证券研究报告 ➢ siRNA药物机制优势突出，递送为核心技术 相较于传统小分子和生物药，siRNA药物为代表的核酸疗法可精准沉默致病蛋白，高效降解且作用时间长，目前已成为新药开发热门方向。 技术层面主要包括修饰和递送，其中递送为核心技术，肝外递送是目前的突破重心，技术路径包括LNP、抗体、肽类以及VLP递送，各有优劣， 其中AOC发展稍快。 ➢ 海外巨头渐入收获期，静待肝外递送POC 黎明已至，国产争先 ——siRNA药物行业深度报告 行业投资评级：强大于市|维持 盛丽华/陈灿 中邮证券研究所 医药生物团队 中邮证券 1 1 发布时间：2026-02-27 投资要点 siRNA行业先驱Alnylam开发的GalNAc肝内递送凭借递送效率极高、特异性强以及作用持久等优势，已成为肝递送的"标准答案"，其他海 外巨头如Arrowhead和Dicerna等针对PCSK9、AGT、Lp(a)以及ApoC3等心血管常见靶点的siRNA药物已进入临床后期或商业化的收获期，而 针对肌肉、神经系统以及眼部等肝外器官目前仍处于研发早期阶段，目前Alnylam的C16递送平台已在CNS领域、Arrowhead的TRiM平台在脂 肪 ...

Core Insights - Sanofi is recognized as a top blue-chip stock for investment in 2026, following the FDA's approval of Cablivi for pediatric patients with acquired thrombotic thrombocytopenic purpura (aTTP) [1] Group 1: Product Approvals - Cablivi was initially approved in 2019 for adults with aTTP and is notable for its effectiveness in treating rare blood disorders affecting 1 to 10 million children annually, with 80% of patients achieving clinical remission [2] - Sanofi has also received approval for plozasiran in China, aimed at reducing triglyceride levels in adult patients with familial chylomicronemia syndrome (FCS), following its approvals in the US and Canada [3][4] Group 2: Market Sentiment and Analyst Ratings - Jefferies maintained a Buy rating on Sanofi with a price target of €100, despite some investor concerns regarding management communication after the FDA's Complete Response Letter for tolebrutinib [4]

Core Viewpoint - China National Pharmaceutical Group (stock code: 01177.HK) announced the acquisition of Hegia Biotech for a total consideration of 1.2 billion RMB, marking a strategic move into the siRNA innovation drug sector [1][7] Group 1: Acquisition Details - The acquisition will be financed through a combination of cash and equity, with approximately 1.1 billion RMB paid in cash and the remaining 97 million RMB through the issuance of new shares at HKD 6.66 per share [1][7] - Following the transaction, Hegia will become a wholly-owned subsidiary of China National Pharmaceutical Group, integrating its R&D pipeline and technology platform into the company's chronic disease treatment strategy [1][7] Group 2: Hegia Biotech Overview - Founded in 2018, Hegia has emerged as a "dark horse" in the domestic siRNA field, leveraging its proprietary multi-organ targeted delivery technology [2][8] - Hegia's key advantages include a clinically validated liver delivery platform capable of "once-a-year" dosing, a dual-chain conjugation technology platform, and a neural delivery platform [2][8] - Hegia currently has four clinical-stage projects and over 20 preclinical projects, with the most advanced being Kylo-11, which targets lipoprotein(a) and has initiated a multi-center Phase II clinical trial in October 2025 [2][8] Group 3: Market Context and Valuation - The global market for siRNA is projected to reach USD 15 billion, with no approved targeted drugs currently available, indicating a pressing clinical need [2][8] - The acquisition valuation of 1.2 billion RMB corresponds to an 18.75x market cap/research spending ratio based on Hegia's R&D expenditure for 2024, which is considered low compared to similar overseas companies [3][9] - The acquisition is seen as a strategic move to fill gaps in China National Pharmaceutical Group's cardiovascular treatment portfolio and create synergies with existing chronic disease pipelines [2][3][9] Group 4: Financial Strength and Industry Trends - As of June 2025, China National Pharmaceutical Group had over 30 billion RMB in cash and liquid assets, providing a solid foundation for ongoing investments in innovative drugs [4][10] - The siRNA sector has become a focal point for global pharmaceutical companies, with a total transaction volume of USD 35 billion in 2025, reflecting a 40% year-on-year growth [4][10] - The competitive landscape includes established international players like Alnylam, which has a market cap exceeding USD 50 billion, and domestic companies like Reebio, which recently went public [4][10] Group 5: Challenges and Future Prospects - The acquisition faces challenges, including Hegia's core pipelines being in early to mid-clinical stages, requiring lengthy R&D and approval processes [5][12] - Hegia's external delivery technologies have not yet been clinically validated, and scaling production of siRNA drugs remains an industry bottleneck [5][12] - Despite these challenges, the acquisition's synergy potential is significant, as China National Pharmaceutical Group's industrial capabilities could help Hegia navigate the "valley of death" in biotech [6][12]

Core Viewpoint - The article discusses the revolutionary shift in small nucleic acid drugs, highlighting their potential to transition from symptomatic treatment to addressing root causes, marking a significant advancement in the pharmaceutical industry [4]. Group 1: Small Nucleic Acid Drug Technology - Small nucleic acid drugs (siRNA, ASO, etc.) are considered the "third wave" of drug development, following small molecules and antibody drugs [4]. - These drugs are not limited by their molecular structure and can target a broader range of disease pathways, significantly increasing the probability of successful drug development [4]. - Current advancements in delivery technologies and chemical modifications have led to extended half-lives for these drugs, improving patient compliance in chronic disease management [4]. Group 2: Market Growth and Commercialization - The global small nucleic acid drug market is projected to reach $20.6 billion by 2029 and $54.9 billion by 2034, with a compound annual growth rate (CAGR) of 21.6% [5]. - Major players like Alnylam, Ionis, and Arrowhead are leading the market, with multinational corporations (MNCs) such as Novartis and Roche investing heavily in this sector [5]. - Alnylam's core product, Amvuttra, is expected to exceed $2 billion in sales by 2025, indicating strong market performance [6]. Group 3: Technological Breakthroughs - Arrowhead has developed RNAi therapies targeting various diseases through its TRiM platform, expanding the application of small nucleic acid drugs beyond liver diseases [7]. - Avidity Biosciences has made significant progress in muscle tissue delivery using antibody-oligonucleotide conjugates (AOC) technology, indicating a broader therapeutic potential [7]. Group 4: China's Small Nucleic Acid Drug Industry - The Chinese small nucleic acid drug industry is experiencing a qualitative leap, overcoming delivery patent barriers and demonstrating global competitiveness in target selection and molecular design [8]. - A complete industrial chain has emerged in China, with domestic raw materials achieving localization, thus reducing R&D costs [8]. - Significant business development (BD) transactions have occurred, including a record $5 billion deal between Wobang Pharmaceutical and Novartis, showcasing the global recognition of Chinese innovation [8].

Investment Rating - The report maintains an "Overweight" rating for the small nucleic acid drug industry [1] Core Insights - The small nucleic acid drug sector is experiencing a paradigm shift from "symptomatic treatment" to "root cause treatment," marking it as the "third wave of pharmaceutical innovation" following small molecules and antibody drugs. This innovation is driven by the ability of RNA drugs to overcome traditional drug development limitations, significantly expanding target ranges and improving drug development efficiency [4][5] - The global small nucleic acid drug market is projected to reach USD 20.6 billion by 2029 and USD 54.9 billion by 2034, with a compound annual growth rate (CAGR) of 21.6%, indicating high growth potential [5] - The industry is entering a commercialization phase, with key players like Alnylam, Ionis, and Arrowhead leading the market, supported by significant investments from multinational corporations (MNCs) [5] Summary by Sections Market Growth and Trends - The small nucleic acid drug market is expected to see rapid expansion, particularly in the fields of rare diseases and major diseases such as cardiovascular and metabolic disorders [5] - Alnylam's core product, Amvuttra, is projected to exceed USD 2 billion in sales by 2025, contributing to the company's profitability [5] - Domestic companies in China are overcoming delivery technology barriers and demonstrating global competitiveness in target selection and molecular design [7] Technological Advancements - Breakthroughs in delivery technologies and chemical modifications are enhancing the efficacy and half-life of small nucleic acid drugs, improving patient compliance in chronic disease management [4][5] - Arrowhead's TRiM platform has successfully developed RNAi therapies for various diseases, expanding the application of small nucleic acid drugs beyond liver diseases [5] Industry Ecosystem - The domestic small nucleic acid drug industry has established a complete industrial chain, with upstream raw materials achieving localization, thus reducing research and development costs [9] - Significant business development (BD) transactions have occurred, with notable collaborations between Chinese companies and global pharmaceutical giants, marking a historic high for the industry [9]

Core Viewpoint - The article highlights the significant potential of Ribobio, a company specializing in siRNA drug development, particularly with its innovative therapies targeting thrombotic diseases and hypertriglyceridemia, as it prepares for its IPO in Hong Kong and aims to capture a leading position in the growing small nucleic acid drug market [2][3][10]. Group 1: Company Overview - Ribobio has focused on small nucleic acid drugs, especially siRNA therapies, for 18 years and has established one of the largest siRNA drug pipelines globally [3][5]. - The company plans to issue approximately 27.5 million shares at a price of HKD 57.97, aiming to raise around HKD 1.59 billion (approximately USD 205 million) during its IPO scheduled for December 31, 2025 [3][5]. Group 2: Product Pipeline - Ribobio's core product, RBD4059, is the world's first siRNA drug for treating thrombotic diseases, currently in Phase 2a clinical trials, with plans to start Phase 2b trials in 2026 [6]. - RBD5044, another product targeting APOC3 for treating hypertriglyceridemia, is in Phase 2 clinical trials and has the potential to capture a share of the over USD 100 billion lipid-lowering drug market [7][8]. Group 3: International Strategy - Ribobio has established research centers in Beijing and Suzhou, China, and a subsidiary in Sweden to facilitate international clinical trials, enhancing its presence in the lucrative European pharmaceutical market [9]. - The company has formed strategic partnerships, including a collaboration with Qilu Pharmaceutical for the development of RBD7022 and with Boehringer Ingelheim for innovative therapies targeting NASH/MASH, with a combined value of USD 2 billion [9]. Group 4: Financial Performance - Ribobio has completed nine rounds of financing, with a valuation reaching CNY 5.02 billion after the latest round in June 2025, indicating strong growth potential [10]. - The company's revenue is projected to grow from nearly zero in 2023 to CNY 143 million in 2024, with a reduction in losses from CNY 142 million in the previous year to CNY 97.8 million in the first half of 2025 [10].

Group 1 - The core viewpoint of the article highlights a breakthrough in the small nucleic acid field with Arrowhead Pharmaceuticals' first small nucleic acid product, Plozasiran, receiving FDA approval, marking a new phase of commercialization in this sector [1] - The intersection of AI and biomedicine is accelerating innovation, with AI-native biotech companies valued at nearly twice that of their peers, and venture capital investment in AI drug development reaching $2.7 billion [1] - Over the next 5-10 years, global biomedicine is expected to see innovations driven by advancements in AI technology, explosive biological data, and interdisciplinary research, particularly in cardiovascular, metabolic chronic diseases, and CNS disorders [1] Group 2 - A significant wave of drug patent expirations is anticipated in 2026, covering oncology, metabolic, and CNS fields, with annual sales of approximately $230 billion facing generic competition, prompting pharmaceutical companies to respond through mergers and accelerated R&D to address the "patent cliff" [1] - Cell and gene therapies, AI drug development, and the small nucleic acid field are expected to become new hotspots in the coming year [1] - The ChiNext Medical ETF (159377) tracks the Innovation Medicine Index (399275), which saw a daily fluctuation of 20%, focusing on leading companies in biopharmaceuticals, chemical pharmaceuticals, and medical devices, emphasizing high R&D investment, innovation capability, and significant growth potential [1]

Core Viewpoint - The medical ETF (159828) has seen a net inflow for five consecutive days, driven by the advancements in the small nucleic acid sector, particularly with Arrowhead Pharmaceuticals making significant strides in chronic disease treatment and CNS (central nervous system) breakthroughs [1]. Group 1: Company Developments - Arrowhead Pharmaceuticals' market capitalization increased by $1.66 billion last week, indicating strong investor confidence [1]. - The company's first small nucleic acid product, Plozasiran, is set to receive FDA approval on November 18, 2025, marking a pivotal moment in its commercialization journey [1]. - Arrowhead is advancing its pipeline products towards larger patient markets in chronic diseases and CNS, showcasing its growth potential [1]. Group 2: Industry Insights - The medical ETF (159828) tracks the CSI Medical Index (399989), which selects listed companies in the pharmaceutical and healthcare sectors from the Shanghai and Shenzhen markets [1]. - The index primarily covers sectors such as medical devices, medical services, and medical R&D outsourcing, reflecting the overall performance of related listed companies [1]. - The constituent stocks of the index tend to be small to mid-cap, characterized by high growth potential and volatility [1].

Arrowhead Pharmaceuticals FY Conference Summary Company Overview - **Company**: Arrowhead Pharmaceuticals (NasdaqGS:ARWR) - **Event**: FY Conference held on December 03, 2025 Key Industry Insights - **Market Opportunity**: Arrowhead's first drug, Plozasiran, has been approved, targeting familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG) [3][4] - **Patient Need**: Approximately 10,000 patients with FCS require treatment to prevent severe pancreatitis, which can be fatal [4] - **Phase Three Data**: Plozasiran demonstrated an 80% reduction in triglycerides and a numerical risk reduction in pancreatitis [5] Competitive Landscape - **Pricing Strategy**: Plozasiran is priced lower than competitors like Tryngolza, which is priced at $595,000 per year per patient. Arrowhead aims to establish value in the SHTG market by initially targeting high-risk patients [6][7] - **Health Economics**: The cost of treating pancreatitis can exceed $60,000 per event, making Plozasiran's pricing compelling from both economic and human perspectives [8][9] Pipeline Developments - **New Candidates**: Arrowhead is developing a dual dimer targeting PCSK9 and ApoC3, which aims to lower LDL and remnant cholesterol [11][12] - **Obesity Programs**: Two programs, ARO-INHBE and ARO-ALK7, are in phase 1/2 studies, focusing on increasing lipolysis without affecting appetite [15][16] - **CNS Delivery**: ARO-MAPT targets tau tangles in Alzheimer's and tauopathies, with expectations for significant knockdown in cerebrospinal fluid (CSF) [22][24] Financial Position - **Cash Reserves**: Ended the fiscal year with $782 million, with additional capital from Sarepta and Novartis bringing total cash close to $1.2 billion [32] - **Funding Strategy**: The capital allows Arrowhead to advance core programs and aims for profitability by 2028, while reducing reliance on capital markets [32][33] Partnerships - **Sarepta Collaboration**: A significant partnership with Sarepta, valued at $800 million upfront and potential $10 billion in milestones, focuses on skeletal muscle programs [26][28] - **Novartis Partnership**: A $200 million upfront deal with Novartis for a preclinical Parkinson's disease drug, with potential for $2 billion in milestone payments [30][31] Conclusion - Arrowhead Pharmaceuticals is positioned for growth with a strong pipeline, strategic pricing, and significant partnerships, aiming to address critical health needs in cardiometabolic diseases and CNS disorders while maintaining a robust financial outlook.

Investment Rating - The report maintains a positive outlook on the pharmaceutical industry, indicating an "Overweight" rating, suggesting that the industry is expected to outperform the overall market [28]. Core Insights - The report highlights a 2.7% increase in the Shenwan Pharmaceutical and Biological Index, outperforming the Shanghai Composite Index, which rose by 1.4% [3][5]. - The report emphasizes the importance of monitoring changes in flu epidemics and their impact on the pharmaceutical sector, particularly regarding vaccine and treatment demand [2]. - Key domestic developments include the approval of new indications for innovative drugs and significant stock purchases by company executives, indicating confidence in the sector [12][13]. Market Performance - The Shenwan Pharmaceutical and Biological Index rose by 2.7% this week, ranking 17th among 31 Shenwan first-level sub-industries [3][5]. - The overall valuation of the pharmaceutical sector stands at 29.5 times earnings, placing it 10th among 31 Shenwan first-level industries [5][10]. Recent Key Events Domestic Developments - The State Council meeting discussed enhancing the basic medical insurance system, which is expected to improve the efficiency of fund management and healthcare resource allocation [11]. - Major companies like Mindray Medical and Huyuan Bio are making significant moves, such as stock buybacks and new product approvals, which are seen as positive indicators for the industry [12][13]. International Developments - The report notes the approval of groundbreaking drugs, including the first siRNA drug for treating familial chylomicronemia syndrome, and highlights the challenges faced by other drugs in clinical trials [15][16][17]. Investment Recommendations - The report suggests focusing on innovative drug sectors and companies with strong performance metrics, including Heng Rui Pharmaceutical, Changchun High-tech, and Mindray Medical, among others [2][12]. - It also recommends monitoring companies involved in flu vaccines and treatments as flu activity increases [2].