Core Viewpoint - Small nucleic acid drugs are expected to become the third major category of drugs following small molecules and antibody drugs due to their ability to target traditionally undruggable targets and their long-lasting effects [1] Industry Developments - The breakthrough of GalNAc technology in 2014 established a successful paradigm for liver-targeted delivery, significantly activating industry development [1] - The global small nucleic acid drug industry is currently achieving commercial profitability, breakthroughs in indications, advancements in extrahepatic delivery, and dual-target breakthroughs [1] Competitive Landscape - Chinese companies are advancing alongside the global industry, demonstrating strong global competitiveness in the small nucleic acid drug sector [1]

Core Viewpoint - Small nucleic acid drugs are expected to become the third major category of drugs following small molecules and antibody drugs, driven by their ability to target traditionally undruggable targets and their long-lasting effects [1][2]. Group 1: Mechanism and Advantages - The mechanism of small nucleic acid drugs involves three main steps: endocytosis, endosomal escape, and gene silencing [2]. - Key factors for their effectiveness include receptor selection, optimization of delivery systems to enhance endosomal escape efficiency, and chemical modifications to improve stability [2]. - Compared to other drug types, small nucleic acid drugs offer advantages such as a rich target pool, strong specificity, and long-lasting effects [2]. Group 2: Industry Breakthroughs - The global small nucleic acid drug industry is achieving multi-dimensional breakthroughs, with drugs like Amvuttra and Leqvio showing significant potential, and Alnylam expected to achieve profitability this year [3]. - The years 2025-2026 are critical for validating new indications, with weight loss indications anticipated to reach proof of concept (POC) and CNS indications expected to begin exploration [3]. - Technological advancements include breakthroughs in extrahepatic delivery methods, with Avidity's AOC drug Del-zota showing promising efficacy and expected to be commercially available by 2026 [3]. Group 3: China's Competitive Edge - Chinese small nucleic acid drug companies are demonstrating global competitiveness, with an accelerated growth in research pipelines [4]. - Companies like Bosheng and Ruibo have established business development (BD) deals with multinational corporations (MNCs), highlighting China's competitive position [4]. - The focus of Chinese small nucleic acid drug pipelines has expanded 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 [4].