MWN109—A Novel Fatty Acid–Modified GLP-1/GIP/GCG Triagonist for Dual-Format Weight Management Demonstrates Superior Efficacy in Nonhuman Primates

Introduction and Objective: GLP-1/GIP/GCG receptor triagonists offer a promising approach to obesity treatment. While retatrutide demonstrates potent weight loss effects, oral peptide bioavailability remains a challenge. MWN109, a novel fatty acid-modified triagonist, is designed for both subcutaneous (SC) and oral administration, addressing absorption limitations. This study evaluates its weight loss efficacy, pharmacokinetics, and safety in NHP. Methods: In diet-induced obesity (DIO) monkey studies, SC MWN109 was compared with tirzepatide and retatrutide. A parallel study in healthy cynomolgus monkeys assessed systemic exposure following oral administration. A 10-week NHP toxicology study assessed cardiovascular safety, including heart rate effects. Results: MWN109 demonstrated greater weight loss efficacy in DIO monkeys. A one-tenth dose of MWN109 had comparable weight reduction similar to a full dose of tirzepatide (26.6% vs. 22.7%), while a one-third dose was comparable to retatrutide (11.2% vs. 14.0%). At an equivalent dose, MWN109 induced greater weight loss than retatrutide (22.2% vs. 14.0%) with improved lean mass preservation. Pharmacokinetic analysis confirmed systemic exposure following oral administration. In the 10-week study, MWN109 showed minimal heart rate increase, indicating good cardiovascular safety. Conclusion: MWN109 exhibits greater weight loss efficacy, favorable pharmacokinetics, and a promising safety profile, supporting its potential as a next-generation obesity treatment. The SC formulation has received IND clearance from both the NMPA and FDA and is currently in Phase 1 trials. Disclosure: W. Song: Employee; Shanghai minwei biotechnology Co,,LTD.