Ionis reports third quarter 2026 financial results and highlights progress on key programs

– ZANVASTRO^™ (zilganersen) first approved medicine for Alexander disease; first independent launch underway from leading neurology pipeline –

– TRYNGOLZA^® (olezarsen) 2026 product sales guidance lowered as sHTG launch ramps more gradually than expected reflecting early dynamics of establishing a new treatment paradigm –

– DAWNZERA^® (donidalorsen) launch momentum continues; reaffirming 2026 product revenue guidance –

– Reaffirming 2026 total revenue, operating loss and cash guidance –

CARLSBAD, Calif.--(BUSINESS WIRE)--Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the “Company”) today reported financial results and provided key updates for the third quarter ended September 30, 2026.

“In 2026, we continue to advance innovative medicines for people with serious diseases, underscored by three approvals for groundbreaking first-in-class medicines, two of which are Ionis-owned,” said Brett P. Monia, Ph.D., chief executive officer of Ionis. “TRYNGOLZA, our first launch in a large indication, represents a new treatment paradigm for the underserved sHTG population. While initial sales progress has been more gradual than anticipated, we are encouraged by the underlying launch fundamentals. Importantly, we have identified clear opportunities to improve performance, and we remain confident in TRYNGOLZA's long-term growth potential. ZANVASTRO for people with Alexander disease marks our first independent neurology launch and lays the foundation for future launches from our leading neurology pipeline. In addition, our partnered pipeline continues to advance, with the recent approval of HIBSAGO for chronic hepatitis B and two additional positive Phase 3 outcomes creating near-term opportunities for additional potential approvals and revenue growth.”

Third Quarter 2026 Summary Financial Results⁽¹⁾:

Third Quarter 2026 Financial Highlights

• Revenue in the third quarter and nine months ended September 30, 2026 increased by 55% and 64% respectively, compared to the same periods last year, excluding the one-time sapablursen upfront payment recognized in the second quarter of 2025, driven by increased commercial revenue and substantial R&D revenue from multiple partnerships
• Operating expenses for the third quarter and nine months ended September 30, 2026 were in line with expectations and increased year over year primarily from investments related to the commercialization efforts for TRYNGOLZA, DAWNZERA and ZANVASTRO
• Ended the third quarter of 2026 with cash and short-term investments of $1.9 billion

Third Quarter 2026 Financial Results

“In the third quarter, we generated higher quarter-over-quarter commercial revenue and substantial R&D revenue from partnered medicines while continuing to invest in our innovative wholly owned pipeline. Our commercial revenue growth was driven by DAWNZERA, which continues to gain momentum, supporting our confidence in achieving full-year DAWNZERA product sales guidance. These results keep us on track to achieve our 2026 total revenue, operating loss and cash guidance,” said Elizabeth L. Hougen, chief financial officer of Ionis. “We are lowering our 2026 TRYNGOLZA product sales guidance to reflect a more gradual ramp than we anticipated. We remain confident in TRYNGOLZA’s potential to deliver sustained, long-term revenue growth and multi-billion-dollar peak sales. As we execute on our independent launches and advance the many additional opportunities across our rich pipeline, we remain committed to achieving our goal of sustained positive cash flow and long-term value creation.”

Recent Highlights - Wholly Owned Medicines

• TRYNGOLZA^® (olezarsen), the first FDA-approved treatment to reduce triglycerides and acute pancreatitis risk in adults with severe hypertriglyceridemia (sHTG) as an adjunct to diet
  • Generated U.S. net product sales of $9 million and $41 million in the third quarter and nine months ended September 30, 2026, respectively
    • Full year 2026 product sales guidance lowered to approximately $50 million, reflecting a more gradual launch ramp than anticipated as Ionis establishes a new treatment paradigm for people with sHTG
  • FCS launch outside the U.S. underway; received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for sHTG (sHTG fasting triglyceride levels of ≥880 mg/dL [≥10 mmol/L]), paving the way to bring TRYNGOLZA to sHTG patients across Europe with a final approval decision expected in the fourth quarter of 2026
  • Presented positive results from the CORE and CORE2 open-label extension study (CORE-OLE) at the European Society of Cardiology (ESC) Congress in August 2026
• DAWNZERA^® (donidalorsen), the first and only RNA-targeted prophylactic therapy for hereditary angioedema (HAE) in patients 12 years of age and older
  • Generated U.S. net product sales of $37 million and $79 million in the third quarter and nine months ended September 30, 2026, respectively
  • On track to achieve full year 2026 product sales guidance of $110-120 million, representing a continuing driver of year-over-year revenue growth
  • Launch outside the U.S. underway, with new market approvals in Europe and Canada
• ZANVASTRO^™ (zilganersen), the first and only disease-modifying treatment approved for children and adults with Alexander disease (AxD)
  • Launch underway with first patients dosed with commercial drug
  • Commercializing outside the U.S. with Recordati, assuming approval
• Obudanersen, a potential first-in-class treatment for Angelman syndrome (AS)
  • Completed enrollment in the Phase 3 REVEAL study, with data expected in the second half of 2027
  • Initiated Phase 3 CHAMPION study in people with AS due to paternal uniparental disomy (UPD), or imprinting center defects (abbreviated as either ID or ICD)
• ION775, an investigational siRNA for sHTG with the potential for semiannual or less frequent dosing, entered a Phase 2 study in people with sHTG and moderately elevated triglycerides (HTG), based on Phase 1 results showing robust triglyceride lowering with potential for extended dosing intervals
  • Presented and published positive results from the Phase 1 study at ESC and in the Journal of Clinical Lipidology in August 2026

Recent Highlights – Partnered Medicines

• SPINRAZA^® (nusinersen) for the treatment of spinal muscular atrophy (SMA) generated global sales of $461 million in the third quarter of 2026, an increase of 23% compared to the same period in 2025, resulting in royalty revenue of $69 million
• WAINUA^® (eplontersen) (WAINZUA in EU) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) generated global sales of $68 million in the third quarter of 2026, resulting in royalty revenue of $7 million
  • Global WAINUA ATTRv-PN launches continuing with additional submissions in progress to further expand global WAINUA access
  • Presented and published Phase 3 CARDIO-TTRansform study results of eplontersen for the treatment of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) at ESC and in the New England Journal of Medicine in August 2026. Although the study missed the primary composite endpoint in the overall population, eplontersen demonstrated nominal significance in the pre-specified monotherapy population and a favorable safety and tolerability profile
• HIBSAGO^™ (bepirovirsen), first-in-class treatment for chronic hepatitis B (CHB)
  • Approved in the U.S., Japan and Canada
  • Under regulatory review in additional countries, including the EU and China
• Sefaxersen, first RNA-targeted potential treatment for Immunoglobulin A Nephropathy (IgAN)
  • Presented positive results from the Phase 3 IMAgINATION study at ASN in October 2026. The study met its primary endpoint, demonstrating a clinically meaningful 43.1% reduction in proteinuria relative to placebo at week 37 (p<0.0001), with a safety profile consistent with previous data. Results will be shared with health authorities
• Ulefnersen Phase 3 study in patients with Fused in Sarcoma (FUS) Amyotrophic Lateral Sclerosis (ALS) met its primary endpoint (p=0.0005) and demonstrated a favorable safety and tolerability profile; data to be shared with health authorities
• Sapablursen, a potential treatment for polycythemia vera, received Orphan Drug Designations in the U.S., EU and Japan

Revenue

Ionis’ revenue was comprised of the following:

Commercial revenue for the third quarter and nine months ended September 30, 2026 increased 18% and 23%, respectively, compared to the same periods in 2025. This increase was primarily driven by DAWNZERA product sales. Research and development revenue was also higher in the third quarter and nine months ended September 30, 2026, compared to the same periods in 2025, driven by multiple payments for programs advancing under the Company’s R&D collaborations, and excluding the $280 million upfront payment for the global license of sapablursen to Ono Pharmaceutical Co., Ltd. the Company received in the second quarter of 2025.

Operating Expenses

Operating expenses for the third quarter and nine months ended September 30, 2026 increased year over year, in line with expectations, primarily from investments related to the commercialization efforts for TRYNGOLZA, DAWNZERA and ZANVASTRO, with full-year expenses remaining on track for low-teens percentage growth year-over-year.

Balance Sheet

As of September 30, 2026, Ionis’ cash, cash equivalents and short-term investments decreased to $1.9 billion, compared to $2.7 billion on December 31, 2025, primarily due to repayment of the 0% convertible notes on April 1, 2026 and cash used to fund operations.

2026 Financial Guidance

Ionis reaffirms its 2026 total revenue, including DAWNZERA product sales, operating loss and cash guidance based on its year-to-date results and fourth quarter outlook. Following the first full quarter of the TRYNGOLZA launch as the first and only treatment to reduce triglycerides and acute pancreatitis in people living with severe hypertriglyceridemia, Ionis is lowering TRYNGOLZA 2026 product sales guidance to reflect a more gradual-than-anticipated near-term launch ramp, while remaining confident in TRYNGOLZA’s long-term growth potential.

Webcast and Other Updates

Management will host a conference call and webcast to discuss Ionis’ third quarter 2026 results at 9:00 a.m. Eastern time on Monday, November 9, 2026. 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 third quarter 2026 earnings slides click here.

Ionis’ Marketed Medicines

TRYNGOLZA^® (olezarsen): TRYNGOLZA was approved by the U.S. Food and Drug Administration as an adjunct to diet to reduce triglycerides (TG) and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG: TG ≥500 mg/dL) and as an adjunct to diet to reduce TG in adults with familial chylomicronemia syndrome (FCS). For more information about TRYNGOLZA, including the full U.S. Prescribing Information, visit tryngolza.com.

DAWNZERA^® (donidalorsen): DAWNZERA was approved by the U.S. Food and Drug Administration for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. For more information about DAWNZERA, including the full U.S. Prescribing Information, visit dawnzera.com.

ZANVASTRO^™ (zilganersen): ZANVASTRO was approved by the U.S. Food and Drug Administration for the treatment of Alexander disease (AxD) in pediatric and adult patients. For more information about ZANVASTRO, including the full U.S. Prescribing Information, visit zanvastro.com.

For more information about SPINRAZA, WAINUA, HIBSAGO and QALSODY, visit spinraza.com, wainua.com, hibsago.com, 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).

About Ionis Pharmaceuticals, Inc.

For more than three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has marketed medicines and a leading pipeline in neurology, cardiometabolic disease 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 and follow us on X (Twitter), LinkedIn and Instagram.

Ionis Forward-looking Statements

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, technologies and our expectations regarding development and regulatory milestones. 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, 2025, 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. TRYNGOLZA^® is a registered trademark of Ionis Pharmaceuticals, Inc. DAWNZERA^® is a registered trademark of Ionis Pharmaceuticals, Inc. ZANVASTRO^™ is a trademark of Ionis Pharmaceuticals, Inc. AKCEA^™ is a trademark of Akcea Therapeutics, Inc. TEGSEDI^™ is a trademark of Akcea Therapeutics, Inc. WAYLIVRA^™ is a trademark of Akcea Therapeutics, Inc. SPINRAZA^® and QALSODY^® are registered trademarks of Biogen. WAINUA^® is a registered trademark of the AstraZeneca group of companies. HIBSAGO^™ is a trademark of the GSK group of companies.

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.

Key 2026 and 2027 Value Driving Events⁽¹⁾

Ionis Investor Contact:
D. Wade Walke, Ph.D.
IR@ionis.com
760-603-2331

Ionis Media Contact:
Hayley Soffer
media@ionis.com
760-603-4679