalents and short-term investments at June 30, 2023.