Sapablursen

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.

更多精彩，请点击上方蓝字关注我们！ 【华西医药崔文亮团队】️我们2026年2月2日最新发布详细【23页】️《小核酸药物行业深度研究报告：RNA 精准医疗时代的崛起与挑战》 摘要 ►小核酸药物凭借技术突破性与治疗差异化，成为精准医疗核心赛道 投资价值聚焦技术突破与临床转化，小核酸药物通过 ASO、siRNA等类型在 mRNA 水平调控基因，突破传统 “不可成药”靶点局限，覆盖上万种罕见病及慢性病相关靶点；化学修饰（如 PS、2'-O-Me）解决稳定性与免疫原性问题，使药物半衰期大幅延长，免疫原性降低；递送系统持续升级：GalNAc 技术推动肝靶向药物商业化（如英克司兰），LNP、TRiM等肝外递送技术突破肌肉、CNS 靶向瓶颈，打开 5 亿潜在患者市场。同时，AI 赋能序列设计降低脱靶风险，研发周期较抗体药物缩短，早期成本降低，临床转化效率显著提升。 ►全球市场加速扩容且结构优化，行业进入高增长期 根据沙利文数据，2019-2024年全球市场规模从 27 亿美元增至57 亿美元（CAGR=16.2%），预计 2029 年达206亿美元（CAGR=29.4%），增长动力来自慢性病放量（全球高血脂患者超 10 亿、乙肝携带者超 2.5 亿）、肝外技术突破及重磅药商业化（如英克司兰 2024 年销售额7.5 亿美元，yoy+114%）。当前全球 19 款在售药物中50%+ 针对罕见病，但慢性病占比将逐步提升，且定价机制灵活（罕见病药通过医保谈判降价换量，慢性病药凭长效性降成本）。行业呈 “国际龙头主导+ 本土突围” 格局，Alnylam（7款上市药）、Ionis（9款上市药）凭技术壁垒占据主导，本土企业如瑞博生物（血栓管线全球领先）、舶望制药（与诺华 90 亿美元合作）聚焦细分领域。 ►风险与机遇并存，需平衡技术迭代与商业化落地 2025年是小核酸元年，领域催化不断：诺华降脂针英克司兰获美国FDA批准一线用药地位；Alnylam的Amvuttra获批ATTR CM适应症，2025Q3销售大超预期，有望成为首个销售额突破20亿美元的小核酸重磅药物；GSK 乙肝药物Bepirovirsen达到三期临床终点。Ionis的olezarsen大适应症sHTG 3期临床达到终点。 接下来：诺华LP（a）药物Pelacarsen将于2026H1读出3期临床数据；减肥领域，INHBE靶点和ALK7靶点数据持续验证；后续还有多个靶点临床数据持续读出。 我们建议标的筛选可围绕三类方向：临床进度型（III 期数据关键标的 + 医保受益标的）、技术平台型（肝外递送 + 多靶点技术企业）、国际化合作型（获 MNC 背书的本土企业），把握新药上市与数据读出窗口期，捕捉技术突破与商业化放量双重红利。 受益标的：瑞博生物、舶望制药、中国生物制药、悦康药业、必贝特、前沿生物等； ►风险提示 研发失败风险（如脱靶致肝损伤、CRISPR 技术替代）、政策变动（医保谈判降价超预期）及专利纠纷风险（国际龙头上千项专利构筑壁垒） 目录 正文 1.行业综述：从基因调控到药物革命 小核酸技术优势与分类：从“不可成药” 到 “精准可及”。与传统小分子药物、抗体药物不同，小核酸药物核心在于通过 siRNA（小干扰 RNA）、ASO（反义寡核苷酸antisense oligonucleotides）、miRNA（微小 RNA）等短链核酸分子，在转录后水平实现对基因表达的精准调控，由此具备三大传统药物难以企及的核心优势。 1.突破“不可成药” 靶点局限：传统药物受作用机制限制，难以靶向转录因子、非编码 RNA 等与疾病密切相关的靶点，而这类靶点在超上万种罕见病及慢性病的发病机制中扮演关键角色。根据弗若斯特沙利文，在约20,000种人类蛋白质中，传统小分子药物仅能靶向约15%的可成药蛋白。抗体药物虽在一定程度上扩展了靶向范围，但仍局限于细胞表面蛋白质，无法触及占人体蛋白质总量约80%的细胞内蛋白质。目前已获批疗法特异性靶向的人类蛋白质靶点总数不足700个。小核酸药物凭借碱基互补配对的特异性，可直接作用于这些 “不可成药” 靶点，为疾病治疗开辟新路径。例如，针对脊髓性肌萎缩症（SMA）的 ASO 药物诺西那生钠，正是通过靶向 SMN2 基因，弥补了传统药物无法干预该疾病关键基因的空白。 2.精准性与长效性双重优势：在精准性上，小核酸药物通过严格的碱基互补配对沉默靶基因，脱靶率较小分子药物大幅降低，显著提升治疗安全性；在长效性上，其半衰期大幅延长，以降脂 siRNA 药物英克司兰为例，每 6 个月给药 1 次即可维持疗效，较传统每日口服降脂药，患者用药负担大幅降低，治疗依从性提升。 3.研发效率与临床开发成功率显著：基于序列设计的模块化开发模式，小核酸药物研发周期较抗体药物缩短 2-3 年；根据Alnylam披露的数据，在临床1期至3期阶段，其累计转化率达到64.4%，而靶向药领域、医药行业整体的转化率分别只有10.3%和5.7%，小核酸临床转化率显著。 小核酸药物家族涵盖多种类型，1998年首款ASO药物获批后，小核酸疗法历经数代创新：早期ASO受生物利用度差、脱靶等问题限制，同年RNAi机制被发现，siRNA因特异性基因沉默能力、靶向难成药靶点的潜力，成为罕见遗传病、慢病、癌症等的治疗工具。 siRNA转化为临床疗法耗时二十余年，攻克了递送等技术难题，Insight数据显示，目前全球仅23款siRNA药物上市，靶向递送、化学修饰的进步使其进入发展转折点，预计未来十年临床与商业应用将显著增长；当前上百个siRNA候选药处于临床阶段。 核心技术突破：推动行业商业化落地，构筑投资护城河。小核酸药物的商业化进程，本质是技术瓶颈持续突破的过程，化学修饰、递送系统、合成与筛选三大核心技术的创新，共同推动行业从实验室走向临床。 1.化学修饰：解决稳定性与免疫原性难题，奠定商业化基础。早期小核酸药物因未修饰核酸在体内易被核酸酶降解，半衰期很短，且易引发免疫反应。siRNA的化学修饰主要集中在三个关键位置：糖修饰（2'-O－甲基和2'－氟）、主链修饰（硫代磷酸酯键）和末端修饰（3'和5'端）。这些修饰在保持基因沉默活性的同时，战略性地抑制免疫刺激效应，增强核酸酶抗性，提高靶向特异性。最佳修饰模式需要平衡，以实现最大的稳定性和有效性，同时最大限度地减少脱靶毒性。 2.递送系统：突破组织靶向性限制，打开千亿增量市场。递送系统是小核酸药物发挥疗效的关键，不同递送技术针对不同组织靶点形成差异化解决方案： 肝靶向递送成熟化：GalNAc（N-乙酰半乳糖胺）偶联技术成为主流，利用了去唾液酸糖蛋白受体(ASGPR)在肝细胞上的高表达，实现了受体介导的内吞作用。GalNAc-siRNA偶联物具有高效、安全性好、效果持久等优势。  肝外递送突破：脂质纳米颗粒（LNP）、病毒载体（如 AAV 变体）等技术突破肌肉、中枢神经系统（CNS）递送障碍。Arrowhead公司的 TRiM 平台通过转铁蛋白受体 1 介导，突破血脑屏障，为阿尔茨海默病等 CNS 疾病治疗提供可能。 3. siRNA合成与筛选技术：siRNA疗法的开发涉及一个涵盖设计、合成和筛选的系统性过程。siRNA疗法的设计不仅着重于与靶向疾病基因互补的RNA序列，还力求避免潜在作用于其他基因（已知的其他脱靶效应）或触发身体的免疫反应。目前已经探索使用多种siRNA合成路径，包括通过化学合成、体外转录和载体表达系统来产生功能性siRNA分子，但处于临床和临床前开发阶段的siRNA疗法大多是通过使用固相RNA合成仪进行化学合成生产的，而液相合成siRNA以及酶促合成siRNA的方法也已经过尝试并取得了初步成功。 2.市场扩容：从罕见病到常见病的扩张之路 全球小核酸药物市场增长强劲且持续：根据沙利文数据，2019-2024年全球小核酸药物市场规模从 27 亿美元增长至 57 亿美元，年复合增长率（CAGR）达16.2%；其中2024年siRNA药物市场占比达44.5%，有望在未来十年占据更大的市场份额，超过其他小核酸药物。受益于慢性病适应症拓展与肝外递送技术突破，预计 2029 年市场规模可达 206 亿美元，2034 年进一步升至 549 亿美元；其中 2024-2029 年CAGR为 29.4%，2029-2034 年为 21.6%。核心驱动因素如下： 1、重磅品种放量：BI的脊髓性肌肉萎缩症（SMA）治疗药物诺西那生钠自 2016 年美国上市以来，全球累计销售额超 138 亿美元，2023 年销售额达 17.4 亿美元；诺华的长效降脂药英克司兰 2024 年销售额 7.5 亿美元（yoy+114%），成为首个年销售额突破 5 亿美元的慢性病小核酸药物。 2、适应症从罕见病向慢性病延伸：截至 2026年1 月，全球已上市小核酸药物共 23款（撤市2款），包括15款ASO药物、8款siRNA药物。其中约 80% 用于治疗罕见遗传病如SMA（脊髓性肌萎缩症）、DMD（杜氏肌营养不良症）、hATTR（遗传性转甲状腺素蛋白淀粉样变性）等，少数产品用于心血管（如 Inclisiran）、代谢等常见病领域。根据沙利文数据，2024 年全球小核酸药物市场规模达约60 亿美元，其中罕见病药物贡献了超50%的销售额。核心产品包括Spinraza（SMA，2024 年销售额 15.7 亿美元）、AMVUTTRA（hATTR，2024 年销售额 9.7 亿美元）、Onpattro（hATTR，2024 年销售额 2.53 亿美元）、DMD 领域 4 款 ASO 药物（2024 年合计销售额超 11.2 亿美元）等。随着 Inclisiran（高血脂）等慢病小核酸药物的快速放量，以及更多慢病适应症产品获批上市，预计罕见病在小核酸药物市场的占比将逐步下降。结构变化系：1）慢病患者基数庞大（如高血脂患者全球超 10 亿，乙肝病毒携带者超 2.5 亿），市场空间远超罕见病；2）小核酸药物的长效优势（如1年 2 针）在慢病管理中具有显著价值，提升患者依从性； 3、技术突破推动用药人群扩大：GalNAc 修饰技术使肝靶向药物适用人群从罕见病患者（约 10 万人）扩展至慢性病患者（超10亿人）；肝外递送技术突破后，肌肉、CNS 疾病患者（约 5 亿人）成为潜在市场，进一步扩大行业空间。2025年，全球小核酸领域交易活动频繁，已披露30多笔BD合作，交易总额超过360亿美元，同比激增超300%。 海外龙头主导，本土企业差异化突围。根据瑞博生物招股书显示，海外龙头 Alnylam（siRNA 领域）拥有7款上市药物，其中多款自主商业化（如Onpattro、Givlaari、Oxlumo、Amvuttra），2 款通过授权合作商业化（Leqvio 由诺华、Qfitlia 由赛诺菲负责）； 中国市场：从进口依赖到国产创新突围。中国小核酸药物已上市6款，均为进口药（诺西那生钠、英克司兰等）；本土企业通过聚焦细分领域实现突破，不少上市药企如中生制药（通过全资收购赫吉亚生物）、恒瑞医药、石药集团等均有管线进入临床，但基本处于早期阶段；根据insight数据，截至2026年1月，中国小核酸药物在研管线超 100 条，主要聚焦慢性病（高血脂、乙肝、肾病）肿瘤以及罕见病，慢性病占比显著提升，体现本土企业向大适应症倾斜的战略方向。 3.竞争格局：全球巨头引领行业，本土企业 “差异化突围” 3.1.国际龙头企业：技术壁垒构筑行业护城河 国际龙头凭借技术积累、管线布局与商业化能力，占据全球市场主导地位，部分核心企业优势如下： 1. Alnylam Pharmace（ALNY.O）：siRNA 领域绝对领导者 核心产品矩阵稳健放量，商业化进入盈利兑现期。作为全球RNAi疗法开创者，截至2026 年 1 月，公司已构建7款商业化产品梯队，2025年前三季度公司实现营收26.2亿美元、净利润1.27亿美元，首次实现连续盈利，经营活动现金流净额达3.61亿美元，商业化成效显著。核心品种Amvuttra（Vutrisiran）针对ATTR淀粉样变性，凭借“每3个月一针”的长效优势快速替代传统疗法，2025H1销售额达8.02亿美元（yoy+88.5%），同时持续拓展新适应症，即将在全球多地启动ATTR心肌病适应症上市；Patisiran作为首款RNAi疗法，于2018年获批，HELIOS-B III期数据证实可降低全因死亡率28.2%，稳固罕见病治疗标杆地位。公司产品覆盖全球主要市场，依托成熟销售网络实现持续渗透，TTR淀粉样变性领域市场份额超60%。 技术平台壁垒深厚，研发效率行业领先。公司自主ESC+ GalNAc化学修饰技术平台，实现siRNA药物“高效肝靶向+长效持久+高安全性”三重突破，根据公司披露数据，在临床1期至3期阶段，其累计转化率达到64.4%，而靶向药领域、医药行业整体的转化率分别只有10.3%和5.7%。该平台支撑了除首款产品外的所有商业化及后期管线开发，同时通过1200项全球专利构建知识产权护城河，覆盖GalNAc靶头、连接臂等核心环节，有效阻碍竞争者入局。此外，公司前瞻性布局C16等肝外递送技术，拓展RNAi疗法在神经、肺部等领域的应用场景，技术平台的延展性为长期增长奠定基础。 创新管线全球领先，慢病与肝外赛道突破行业瓶颈。公司以ESC+ GalNAc核心平台为基础，布局覆盖心代谢、CNS、罕见病等领域的全周期管线，多款产品推进关键临床，部分如下： ①Zilebesiran（长效降压）：与罗氏合作开发的靶向AGT siRNA疗法，每半年给药一次即可实现持久降压，II期数据显示300mg剂量组24h收缩压降幅达16.7mmHg，2026年1月已获中国NMPA临床批准，全球关键III期试验正在推进，直面全球12亿高血压患者，合作潜在交易额达28亿美元，获3.1亿美元首付款加持； ②ALN-APP（CNS疾病）：采用自主C16肝外递送平台，靶向阿尔茨海默病相关蛋白，通过鞘内注射实现脑部靶向，I期数据证实可显著降低致病蛋白水平，有望突破RNAi疗法局限于肝脏的行业瓶颈； ③Nucresiran注射液：基于IKARIA平台开发，单次给药可实现TTR蛋白水平降低超90%，持续疗效达6个月，2026年1月获中国批准临床，针对ATTR淀粉样变性的两项关键III期研究正在开展，具备每半年或每年给药的潜力。 2. Ionis Pharmaceuticals（IONS.O）： ASO龙头商业化加速+后期管线密集兑现 核心产品矩阵持续扩容，商业化进入价值释放期。作为全球反义寡核苷酸（ASO）疗法开创者，截至2026年1月，9款药物获批上市，2025年前三季度实现营收7.4亿美元（yoy+54.7%），核心驱动力来自新增获批产品与成熟品种的稳步渗透。2025年8月，首款RNA靶向遗传性血管水肿（HAE）治疗药物Dawnzera(donidalorsen）获FDA批准上市，成为全球首个针对遗传性血管性水肿的ASO疗法，III期数据显示每4周给药可使患者月均发作率降低81%，中重度发作减少90%，长效给药方案（每4-8周一次）显著提升依从性，上市后快速获得临床认可。自主商业化品种Tryngolza（Olezarsen）用于家族性乳糜微粒血症综合征，2025Q3销售额达3200 万美元，环比增长近70%，同时推进重度高甘油三酯血症适应症补充NDA申报。 技术平台壁垒深厚，专利护城河稳固。公司深耕ASO领域近30年，核心化学修饰技术（2'-MOE、2'-OMe、PS骨架）定义行业标准，实现药物“高稳定性+高靶向性+低毒性”三重突破，支持皮下/静脉给药及长效治疗。创新反义寡核苷酸配体偶联（LICA）技术成功应用于Dawnzera，大幅提升靶向精准度。全球专利布局覆盖ASO设计、化学修饰、递送等核心环节，构建广泛知识产权壁垒，有效阻碍竞争者入局，巩固行业领军地位。 多元合作赋能全球化，财务储备支撑战略推进。公司构建“自主商业化+对外授权”协同模式，除与小野制药的重磅合作外，与Biogen、阿斯利康等跨国药企的长期合作持续贡献收入。财务层面，截至2025Q3现金及等价物余额3.38亿美元，虽短期仍存在净亏损（-1.52亿美元），但充足储备可支撑多款管线推进至上市。2026年有望实现现金流自我维持。 后期管线梯队完善，突破性品种密集推进。公司聚焦神经、罕见病、心血管等高价值领域，多款管线进入关键临床阶段，里程碑确定性强，部分如下： ①Zilganersen（亚历山大病，罕见病）：获FDA突破性疗法认定，2025年9月公布关键性III期积极数据，治疗组患者步行速度保持稳定，达到主要终点，计划2026Q1提交NDA，有望成为首个自主商业化的神经领域药物； ②Sapablursen（真性红细胞增多症，孤儿药）：通过靶向TMPRSS6提升铁调素水平，获FDA快速通道与孤儿药资格，目前II期研究推进中，2025年3月以9.4亿美元（2.8亿首付款+6.6亿里程碑）授权小野制药全球权益，公司保留中等比例销售提成，合作模式验证技术价值； 3.ArrowheadPharmaceuticals（ARWR.O）： RNAi领军者商业化破局 核心产品成功商业化，转型进入价值释放期。作为全球RNAi疗法领域的资深企业箭头制药（Arrowhead），公司首款产品Plozasiran（商品名Redemplo）2025年成功获FDA批准，用于治疗家族性乳糜微粒血症综合征（FCS），标志着从临床研发型企业正式迈入商业化阶段。该产品靶向APOC3基因，通过RNAi机制强效降低甘油三酯，临床数据显示降幅达80%，且采用每季度一次的皮下给药方案，相较Ionis的Tryngolza（每月一次）便利性更优，年治疗费用更低，具备显著竞争优势。同时针对严重高甘油三酯血症（SHTG）的两项III期研究已全面入组，计划2026年底提交补充NDA，获批后将切入300-400万患者的广阔市场。 技术平台壁垒深厚，研发效率行业领先。公司自主TRiM（Targeted RNAi Molecule）平台通过转铁蛋白受体 1 介导，实现 CNS、肝脏、肾脏等多组织靶向，技术差异化显著。公司与Sarepta的合作已触发1亿美元里程碑付款，后续2025年底前还将有2亿美元里程碑待兑现，合作覆盖4款CNS/肌肉疾病管线。同时与诺华、安进等跨国药企深度协同，借助伙伴资源加速管线全球化。财务层面，2025年三季报显示现金及等价物余额1.3亿美元，叠加合作资金加持，可充分支撑多款管线推进至后期临床及商业化准备。 多赛道管线梯队完善，差异化优势显著。公司构建覆盖心代谢、肥胖、CNS等领域的多元化管线矩阵，多个项目推进关键节点，部分如下： ① Zodasiran（靶向ANGPTL3）：针对纯合子家族性高胆固醇血症（HoFH），临床数据显示可有效降低LDL-C，目前全球临床3期中，公司计划自主商业化，借助Plozasiran的医生资源实现低成本拓展； ②肥胖领域布局（ARO-INHBE和ARO-ALK7）：通过调节脂肪信号通路实现“保肌减重”，无需严格限制热量，胃肠道副作用更少，有望与GLP-1类药物协同或作为维持疗法，2026年初I/IIa期研究中期结果显示，肥胖成人受试者的内脏脂肪等多个关键指标均显著降低； ③ CNS领域突破：ARO-MAPT采用转铁蛋白受体靶向技术，可高效穿越血脑屏障并覆盖深部脑区，靶向tau蛋白治疗阿尔茨海默病等神经退行性疾病，于2025H2进入Ⅱ期临床； ④ ARO-DIMER-PA：双靶点RNA二聚体平台：首款PCSK9/APOC3双靶点药物即将进入1/2a期临床，可同步调控血脂多重指标，技术风险低且临床价值突出。 3.2.中国创新药企：聚焦细分赛道差异化突围 中国企业避开国际龙头优势领域，聚焦细分市场（如肝癌、乙肝、血栓），通过技术创新与国际合作实现突围，部分如下： 1. 瑞博生物（6938.HK）：血栓与乙肝领域双轮驱动 递送技术壁垒构筑护城河。公司拥有全球少有的自主临床验证 GalNAc 递送技术，核心平台 RiboGalSTAR™可实现 siRNA 精准靶向肝实质细胞，且是中国首个对外授权跨国药企的 RNAi 平台（2023 年与BI达成 20 亿美元级 MASH 领域合作）；同时布局肝外递送（RiboPepSTAR™）（覆盖肾脏、中枢神经）、肿瘤靶向（RiboOncoSTAR™）平台，全球拥有 255 项授权专利，技术实力获国际认可。 管线全球领先且差异化突出。根据公司官网显示，公司拥有 7 款自研处于临床阶段药物（4 款 II 期），覆盖心血管、代谢、肝肾疾病等大病种；20+临床前项目储备充足，部分如下： RBD4059：是全球首款靶向 FXI 的 siRNA 血栓药，出血风险远低于传统抗凝药，2025 年 2 月已完成 IIa 期入组；我们预计2028年有望获批上市； RBD5044 ：是全球第二款进入临床开发的靶向 APOC3 的高血脂 siRNA，2 期试验正于瑞典推进； RBD1016 ：为慢乙肝 / 丁肝功能性治愈潜力疗法，通过沉默 HBV RNA，抑制病毒复制；2025 年 10 月获 EMA 孤儿药资格；II期全球多中心试验推进中，填补全球HDV治疗空白。 商业化能力初显：合作+国际化打开空间。头部合作背书：2023年起先后与齐鲁制药（授权RBD7022中国权益，全球第二个进入临床开发的靶向PCSK9的siRNA，总额超7亿元的首付款及里程碑付，推进高胆固醇血症II期）、勃林格殷格翰BI（平台级合作）达成合作。全球化布局落地：在瑞典设立临床基地（负责II期试验），采用“中国研发生产+欧洲临床注册”双核模式，核心产品同步申报中、欧、美市场，为全球商业化奠定基础。 财务健康度良好： 2024年营收1.43亿元（2025H1营收1.04亿元，yoy+58%），毛利率高达93.6%（2025H1），商业化路径清晰。截至2025年10月，现金及银行结余4.5亿元，流动负债5.9亿元，流动资产净值3723万元，支撑临床研发推进；虽暂未盈利（2025H1净亏损9776万元），但营收增速已体现平台变现潜力。 2. 前沿生物（688221.SH）：HIV成熟产品创收+肾病创新管线拓空间 核心产品艾可宁商业化稳健，基层渗透打开增量空间。作为全球首款获批的长效HIV融合抑制剂，艾可宁2025H1收入5353万元（yoy+20.5%），目前已覆盖全国300余家HIV定点医院及200余家DTP药房；通过医共体处方流转深化基层布局，住院端巩固首选用药地位、门诊端锁定高病载等三类潜力患者，同时拓展免疫重建不全等新适应症（II期临床推进中），循证医学成果获IAS 2025等国际会议认可，叠加医保助力可及性，持续放量确定性强。 小核酸管线差异化突出，瞄准千亿慢性病市场。公司依托自主ACORDE递送平台（具备肝外组织精准靶向能力），布局多款First-in-Class潜力药物： ①FB7013（IgA肾病）：靶向MASP-2单靶点，临床前健康猴单次给药后靶蛋白16周持续降低（最大降幅98%），食蟹猴模型中尿蛋白、肾小球滤过率指标显著改善，已于2025年底递交IND； ②FB7011（IgA肾病）：双靶点（MASP-2+CFB）设计，目前处于临床前阶段，临床前数据显示，关键疗效优于已上市补体抑制剂伊普可泮； 财务改善趋势明确。2025Q1-Q3营收1.03亿元（同比+12.8%），归母净利润亏损收窄至-1.60亿元（同比减亏3364.92万元），毛利率提升至34.84%（同比+1.35pct），费用管控成效显著；研发投入持续聚焦核心赛道（25Q3研发费用3593.42万元），2025年9月推出限制性股票激励计划（覆盖27名核心人员）绑定长期发展； 3. 悦康药业（688658.SH）：传统制剂转型+核酸创新管线破局 核心产品战略转型推进，成熟制剂筑牢基本盘。公司传统核心大单品银杏叶提取物注射液因行业合规整治进行价格调整（2025年初全国挂网价统一降至11.2元/支，较此前最高价下调53%），导致2025年营收阶段性承压，前三季度实现营收17.6亿元（yoy-41.2%）。但该产品作为心脑血管领域经典品种，此前市场占有率接近80%，具备深厚的临床使用基础，价格合规后有望通过院内渠道稳定覆盖实现销量回升。同时，公司头孢类抗生素、奥美拉唑等成熟制剂持续贡献现金流，通过渠道优化与成本控制维持业务基本盘，为创新转型提供支撑。 核酸创新管线多点突破，构建差异化竞争壁垒。公司聚焦mRNA、siRNA等前沿领域，依托自主YK-009阳离子脂质LNP递送系统，打造覆盖感染、肿瘤、代谢等多领域的创新管线矩阵，多款产品推进国际多中心临床： YKYY013注射液（慢性乙肝）：GalNAc偶联siRNA药物，覆盖HBV 10种基因型，临床前可显著降低病毒标志物并诱导抗体产生，已获中美两国临床试验批准，即将开展I期临床，有望实现慢乙肝功能性治愈； YKYY015注射液（靶向PCSK9）：超长效降脂小核酸药，目前开展2期临床； YKYY031（晚期实体瘤）：通用型mRNA肿瘤疫苗，采用自主LNP冻干工艺突破超低温冷链依赖，可诱导特异性杀瘤T细胞反应，联合PD-1抗体增效显著，2025年12月获NMPA临床批准； mRNA疫苗矩阵：带状疱疹疫苗YKYY026、RSV疫苗YKYY025均已获FDA临床批准； 研发投入持续加码，转型基础坚实。公司坚定推进创新转型，2025年研发投入占比显著提升，前三季度研发费用高达3.2亿元，研发费用率达18.0%（yoy+21.2%）。截至目前，多款核酸药物已完成国际专利布局并获得国内发明专利授权，形成自主知识产权壁垒。财务层面，公司前三季度经营活动现金流净额1.68亿元，总资产52.3亿元，净资产34.3亿元，充足的资产储备与现金流可支撑创新管线持续推进。 4. 舶望制药：心血管领域为战略核心 舶望制药是成立4年的临床阶段siRNA创新药企，依托自主RADS技术平台构建覆盖心血管、罕见病、病毒感染等领域的20余条管线（多款进入临床，公司官网显示），凭借高质量资产两度与诺华达成战略合作（累计首付款3.45亿美元，潜在总价值超90亿美元），目前已启动港股上市准备，核心投资价值如下： 技术平台壁垒深厚：RADS平台定义新一代siRNA标准。公司自研的RADS（RNA with superior Activity、Durability、Safety）平台，通过序列设计优化（高效靶点筛选提升药效特异性）、化学修饰创新（降低脱靶毒性）、递送策略升级（适配肝靶向与肝外场景），实现“更强活性+更长效力+更优安全性”三重突破——支持季度、半年乃至年度给药方案，完美契合慢性病长期用药需求，临床前数据显示靶蛋白抑制持续时间超同类技术，且规模化生产工艺成熟（寡聚核酸合成效率提升40%），为管线快速推进奠定基础，该平台技术获诺华两度合作背书，彰显国际竞争力。 核心管线差异化突出，聚焦千亿慢性病市场。心血管领域为战略核心： ①BW-02（靶向AGT）是全球进度领先的长效降压siRNA，对标Alnylam的Zilebesiran，II期临床中，从源头抑制血管紧张素生成，给药间隔有望突破半年，直面全球约14亿高血压患者（根据世卫发布第二版《全球高血压报告》）； ②BW-00112（靶向ANGPTL3）中美同步推进II期，针对重度高甘油三酯血症，联合用药试验由公司主导，具备全球竞争潜力。此外，罕见病管线BW-20805（靶向PKK的HAE疗法）2025年ACAAI会议披露I期数据，可快速深度降低血浆PKK水平且安全性优异；抗病毒管线BW-20507（靶向HBV）聚焦功能性治愈，已在中港、澳、泰开展I/II期，多赛道布局对冲单一领域风险。 诺华战略合作构建“资金+资源+背书”三重优势。2024-2025年两次合作累计斩获3.45亿美元首付款，潜在里程碑超90亿美元，合作模式兼具灵活性与主导权：首次合作授权2款临床阶段心血管管线海外权益，二次合作新增2款早研分子海外选择权及BW-00112优先谈判权。该合作不仅为公司提供充足研发资金（支撑6条临床管线推进），更借助诺华心血管领域商业化能力（如Leqvio全球推广经验）加速产品出海。 顶尖团队与资本加持保障落地能力。核心成员均来自Arrowhead、默克、礼来、诺华等全球顶尖药企：CEO舒东旭博士曾主导Arrowhead肝外递送平台开发，CSO邵鹏程博士深耕siRNA药物化学20年，CMO金建军博士曾牵头诺华siRNA药物Leqvio亚洲III期临床，团队在靶点筛选、临床推进、国际合作上经验丰富。 5.靖因药业：与CRISPR公司深度合作 2025年9月，成立仅4年的siRNA创新药企靖因药业正式向港交所递交上市申请，成为“3款临床阶段管线+自主PEPR技术平台+CRISPR公司 8.95亿美元co-de合作+腾讯参投”的稀缺标的： 自主研发的PEPR平台定义siRNA慢病治疗新标准。PEPR（Precision siRNA Engineering and RNAi Platform）平台，通过化学修饰优化、序列设计创新及靶向递送升级，解决siRNA“稳定性差、靶向性弱、脱靶风险高”三大痛点；前瞻性布局肝外递送系统（脂肪、骨骼肌、心脏靶向），突破当前siRNA多局限于肝脏的行业瓶颈，为肥胖、心肌病等非肝源性慢病拓展奠定基础，目前已围绕平台构建65项专利壁垒，技术实力获国际认可。 三大管线精准切入“抗凝+降脂+肥胖”无药/少药领域，均具备FIC/BIC潜力： ①SRSD107（靶向FXI抗凝）：全球进度第二的FXI靶向siRNA，欧洲II期推进中；相较传统抗凝药（阿哌沙班等），可在不增加出血风险的前提下实现长效抗凝（半年一针），2025年5月与CRISPR达成全球co-de合作（50:50成本/利润分摊），获9500万美元首付款，潜在总付款超8.95亿美元，公司保留大中华区商业化权益； ②SRSD216（靶向Lp(a)降脂）：中美同步推进IIa期，临床前给药后Lp(a)降幅超95%且持续12周以上，有望实现“半年一针”，填补全球空白； ③SRSD384（靶向INHBE肥胖）：区别于GLP-1类药物，通过调节能量消耗实现“保肌减重”，解决GLP-1肌肉流失、胃肠道副作用痛点，目前推进IND申报，计划2026年进入临床，切入千亿肥胖市场。 合作端，与CRISPR的深度co-de合作突破传统license-out模式，不仅获得充足研发资金（支撑II期临床推进），更可共享其全球临床开发经验与美国商业化资源，同时保留大中华区权益，为未来全球利润分成奠定基础，是中国siRNA企业“深度出海”的标杆案例。 4.风险提示 （一）新药研发失败风险：疗效不达预期；安全性问题：部分 siRNA 药物因脱靶效应导致肝损伤；技术迭代风险：若新的技术（如 CRISPR）替代小核酸药物，将导致现有管线价值下降。 （二） 政策变动风险：集采、医保谈判降价超预期； （三） 技术专利纠纷风险：侵权风险；专利到期风险等 （四）成本与竞争风险：生产成本高企；传统疗法竞争等 以上为正文 华西医药崔文亮团队 注：文中报告节选自华西证券研究所已公开发布研究报告，具体报告内容及相关风险提示等详见完整版报告。 分析师：崔文亮 分析师执业编号：S1120519110002 证券研究报告：《小核酸药物行业深度研究报告：RNA 精准医疗时代的崛起与挑战》 报告发布日期：2026年2月2日 分析师承诺               作者具有中国证券业协会授予的证券投资咨询执业资格或相当的专业胜任能力，保证报告所采用的数据均来自合规渠道，分析逻辑基于作者的职业理解，通过合理判断并得出结论，力求客观、公正，结论不受任何第三方的授意、影响，特此声明。 重要提示： 《证券期货投资者适当性管理办法》于2017年7月1日起正式实施。通过本订阅号发布的观点和信息仅面向华西证券的专业投资机构客户。若您并非华西证券客户中的专业投资机构客户，为控制投资风险，请取消订阅、接收或使用本订阅号中的任何信息。因本订阅号受限于访问权限设置，若给您造成不便，敬请谅解。市场有风险，投资需谨慎。 法律声明： 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