Ionis reports first quarter 2024 financial results WAINUA TM launch on track; EU and Canada approval decisions expected this year Olezarsen NDA submitted to FDA for FCS; preparing EU regulatory submission Positive Phase

Ionis reports first quarter 2024 financial results

WAINUATM launch on track; EU and Canada approval decisions expected this year

Olezarsen NDA submitted to FDA for FCS; preparing EU regulatory submission

Positive Phase 3 donidalorsen data for HAE; preparing regulatory submissions

On track to achieve 2024 financial guidance

CARLSBAD, Calif., May 7, 2024 - Ionis

Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company"), today reported financial results for the first quarter ended March 31, 2024.

"Ionis is off to a great start in 2024, as we continue to execute on our vision to bring better futures to people with serious diseases. The WAINUA launch for hereditary

ATTR polyneuropathy is progressing well with AstraZeneca. And we are one step closer to our first independent launch with our NDA submission for olezarsen, which is supported by robust data positioning olezarsen to make a profound difference for

people with FCS," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "We look forward to presenting positive Phase 3 donidalorsen data, along with data from our open-label extension and switch' studies in patients with HAE at EAACI later

this month, setting the stage for Ionis' second independent launch. Additionally, we have multiple upcoming data readouts from our mid-stage programs that, if positive, could advance into Phase 3 development, further strengthening our ability to

deliver a steady cadence of potentially transformational medicines for years to come."

First Quarter 2024 Summary Financial Results(1):

Financial Highlights

Recent Marketed Medicines Highlights

Recent Late-Stage Pipeline Highlights

Recent Other Pipeline Highlights

First Quarter 2024 Financial Results

"Our first quarter results keep us on track to achieve our 2024 financial guidance. With the launch of WAINUA in the U.S. underway, we are excited to add WAINUA

royalties to our meaningful revenues in the first quarter. We believe WAINUA is uniquely positioned in this growing market to address the needs of ATTRv-PN patients who remain significantly underserved, especially as it is the only approved medicine

with monthly dosing that can be self-administered via an auto injector," said Elizabeth L. Hougen, chief financial officer of Ionis. "We continued to invest our capital resources in our near-term commercial opportunities, wholly owned pipeline and

technology. We expect our modest expense growth this year to be driven by our activities to support the WAINUA launch and planned launches for olezarsen and donidalorsen with R&D expenses

approaching steady state as several late-stage studies have recently ended. We believe the investments we are making today and plan to make over the next few years position Ionis to drive increasing value for patients and stakeholders."

Ionis' revenue was comprised of the following:

Commercial revenue in the first quarter of 2024 included a new source of royalty revenue with the launch of WAINUA in the U.S. during the first quarter of 2024. While

the number of patients on SPINRAZA treatment remained consistent globally, royalties decreased year over year primarily due to the timing of shipments in several markets outside the U.S. Ionis' commercial revenue in the first quarter of 2024 also

included royalties from the net sales of QALSODY, which Biogen launched in the second quarter of 2023.

R&D revenue in the first quarter of 2024 included increased revenue from the amortization of upfront payments compared to the same period last year due to the new

collaborations Ionis entered into last year with Roche and Novartis. This increase was offset by decreases in milestone payments due to timing and WAINUA joint development revenue, which decreased as development activities relating to ATTRv-PN

wound down with the launch of WAINUA underway.

Ionis' operating expenses increased in the first quarter of 2024 compared to the same period in 2023, consistent with expectations. SG&A expenses increased year

over year primarily due to the launch of WAINUA in the U.S. and launch preparation activities for olezarsen and donidalorsen. R&D expenses increased compared to the same period last year due to the timing of development activities and are

expected to stabilize in 2024 as several late-stage studies have ended.

As of March 31, 2024, Ionis' cash, cash equivalents and short-term investments decreased to $2.2 billion compared to $2.3 billion at December 31, 2023. As the year

progresses, the Company plans to continue deploying its capital resources toward growth opportunities. Ionis' working capital also decreased over the same period primarily due to the Company's lower cash and short-term investments balance.

Management will host a conference call and webcast to discuss Ionis' first quarter 2024 results at

11:30 a.m. Eastern time on Tuesday, May 7, 2024. Interested parties may access the webcast here. A webcast replay

will be available for a limited time at the same address. To access the Company's first quarter 2024 earnings slides click here.

For more information about SPINRAZA and QALSODY, visit https://www.spinraza.com/ and https://www.qalsody.com/, respectively. QALSODY is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY.

Continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s).

INDICATION for WAINUA (eplontersen)

WAINUA injection, for subcutaneous use, 45 mg is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

IMPORTANT SAFETY INFORMATION for WAINUA (eplontersen)

WARNINGS AND PRECAUTIONS

Reduced Serum Vitamin A Levels and Recommended Supplementation WAINUA leads to a decrease in serum vitamin A levels. Supplement with recommended daily allowance of vitamin A. Refer patient to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur.

Most common adverse reactions ( 9% in WAINUA-treated patients) were vitamin A decreased (15%) and vomiting (9%).

Please see link to U.S. Full Prescribing

Information for WAINUA.

About Ionis Pharmaceuticals, Inc.

For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading

pipeline in neurology, cardiology, and other 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

(Twitter) and LinkedIn.

Ionis' Forward-looking Statement

This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of our commercial

medicines, additional medicines in development and technologies. 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, 2023, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company.

In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer 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 registered 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. WAINUATM is a registered trademark of the AstraZeneca group of companies.

Ionis Investor Contact:

D. Wade Walke, Ph.D.

info@ionisph.com 760-603-2331

Ionis Media Contact:

CorporateCommunications@ionisph.com 760-603-4679

IONIS PHARMACEUTICALS, INC.

SELECTED FINANCIAL INFORMATION

Condensed Consolidated Statements of Operations

(In Millions, Except Per Share Data)

IONIS PHARMACEUTICALS, INC.

Reconciliation of GAAP to Non-GAAP Basis:

Condensed Consolidated Operating Expenses, Loss From Operations, and Net Loss

Reconciliation of GAAP to Non-GAAP Basis

As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP loss from operations, and non-GAAP net loss were

adjusted from GAAP to exclude compensation expense related to equity awards and the related tax effects. Compensation expense related to equity awards are non-cash. These measures are provided as supplementary information and are not a substitute for

financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further,

the presentation of Ionis' non-GAAP results is consistent with how Ionis' management internally evaluates the performance of its operations.

IONIS PHARMACEUTICALS, INC.

Condensed Consolidated Balance Sheets

Key 2024 Value Driving Events(1)