Vitamin A

CARLSBAD, Calif.--(BUSINESS WIRE)--Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the “Company”) today reported financial results and provided key updates for the fourth quarter and year ended December 31, 2025. "2025 was a defining year for Ionis, marked by the successful execution of our first two independent launches and multiple positive data readouts across our pipeline, positioning Ionis for continued success in 2026,” said Brett P. Monia, Ph.D., chief executive officer of Ionis. “This year, we are poised for two additional independent launches of groundbreaking therapies — olezarsen for severe hypertriglyceridemia, our first launch in a broad patient population, and zilganersen for Alexander disease, our first launch from our leading neurology pipeline. Our partnered pipeline is also on track for multiple groundbreaking Phase 3 readouts, beginning with the recent positive data for bepirovirsen in chronic hepatitis B to be followed by two cardiovascular outcome trials — the pelacarsen Lp(a) HORIZON trial mid-year 2026 and the eplontersen CARDIO-TTRansform trial in the second half of 2026. Together, this progress positions Ionis to continue delivering a steady cadence of transformative medicines to people living with serious diseases, fueling substantial growth and long-term value creation." Fourth Quarter and Full Year 2025 Summary Financial Results(1): Three months ended Year ended December 31, December 31, 2025 2024 2025 2024 (amounts in millions) Total revenue $203 $227 $944 $705 Operating expenses $418 $337 $1,326 $1,180 Operating expenses on a non-GAAP basis $375 $301 $1,192 $1,050 Loss from operations ($215) ($110) ($382) ($475) Loss from operations on a non-GAAP basis ($172) ($74) ($248) ($345) (1) Reconciliation of GAAP to non-GAAP basis contained later in this release. Recent Financial Highlights Revenue for the year ended December 31, 2025 substantially exceeded expectations due to continued commercial success. In addition, Ionis earned substantial R&D revenue, including a $280 million upfront payment for the global license of sapablursen to Ono Pharmaceutical Co., Ltd. in the second quarter of 2025 Operating expenses for the year ended December 31, 2025 were in line with expectations and increased year over year from investments related to commercialization efforts for TRYNGOLZA, DAWNZERA and WAINUA Cash and short-term investments of $2.7 billion as of December 31, 2025, included refinancing proceeds Ionis plans to use to repay its 2026 Convertible Notes Fourth Quarter and Full Year 2025 Financial Results "In 2025 we exceeded our revenue guidance, driven by growing commercial revenue from our independent launches and substantial R&D revenue from continued pipeline success," said Elizabeth L. Hougen, chief financial officer of Ionis. "In 2026, we will continue to invest in go-to-market activities to support our ongoing and upcoming independent launches, including the recent expansion of our top-tier sales force ahead of our expected olezarsen sHTG launch. We anticipate growth in product revenues, together with additional royalties, to position Ionis to achieve cash flow breakeven in 2028 and generate substantial and sustainable positive cash flow for years to come." Recent Highlights - Wholly Owned Medicines TRYNGOLZA ® (olezarsen), the first FDA-approved treatment for adults living with familial chylomicronemia syndrome (FCS) as an adjunct to diet Generated net product sales of $50 million in the fourth quarter of 2025, a 56% increase over the prior quarter, and $108 million for the year ended December 31, 2025 Approved and launched in the European Union (EU) as an adjunct to diet in adult patients for the treatment of genetically confirmed FCS Generated net product sales of $50 million in the fourth quarter of 2025, a 56% increase over the prior quarter, and $108 million for the year ended December 31, 2025 Approved and launched in the European Union (EU) as an adjunct to diet in adult patients for the treatment of genetically confirmed FCS Olezarsen on track to launch this year as a transformational medicine for severely elevated triglycerides (sHTG), assuming approval Positive groundbreaking results in the pivotal Phase 3 CORE and CORE2 studies in sHTG presented at the American Heart Association Conference, in a late-breaking session, and published in the New England Journal of Medicine sNDA submitted for marketing approval in U.S. Positive groundbreaking results in the pivotal Phase 3 CORE and CORE2 studies in sHTG presented at the American Heart Association Conference, in a late-breaking session, and published in the New England Journal of Medicine sNDA submitted for marketing approval in U.S. DAWNZERA™ (donidalorsen), the first and only RNA-targeted prophylactic therapy for hereditary angioedema (HAE) in patients 12 years of age and older Generated net product sales of $7 million in the fourth quarter of 2025, in the first full quarter on the market Encouraging early launch momentum with prescriptions written for all patient segments and growing number of repeat prescribers Approved in the European Union (EU) in January and recently launched for the routine prevention of recurrent attacks of HAE in patients 12 years of age and older Positive one-year results from OASISplus open-label extension cohort published in the Journal of Asthma and Allergy Generated net product sales of $7 million in the fourth quarter of 2025, in the first full quarter on the market Encouraging early launch momentum with prescriptions written for all patient segments and growing number of repeat prescribers Approved in the European Union (EU) in January and recently launched for the routine prevention of recurrent attacks of HAE in patients 12 years of age and older Positive one-year results from OASISplus open-label extension cohort published in the Journal of Asthma and Allergy Zilganersen on track for launch this year as the first and only medicine to demonstrate clinically meaningful and disease-modifying impact in children and adults with Alexander disease (AxD), assuming approval NDA submitted with approval decision anticipated in H2:2026 Expanded access program (EAP) in U.S. underway NDA submitted with approval decision anticipated in H2:2026 Expanded access program (EAP) in U.S. underway Recent Highlights – Partnered Medicines SPINRAZA ® (nusinersen) for the treatment of spinal muscular atrophy (SMA) generated global sales of $356 million and $1.5 billion resulting in royalty revenue of $54 million and $212 million in the fourth quarter and the year ended December 31, 2025, respectively High dose approved and launched in the EU; under review for marketing approval in U.S. (PDUFA date of April 3, 2026) Positive high dose results from pivotal DEVOTE study published in Nature Medicine High dose approved and launched in the EU; under review for marketing approval in U.S. (PDUFA date of April 3, 2026) Positive high dose results from pivotal DEVOTE study published in Nature Medicine WAINUA ® (eplontersen) (WAINZUA in EU) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) generated sales of $69 million and $212 million resulting in royalty revenue of $16 million and $49 million in the fourth quarter and the year ended December 31, 2025, respectively Launches underway in numerous regions, including the EU; recently approved in China; additional submissions in progress to expand WAINUA access globally Launches underway in numerous regions, including the EU; recently approved in China; additional submissions in progress to expand WAINUA access globally Bepirovirsen, a potential first-in-class medicine for chronic hepatitis B (CHB), achieved primary endpoint and demonstrated a statistically significant and clinically meaningful functional cure rate in B-Well 1 and B-Well 2 Phase 3 studies Presentation planned for European Association for the Study of the Liver (EASL) Congress 2026, assuming acceptance Global regulatory filings planned beginning in Q1:2026 with 2026 anticipated launch, assuming approval Presentation planned for European Association for the Study of the Liver (EASL) Congress 2026, assuming acceptance Global regulatory filings planned beginning in Q1:2026 with 2026 anticipated launch, assuming approval Ulefnersen for the treatment of FUS-ALS granted U.S. Fast Track designation Sapablursen for the treatment of polycythemia vera (PV) demonstrated positive Phase 2 results, which were presented at American Society of Hematology (ASH) conference; Ono advancing sapablursen into Phase 3 development Opemalirsen for the treatment of APOL1-mediated chronic kidney disease (AMKD) granted U.S. Fast Track designation Revenue Ionis’ revenue was comprised of the following: Three months ended Year ended December 31, December 31, 2025 2024 2025 2024 Revenue: (amounts in millions) Commercial revenue: Product sales, net: TRYNGOLZA sales, net $50 $- $108 $- DAWNZERA sales, net 7 - 8 - Total product sales, net 57 - 116 - Royalty revenue: SPINRAZA royalties 54 64 212 216 WAINUA royalties 16 10 49 20 Other royalties 6 3 24 21 Total royalty revenue 76 77 285 257 Other commercial revenue 8 9 35 36 Total commercial revenue 141 86 436 293 Research and development revenue: Collaborative agreement revenue 52 97 466 333 WAINUA joint development revenue 10 44 42 79 Total research and development revenue 62 141 508 412 Total revenue $203 $227 $944 $705 Commercial revenue for the fourth quarter and the year ended December 31, 2025, increased 64% and 49%, respectively, compared to the same periods in 2024. This increase was primarily driven by TRYNGOLZA product sales. Higher royalty revenue also contributed to the year over year increase. The remainder of the Company’s revenue came from programs under its R&D collaborations, including a $280 million upfront payment for the global license of sapablursen to Ono Pharmaceutical Co., Ltd. in the second quarter of 2025, reflecting the value that Ionis’ pipeline and technology continue to generate. Operating Expenses Operating expenses increased modestly for the fourth quarter and the year ended December 31, 2025, which was in line with expectations. The increase was driven by investments to support the launches of TRYNGOLZA, DAWNZERA and WAINUA. Balance Sheet As of December 31, 2025, Ionis’ cash, cash equivalents and short-term investments increased to $2.7 billion, compared to $2.3 billion on December 31, 2024, primarily due to the refinancing proceeds Ionis received from its convertible debt issuance in the fourth quarter, which Ionis plans to use to repay its 2026 Convertible Notes. 2026 Financial Guidance The Company’s 2026 financial guidance reflects its evolution to a fully integrated commercial-stage biotechnology company independently launching multiple medicines and advancing commercialization efforts for additional upcoming planned launches. As a result, the Company expects to earn substantial revenue from numerous diverse sources, including increasing commercial revenue. The Company is currently awaiting acceptance of its olezarsen sNDA submission, as such the Company’s 2026 financial guidance assumes a standard review timeline. With acceptance anticipated shortly, the Company expects to provide TRYNGOLZA and DAWNZERA product level guidance at its first quarter 2026 earnings. The Company expects a modest increase in its non-GAAP operating expenses in line with its plan to invest in independent launches and advance its wholly owned pipeline of innovative medicines. The Company expects that these investments will enable Ionis to deliver accelerating value. Overall, the Company anticipates total revenue to grow approximately 20 percent year over year and its non-GAAP operating loss to be similar to 2025, excluding the one-time sapablursen upfront payment recognized in 2025. Full Year 2026 Guidance Revenue $800- $825 million Operating loss on a non-GAAP basis $500-550 million Cash, cash equivalents and short-term investments ~$1.6 billion Webcast and Other Updates Management will host a conference call and webcast to discuss Ionis’ fourth quarter and full year 2025 results at 8:30 a.m. Eastern time on Wednesday, February 25, 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 fourth quarter and full year 2025 earnings slides click here. Ionis’ Marketed Medicines 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 syndrome (FCS). IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS 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. ADVERSE REACTIONS 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 DAWNZERATM (donidalorsen) DAWNZERA™ (donidalorsen) 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. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS DAWNZERA is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with DAWNZERA. If signs and symptoms of serious hypersensitivity reactions occur, discontinue DAWNZERA and institute appropriate therapy. ADVERSE REACTIONS Most common adverse reactions (incidence ≥ 5%) are injection site reactions, upper respiratory tract infection, urinary tract infection, and abdominal discomfort. Please see full Prescribing Information for DAWNZERA. 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. ADVERSE REACTIONS 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. 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). About Ionis Pharmaceuticals, Inc. For 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, 2024, 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® is a registered trademark of Ionis Pharmaceuticals, Inc. TRYNGOLZA® is a registered trademark of Ionis Pharmaceuticals, Inc. DAWNZERATM is a trademark of Ionis Pharmaceuticals, Inc. AKCEATM is a trademark of Akcea Therapeutics, Inc. TEGSEDITM is a trademark of Akcea Therapeutics, Inc. WAYLIVRATM 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. IONIS PHARMACEUTICALS, INC. SELECTED FINANCIAL INFORMATION Condensed Consolidated Statements of Operations (In Millions, Except Per Share Data) Three months ended Year ended December 31, December 31, 2025 2024 2025 2024 (unaudited) Revenue: Commercial revenue: Product sales, net $57 $- $116 $- Royalty revenue 76 77 285 257 Other commercial revenue 8 9 35 36 Total commercial revenue 141 86 436 293 Research and development revenue: Collaborative agreement revenue 52 97 466 333 WAINUA joint development revenue 10 44 42 79 Total research and development revenue 62 141 508 412 Total revenue 203 227 944 705 Expenses: Cost of sales 8 4 16 11 Research, development and patent 280 245 916 902 Selling, general and administrative 130 88 394 267 Total operating expenses 418 337 1,326 1,180 Loss from operations (215) (110) (382) (475) Other income (expense): Interest expense related to the sale of future royalties (18) (19) (73) (73) Other income, net 5 22 75 88 Loss before income tax benefit (expense) (228) (107) (380) (460) Income tax benefit (expense) (1) 3 (1) 6 Net loss ($229) ($104) ($381) ($454) Basic and diluted net loss per share ($1.41) ($0.66) ($2.38) ($3.04) Shares used in computing basic and diluted net loss per share 162 158 160 150 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 December 31, Year ended December 31, 2025 2024 2025 2024 (unaudited) As reported research, development and patent expenses according to GAAP $280 $245 $916 $902 Excluding compensation expense related to equity awards (29) (25) (90) (92) Non-GAAP research, development and patent expenses $251 $220 $826 $810 As reported selling, general and administrative expenses according to GAAP $130 $88 $394 $267 Excluding compensation expense related to equity awards (13) (11) (42) (37) Non-GAAP selling, general and administrative expenses $117 $77 $352 $230 As reported operating expenses according to GAAP $418 $337 $1,326 $1,180 Excluding compensation expense related to equity awards (43) (36) (134) (130) Non-GAAP operating expenses $375 $301 $1,192 $1,050 As reported loss from operations according to GAAP ($215) ($110) ($382) ($475) Excluding compensation expense related to equity awards (43) (36) (134) (130) Non-GAAP loss from operations ($172) ($74) ($248) ($345) As reported net loss according to GAAP ($229) ($104) ($381) ($454) Excluding compensation expense related to equity awards and related tax effects (43) (36) (134) (130) Non-GAAP net loss ($186) ($68) ($247) ($324) 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) December 31, December 31, 2025 2024 (unaudited) Assets: Cash, cash equivalents and short-term investments $2,677 $2,298 Contracts receivable 66 92 Other current assets 247 230 Property, plant and equipment, net 123 94 Right-of-use assets 239 162 Other assets 172 127 Total assets $3,524 $3,003 Liabilities and stockholders’ equity: Current portion of deferred contract revenue $74 $79 0% convertible senior notes due 2026, net – current 432 - Other current liabilities 277 229 0% convertible senior notes due 2030, net 751 - 1.75% convertible senior notes due 2028, net 568 565 0% convertible senior notes due 2026, net - 629 Liability related to sale of future royalties, net 551 542 Long-term lease liabilities 262 162 Long-term obligations, less current portion 28 52 Long-term deferred contract revenue 92 157 Total stockholders’ equity 489 588 Total liabilities and stockholders’ equity $3,524 $3,003 Key 2026 Value Driving Events(1) New Product Launches Program Indication Location DAWNZERA HAE EU Achieved Olezarsen sHTG U.S. ● Zilganersen Alexander disease U.S. ● Bepirovirsen CHB U.S. & Japan ● Regulatory Actions Program Indication Regulatory Action Donidalorsen HAE EU approval decision Achieved Olezarsen sHTG U.S. approval decision ● EU submission ● Zilganersen Alexander disease U.S. submission ● U.S. approval decision ● Nusinersen (high dose) SMA EU approval decision Achieved U.S. approval decision ● Eplontersen ATTR-CM Regulatory submission(s) ● Bepirovirsen HBV Regulatory submission(s) ● Regulatory decision(s) ● Pelacarsen Lp(a)- CVD U.S. submission ● Key Phase 3 Clinical Events Program Indication Event Obudanersen Angelman syndrome Phase 3 enrollment completion ● Bepirovirsen HBV B-Well data Achieved Pelacarsen Lp(a)-CVD Lp(a) HORIZON data ● Eplontersen ATTR-CM CARDIO-TTRansform data ● Sefaxersen IgAN IMAGINATION data ● Ulefnersen FUS-ALS FUSION data ● Salanersen SMA Phase 3 initiation ● Sapablursen Polycythemia Vera Phase 3 initiation ● Key Phase 2 Clinical Events Program Indication Event IONIS-MAPTRx/ BIIB080 Alzheimer’s disease Phase 2 CELIA data ● Tominersen Huntington’s disease Phase 2 GENERATION HD2 data ● Tonlamarsen Uncontrolled hypertension Phase 2 data ● (1) Timing expectations based on current assumptions and subject to change.