Financial Data and Key Metrics Changes - The net loss for fiscal year 2025 was $2 million, a significant improvement from a net loss of approximately $599 million in fiscal year 2024, resulting in a loss of $0.01 per share compared to a loss of $5 per share [32] - Revenue for fiscal year 2025 totaled $829 million, driven primarily by licensing and collaboration agreements, with $697 million from Sarepta Therapeutics [32][33] - Total operating expenses for fiscal year 2025 were approximately $731 million, an increase from $605 million in fiscal 2024, primarily due to higher R&D and SG&A costs [33][34] - Cash and investments totaled $919 million as of September 30, 2025, up from $681 million a year earlier, reflecting strong cash flow from licensing agreements [35][36] Business Line Data and Key Metrics Changes - The FDA approved Redemplo, Arrowhead's first FDA-approved medicine, marking a major milestone as it transitions into the commercial stage [6][7] - Redemplo is indicated for reducing triglycerides in adults with familial chylomicronemia syndrome (FCS) and can be self-administered at home [19][20] - The One Redemplo pricing model is set at $60,000 annually, aimed at providing consistent pricing across indications [11][25] Market Data and Key Metrics Changes - There are an estimated 6,500 people in the U.S. living with genetic or clinical FCS, with a prescriber base comprising specialists such as lipidologists and endocrinologists [25] - The broader patient population at risk of acute pancreatitis includes approximately 750,000 patients with persistent chylomicronemia [10] Company Strategy and Development Direction - The company is focusing on the cardiometabolic space, with ongoing clinical trials for Zodasiran and ArrowDiamond PA, targeting conditions like homozygous familial hypercholesterolemia and atherosclerotic cardiovascular disease [12][13] - Arrowhead aims to have 20 individual drug candidates in clinical trials by the end of 2025, with a balanced pipeline of wholly owned and partnered programs [39] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the commercial launch of Redemplo and the encouraging feedback from the FCS community [39] - The company does not anticipate substantial financial impact from Redemplo sales in fiscal year 2026 but believes its cash runway is sufficient to support operations into fiscal year 2028 [38] Other Important Information - Arrowhead received a $200 million upfront payment from Novartis for a licensing agreement and is eligible for up to $2 billion in future milestone payments [36][37] - The company has made significant progress in business development, including a $200 million milestone payment from Sarepta for ARO-DM1 [17][38] Q&A Session Summary Question: What is the plan to show benefit in terms of acute pancreatitis for Plozasiran? - Management indicated that while shots at three and four were powered for triglyceride reduction, there is reasonable power to see a difference in acute pancreatitis, with a specific design for SHASTA-5 to demonstrate benefit [42][44][45] Question: Can you provide details on the upcoming data for obesity programs? - Management confirmed that initial data from the ARO-INHBE program will be shared in early January, with a focus on safety and biomarker data [48][50] Question: What are the estimates on acute pancreatitis events accrual based on patient baseline characteristics? - Management noted that it is challenging to predict due to the adoption of modified Atlanta criteria for adjudication, but they expect a sufficient number of events based on patient history [53][54] Question: Can you discuss the differentiation of ArrowMapT from J&J's failed anti-tau antibody? - Management highlighted that ArrowMapT targets intracellular tau, potentially reducing both intracellular and extracellular tau levels, unlike J&J's approach [57][59] Question: What is the visibility on launching a CBOT study? - Management stated that they expect to have a clearer idea by summer 2026 based on data from ongoing studies, with plans to move into pivotal studies if results are favorable [62][63]

Market Overview - The major indices experienced significant declines, with the Shanghai Composite Index down 3.90%, the Shenzhen Component down 5.13%, and the ChiNext Index down 6.15% during the week of November 17-21, 2025[6] - The average daily trading volume decreased to 1.87 trillion yuan, down from 2.04 trillion yuan the previous week[6] E-commerce in Southeast Asia - The e-commerce market in Southeast Asia is evolving towards a more mature and compliant structure, with a projected GMV of $128.4 billion in 2024, reflecting a 12% year-on-year growth[16] - Indonesia remains the largest market, accounting for 44% of the total GMV in Southeast Asia, although its growth rate slowed to 5% in 2024[17] - Content-driven e-commerce is emerging as a key growth driver, with live-streaming e-commerce expected to reach $17.6 billion in GMV, representing 14% of the total e-commerce market in the region[27] High-end Manufacturing: Power Batteries - Global demand for power batteries is expected to exceed 1 TWh in 2024, with electric vehicles contributing over 85% of this demand, reaching 950 GWh, a 25% increase year-on-year[29] - China's power battery production capacity is projected to grow by 41.49% in 2025, reaching 548.5 GWh, aligning closely with the sales of new energy vehicles[35] - The industry is transitioning from rapid expansion to a focus on quality and technological upgrades, driven by stricter regulations and self-discipline among leading companies[40] Hard Technology: Storage Prices - Storage prices are on the rise, with DDR4 and DDR5 prices increasing by 158% and 307% respectively since September 2025, leading to a contraction in transaction volumes[41] - The anticipated increase in smartphone and laptop costs due to rising storage prices is estimated to be around 5-7% in 2026, with potential impacts on demand[42] Health Sector: Small Nucleic Acids - The global market for RNAi therapies is projected to grow from $3.459 billion in 2024 to $25.195 billion by 2030, with a CAGR of 39.2%[49] - Over 20 small nucleic acid drugs have been approved globally, with nearly 170 projects in clinical stages, indicating a robust pipeline in oncology and chronic disease treatment[49]

证券研究报告 创新药周报20251123： 首个APOC3 siRNA疗法获批上市用于治疗FCS 2025-11-23 证券分析师 刘浩 执业编号：S0360520120002 邮箱：liuhao@hcyjs.com 联系人 段江瑶 邮箱：duanjiangyao@hcyjs.com 联系人 吴昱爽 邮箱：wuyushuang@hcyjs.com 本报告由华创证券有限责任公司编制 卖的出价或询价。本报告所载信息均为个人观点，并不构成对所涉及证券的个人投资建议。 请仔细阅读PPT后部分的分析师声明及免责声明。 @2021 华创版权所有 第一部分 本周创新药重点关注 国内创新药回顾 02 全球新药速递 03 01 代谢疾病与核酸靶向疗法 证券研究报告 资料来源：Umidakhon Makhmudova, et al.，Advances in nucleic acid-targeted therapies for cardiovascular disease prevention，Eliot A. Brinton, et al.，Familial chylomicronemia syndrome and treat ...

Summary of Alnylam Pharmaceuticals Conference Call Company Overview - **Company**: Alnylam Pharmaceuticals (NasdaqGS:ALNY) - **Event**: UBS Healthcare Conference - **Date**: November 10, 2025 Key Highlights from the Conference Call Financial Performance - **Third Quarter Earnings**: Alnylam reported $300 million in cardiomyopathy (CM) revenue for Q3, doubling the $150 million from Q2, leading to an upgraded full-year guidance by $275 million [6][11][24] - **Five-Year Goals**: The company has achieved its five-year goals set for 2025, including: - 500,000 patients on RNAi therapeutics - Six commercial products launched - 20 clinical programs - 40% compound annual growth rate (CAGR) in top-line growth - Non-GAAP profitability [10][11] Product Launch and Market Dynamics - **Cardiomyopathy Launch**: The launch has seen strong early momentum, with successful access to 170 health systems and first-line access to payers, primarily in a Medicare population (80%) [15][18][29] - **Pricing Strategy**: Alnylam anticipates a mid-single-digit year-over-year price decline for the TTR business in 2025, while volume growth is expected to offset the price decline [24][26] Pipeline and Future Goals - **2030 Goals**: The company plans to announce new goals at the JPMorgan conference, focusing on TTR leadership, pipeline progression, and financial profile evolution [12][14] - **Next-Generation Products**: Zilebesiran is expected to achieve over 95% TTR reduction with a twice-annual dosing regimen, with ongoing studies in both cardiomyopathy and hereditary polyneuropathy [32][33] Competitive Landscape - **Market Positioning**: Alnylam is focused on first-line positioning against competitors, with expectations of expanding the market pie rather than just taking market share [30][45] - **Combination Therapy**: The company is preparing for a potential shift towards combination therapies as Tafamidis goes generic, leveraging data from ongoing studies [45][46] Early-Stage Pipeline - **Mivelsiran**: Targeting amyloid precursor protein for Alzheimer's and cerebral amyloid angiopathy, with promising early results [48][49] - **Huntington's Disease**: The company is optimistic about its differentiated approach targeting both full-length and variant proteins [50][52] - **ALN-6400**: Aiming to be a universal hemostatic agent, with initial focus on hereditary hemorrhagic telangiectasia [54] Additional Insights - **Value-Based Agreements**: Alnylam has implemented value-based agreements with payers to ensure patient compliance and reduce costs associated with non-compliance [29] - **Patient Enrollment**: The company is confident in its ability to enroll patients in ongoing studies without significant impact from competitive dynamics [36] This summary encapsulates the key points discussed during the conference call, highlighting Alnylam Pharmaceuticals' financial performance, product launches, pipeline developments, and strategic positioning in the market.

RNAi药物是一类新型疗法，通过"沉默"编码与疾病相关蛋白质的信使RNA分子来发挥作用。据悉，双 方将基于圣因生物专有的LEAD™平台共同推动针对代谢性疾病的RNAi候选药物的开发。 LEAD™(Ligand and Enhancer Assisted Delivery，新型配体与增效基团协同递送)平台是圣因生物自主研 发的一种组织选择性递送技术，能够实现RNAi药物在肝外组织与细胞中的高效、特异性递送。基于该 平台，有望开发出每年仅需两次皮下给药的代谢性疾病突破性疗法。圣因生物将负责基于LEAD™平台 为双方合作项目筛选并确定最优RNAi活性分子，礼来将负责后续药物的IND申报研究、临床开发和商 业化。 智通财经APP获悉，礼来(LLY.US)上周六宣布，与圣因生物(SanegeneBio)达成一项价值最高达12亿美元 的全球研发合作与许可协议，共同开发和商业化用于代谢性疾病的RNAi疗法。 根据协议，礼来将向圣因生物支付预付款和股权投资，同时接手由圣因生物发现的RNAi分子的临床前 研究(IND申报前研究)、临床开发以及商业化工作。此外，圣因生物还有资格获得最高达12亿美元的发 现、开发、监管及商业化里程 ...

Core Insights - The article highlights the transformative potential of small nucleic acid drugs, moving from chronic medication to one-time treatments or long-term interventions, indicating a "blue ocean" market for these therapies [1] - The global small nucleic acid therapy market is projected to grow from $5.1 billion in 2024 to $18.6 billion by 2029, with a compound annual growth rate (CAGR) of 29.5%, and further to $49.4 billion by 2034, with a CAGR of 21.6% [1] - Suzhou Ribocure Biotechnology Co., Ltd. (Ribocure) is preparing for an IPO on the Hong Kong Stock Exchange, positioning itself as a key player in the small nucleic acid drug market [2] Company Overview - Ribocure, founded in 2007, is a major participant in the global small nucleic acid drug development space, particularly focusing on siRNA therapies [1][3] - The company has developed one of the largest siRNA drug pipelines globally, with seven self-developed drug assets currently in clinical trials targeting cardiovascular, metabolic, renal, and liver diseases, four of which are in Phase 2 trials [3][6] Product Pipeline - Ribocure's core product, RBD4059, is the world's first and fastest clinically developed siRNA drug for treating thrombotic diseases, which are a leading cause of death globally, claiming over 10 million lives annually [6] - RBD4059 selectively inhibits FXI to reduce thrombus formation risk without significantly increasing bleeding risk, offering a promising treatment option [6] - Other notable candidates include RBD5044 for hypertriglyceridemia and RBD7022 for hypercholesterolemia, both of which are in advanced clinical development stages [7] Market Positioning - Ribocure's product pipeline is well-balanced and focuses on major diseases with high market potential, including cardiovascular and metabolic disorders, which enhances its commercial prospects [7][8] - The company is building an integrated research, production, and sales capability to create a sustainable "innovation-profit" cycle, essential for long-term success in the biotech sector [8] Financial Performance - Ribocure's R&D expenditures from 2023 to mid-2025 are projected to total approximately 730 million yuan, reflecting its commitment to long-term innovation over short-term profits [8] - The company has successfully raised over 380 million yuan in recent financing rounds to support its clinical pipelines and technology development [9] - Revenue growth has been significant, with reported revenues of 440,000 yuan, 143 million yuan, and 103 million yuan from 2023 to mid-2025, alongside a notable reduction in losses [10] Strategic Collaborations - Ribocure has established strategic partnerships with several well-known pharmaceutical companies, enhancing its credibility and market valuation [9] - The company has received orphan drug designation for its product RBD1016, which is aimed at treating hepatitis D virus infections, facilitating its development and commercialization in the EU [9]

Financial Data and Key Metrics Changes - Alnylam Pharmaceuticals reported total net product revenues of $851 million for Q3 2025, representing a 103% year-over-year growth [8][26] - The TTR franchise revenues reached $724 million, reflecting a 135% increase year-over-year, driven primarily by the AMVUTTRA® ATTR-CM launch in the U.S. [7][10] - The company increased its total net product revenue guidance for 2025 from a range of $2.65 billion-$2.8 billion to $2.95 billion-$3.05 billion, marking a 10% increase at the midpoint [8][30] Business Line Data and Key Metrics Changes - The rare disease portfolio achieved $127 million in sales, up 14% compared to Q3 2024, indicating steady performance despite a focus on TTR growth [9][10] - U.S. net sales for the TTR franchise grew 42% quarter-over-quarter and 194% year-over-year, reflecting strong adoption following the AMVUTTRA® ATTR-CM label expansion [10][11] - International revenues grew 13% quarter-over-quarter and 46% year-over-year, highlighting continued global momentum [11][12] Market Data and Key Metrics Changes - The U.S. TTR franchise generated $543 million in net product revenues, with patient demand roughly doubling compared to Q2 [14][15] - The company anticipates further international AMVUTTRA® ATTR-CM launches in 2026, following local pricing and reimbursement reviews [11][16] - The hereditary ATTR polyneuropathy legacy business remains robust despite new competition, with a 46% year-over-year growth in ex-U.S. TTR markets [12][58] Company Strategy and Development Direction - Alnylam focuses on three core pillars: TTR leadership, growth through innovation, and strong financial performance [5][6] - The company is advancing its pipeline of RNAi therapeutics, with two new phase III trials underway and additional programs in development for various conditions [8][20] - The company aims to establish long-term leadership in TTR and expand its global reach through upcoming product launches [16][58] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the AMVUTTRA® ATTR-CM launch, highlighting strong execution and a solid foundation for future growth [9][10] - The management team noted that the majority of ex-U.S. launches are expected to begin in 2026, which will extend global reach and contribute to launch momentum [16][58] - The company remains optimistic about the potential of RNAi therapeutics to become the standard of care in TTR amyloidosis [18][19] Other Important Information - The gross margin on product sales was 77% for Q3 2025, down from 80% in Q3 2024, primarily due to increased royalties on AMVUTTRA® [27] - The company ended the quarter with cash, cash equivalents, and marketable securities of $2.7 billion, reflecting a stable financial position [29] Q&A Session Summary Question: AMVUTTRA® momentum in first line vs switch population - Management noted strong momentum in TTR business with patient demand doubling for AMVUTTRA® and broad adoption across various settings [35][36] Question: Confidence in continued patient additions for AMVUTTRA® - Management indicated that the guidance has been raised twice, reflecting confidence in the depth and durability of the product's momentum [39][41] Question: Payer dynamics and feedback - Management reported no payer headwinds and positive feedback from payers regarding the value of AMVUTTRA® [46][48] Question: Inventory demand and expectations for Europe - Management explained that inventory dynamics were stable, with modest contributions expected from ex-U.S. markets in Q4 [53][56] Question: Price changes for AMVUTTRA® in the U.S. and Europe - Management anticipates a gradual decline in net price over time, with ongoing negotiations for European pricing [72][73]

Financial Data and Key Metrics Changes - Alnylam Pharmaceuticals reported total net product revenues of $851 million for Q3 2025, reflecting a 103% year-over-year growth [8][27] - The TTR franchise revenues reached $724 million, representing a 135% increase year-over-year and a 33% increase compared to the previous quarter [7][10] - The company increased its total net product revenue guidance for 2025 from a range of $2.65 billion to $2.8 billion to a revised range of $2.95 billion to $3.05 billion, indicating a 10% increase at the midpoint [8][30] Business Line Data and Key Metrics Changes - The rare disease portfolio achieved $127 million in sales, up 14% year-over-year, driven by ongoing patient demand [9][10] - U.S. net sales for the TTR franchise grew 42% quarter-over-quarter and 194% year-over-year, primarily due to the AMVUTTRA ATTR CM label expansion [11][14] - International revenues grew 13% quarter-over-quarter and 46% year-over-year, with strong performance in Japan and Germany [11][12] Market Data and Key Metrics Changes - The U.S. TTR franchise generated $543 million in net product revenues, reflecting a significant increase in patient demand [14][16] - The company noted that the international performance is benefiting from increased awareness and diagnosis in the hereditary ATTR polyneuropathy market [13] Company Strategy and Development Direction - Alnylam focuses on three core pillars: TTR leadership, growth through innovation, and strong financial performance [5][6] - The company is advancing its pipeline with new Phase 3 trials for zilebesiran and ALN-APP, targeting significant market opportunities [8][20] - The strategy includes expanding the AMVUTTRA ATTR CM launch globally, with expectations for further launches in 2026 [16][30] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the long-term opportunity for AMVUTTRA, highlighting substantial growth potential in the TTR category [16][17] - The company is optimistic about the ongoing demand and adoption of its therapies, particularly in the U.S. market [10][14] - Management acknowledged the competitive landscape but emphasized their strong positioning and execution capabilities [11][13] Other Important Information - The gross margin on product sales was reported at 77%, down from 80% in the same quarter last year, primarily due to increased royalties on AMVUTTRA [27] - The company ended the quarter with cash, cash equivalents, and marketable securities of $2.7 billion [29] Q&A Session Summary Question: Momentum of AMVUTTRA in first line versus switch population - Management noted that patient demand for AMVUTTRA has doubled, with broad adoption across various settings, indicating strong momentum [34][35] Question: Confidence in continued patient additions - Management highlighted the strong launch and raised guidance twice, indicating confidence in sustained momentum despite a decline in ONPATTRO [38][40] Question: Payer dynamics and feedback - Management reported no significant payer headwinds and positive feedback regarding the value of AMVUTTRA, with ongoing negotiations for 2026 [45][48] Question: Inventory demand and expectations for Europe - Management explained that inventory growth was offset by increased gross to net deductions, with modest contributions expected from the ex-U.S. market in Q4 [52][56] Question: TTR franchise guidance update - Management indicated that the updated guidance reflects expectations for Q4 revenues, estimating total TTR global revenue of $850 million to $900 million [60][61] Question: Impact of reimbursement cuts on diagnostics and therapeutics - Management acknowledged the importance of reimbursement for growth and expressed confidence in managing potential changes as policies become clearer [66][68]

Core Viewpoint - The strategic collaboration between 舶望制药 and Novartis aims to develop multiple cardiovascular products, with 舶望制药 receiving an upfront payment of $160 million and potential milestone payments totaling up to $5.2 billion [1][2] Group 1: Collaboration Details - 舶望制药 will grant Novartis rights to two early-stage siRNA molecules outside of China for treating severe hypertriglyceridemia (sHTG) and mixed dyslipidemia, along with priority negotiation rights for the BW-00112 (ANGPTL3) product, which is currently in Phase II clinical trials in the US and China [1] - A separate siRNA candidate in preclinical research will have exclusive licensing rights granted to Novartis outside of China, with plans to initiate Phase I clinical trials in 2026 [2] - The new agreement builds on a previous collaboration where 舶望制药 and Novartis established licensing agreements for multiple siRNA drugs, with milestone payments not exceeding $4.165 billion [2] Group 2: Company Vision and Market Position - 舶望制药 aims to become a global biotechnology company, focusing on developing best-in-class siRNA therapies and building a top-tier clinical development team across various regions [2] - The collaboration is expected to enhance 舶望制药's innovation engine and strengthen its influence in the liver and extrahepatic siRNA therapy market [2] - Novartis recognizes the long-acting siRNA technology as a significant advancement in the prevention and treatment of cardiovascular diseases, indicating a strong commitment to addressing unmet clinical needs through this partnership [2]

Core Insights - Alnylam's RNAi therapy Amvuttra has achieved remarkable sales growth, reaching $492 million in its first quarter post-approval for ATTR-CM, a 114% increase year-over-year, significantly surpassing analyst expectations of $365 million [1][4] - The company has raised its full-year revenue guidance from $2.05-2.25 billion to $2.65-2.8 billion, driven by the strong performance of Amvuttra [1][4] - Alnylam's CEO indicated that Amvuttra's approval marks a new growth phase for the company, with expectations of achieving sustainable non-GAAP profitability this year [2][5] Sales Performance - Amvuttra's sales performance in the second quarter was driven by approximately 1,400 patients receiving treatment, contributing $150 million in revenue [4] - The TTR product portfolio, including Amvuttra and another RNAi therapy Onpattro, has seen its revenue guidance increased from $1.6-1.73 billion to $2.18-2.28 billion [4] Market Dynamics - The ATTR-CM market is projected to exceed $11.2 billion by 2030, with significant unmet clinical needs due to limited treatment options [3] - Despite Tafamidis's established market presence, Amvuttra has quickly gained traction, with about 50% of its current patients being treated as first-line therapy [6][8] Competitive Landscape - Alnylam's strategy has successfully challenged the long-standing dominance of Pfizer in the ATTR-CM market, with expectations that Amvuttra could capture a significant market share [10][11] - The rapid acceptance of Amvuttra by physicians and its inclusion in insurance coverage have been key factors in its swift market penetration [7][8] Future Outlook - Alnylam's proactive approach in market access and patient payment strategies has positioned it favorably against larger pharmaceutical companies [11][12] - The company's experience and execution in commercializing Amvuttra may serve as a model for other biotech firms aiming to compete with established players in the industry [13]