Ionis Pharmaceuticals(IONS) - 2025 Q2 - Quarterly Results

Executive Summary & Financial Highlights Second Quarter 2025 Performance Overview Ionis reported strong Q2 2025 financial results with revenue doubling year-over-year, driven by a successful TRYNGOLZA launch - Revenue doubled in the second quarter of 2025 and increased nearly 70% in the first half compared to the same period last year[4] - TRYNGOLZATM delivered $19 million in net product sales in the second quarter 2025[1] - Donidalorsen approval in hereditary angioedema (HAE) is anticipated next month, marking Ionis' second independent launch[1] - Phase 3 data from the pivotal CORE and CORE2 studies in severe hypertriglyceridemia (sHTG) is expected in September 2025[1] Financial Guidance Update Ionis significantly raised its full-year 2025 financial guidance, reflecting strong revenue performance and an improved outlook - Ionis is increasing its 2025 financial guidance based on strong performance and an improved outlook[1] Full Year 2025 Financial Guidance Update | Full Year 2025 Guidance | Previous Guidance | New Guidance | | :---------------------- | :---------------- | :----------- | | Total Revenue | $725-750 million | $825-850 million | | TRYNGOLZA product sales, net | Not provided | $75-80 million | | Operating loss on a non-GAAP basis | <$375 million | $300-325 million | | Cash, cash equivalents and short-term investments | ~$1.9 billion | ~$2.0 billion | - Three additional independent launches anticipated over the next eighteen months are expected to deliver substantial and growing product revenue[6] Financial Results Consolidated Statements of Operations (GAAP) The company reported a significant increase in total revenue and a shift from operating loss to income in Q2 2025 Condensed Consolidated Statements of Operations (GAAP) | Metric (GAAP) | Q2 2025 (in Millions) | Q2 2024 (in Millions) | H1 2025 (in Millions) | H1 2024 (in Millions) | | :-------------- | :----------------- | :----------------- | :----------------- | :----------------- | | Total revenue | $452 | $225 | $584 | $345 | | Operating expenses | $312 | $291 | $591 | $560 | | Income (loss) from operations | $140 | $(66) | $(7) | $(215) | | Net income (loss) | $124 | $(66) | $(23) | $(209) | | Basic net income (loss) per share | $0.78 | $(0.45) | $(0.15) | $(1.43) | | Diluted net income (loss) per share | $0.70 | $(0.45) | $(0.15) | $(1.43) | Revenue Analysis Total revenue more than doubled year-over-year to $452 million in Q2 2025, driven by TRYNGOLZA sales and collaborative agreement revenue Revenue Breakdown | Revenue Category | Q2 2025 (in Millions) | Q2 2024 (in Millions) | H1 2025 (in Millions) | H1 2024 (in Millions) | | :--------------- | :----------------- | :----------------- | :----------------- | :----------------- | | TRYNGOLZA sales, net | $19 | $- | $26 | $- | | Total product sales, net | $19 | $- | $26 | $- | | SPINRAZA royalties | $54 | $57 | $102 | $95 | | WAINUA royalties | $10 | $4 | $20 | $5 | | Total royalty revenue | $70 | $64 | $134 | $113 | | Total commercial revenue | $103 | $72 | $179 | $132 | | Collaborative agreement revenue | $337 | $141 | $382 | $191 | | Total R&D revenue | $349 | $153 | $405 | $213 | | Total revenue | $452 | $225 | $584 | $345 | - Commercial revenue for Q2 and H1 2025 increased 43% and 36% respectively, driven by TRYNGOLZA product sales and higher royalty revenue[13] - R&D collaborations contributed significantly, including a $280 million upfront payment for the global license of sapablursen[14] Operating Expenses Operating expenses increased modestly due to commercialization investments for key products, partially offset by lower R&D expenses - Operating expenses increased by single digits in Q2 and H1 2025, primarily due to investments in commercialization for TRYNGOLZA, donidalorsen, and WAINUA[8] - SG&A expenses increased due to launch activities, partially offset by a decrease in R&D expenses as late-stage studies concluded[15] Balance Sheet Highlights Ionis maintained strong liquidity with $2.3 billion in cash and equivalents, while working capital decreased due to a debt reclassification Condensed Consolidated Balance Sheets Highlights | Balance Sheet Item | June 30, 2025 (in Millions) | December 31, 2024 (in Millions) | | :----------------- | :----------------------- | :--------------------------- | | Cash, cash equivalents and short-term investments | $2,290 | $2,298 | | Total assets | $2,985 | $3,003 | | 0% convertible senior notes, net – current | $630 | $- | | Total stockholders' equity | $632 | $588 | - Ionis received $280 million from the global license of sapablursen in Q2 2025[16] - Working capital decreased primarily due to the reclassification of the Company's 0% convertible notes as a current liability[16] Non-GAAP Reconciliation The company reported non-GAAP income from operations for Q2 and H1 2025, a significant improvement from the prior year's losses Non-GAAP Financial Results | Metric (Non-GAAP) | Q2 2025 (in Millions) | Q2 2024 (in Millions) | H1 2025 (in Millions) | H1 2024 (in Millions) | | :---------------- | :----------------- | :----------------- | :----------------- | :----------------- | | Operating expenses | $282 | $260 | $532 | $498 | | Income (loss) from operations | $170 | $(35) | $52 | $(153) | | Net income (loss) | $154 | $(35) | $36 | $(147) | - Non-GAAP measures exclude non-cash compensation expense related to equity awards and related tax effects to better assess performance[37] Pipeline and Program Updates Wholly Owned Medicines Ionis advanced its wholly-owned pipeline with strong TRYNGOLZA performance, anticipated donidalorsen approval, and upcoming olezarsen data - TRYNGOLZATM (olezarsen) is the first and only FDA approved treatment for adults living with familial chylomicronemia syndrome (FCS)[9] - Donidalorsen is on track to launch this year, assuming approval, with a U.S. PDUFA date of August 21, 2025[9] - Olezarsen is on track for topline Phase 3 data from pivotal CORE and CORE2 studies in patients with sHTG in September 2025[9] - The first patient was dosed in the Phase 3 REVEAL study of ION582 for Angelman syndrome (AS)[9] TRYNGOLZA™ (olezarsen) TRYNGOLZA generated $19 million in Q2 2025 net sales and received a positive CHMP opinion, advancing its availability in Europe - Generated net product sales of $19 million in Q2 2025 and $26 million in H1 2025[9] - Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), paving the way for availability in Europe[9] Donidalorsen Donidalorsen is on track for a U.S. launch this year for hereditary angioedema, with a PDUFA date of August 21, 2025 - Donidalorsen is on track for launch this year, assuming approval, with a U.S. PDUFA date of August 21, 2025[9] - It is poised to transform HAE treatment as the first and only RNA-targeted prophylactic therapy with a long dosing interval[9] - Donidalorsen is currently under regulatory review in the EU[9] Olezarsen (sHTG) Olezarsen is on track for topline Phase 3 data in sHTG in September 2025 and announced positive results from the Essence study - Olezarsen is on track for topline Phase 3 data from pivotal CORE and CORE2 studies in sHTG in September 2025[9] - Positive topline results from the Essence study in moderately elevated triglycerides achieved all primary and key secondary endpoints[9] ION582 (Angelman syndrome) The first patient has been dosed in the Phase 3 REVEAL study of ION582 for the rare neurodevelopmental disorder Angelman syndrome - First patient dosed in the Phase 3 REVEAL study of ION582 for Angelman syndrome (AS)[9] Partnered Medicines Partnered medicines WAINUA and SPINRAZA continued strong commercial performance, while key pipeline programs advanced - WAINUATM (eplontersen) continues to perform well, achieving several important commercial milestones[12] - SPINRAZA® (nusinersen) generated global sales of $393 million and $817 million, resulting in royalty revenue of $54 million and $102 million in Q2 and H1 2025, respectively[12] - Biogen will advance salanersen for SMA into registrational studies based on positive interim Phase 1 results[12] - AstraZeneca initiated the Phase 2b study of opemalirsen for AMKD, triggering a $30 million milestone payment[12] WAINUA™ (eplontersen) WAINUA generated $44 million in sales and $10 million in royalty revenue in Q2 2025, with new launches underway in Europe WAINUA Sales and Royalty Revenue | Metric | Q2 2025 (in Millions) | H1 2025 (in Millions) | | :----- | :----------------- | :----------------- | | Sales | $44 | $84 | | Royalty Revenue | $10 | $20 | - New launches are underway in numerous regions, including the EU, with additional submissions in progress to expand global access[12] SPINRAZA® (nusinersen) SPINRAZA generated $393 million in global sales in Q2 2025, with a higher dose of the treatment currently under regulatory review SPINRAZA Global Sales and Royalty Revenue | Metric | Q2 2025 (in Millions) | H1 2025 (in Millions) | | :----- | :----------------- | :----------------- | | Global Sales | $393 | $817 | | Royalty Revenue | $54 | $102 | - A higher dose of nusinersen is under review for marketing approval in the U.S. (PDUFA date of September 22, 2025) and in the EU[12] Salanersen (SMA) Biogen will advance salanersen into registrational studies for SMA following positive interim Phase 1 results showing clinical improvements - Biogen will advance salanersen for SMA into registrational studies based on positive interim Phase 1 results[12] - Phase 1 data showed substantial slowing of neurodegeneration and clinically meaningful improvements in SMA patients previously treated with gene therapy[12] Opemalirsen (AMKD) AstraZeneca initiated a Phase 2b study for opemalirsen in APOL1-mediated kidney disease, triggering a $30 million milestone payment - AstraZeneca initiated the Phase 2b study of opemalirsen for APOL1-mediated kidney disease (AMKD), triggering a $30 million milestone payment to Ionis[12] Corporate Updates & Outlook Corporate Announcements The company announced the planned retirement of its Chief Development Officer and named his successor from within the organization - Richard Geary, Ph.D., Executive Vice President and Chief Development Officer, will retire effective January 2026[11] - Holly Kordasiewicz, Ph.D., Senior Vice President, Neurology, will succeed Richard Geary[11] Upcoming Milestones (2025-2026) Ionis provided a comprehensive roadmap of anticipated new product launches, regulatory actions, and key Phase 3 clinical events New Product Launches (2025-2026) | Program | Indication | 2025 (Anticipated) | 2026 (Anticipated) | | :---------------- | :---------------- | :----------------- | :----------------- | | Donidalorsen (U.S.) | HAE | • | | | TRYNGOLZA (U.S.) | FCS | Achieved | | | WAINZUA (EU) | ATTRv-PN | Achieved | | | Olezarsen (U.S.) | sHTG | | • | | Zilganersen (U.S.)| Alexander disease | | • | Regulatory Actions (2025-2026) | Program | Indication | Regulatory Action | 2025 (Anticipated) | 2026 (Anticipated) | | :---------------- | :---------------- | :-------------------- | :----------------- | :----------------- | | Donidalorsen | HAE | U.S. approval decision| • | | | | | EU approval decision | | • | | TRYNGOLZA | FCS | EU approval decision | • | | | Olezarsen | sHTG | U.S. submission | • | | | | | U.S. approval decision| | • | | Zilganersen | Alexander disease | U.S. submission | | • | | | | U.S. approval decision| | • | | Nusinersen (higher dose) | SMA | U.S. and EU submissions | Achieved | | | | | U.S. approval decision| • | | | WAINZUA | ATTRv-PN | EU approval decision | Achieved | | | Pelacarsen | Lp(a)-CVD | U.S. submission | | • | | Bepirovirsen | HBV | Regulatory submission(s)| | • | | | | Regulatory decision(s)| | • | Key Phase 3 Clinical Events (2025-2026) | Program | Indication | Event | 2025 (Anticipated) | 2026 (Anticipated) | | :---------------- | :---------------- | :-------------------- | :----------------- | :----------------- | | Olezarsen | sHTG | CORE, CORE2 data | • | | | | | Essence data | Achieved | | | Zilganersen | Alexander disease | Phase 3 data | • | | | ION582 | Angelman syndrome | Phase 3 study start | Achieved | | | | | Phase 3 enrollment completion | | • | | Pelacarsen | Lp(a)-CVD | Lp(a) HORIZON data | | • | | Bepirovirsen | HBV | B-Well data | | • | | Eplontersen | ATTR-CM | CARDIO-TTRansform data| | • | | Sefaxersen | IgAN | IMAGINATION data | | • | | Ulefnersen | FUS-ALS | FUSION data | | • | Webcast and Quiet Period Ionis will host a webcast to discuss Q2 results on July 30, 2025, followed by a quiet period ahead of key clinical data release - Management will host a conference call and webcast to discuss Q2 2025 results on Wednesday, July 30, 2025[17] - A quiet period will begin July 31, 2025, until the announcement of topline CORE and CORE2 study results expected in September[18] Marketed Medicines: Indications and Safety Information TRYNGOLZA™ (olezarsen) TRYNGOLZA is an FDA-approved adjunct to diet for adults with FCS, with warnings for hypersensitivity and common adverse reactions - TRYNGOLZA™ (olezarsen) is FDA approved as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS)[19] - Contraindicated in patients with a history of serious hypersensitivity to TRYNGOLZA or any excipients[20] - Warnings and precautions include hypersensitivity reactions (e.g., bronchospasm, facial swelling, urticaria)[21] - Most common adverse reactions (>5% incidence) were injection site reactions, decreased platelet count, and arthralgia[22] WAINUA™ (eplontersen) WAINUA is indicated for ATTRv-PN in adults, with warnings for reduced serum vitamin A levels requiring supplementation - WAINUA injection is indicated for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults[24] - Warnings and precautions include reduced serum Vitamin A levels, requiring supplementation and potential ophthalmologist referral[25] - Most common adverse reactions (≥9%) were vitamin A decreased (15%) and vomiting (9%)[26] Other Marketed Medicines (SPINRAZA®, QALSODY®) QALSODY is approved under accelerated approval based on a reduction in plasma neurofilament light chain, with continued approval contingent on clinical benefit - For more information about SPINRAZA and QALSODY, visit their respective websites[27] - QALSODY is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL), with continued approval contingent upon verification of clinical benefit[27] Company Information & Disclosures About Ionis Pharmaceuticals, Inc. Ionis Pharmaceuticals is a pioneer in RNA-targeted medicines with marketed products and a leading pipeline in neurology and cardiology - For three decades, Ionis has invented medicines that bring better futures to people with serious diseases[28] - Ionis has marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need[28] - As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies and gene editing[28] Forward-looking Statements The press release contains forward-looking statements subject to risks and uncertainties inherent in drug development and commercialization - This press release includes forward-looking statements regarding Ionis' business, financial guidance, and the potential of its medicines[29] - Such statements are subject to risks and uncertainties inherent in discovering, developing, and commercializing human therapeutics[29] - Readers are cautioned not to rely on these forward-looking statements[29] Trademarks and Contacts This section provides company definitions, lists registered trademarks, and includes contact information for investor and media relations - The terms 'Ionis,' 'Company,' 'we,' 'our,' and 'us' refer to Ionis Pharmaceuticals and its subsidiaries[30] - Lists registered trademarks including IONIS®, TRYNGOLZA®, SPINRAZA®, QALSODY®, and WAINUA®[31] - Provides contact information for Ionis Investor Relations and Media Contact[32]