——小核酸行业跟踪报告 要点 行业研究 全球小核酸药物市场高增，蓝晓科技、联化科技引领关键环节突破 小核酸药物以 SiRNA 和 ASO 为核心，迎来从技术突破到规模化商业化的快速增 长期。小核酸药物是指长度小于 30nt 的寡核苷酸序列，药物机制为作用于 mRNA，通过干预靶标基因表达实现疾病治疗目的的药物。根据小核酸结构、药 物机制、作用靶点的不同，发展出了多种类型，广义的小核酸包括小干扰 RNA(SiRNA)、反义寡核苷酸(ASO)、微 RNA(MiRNA)、核酸适配体(Aptamer)等， 已获批和在研的核酸药物以 ASO 和 SiRNA 为主。其中小核酸的常见工艺流程为 固相合成、裂解和脱保护、纯化、超滤换液、分析、制剂、药品。据弗若斯特沙 利文数据显示，小核酸药物全球市场规模从 2016 年 0.1 亿美元已增长至 2021 年 32.5 亿美元，年复合增长率高达 217.8%。据 Evaluate 和 BCG 预测，2026 年全球寡核苷酸类药物市场规模将超 150 亿美元，2020 年-2025 年复合年增长 率 35%。 蓝晓科技以固相合成载体为战略支点，构建"合成—纯化"全链条供应能力。蓝 ...

Summary of Key Points from the Conference Call Industry Overview - The conference call focuses on the small nucleic acid drug industry, specifically the production and cost structure of active pharmaceutical ingredients (APIs) and formulations [1][2][3]. Cost Structure and Value Distribution - The cost structure of small nucleic acid drugs shows that the API accounts for 13%-14% of the terminal sales cost, while the formulation part constitutes 20% [1][2]. - The primary costs arise from the commercial GMP (Good Manufacturing Practice) system rather than just raw materials [2]. - The production of small nucleic acid drugs involves key intermediates and raw materials, including carriers (e.g., L96, CCTP), monomers (e.g., phosphoramidite), and solvent reagents [1][4]. Key Components and Their Cost Impact - Monomer costs represent 30%-40% of total production costs, while solvent reagents account for approximately 30% [1][5]. - The delivery system, such as GalNAc, contributes about 6% to the total production cost [6]. - The market price for L96 ranges from 400,000 to 500,000 yuan per kilogram, with leading manufacturers like Zhaowei charging up to 700,000 yuan per kilogram [7]. Production Requirements and Challenges - Producing 1 gram of siRNA API requires 30-40 grams of monomer and about 100 liters of acetonitrile, while producing 1 gram of ASO requires about 20 grams of monomer [8][10]. - Different modifications affect the synthesis yield, necessitating a re-evaluation of processes [11]. - Key raw materials such as core monomers, carriers, coupling reagents, and critical solvents cannot be easily changed without thorough justification and regulatory approval [12]. Production Technology and Market Dynamics - The mainstream production technology for small nucleic acid APIs is solid-phase synthesis, which is well-established [13]. - Domestic CDMO (Contract Development and Manufacturing Organization) companies include Hequn Pharmaceutical and Kailaiying, while global leaders include Alice Belgium, Agent Biotech, and Sermon XT [15][16]. - The tension in China-U.S. relations presents structural opportunities for China's CDMO industry, which could become the second-largest supplier globally due to its cost advantages and scale of production [18]. Clinical Stage Cost Variations - There are significant cost differences between early-stage and late-stage clinical trials, with late-stage trials incurring higher costs due to stricter impurity control and product consistency requirements [14]. Conclusion - The small nucleic acid drug industry is characterized by a complex cost structure influenced by various factors, including the type of product, production technology, and regulatory requirements. The industry is poised for growth, particularly in the context of evolving global supply chains and increasing demand for high-quality CDMO services.

Summary of Key Points from the Conference Call Industry Overview - The small nucleic acid drug market has significant growth potential, expected to reach a scale of hundreds of billions of dollars in the long term, particularly in chronic and metabolic disease areas, presenting over ten billion dollars in investment opportunities for the upstream and downstream industry chain [1][2][6]. Market Growth and Projections - The global small nucleic acid drug market size grew from $2.7 billion in 2019 to $5.1 billion in 2024, with an anticipated compound annual growth rate (CAGR) of nearly 26%, projected to reach $40 billion by 2035 [1][6]. Key Players and Competitive Landscape - Major multinational corporations (MNCs) such as Novartis and Sanofi dominate the commercialization of small nucleic acid drugs, leveraging their patent portfolios, sales channels, and product layouts to maintain stable gross margins [1][3][10]. - The entry barrier for domestic Chinese companies into the supply chains of these MNCs is high, with traditional raw material suppliers facing challenges due to the high production costs associated with small nucleic acid drugs [3][8]. Advantages of Small Nucleic Acid Drugs - Small nucleic acid drugs offer several significant advantages: 1. Precise targeting of genetic origins, directly regulating gene expression to prevent the production of pathogenic proteins [5]. 2. Broad target range, including traditionally undruggable targets such as non-coding RNA and mutated genes [5]. 3. Long-lasting treatment effects, suitable for chronic disease management [5]. 4. Shorter research and development cycles, allowing for rapid design and reduced costs [5]. 5. Compatibility with combination therapies and personalized medicine [5]. Challenges in Production - The production of small nucleic acid drugs faces several challenges: 1. Limited production throughput due to the solid-phase synthesis method [9]. 2. High costs of raw materials, which can account for a significant portion of overall production costs [9]. 3. Dependency on China for key raw materials, complicating supply chain management [9]. 4. High industrialization requirements as more drugs enter late-stage clinical trials or commercialization [9]. Investment Opportunities - The manufacturing segment of small nucleic acid drugs represents a considerable investment opportunity, as production costs account for about 20% of terminal sales [8]. - China is expected to remain a major supplier of small molecule raw materials and intermediates due to its advantages in solid-phase synthesis and monomer production [8]. Key Year: 2025 - The year 2025 is highlighted as a critical period for small nucleic acid drug development, with multiple key drugs entering Phase III clinical trials and expected to receive approvals across various indications, including cardiovascular diseases, non-alcoholic fatty liver disease, weight loss, and tumors [7][10]. Notable Developments and Strategies - Novartis has been actively investing and acquiring in the small nucleic acid space, with plans to advance seven small nucleic acid drugs through clinical trials from 2023 to 2025, encompassing 19 pipelines [10][14]. - Other large multinational companies, including Pfizer, Roche, Eli Lilly, Merck, and Novo Nordisk, are also making significant moves in this burgeoning market [10][13]. Conclusion - The small nucleic acid drug industry is poised for substantial growth, driven by innovative therapeutic advantages and increasing market demand, while facing challenges that require strategic management and investment in production capabilities.