Sefaxersen

- First independent launch underway following TRYNGOLZATM approval - - Second independent launch on track with donidalorsen PDUFA - - WAINUATM launch delivering accelerating sequential growth - - Ionis exceeds 2024 financial guidance and provides full year 2025 guidance - CARLSBAD, Calif. --(BUSINESS WIRE)--Feb. 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): Three months ended December 31 , Year ended December 31 , 2024 2023 2024 2023 (amounts in millions) Total revenue $ 227 $ 325 $ 705 $ 788 Operating expenses $ 337 $ 331 $ 1,180 $ 1,141 Operating expenses on a non-GAAP basis $ 301 $ 305 $ 1,050 $ 1,035 Loss from operations $ (110 ) $ (6 ) $ (475 ) $ (353 ) Income (Loss) from operations on a non-GAAP basis $ (74 ) $ 20 $ (345 ) $ (247 ) (1) Reconciliation of GAAP to non-GAAP basis contained later in this release. Financial Highlights Revenue for the year ended December 31, 2024 substantially exceeded guidance as Ionis continued to generate revenue from diverse sources. Ionis added new sources of revenue in 2024 with the launch of WAINUA and TRYNGOLZA in the U.S. in late January and late December, respectively Operating expenses for the year ended December 31, 2024 were in line with expectations with increased expenses from commercialization efforts for WAINUA, TRYNGOLZA and donidalorsen Cash, cash equivalents and short-term investments of $2.3 billion as of December 31, 2024 exceeded revised guidance and enable continued investments to support ongoing and upcoming planned launches and advancing wholly owned medicines in development Recent Highlights- Marketed Medicines TRYNGOLZATM (olezarsen) launch underway following approval on December 19, 2024 in the U.S as first-ever treatment for adults living with familial chylomicronemia syndrome (FCS) as an adjunct to diet WAINUATM (eplontersen) (WAINZUA in EU) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) achieved multiple commercial and regulatory milestones: Generated sales of $85 million resulting in royalty revenue of $20 million in the year ended December 31, 2024 . Substantial sequential growth throughout 2024 as launch progressed, including an 84% increase in product sales in the fourth quarter, compared to the third quarter Launch underway in numerous countries, including the UK , following approval by the Medicines and Healthcare products Regulatory Agency (MHRA) with an accelerated National Institute for Health and Care Excellence (NICE) recommendation Received positive Committee for Medicinal Products for Human Use (CHMP) opinion from European Medicines Agency (EMA) for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy SPINRAZA® (nusinersen) for the treatment of spinal muscular atrophy (SMA) generated global sales of $1.6 billion resulting in royalty revenue of $216 million in year ended December 31, 2024 . Product sales increased 2% in the fourth quarter of 2024, compared to the same period in 2023 Higher dose nusinersen under regulatory review in U.S. (PDUFA date of September 22, 2025 ) and EU QALSODY® (tofersen) for the treatment of SOD1-ALS generated global sales of $32 million resulting in royalty revenue of $4 million in the year ended December 31, 2024 . Product sales grew sequentially throughout 2024 Granted marketing approval in China and Japan Generated sales of $85 million resulting in royalty revenue of $20 million in the year ended December 31, 2024 . Substantial sequential growth throughout 2024 as launch progressed, including an 84% increase in product sales in the fourth quarter, compared to the third quarter Launch underway in numerous countries, including the UK , following approval by the Medicines and Healthcare products Regulatory Agency (MHRA) with an accelerated National Institute for Health and Care Excellence (NICE) recommendation Received positive Committee for Medicinal Products for Human Use (CHMP) opinion from European Medicines Agency (EMA) for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy Higher dose nusinersen under regulatory review in U.S. (PDUFA date of September 22, 2025 ) and EU Granted marketing approval in China and Japan Recent Highlights- Late-Stage Pipeline Olezarsen on track for Phase 3 data in patients with severe hypertriglyceridemia (sHTG) in H2:2025, positioning it to potentially treat this second more prevalent patient population with urgent unmet need Olezarsen and donidalorsen Canadian commercialization rights licensed to Theratechnologies Donidalorsen on track for potential launch this year as the first RNA-targeted prophylactic treatment for people with hereditary angioedema (HAE): Under review in U.S. (PDUFA date of August 21, 2025 ) and EU Presented positive Phase 2 open label extension (OLE) study data demonstrating an overall sustained mean reduction in HAE attack rates of 96% in patients treated up to three years with every four weeks or every eight weeks dosing ION582 on track to initiate Phase 3 development in Angelman syndrome (AS) in H1:2025 Ulefnersen global commercialization rights licensed to Otsuka; Phase 3 development ongoing for the treatment of patients with FUS-ALS Under review in U.S. (PDUFA date of August 21, 2025 ) and EU Presented positive Phase 2 open label extension (OLE) study data demonstrating an overall sustained mean reduction in HAE attack rates of 96% in patients treated up to three years with every four weeks or every eight weeks dosing 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.” Revenue Ionis’ revenue was comprised of the following: Three months ended Year ended December 31 , December 31 , 2024 2023 2024 2023 Revenue: (amounts in millions) Commercial revenue: SPINRAZA royalties $ 64 $ 62 $ 216 $ 240 WAINUA royalties 10 - 20 - Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 8 9 34 35 Other revenue 4 8 23 34 Total commercial revenue 86 79 293 309 Research and development revenue: Amortization from upfront payments 27 76 132 125 Milestone payments 30 11 106 101 License fees 34 92 71 117 Other services 6 - 24 10 Collaborative agreement revenue 97 179 333 353 WAINUA joint development revenue 44 67 79 126 Total research and development revenue 141 246 412 479 Total revenue $ 227 $ 325 $ 705 $ 788 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 recur in 2024. 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. Operating Expenses 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. Balance Sheet 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. Full Year 2025 Guidance Revenue > $600 million Operating loss on a non-GAAP basis < $495 million Cash, cash equivalents and short-term investments ~$1.7 billion Webcast 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 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 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 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 and follow us on X (Twitter), LinkedIn and Instagram. 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 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 , 2024 2023 2024 2023 (unaudited) Revenue: Commercial revenue: SPINRAZA royalties $ 64 $ 62 $ 216 $ 240 WAINUA royalties 10 - 20 - Other commercial revenue 12 17 57 69 Total commercial revenue 86 79 293 309 Research and development revenue: Collaborative agreement revenue 97 179 333 353 WAINUA joint development revenue 44 67 79 126 Total research and development revenue 141 246 412 479 Total revenue 227 325 705 788 Expenses: Cost of sales 4 3 11 9 Research, development and patent 245 257 902 900 Selling, general and administrative 88 71 267 232 Total operating expenses 337 331 1,180 1,141 Loss from operations (110 ) (6 ) (475 ) (353 ) Other income (expense): Interest expense related to the sale of future royalties (19 ) (18 ) (73 ) (69 ) Other income, net 22 21 88 88 Loss before income tax benefit (expense) (107 ) (3 ) (460 ) (334 ) Income tax benefit (expense) 3 (6 ) 6 (32 ) Net loss $ (104 ) $ (9 ) $ (454 ) $ (366 ) Basic and diluted net loss per share $ (0.66 ) $ (0.06 ) $ (3.04 ) $ (2.56 ) Shares used in computing basic and diluted net loss per share 158 144 150 143 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 , 2024 2023 2024 2023 (unaudited) As reported research, development and patent expenses according to GAAP $ 245 $ 257 $ 902 $ 900 Excluding compensation expense related to equity awards (25 ) (20 ) (92 ) (78 ) Non-GAAP research, development and patent expenses $ 220 $ 237 $ 810 $ 822 As reported selling, general and administrative expenses according to GAAP $ 88 $ 71 $ 267 $ 232 Excluding compensation expense related to equity awards (11 ) (6 ) (37 ) (27 ) Non-GAAP selling, general and administrative expenses $ 77 $ 65 $ 230 $ 205 As reported operating expenses according to GAAP $ 337 $ 331 $ 1,180 $ 1,141 Excluding compensation expense related to equity awards (36 ) (26 ) (130 ) (106 ) Non-GAAP operating expenses $ 301 $ 305 $ 1,050 $ 1,035 As reported loss from operations according to GAAP $ (110 ) $ (6 ) $ (475 ) $ (353 ) Excluding compensation expense related to equity awards (36 ) (26 ) (130 ) (106 ) Non-GAAP loss from operations $ (74 ) $ 20 $ (345 ) $ (247 ) As reported net loss according to GAAP $ (104 ) $ (9 ) $ (454 ) $ (366 ) Excluding compensation expense related to equity awards and related tax effects (36 ) (26 ) (130 ) (106 ) Non-GAAP net loss $ (68 ) $ 17 $ (324 ) $ (260 ) 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 , 2024 2023 (unaudited) Assets: Cash, cash equivalents and short-term investments $ 2,298 $ 2,331 Contracts receivable 92 98 Other current assets 230 213 Property, plant and equipment, net 94 71 Right-of-use assets 162 172 Other assets 127 105 Total assets $ 3,003 $ 2,990 Liabilities and stockholders’ equity: Current portion of deferred contract revenue $ 79 $ 151 0.125% convertible senior notes, net – short-term - 44 Other current liabilities 229 253 1.75% convertible senior notes, net 565 562 0% convertible senior notes, net 629 625 Liability related to sale of future royalties, net 542 514 Long-term lease liabilities 162 171 Long-term obligations, less current portion 52 42 Long-term deferred contract revenue 157 241 Total stockholders’ equity 588 387 Total liabilities and stockholders’ equity $ 3,003 $ 2,990 Key 2025 and 2026 Value Driving Events(1) New Product Launches Program Indication 2025 2026 Donidalorsen ( U.S. ) HAE • TRYNGOLZA ( U.S. ) FCS Achieved WAINZUA (EU) ATTRv-PN • Olezarsen ( U.S. ) sHTG • Zilganersen ( U.S. ) Alexander disease • Regulatory Actions Program Indication Regulatory Action 2025 2026 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 • Pelacarsen Lp(a)- CVD U.S. submission • Bepirovirsen HBV Regulatory submission(s) • Regulatory decision(s) • Key Phase 3 Clinical Events Program Indication Event 2025 2026 Olezarsen sHTG CORE, CORE2 and Essence data • Zilganersen Alexander disease Phase 3 data • ION582 Angelman syndrome Phase 3 study start • Phase 3 enrollment completion • Pelacarsen Lp(a)-CVD HORIZON data • Bepirovirsen HBV B-Well data • Eplontersen ATTR-CM CARDIO-TTRansform data • Sefaxersen IgAN IMAGINATION data • Ulefnersen FUS-ALS Phase 3 data • (1) Timing expectations based on current assumptions and subject to change. • View source version on businesswire.com: https://www.businesswire.com/news/home/20250219347982/en/ 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 Source: Ionis Pharmaceuticals, Inc.