3090-LB: UBT251, a Triple Hormone Receptor Agonist in Adults with Overweight or Obesity: A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 2 Trial

Introduction and Objective: To assess UBT251, a novel triple agonist targeting the glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors, for the treatment of obesity. Methods: In this phase 2 trial (NCT07177469), Chinese adults with overweight (BMI 24. 0-28. 0 kg/m²) plus ≥1 weight-related condition or obesity (BMI ≥28. 0 kg/m²) were enrolled and randomly assigned (2: 1: 1: 2: 2) to receive once-weekly s. c. UBT251 (2. 0 mg, 4. 0 mg initial dose ID, 0. 5 mg, 4. 0 mg ID, 1. 0 mg and 6. 0 mg) or placebo (pbo) for 24 weeks. The primary endpoint was percentage weight loss (%WL) from baseline to week 24. Results: Of 205 randomized adults (59% were female), mean age was 34. 1 yrs, weight 92. 2 kg, BMI 33. 1 kg/m2, waist circumference WC 104. 1 cm. At week 24, least-square mean %WL with UBT251 was 13. 6% (2. 0 mg), 16. 2% (4. 0 mg ID, 0. 5 mg), 19. 7% (4. 0 mg ID, 1. 0 mg), and 18. 7% (6. 0 mg) vs. 2. 0% with pbo (all P0. 001), and higher proportions of 5, 10, 15 and 20 %WL were achieved with UBT251 (Fig. ). Absolute reduction in body weight, WC and BMI was greater with UBT251 vs. pbo (all P0. 001). The most frequent adverse events associated with UBT251 were gastrointestinal disorders, primarily mild to moderate in severity. Conclusion: In adults with overweight or obesity, UBT251 showed significant and dose-dependent %WL up to 19. 7%, and was generally well-tolerated. Disclosure Z. Zhou: None. Z. Cheng: None. P. Jin: None. G. Yang: None. H. Wang: None. B. Shi: None. Q. Dong: None. X. Shi: None. X. Shi: None. H. Shu: None. W. Sun: None. C. Huang: None. S. Zhao: None. L. Mao: None. W. Bian: Employee; Current; The United Laboratories International Holdings Limited (TUL), The United Bio-Technology (Hengqin) Co. , Ltd. H. Yan: Employee; Current; The United Laboratories International Holdings Limited (TUL), The United Bio-Technology (Hengqin) Co. , Ltd. T. Su: Employee; Current; The United Laboratories International Holdings Limited (TUL), The United Bio-Technology (Hengqin) Co. , Ltd. L. Huang: Employee; Current; The United Laboratories International Holdings Limited (TUL), The United Bio-Technology (Hengqin) Co. , Ltd. S. B. Simony: Employee; Current; Novo Nordisk A/S. T. Holst-Hansen: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Novo Nordisk. Funding The United Laboratories International Holdings Limited (TUL) and The United Bio-Technology (Hengqin) Co. , Ltd.