ASCLETIS-B(01672): Preclinical study of ASC36_35FDC presented at EASD 2026, demonstrating potential for once-monthly to once-quarterly dosing and strong weight loss effects

ASCLETIS-B(01672) announced that key preclinical data for ASC36_35FDC (ASC36_35 fixed-dose combination) were presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD), held in Milan, Italy, from September 28 to October 2, 2026 (EASD 2026). ASC36_35FDC is a once-monthly to once-quarterly fixed-dose combination injectable of ASC36 (a peptide amylin receptor agonist) and ASC35 (a peptide GLP-1R/GIPR agonist). The study was presented in a short oral discussion session. The data showed that ASC36_35FDC demonstrated a superior weight loss trend compared with eloralintide/tirzepatide or MET-233i/tirzepatide combination formulations in a diet-induced obesity (DIO) rat model, and possessed superior formulation stability. In addition, the company has developed a once-weekly oral tablet of ASC36_35FDC. Key Highlights Strong weight loss effect: potential synergistic effect demonstrated in preclinical models In DIO rat and non-human primate (NHP) models, ASC36_35FDC showed more significant additional weight loss effects and food intake suppression effects compared with ASC35 monotherapy, suggesting a potential synergistic effect of the combination. In the DIO rat model, ASC36_35FDC at doses of 5 nmol/kg_8 nmol/kg, administered once every 2 days for a total of 7 doses, demonstrated a strong weight loss effect. Under the same dosing regimen, on Day 14, the eloralintide/tirzepatide combination group lost 12.5% of body weight, the MET-233i/tirzepatide combination group lost 16.8%, and the ASC36_35FDC group lost 24.8%, representing relative improvements in weight loss of 98% and 47%, respectively. At the same time, cumulative food intake in the ASC36_35FDC group was also significantly lower than in the above two control groups. Superior physicochemical stability: no fibrillar aggregation observed For peptide drugs, long-term formulation stability is crucial. Under simulated storage conditions (200 rpm, 25C, 168 hours), no aggregation caused by fibrillation was observed for ASC36_35FDC under different concentrations, vehicles, and pH conditions. In contrast, under the same conditions described above, cagrilintide showed significant fibrillar aggregation. These findings demonstrate that ASC36_35FDC has superior physicochemical stability and lay a solid foundation for its further clinical development and potential large-scale manufacturing. Pharmacokinetic profile: expected to support once-monthly to once-quarterly dosing In non-human primates, the pharmacokinetic (PK) profile of ASC36_35FDC was comparable to that observed after administration of ASC36 or ASC35 alone. The observed half-life of ASC36 and ASC35 in ASC36_35FDC was as long as 781 hours (approximately 33 days) and 721 hours (approximately 30 days), respectively, supporting once-monthly and potentially once-quarterly subcutaneous administration in humans. This ultra-long-acting property is expected to improve treatment convenience and patient compliance, providing a more convenient treatment option for long-term weight management. In addition, ASC36_35FDC is a combination therapy independently developed using Ascletis' proprietary structure-based AI-assisted drug discovery (AISBDD) and ultra-long-acting drug development platform (ULAP) technologies. By combining an amylin receptor agonist and a GLP-1R/GIPR dual-target agonist, ASC36_35FDC is designed to leverage the complementary effects of these two therapeutic mechanisms. Preliminary preclinical data indicate that ASC36_35FDC shows favorable characteristics in weight loss, appetite suppression, formulation stability, and pharmacokinetics, and has the potential to become a best-in-class therapeutic candidate.