2594-P: XTL6001: A Novel Triple MasR/GCGR/GLP-1R Agonist for Weight Loss and Obesity-Related Complications

Introduction and Objective: XTL6001 is a novel triple agonist at the MasR (Mas receptor), GCGR, and GLP-1R. To investigate its efficacy and safety in weight loss and obesity-related complications, animal studies and a first-in-human study was performed. Methods: DIO mice were dosed subcutaneously twice weekly for 56 days with XTL6001. Body weight and food intake were measured daily. Biochemical parameters in plasma and liver tissue, visceral fat, lean and fat mass were analyzed at terminal necropsy. A phase I Study (NCT07205432), XTL6001 was evaluated at single ascending doses of 37.5-300 mg in 32 healthy participants. Results: XTL6001 outperforms Semaglutide in weight reduction at equivalent dose with minimal weight rebound after treatment cessation and without substantial impact on food intake suggesting favorable long-term safety and tolerability. Furthermore, XTL6001 outperforms Semaglutide in decrease in visceral fat weight, increase the proportion of muscle mass and decrease proportion of fat mass, thereby reverse muscle-to-fat ratio. XTL6001 improves blood and hepatic lipid metabolism(Table 1). In a phase I single ascending dose study in health volunteer, XTL6001 showed a favorable safety and tolerability profile. Its pharmacokinetic profile supported once-weekly dosing. Conclusion: These findings indicate XTL6001 confers superior improvements in body weight loss and obesity complications with good safety and tolerability and warrant further clinical assessment. Disclosure Y. Wang: Employee; Current; Shaanxi Micot Pharmaceutical Technology Co., Ltd. Y. Liu: Employee; Current; Shaanxi Micot Pharmaceutical Technology Co., Ltd. X. Wang: None. L. Wang: None. Z. Huang: Employee; Current; Shaanxi Micot Pharmaceutical Technology Co., Ltd.