Ascletis Pharma Inc. (Ascletis) reported new preclinical results for ASC36_35FDC—its fixed-dose combination of the amylin receptor agonist ASC36 and the GLP-1R/GIPR dual agonist ASC35—presented at the 62nd European Association for the Study of Diabetes (EASD) Annual Meeting 2026 in Milan. Data disclose three core advantages: superior weight-loss efficacy, strong formulation stability and an ultra-long pharmacokinetic profile that could enable dosing as infrequently as once every three months.
In a diet-induced obesity rat model, seven subcutaneous injections of ASC36_35FDC (5 nmol/kg + 8 nmol/kg, every two days) reduced body weight by 24.8% on Day 14—98% and 47% deeper reductions than the 12.5% and 16.8% achieved by eloralintide/tirzepatide and MET-233i/tirzepatide co-formulations, respectively. Cumulative food intake was also markedly lower in the ASC36_35FDC cohort, indicating a potential synergistic appetite-suppressing effect of the amylin and GLP-1R/GIPR pathways.
Stability tests conducted under accelerated conditions (200 rpm agitation, 25 °C, 168 hours) detected no fibril-induced aggregation for ASC36_35FDC across varying concentrations, vehicles and pH levels. By contrast, cagrilintide displayed significant fibrotic aggregation, underscoring the candidate’s chemical and physical robustness and its suitability for large-scale manufacturing.
Non-human primate pharmacokinetic data revealed half-lives of 781 hours (approximately 33 days) for ASC36 and 721 hours (approximately 30 days) for ASC35 within the combination product, supporting once-monthly—and potentially once-quarterly—subcutaneous administration. Ascletis has also formulated a once-weekly oral tablet version, broadening future dosing flexibility.
ASC36_35FDC was generated using Ascletis’ proprietary Artificial Intelligence-assisted Structure-Based Drug Discovery and Ultra-Long-Acting Platform. The company emphasizes that while preclinical results are encouraging, there is no assurance the candidate will ultimately be successfully developed, manufactured or commercialized.