减重赛道全球前沿进展跟踪（三）：新风口之小核酸药物有望破局千亿美金市场

Investment Rating - The industry investment rating is "Positive" (maintained) [1] Core Viewpoints - The report highlights that the small nucleic acid drug sector is expected to break into a billion-dollar market, focusing on weight loss indications primarily targeting INHBE and ALK7 [5][14] - Arrowhead and Wave are leading the small nucleic acid weight loss sector, with domestic companies rapidly and comprehensively entering the market [6][18] - The combination of small nucleic acid drugs with GLP-1 is anticipated to address multiple unmet clinical needs, potentially enhancing weight loss effects while preserving muscle mass [7][19][22] - Short-term focus is recommended on the data readouts from Arrowhead and Wave's Phase 1 clinical trials, particularly regarding safety, pharmacokinetics, and early efficacy [8][26] Summary by Sections Section 1: Small Nucleic Acid Drugs in Weight Loss - The small nucleic acid drugs are centered around INHBE and ALK7, with INHBE expressed in liver cells and ALK7 in adipose tissue, playing crucial roles in fat metabolism [5][14] - Arrowhead and Wave are at the forefront of this sector, with significant trial data expected in the next six months [6][17] Section 2: Clinical Combination Strategies - Preclinical data suggests that Arrowhead's ALK7 siRNA combined with Tirzepatide may enhance weight loss and provide longer-lasting effects [7][19] - Genetic studies indicate that the INHBE/ALK7 pathway is critical for fat distribution rather than just weight control, suggesting a focus on reducing visceral fat [22][23] Section 3: Investment Recommendations - The report recommends monitoring the upcoming data from Arrowhead and Wave, emphasizing the importance of safety and metabolic indicators [8][26] - Suggested investment targets include YK Pharmaceutical, Sunlight Novo, Rejuve Biotech, and Shiyao Group, with beneficiaries including Frontier Biotech and Hengrui Medicine [8]