745-P: Efficacy and Safety of RAY1225 Once Every Two Weeks in Chinese Adults with Obesity or Overweight (REBUILDING-1)

Introduction and Objective: To investigate the efficacy, safety, and tolerability of RAY1225, a novel once every two weeks GLP-1 and GIP receptor dual agonist, in Chinese nondiabetic adults with overweight or obesity. Methods: This phase 2 double-blind, randomized, placebo-controlled trial included 2 parts. The target dose of part A was 3mg,6mg, and that of part B was 9mg and above with dose escalation and extension. Chinese nondiabetic adults with a BMI ≥28 kg/m2, or 24-28 kg/m2 accompanied by at least one obesity-related comorbidity were randomized. In part A, eligible participants were randomly assigned 1:1:1 to receive 3mg, 6 mg RAY1225 injection or placebo subcutaneously once every two weeks for 24 weeks. In part B, the randomization ratio was 4:1 to receive 9 mg (or above dose) or placebo. The primary endpoint was the percentage change from baseline to week 24 in weight. Results: A total of 132 participants were analyzed from part A and part B with dose escalated up to 9mg till now. At baseline, the mean (standard deviation) body weight was 91.07 (15.09) kg, BMI was 32.33 (3.98) kg/m2, and about 89.4% of participants had a BMI≥28 kg/m2. The mean percentage change in weight at week 24 was -10.06% (95% confidence interval, -11.63 to -8.49) with 3mg of RAY1225, -12.97% (-14.51 to -11.43) with 6mg, and -13.05% (-16.20 to -9.91) with 9mg and -3.62% (-5.19 to -2.05) with placebo (P<0.001). About 73.2% to 95.1% of participants in the RAY1225 group achieved ≥5% weight loss, compared with 30.0% in the placebo.(P<0.05). In addition, RAY1225 is also beneficial in the improvement of cardiometabolic indexes. The most common adverse events (AEs) with RAY1225 were gastrointestinal, most were mild to moderate in severity, occurring primarily during dose escalation. No drug related serious AEs occurred.. Conclusion: This study showed RAY1225 once every two weeks subcutaneous injection was safe and achieved robust body weight reduction in Chinese adults with overweight or obesity. Disclosure L. Ji: None. L. Yan: None. L. Gao: Research Support; Sciwind Biosciences. M. Xu: None. X. Dong: None. C. Wang: None. Y. Zhu: None. J. Li: Employee; Guangdong Raynovent Biotech Co., Ltd. Y. Peng: Employee; Raynovent. H. Li: Employee; Guangdong Raynovent Biotech Co., Ltd. X. Chen: Employee; Guangdong Raynovent Biotech Co., Ltd.