J.P. Morgan Healthcare Conference 2022

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

January 12, 2022

Forward-Looking Statements

This presentation includes forward-looking statements regarding our business, financial guidance and the therapeutic and commercial potential of SPINRAZA® (nusinersen), eplontersen, olezarsen, donidalorsen, 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 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, 2020 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.

2

Executing on a Clear Vision to Become a Leading Fully Integrated Biotechnology Company

Positioned for Substantial Growth

Rich Mid- & Late-

Technology

Compelling

Stage Pipeline

Leadership

Financial Profile

Growing pipeline of

Our technology is advancing

potentially transformational

at an unprecedented pace,

medicines advancing

expanding our opportunities

towards the market

and extending our leadership

position

Ionis' strong financial position enables needed investments to support our vision and drive substantial growth

3

GROWTH

Build

Expand

Deliver

the Ionis

&

Abundance of

Commercial

Diversify

New Medicines

Pipeline

Technology

To Market

Validated

Rich Mid- &

Financial

Commitment to

Highly

Platform

Late-Stage

Strength

Innovation

Dedicated

Technology

Pipeline

Leadership

Employees

4

GROWTH

Build

Expand

Deliver

the Ionis

&

Abundance of

Commercial

Diversify

New Medicines

Pipeline

Technology

To Market

Validated

Rich Mid- &

Financial

Commitment to

Highly

Platform

Late-Stage

Strength

Innovation

Dedicated

Technology

Pipeline

Leadership

Employees

5

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Disclaimer

Ionis Pharmaceuticals Inc. published this content on 12 January 2022 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 12 January 2022 15:25:02 UTC.