Ascletis Pharma-B (01672) has announced key preclinical data for ASC36_35FDC (a fixed-dose combination of ASC36 and ASC35), which was 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 monthly to quarterly fixed-dose combination injectable consisting of ASC36, a peptide amylin receptor agonist, and ASC35, a peptide GLP-1R/GIPR agonist. The study was featured in a short oral discussion session.
The data showed that ASC36_35FDC demonstrated a superior weight loss trend compared to eloralintide/tirzepatide or MET-233i/tirzepatide combinations in diet-induced obese (DIO) rat models, along with superior formulation stability. Additionally, the company has developed a once-weekly oral tablet of ASC36_35FDC.
Key Highlight: Robust Weight Loss Effect: Potential Synergy Demonstrated in Preclinical Models
In both DIO rat and non-human primate (NHP) models, ASC36_35FDC showed more pronounced additional weight loss and food intake suppression compared to ASC35 monotherapy, suggesting a potential synergistic effect of the combination.
In the DIO rat model, ASC36_35FDC administered at doses of 5 nmol/kg and 8 nmol/kg once every 2 days for a total of 7 doses demonstrated robust weight loss. Under the same dosing regimen, by day 14, the eloralintide/tirzepatide combination group experienced 12.5% body weight reduction, the MET-233i/tirzepatide combination group showed 16.8% reduction, and the ASC36_35FDC group achieved 24.8% reduction, representing relative improvements in weight loss of 98% and 47%, respectively. Meanwhile, cumulative food intake in the ASC36_35FDC group was also significantly lower than the two comparison groups.
Superior Physicochemical Stability: No Fibrillation-Related Aggregation Observed
For peptide-based drugs, long-term formulation stability is crucial. Under simulated storage conditions (200 rpm, 25°C, 168 hours), no fibrillation-induced aggregation was observed for ASC36_35FDC across different concentrations, vehicles, and pH conditions. In contrast, under the same conditions, cagrilintide exhibited significant fibrillation aggregation. These findings demonstrate the superior physicochemical stability of ASC36_35FDC and lay a solid foundation for its further clinical development and potential large-scale manufacturing.
Pharmacokinetic Profile: Potentially Supports Monthly to Quarterly Dosing
In non-human primates, the pharmacokinetic (PK) profile of ASC36_35FDC was comparable to that observed with ASC36 or ASC35 administered alone. The observed half-life of ASC36 and ASC35 in ASC36_35FDC reached up to 781 hours (approximately 33 days) and 721 hours (approximately 30 days), respectively, supporting monthly and potentially quarterly subcutaneous dosing in humans. This ultra-long-acting characteristic is expected to improve treatment convenience and patient compliance, offering a more convenient therapeutic option for long-term weight management.
Furthermore, 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 with a GLP-1R/GIPR dual agonist, ASC36_35FDC aims to leverage the complementary effects of these two therapeutic mechanisms. Preliminary preclinical data indicate that ASC36_35FDC shows favorable characteristics in terms of weight loss, appetite suppression, formulation stability, and pharmacokinetics, positioning it as a potential best-in-class therapeutic candidate.