3061-LB: Combination Treatment of Oral Small Molecule GLP-1 Receptor Agonist Aleniglipron and Small Molecule Amylin Receptor Agonist ACCG-2671 Demonstrated Additional Weight Loss than Monotreatment in Obese NHPs

Introduction and Objective: GLP-1 receptor activation and amylin receptor activation are two complementary mechanisms of action for obesity treatments. Combination therapy of long-acting peptides semaglutide and cagrilintide have demonstrated enhanced efficacy over single agents for obesity treatment in clinical trials. Small molecules offer potential advantages over peptides, including scalability, room temperature shipping and storage, and the opportunity for fixed-dose combinations. We evaluated the weight-loss efficacy of the small molecule GLP-1 receptor agonist aleniglipron and dual amylin and calcitonin receptor agonist ACCG-2671, administered alone or in combination, in obese non-human primates (NHPs). Methods: In the monotreatment study, obese NHPs were treated with oral aleniglipron or ACCG-2671 once daily at various doses to evaluate the dose response effect on food intake and body weight. The combination treatment study was subsequently performed by co-administration of aleniglipron and ACCG-2671 and evaluated the effects on food intake and body weight. Results: Both aleniglipron and ACCG-2671 monotreatment demonstrated dose-dependent body weight reductions in obese NHPs. Combination treatment of aleniglipron and ACCG-2671 resulted in a greater inhibition of food intake and a further reduction in body weight compared with either treatment alone. Conclusion: Combination treatment with the small molecule GLP-1R agonist aleniglipron and amylin receptor agonist ACCG-2671 demonstrated further weight loss than monotreatment in obese NHPs. These findings support further development of aleniglipron and ACCG-2671 as a potential oral fixed-dose combination therapy for obesity. Disclosure X. Fang: Employee; Current; Structure Therapeutics. J. Zhang: None. N. Hu: Employee; Current; Structure Therapeutics. X. Jiang: None. X. Lin: None. F. Zhang: Stock/Shareholder; Current; Eli Lilly and Company, Novo Nordisk A/S.