Ionis reports fourth quarter and full year 2024 financial results - First independent launch underway following TRYNGOLZA TM approval - - Second independent launch on track with donidalorsen PDUFA

Ionis reports fourth quarter and full year 2024 financial results

- First independent launch underway following TRYNGOLZATM

- Second independent launch on track with donidalorsen PDUFA

- WAINUATM U.S. launch delivering accelerating

- Ionis exceeds 2024 financial guidance and provides full

year 2025 guidance -

CARLSBAD, Calif., February 19, 2025 - Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company") today reported financial results for the fourth

quarter and full year ended December 31, 2024.

"With the recent launch of our first independent medicine, TRYNGOLZA for familial chylomicronemia syndrome, Ionis has begun a new chapter as a fully integrated

commercial-stage biotechnology company," said Brett P. Monia, Ph.D., chief executive officer, Ionis. "Over the next three years, we expect three more independent launches, including donidalorsen later this year for hereditary angioedema and

olezarsen for severe hypertriglyceridemia in 2026, pending Phase 3 results in the second half of this year. Additionally, our partners are on track to launch four Ionis-discovered medicines over the same time period, including several that address

broad patient populations. Ionis continues to advance our next wave of potentially transformational wholly owned medicines, including ION582 for Angelman syndrome, which is on track to start Phase 3 development in the first half of this year. Our recent achievements, combined with our strong commercial execution and advancing pipeline, position Ionis to deliver increasing value for all our stakeholders."

Fourth Quarter and Full Year 2024 Summary Financial Results(1):

Financial Highlights

Recent Highlights- Marketed Medicines

Recent Highlights- Late-Stage Pipeline

Fourth Quarter, Full Year 2024 Financial Results and 2025 Financial Guidance

"In 2024, we exceeded our revenue guidance due to our continued pipeline and technology successes, which drove a smaller than anticipated operating loss. Importantly,

we added two new sources of commercial revenue with TRYNGOLZA product revenue from Ionis' first independent launch and WAINUA royalties," said Elizabeth L. Hougen, chief financial officer, Ionis. "In 2025, we will continue to invest in go-to-market activities for TRYNGOLZA for FCS and scale our resources to support our next planned launches, including donidalorsen for hereditary angioedema later this year. At the

same time, we are investing in our next wave of medicines, including Phase 3 development and pre-commercialization activities for ION582 for Angelman syndrome. These important investments position Ionis to deliver substantial and growing product

revenue; and when combined with increasing royalty revenue from anticipated partner launches, provides us with a clear path to achieve sustained positive cash flow."

Ionis' revenue was comprised of the following:

Commercial revenue for the year ended December 31, 2024 included new sources of commercial revenue with the launch of WAINUA in the U.S. in late January 2024 and the

launch of TRYNGOLZA in the U.S. in late December 2024. SPINRAZA product sales in the U.S. increased slightly in 2024 compared to 2023. SPINRAZA product sales outside of the U.S. were impacted from an annual order from a single country that did not

R&D revenue decreased for the year ended December 31, 2024 compared to 2023 primarily due to the decrease in WAINUA joint development revenue as development

activities relating to ATTRv-PN wound down with the launch of WAINUA.

Ionis' operating expenses increased slightly for the year ended December 31, 2024 compared to 2023. SG&A expenses increased year over year primarily due to the

launches of WAINUA and TRYNGOLZA, and advancing launch preparation activities for donidalorsen. R&D expenses were flat year over year.

As of December 31, 2024, Ionis' cash, cash equivalents and short-term investments were $2.3 billion, consistent with December 31, 2023. In September 2024, Ionis

generated gross proceeds of $500 million from a public offering of its common stock. Ionis' working capital increased as of December 31, 2024, compared to December 31, 2023 primarily from the Company's lower current liabilities as a result of lower

deferred contract revenue.

2025 Financial Guidance

The Company's 2025 financial guidance reflects its evolution to a fully integrated commercial-stage biotechnology company independently launching its first medicine,

TRYNGOLZA, and advancing commercialization efforts for multiple additional upcoming planned launches. As a result, the Company expects to earn substantial revenue from numerous diverse sources, with a shift toward increasing commercial revenue.

Additionally, the Company expects a modest increase in its non-GAAP operating expenses in line with its plan to invest in the Company's independent launches and advance its wholly owned pipeline of innovative medicines. The Company expects that these

investments will enable Ionis to deliver accelerating value.

Management will host a conference call and webcast to discuss Ionis' fourth quarter and full year 2024 results at 11:30 a.m. Eastern time on Wednesday, February 19,

2025. 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 fourth quarter and full year 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 TRYNGOLZA (olezarsen)

TRYNGOLZA (olezarsen) was approved by the U.S. Food and Drug Administration as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia

IMPORTANT SAFETY INFORMATION

TRYNGOLZA is contraindicated in patients with a history of serious hypersensitivity to TRYNGOLZA or any of the excipients in TRYNGOLZA. Hypersensitivity reactions requiring

medical treatment have occurred.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions (including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills and myalgias) have been reported in patients treated

with TRYNGOLZA. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of TRYNGOLZA if hypersensitivity reactions occur.

The most common adverse reactions (incidence >5% of TRYNGOLZA-treated patients and >3% higher frequency than placebo) were injection site reactions, decreased

platelet count and arthralgia.

Please see full Prescribing Information for TRYNGOLZA.

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 six marketed medicines and a leading

pipeline in neurology, cardiology and select 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 Ionis, visit Ionis.com

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. TRYNGOLZATM is a 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. SPINRAZA

and QALSODY are registered trademarks of Biogen. WAINUATM is a registered trademark of the AstraZeneca group of companies.

Ionis Investor Contact:

D. Wade Walke, Ph.D.

Ionis Media Contact:

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 2025 and 2026 Value Driving Events(1)