Donidalorsen

– 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) : Three months ended Nine months ended September 30, September 30, 2026 2025 2026 2025 (amounts in millions) Total revenue $ 243 $ 157 $ 757 $ 740 Operating expenses $ 373 $ 317 $ 1,107 $ 907 Operating expenses on a non-GAAP basis $ 330 $ 286 $ 975 $ 816 Loss from operations ($ 130 ) ($ 160 ) ($ 350 ) ($ 167 ) Loss from operations on a non-GAAP basis ($ 87 ) ($ 129 ) ($ 218 ) ($ 76 ) (1) Reconciliation of GAAP to non-GAAP basis contained later in this release. 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$1.6 billion Unchanged 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 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. IONIS PHARMACEUTICALS, INC. SELECTED FINANCIAL INFORMATION Condensed Consolidated Statements of Operations (In Millions, Except Per Share Data) Three months ended Nine months ended September 30, September 30, 2026 2025 2026 2025 (unaudited) Revenue: Commercial revenue: Product sales, net $ 48 $ 33 $ 122 $ 58 Royalty revenue 81 76 215 210 Other commercial revenue 7 7 26 26 Total commercial revenue 136 116 363 294 Research and development revenue: Collaborative agreement revenue 103 31 356 414 WAINUA joint development revenue 4 10 38 32 Total research and development revenue 107 41 394 446 Total revenue 243 157 757 740 Expenses: Cost of sales 3 2 9 8 Research, development and patent 216 218 643 636 Selling, general and administrative 154 97 455 263 Total operating expenses 373 317 1,107 907 Loss from operations (130 ) (160 ) (350 ) (167 ) Other income (expense): Interest expense related to the sale of future royalties (4 ) (18 ) (39 ) (55 ) Other income, net 24 49 73 70 Loss before income tax benefit (expense) (110 ) (129 ) (316 ) (152 ) Income tax benefit (expense) - - (1 ) - Net loss ($ 110 ) ($ 129 ) ($ 317 ) ($ 152 ) Basic and diluted net loss per share ($ 0.66 ) ($ 0.80 ) ($ 1.92 ) ($ 0.95 ) Shares used in computing basic and diluted net loss per share 166 160 166 159 IONIS PHARMACEUTICALS, INC. Reconciliation of GAAP to Non-GAAP Basis: Condensed Consolidated Operating Expenses, Loss From Operations, and Net Loss (In Millions) Three months ended September 30, Nine months ended September 30, 2026 2025 2026 2025 (unaudited) As reported cost of sales according to GAAP $ 3 $ 2 $ 9 $ 8 Excluding compensation expense related to equity awards (1) - - - (1 ) Non-GAAP cost of sales $ 3 $ 2 $ 9 $ 7 As reported research, development and patent expenses according to GAAP $ 216 $ 218 $ 643 $ 636 Excluding compensation expense related to equity awards (24 ) (21 ) (74 ) (61 ) Non-GAAP research, development and patent expenses $ 192 $ 197 $ 569 $ 575 As reported selling, general and administrative expenses according to GAAP $ 154 $ 97 $ 455 $ 263 Excluding compensation expense related to equity awards (19 ) (10 ) (58 ) (29 ) Non-GAAP selling, general and administrative expenses $ 135 $ 87 $ 397 $ 234 As reported operating expenses according to GAAP $ 373 $ 317 $ 1,107 $ 907 Excluding compensation expense related to equity awards (43 ) (31 ) (132 ) (91 ) Non-GAAP operating expenses $ 330 $ 286 $ 975 $ 816 As reported loss from operations according to GAAP ($ 130 ) ($ 160 ) ($ 350 ) ($ 167 ) Excluding compensation expense related to equity awards (43 ) (31 ) (132 ) (91 ) Non-GAAP loss from operations ($ 87 ) ($ 129 ) ($ 218 ) ($ 76 ) As reported net loss according to GAAP ($ 110 ) ($ 129 ) ($ 317 ) ($ 152 ) Excluding compensation expense related to equity awards and related tax effects (43 ) (31 ) (132 ) (91 ) Non-GAAP net loss ($ 67 ) ($ 98 ) ($ 185 ) ($ 61 ) (1) Amounts appear as zero due to rounding in millions. 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 (In Millions) September 30, December 31, 2026 2025 (unaudited) Assets: Cash, cash equivalents and short-term investments $ 1,884 $ 2,677 Contracts receivable 88 66 Other current assets 389 247 Property, plant and equipment, net 162 123 Right-of-use assets 228 239 Other assets 162 172 Total assets $ 2,913 $ 3,524 Liabilities and stockholders’ equity: Current portion of deferred contract revenue $ 70 $ 74 0% convertible senior notes due April 2026, net – current - 432 Liability related to sale of future royalties, net – current 138 12 Other current liabilities 227 265 0% convertible senior notes due 2030, net 754 751 1.75% convertible senior notes due 2028, net 570 568 Liability related to sale of future royalties, net 428 551 Long-term lease liabilities 262 262 Long-term obligations, less current portion 21 28 Long-term deferred contract revenue 49 92 Total stockholders’ equity 394 489 Total liabilities and stockholders’ equity $ 2,913 $ 3,524 Key 2026 and 2027 Value Driving Events (1) New Product Launches Program Indication Location 2026 2027 DAWNZERA HAE EU Achieved TRYNGOLZA sHTG U.S. Achieved EU • ZANVASTRO Alexander disease U.S. Achieved HIBSAGO CHB Japan Achieved U.S. • EU • China • Sefaxersen IgAN U.S. • Ulefnersen FUS-ALS U.S. • Regulatory Actions Program Indication Regulatory Action 2026 2027 Donidalorsen HAE EU approval decision Achieved Olezarsen sHTG U.S. approval decision Achieved EU submission Achieved EU approval decision • Zilganersen Alexander disease U.S. submission Achieved U.S. approval decision Achieved Nusinersen (high dose) SMA EU approval decision Achieved U.S. approval decision Achieved Bepirovirsen CHB Regulatory submission(s) Achieved U.S. and Japan approval decisions Achieved EU approval decision • China approval decision • Pelacarsen Lp(a)- CVD U.S. submission Not Achieved Sefaxersen IgAN U.S. submission • U.S. approval • Ulefnersen FUS-ALS U.S. submission • U.S. approval • Key Phase 3 Clinical Events Program Indication Event 2026 2027 Obudanersen Angelman syndrome REVEAL fully enrolled Achieved REVEAL data • Bepirovirsen CHB B-Well data Achieved Pelacarsen Lp(a)-CVD Lp(a) HORIZON data Not Achieved Eplontersen ATTR-CM CARDIO-TTRansform data Not Achieved Sefaxersen IgAN IMAgINATION interim data Achieved IMAgINATION data • Ulefnersen FUS-ALS FUSION data Achieved Salanersen SMA Phase 3 initiation Achieved Sapablursen Polycythemia Vera Phase 3 initiation Achieved Diranersen Alzheimer’s disease Phase 3 initiation • Contacts 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 Read full story here