843-P: A Novel CRFR2 Selective UCN2 Analog, HM17321, Facilitates Weight Loss and Improves Body Composition across Animal Models of Obesity

by sugaradmin



Introduction and Objective: Incretin drugs effectively promote weight loss, but also cause inevitable lean mass loss, compromising weight loss quality (WLQ). Urocortin-2 (UCN2) shows potential for enhancing lipolysis and muscle hypertrophy, offering a strategy to improve WLQ. To achieve these outcomes, a novel corticotropin-releasing factor receptor-2 (CRFR2) selective UCN2 analog, HM17321, was developed. The present study evaluates the potential effects of HM17321 on body weight (BW) and body composition.Methods: In DIO mice and rats, BW, body composition, muscle tissue and blood parameters were analyzed after chronic treatment of HM17321. Semaglutide (Sema) was included as a comparative control. Monkeys were utilized for potential human translation.Results: In DIO mice, HM17321 treatment significantly reduced BW in a dose-dependent manner. Although BW loss was slightly less pronounced, HM17321 showed a greater fat mass loss compared to Sema. Importantly, unlike Sema, HM17321 significantly increased lean mass and reduced lipid content in muscle tissue, indicating both quantitative and qualitative muscle improvement effect. In addition, HM17321 significantly reduced serum BG, total cholesterol, and ALT. As to the mode of action for this WLQ improvement, HM17321 showed a greater fat mass reduction along with a significant muscle hypertrophic effect compared to pair-fed control, suggesting HM17321’s direct actions on adipose tissue catabolism and skeletal muscle anabolism. The favorable body recomposition was reproduced in DIO rats. Most strikingly, HM17321 treatment was associated with fat mass loss-driven BW loss in monkeys.Conclusion: HM17321 demonstrates robust fat mass reduction and lean mass increasing effect across animal models including monkeys. These findings underscore the potential of HM17321 for high quality weight management, supporting its continued development as a differentiated anti-obesity drug.

Disclosure

J. Kim: None. S. Lee: None. E. Kim: None. D. Lee: None. J. Lee: None. H. Kwon: None. E. Park: None. J.A. Kim: None. S. Han: Employee; Hanmi Pharm. Co., Ltd. J. Park: None. S. Hong: None. S. Bae: None. S. Lee: None. I. Choi: None.



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