Group 1 - The core viewpoint is that small nucleic acid drugs are expected to become the third major category of drugs, following small molecules and antibody drugs, due to their advantages such as targeting traditionally non-druggable targets and long-lasting effects [1] - The breakthrough of GalNAc technology in 2014 established a successful paradigm for liver-targeted delivery, significantly activating the development of the small nucleic acid drug industry [1] - The global small nucleic acid drug industry is currently achieving commercial profitability, breakthrough in indications, advancements in extrahepatic delivery, and dual-target breakthroughs [1] Group 2 - From a commercialization perspective, drugs like Amvuttra and Leqvio show significant potential, with global leader Alnylam expected to achieve profitability this year [2] - The years 2025-2026 are critical for indication breakthroughs, with weight loss indications expected to reach proof of concept (POC) and CNS indications likely to begin exploration [2] - Technological advancements in extrahepatic delivery are emerging, with TRiM and AOC delivery methods showing promise, and Avidity's AOC drug Del-zota expected to be commercially available by 2026 [2] Group 3 - Chinese small nucleic acid drug companies are demonstrating global competitiveness, with an accelerated growth in research pipelines [3] - Companies like Bewang and Ruibo have established business development (BD) transactions with multinational corporations (MNCs), showcasing the global competitiveness of Chinese small nucleic acid drugs [3] - The focus of Chinese small nucleic acid drug pipelines is expanding from cardiovascular diseases and hepatitis B to include weight loss and CNS indications, with potential for first-in-class (FIC) and best-in-class (BIC) drugs [3]

中信建投主要观点如下： 中国小核酸药企展现全球竞争力。近年来，随着小核酸创新药公司的兴起，国内小核酸在研管线加速增 长。中国小核酸创新药企舶望、瑞博已与MNC达成BD交易，展现出中国小核酸的全球竞争力。适应症 方面，中国小核酸药物管线此前主要集中在心血管疾病和乙肝等领域。近年来也开始逐步向减重、CNS 等领域拓展。从技术角度来说，目前中国和海外的小核酸技术没有代际差，在具体的靶点适应症上具备 FIC和BIC的潜力，并正进入FIC、BIC药物加速发展期，预计将在26-27年诞生一批新分子进入IND，有 望持续展现全球竞争力。 小核酸药物有望成为第三类药物。在小核酸药物作用机制中，主要为内吞、内体逃逸、基因沉默三步。 关键点在于①受体选择：受体丰度、内化速率，②优化递送系统提高内体逃逸效率，③利用化学修饰增 强稳定性等。小核酸药物相比其他药物类型的优势有：靶点丰富、特异性强、药物作用长效。对于创新 药公司来说，小核酸药物优势还有：研发成功率相对较高、生产相对快速、平台优势明显。回顾小核酸 药物的发展并非一帆风顺，也曾因稳定性、安全性等问题一度被各大药厂停止开发。2014年GalNAc技 术的发现是激活小核酸药物领 ...