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 P<0.001), 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 P<0.001). 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.