Sefaxersen

罗氏于2025年9月22日在伦敦举办的制药业务日，全面展现了罗氏制药业务的战略布局、研发进展、管线动态及未来增长规划。     在战略层面，罗氏围绕肿瘤/血液学、神经学、免疫学、眼科、心血管/肾脏/代谢（CVRM）五大治疗领域（TA），以“开发变革性药物”为核心目标推进“2020-2029十年制药愿景”，截至2025年已上市10款变革性药物，晚期管线中67%项目具备“同类最优（BID）”潜力，平均管线峰值销售额较2023年提升55%，同时通过“研发卓越计划”优化资源分配，将约11亿瑞士法郎研发节约重新投入高潜力项目，加速管线推进。     研发方面，罗氏建立“研发门槛（TheBar）”评估体系，从未满足需求、靶点重要性、药理特性、治疗差异化、商业价值五大维度筛选项目，目前55%新分子实体（NME）符合标准；通过外部合作与收购（如收购89bio获取Pegozafermin、与Zealand Pharma合作开发Petrelintide）补充管线，2025年已有8款NME进入III期临床，涵盖阿尔茨海默病（Trontinemab）、帕金森病（Prasinezumab）、高血压（Zilebesiran）、肥胖症（CT-388）等领域。各治疗领域管线亮点突出：     技术创新方面：靶向递送技术：解决“难递送”靶点/组织难题   1.Brainshuttle™技术：用于神经疾病药物（如trontinemab、Brainshuttle CD20），通过靶向转铁蛋白受体1（TfR1），将药物血脑屏障穿透率提升8-10倍，突破AD、PD等中枢疾病的递送瓶颈；     2.Port Delivery Platform（PDP）：眼科长效递送系统，如Susvimo（雷珠单抗植入剂），每6个月给药1次，7年随访显示50%患者维持20/40视力，后续将整合VEGF×IL6双抗（DutaFab），实现“抗血管生成+抗炎”双效且减少注射次数。     神经学领域，Fenebrutinib（BTKi）在多发性硬化症（MS）中显示双机制疗效，Trontinemab（抗Aβ单抗）通过血脑屏障高效转运实现快速淀粉样蛋白清除，Prasinezumab（抗α-突触核蛋白单抗）有望成为首个帕金森病疾病修饰疗法；     免疫学领域，Gazyva（抗CD20单抗）在狼疮肾炎III期临床达主要终点，Afimkibart（抗TL1A单抗）在炎症性肠病（IBD）中展现深度缓解潜力，Sefaxersen（补体B因子反义寡核苷酸）针对IgA肾病进入III期；     眼科领域，Vabysmo（双抗）在视网膜血管疾病中持续提升市场份额，Susvimo（端口给药系统）实现每6个月给药，OpRegen（RPE细胞疗法）在地理萎缩中显示视力保护效果；     CVRM领域，构建以肥胖为核心的多元化管线，CT-388（GLP-1/GIP双激动剂）、Petrelintide（长效胰淀素类似物）、CT-996（口服GLP-1激动剂）等在I/II期临床中展现体重降低与代谢改善疗效，Zilebesiran（抗血管紧张素原siRNA）进入III期评估高血压心血管结局，Pegozafermin（FGF21类似物）在非酒精性脂肪性肝炎（MASH）中实现肝纤维化逆转。     商业与运营层面，未来增长依赖“在市产品稳步贡献+管线上市驱动”，聚焦CVRM领域的肥胖、高血压等大病种，计划成为肥胖治疗领域前三企业，结合诊断业务（如Elecsys®pTau217血液检测）与数字健康工具（远程监测、AI辅助决策），构建“诊断-治疗-监测”一体化患者服务体系，支撑长期增长。

CARLSBAD, Calif.--(BUSINESS WIRE)--Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the “Company”) today reported financial results and provided key updates for the second quarter ended June 30, 2025. “During the second quarter, we continued to build momentum across our business,” said Brett P. Monia, Ph.D., chief executive officer of Ionis. “Our strong performance included excellent commercial execution, resulting in a substantial increase in TRYNGOLZA revenues, our first independently launched medicine. We expect additional advancements in the second half, including Ionis’ second independent launch with donidalorsen for hereditary angioedema, anticipated next month, and important Phase 3 results for olezarsen in severe hypertriglyceridemia and zilganersen in Alexander disease. We believe these four programs collectively represent multi-billion-dollar revenue potential and a transformational opportunity for Ionis and for patients.” Second Quarter 2025 Summary Financial Results(1): Three months ended Six months ended June 30, June 30, 2025 2024 2025 2024 (amounts in millions) Total revenue $452 $225 $584 $345 Operating expenses $312 $291 $591 $560 Operating expenses on a non-GAAP basis $282 $260 $532 $498 Income (loss) from operations $140 ($66) ($7) ($215) Income (loss) from operations on a non-GAAP basis $170 ($35) $52 ($153) (1) Reconciliation of GAAP to non-GAAP basis contained later in this release. Recent Financial Highlights Revenue doubled in the second quarter of 2025 and increased nearly 70% in the first half compared to the same period last year, driven by the continued successful launch of TRYNGOLZA and increased royalty and R&D revenues Operating expenses increased by single digits in the second quarter and first half of 2025, compared to the same periods last year, primarily due to investments related to commercialization efforts for TRYNGOLZA, donidalorsen and WAINUA Increased 2025 financial guidance reflects an improved outlook for the full year, strong overall revenue performance experienced year-to-date, including the early strength in TRYNGOLZA revenues: 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 Second Quarter 2025 Financial Results “For the second time this year, we are significantly raising our 2025 financial guidance — this time driven by an improved outlook for the year and strong revenue performance to date, which includes the early launch excellence with TRYNGOLZA. In addition to strong commercial performance, our second quarter results included the substantial revenue we earned from licensing sapablursen, a medicine outside our core areas of focus. We are in a strong financial position, with a commitment to drive operating leverage as we continue executing on our strategic priorities,” said Elizabeth L. Hougen, chief financial officer, Ionis. “Moving forward, the three additional independent launches anticipated over the next eighteen months, including donidalorsen for hereditary angioedema, olezarsen in severe hypertriglyceridemia and zilganersen in Alexander disease, position Ionis to deliver substantial and growing product revenue. This product revenue, coupled with anticipated increasing royalty revenue from multiple partner launches, along with disciplined investment, position Ionis to achieve sustained growth and positive cash flow in the next few years.” Recent Highlights - Wholly Owned Medicines TRYNGOLZA TM (olezarsen), the first and only FDA approved treatment for adults living with familial chylomicronemia syndrome (FCS) as an adjunct to diet Generated net product sales of $19 million in the second quarter of 2025, its second full quarter on the market, and $26 million in the first half of 2025 Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), paving the way to bring TRYNGOLZA to patients across Europe Generated net product sales of $19 million in the second quarter of 2025, its second full quarter on the market, and $26 million in the first half of 2025 Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), paving the way to bring TRYNGOLZA to patients across Europe Olezarsen on track for topline Phase 3 data from pivotal CORE and CORE2 studies in patients with sHTG in September 2025, positioning olezarsen to potentially treat this second, more prevalent patient population with high unmet need Announced positive topline results from the Essence study in people with moderately elevated triglycerides; achieved primary and all key secondary endpoints for 80 mg and 50 mg monthly doses with favorable safety and tolerability Announced positive topline results from the Essence study in people with moderately elevated triglycerides; achieved primary and all key secondary endpoints for 80 mg and 50 mg monthly doses with favorable safety and tolerability Donidalorsen on track to launch this year, assuming approval, with a U.S. PDUFA date of August 21, 2025 Poised to transform the treatment paradigm for individuals with hereditary angioedema (HAE) as the first and only RNA-targeted prophylactic therapy that has the potential to offer durable efficacy, a favorable safety and tolerability profile, and the longest available dosing interval, with self-administration via autoinjector monthly or every other month Donidalorsen is currently under regulatory review in the EU Poised to transform the treatment paradigm for individuals with hereditary angioedema (HAE) as the first and only RNA-targeted prophylactic therapy that has the potential to offer durable efficacy, a favorable safety and tolerability profile, and the longest available dosing interval, with self-administration via autoinjector monthly or every other month Donidalorsen is currently under regulatory review in the EU First patient dosed in the Phase 3 REVEAL study of ION582, an investigational medicine for the treatment of people living with Angelman syndrome (AS), a serious and rare neurodevelopmental disorder Recent Highlights – Partnered Medicines WAINUA TM (eplontersen) (WAINZUA in EU) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) continues to perform well, achieving several important commercial milestones: Generated sales of $44 million and $84 million resulting in royalty revenue of $10 million and $20 million in the second quarter and first half of 2025, respectively New launches underway in numerous regions, including the EU; additional submissions in progress to expand WAINUA access globally Generated sales of $44 million and $84 million resulting in royalty revenue of $10 million and $20 million in the second quarter and first half of 2025, respectively New launches underway in numerous regions, including the EU; additional submissions in progress to expand WAINUA access globally SPINRAZA ® (nusinersen) for the treatment of spinal muscular atrophy (SMA) generated global sales of $393 million and $817 million resulting in royalty revenue of $54 million and $102 million in the second quarter and first half of 2025, respectively Higher dose nusinersen under review for marketing approval in the U.S. (PDUFA date of September 22, 2025) and in the EU Higher dose nusinersen under review for marketing approval in the U.S. (PDUFA date of September 22, 2025) and in the EU Biogen to advance salanersen (formerly ION306/BIIB115), an investigational medicine for SMA into registrational studies based on positive interim Phase 1 results; developed using novel Ionis antisense chemistry with the potential to achieve high efficacy and annual dosing Phase 1 data with salanersen in SMA patients showed substantial slowing of neurodegeneration and clinically meaningful improvements in patients previously treated with gene therapy Phase 1 data with salanersen in SMA patients showed substantial slowing of neurodegeneration and clinically meaningful improvements in patients previously treated with gene therapy AstraZeneca initiated the Phase 2b study of opemalirsen (formerly ION532/AZD2373), an investigational medicine designed to reduce the production of apolipoprotein L1 (APOL1) for the treatment of APOL1-mediated kidney disease (AMKD) triggering a $30 million milestone payment to Ionis Corporate Updates In June 2025, Ionis announced that Richard Geary, Ph.D., executive vice president and chief development officer, will retire effective January 2026 and that Holly Kordasiewicz, Ph.D., currently senior vice president, neurology, will succeed him in the role Revenue Ionis’ revenue was comprised of the following: Three months ended Six months ended June 30, June 30, 2025 2024 2025 2024 Revenue: (amounts in millions) Commercial revenue: Product sales, net: TRYNGOLZA sales, net $19 $- $26 $- Total product sales, net 19 - 26 - Royalty revenue: SPINRAZA royalties 54 57 102 95 WAINUA royalties 10 4 20 5 Other royalties 6 3 12 13 Total royalty revenue 70 64 134 113 Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 14 8 19 17 Other revenue - - - 2 Total commercial revenue 103 72 179 132 Research and development revenue: Collaborative agreement revenue 337 141 382 191 WAINUA joint development revenue 12 12 23 22 Total research and development revenue 349 153 405 213 Total revenue $452 $225 $584 $345 Commercial revenue for the second quarter and first half of 2025 increased 43% and 36% respectively, compared to the same periods in 2024. This increase was 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., reflecting the value that Ionis’ pipeline and technology continues to generate. Operating Expenses SG&A expenses increased as anticipated for the second quarter and first half of 2025, compared to the same periods in 2024, primarily due to the launches of TRYNGOLZA and WAINUA, and advancing launch preparation activities for donidalorsen. This increase was partially offset by a decrease in R&D expenses as several late-stage studies ended. Overall, this led to a modest year-over-year increase in total operating expenses. Balance Sheet As of June 30, 2025, Ionis’ cash, cash equivalents and short-term investments were $2.3 billion, consistent with December 31, 2024. Ionis received $280 million from the global license of sapablursen in the second quarter of 2025. Ionis’ working capital decreased over the same period primarily due to the reclassification of the Company’s 0% convertible notes as a current liability. Webcast and Other Updates Management will host a conference call and webcast to discuss Ionis’ second quarter 2025 results at 11:30 a.m. Eastern time on Wednesday, July 30, 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 second quarter 2025 earnings slides click here. Ionis will be initiating a quiet period starting July 31, 2025, as the Company plans to announce the topline results from both the CORE and CORE2 studies simultaneously. The quiet period will be lifted upon the data announcement, expected in September. 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 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, cardiology, and other 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, 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. 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 Six months ended June 30, June 30, 2025 2024 2025 2024 (unaudited) Revenue: Commercial revenue: Product sales, net $19 $- $26 $- Royalty revenue 70 64 134 113 Other commercial revenue 14 8 19 19 Total commercial revenue 103 72 179 132 Research and development revenue: Collaborative agreement revenue 337 141 382 191 WAINUA joint development revenue 12 12 23 22 Total research and development revenue 349 153 405 213 Total revenue 452 225 584 345 Expenses: Cost of sales 4 4 6 6 Research, development and patent 217 222 418 436 Selling, general and administrative 91 65 167 118 Total operating expenses 312 291 591 560 Income (loss) from operations 140 (66) (7) (215) Other income (expense): Interest expense related to the sale of future royalties (19) (18) (37) (36) Other income, net 3 18 21 42 Income (loss) before income tax benefit (expense) 124 (66) (23) (209) Income tax benefit (expense) - - - - 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) Shares used in computing basic net income (loss) per share 159 146 159 146 Shares used in computing diluted net income (loss) per share 182 146 159 146 IONIS PHARMACEUTICALS, INC. Reconciliation of GAAP to Non-GAAP Basis: Condensed Consolidated Operating Expenses, Income (Loss) From Operations, and Net Income (Loss) (In Millions) Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 (unaudited) As reported research, development and patent expenses according to GAAP $217 $222 $418 $436 Excluding compensation expense related to equity awards (20) (23) (40) (45) Non-GAAP research, development and patent expenses $197 $199 $378 $391 As reported selling, general and administrative expenses according to GAAP $91 $65 $167 $118 Excluding compensation expense related to equity awards (10) (8) (19) (17) Non-GAAP selling, general and administrative expenses $81 $57 $148 $101 As reported operating expenses according to GAAP $312 $291 $591 $560 Excluding compensation expense related to equity awards (30) (31) (59) (62) Non-GAAP operating expenses $282 $260 $532 $498 As reported income (loss) from operations according to GAAP $140 ($66) ($7) ($215) Excluding compensation expense related to equity awards (30) (31) (59) (62) Non-GAAP income (loss) from operations $170 ($35) $52 ($153) As reported net income (loss) according to GAAP $124 ($66) ($23) ($209) Excluding compensation expense related to equity awards and related tax effects (30) (31) (59) (62) Non-GAAP net income (loss) $154 ($35) $36 ($147) Reconciliation of GAAP to Non-GAAP Basis As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP income (loss) from operations, and non-GAAP net income (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) June 30, December 31, 2025 2024 (unaudited) Assets: Cash, cash equivalents and short-term investments $2,290 $2,298 Contracts receivable 53 92 Other current assets 235 230 Property, plant and equipment, net 112 94 Right-of-use assets 164 162 Other assets 131 127 Total assets $2,985 $3,003 Liabilities and stockholders’ equity: Current portion of deferred contract revenue $76 $79 0% convertible senior notes, net – current 630 - Other current liabilities 191 229 1.75% convertible senior notes, net 566 565 0% convertible senior notes, net - 629 Liability related to sale of future royalties, net 541 542 Long-term lease liabilities 164 162 Long-term obligations, less current portion 60 52 Long-term deferred contract revenue 125 157 Total stockholders’ equity 632 588 Total liabilities and stockholders’ equity $2,985 $3,003 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 Achieved 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 Achieved 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 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 • (1) Timing expectations based on current assumptions and subject to change. Indicates that the milestone is anticipated in the respective year.