Ascletis Pharma has announced the selection of a Fixed-Dose Combination (FDC) of ASC48, an investigational oral small-molecule Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR) agonist, and ASC30, an oral glucagon-like peptide-1 receptor (GLP-1R) agonist, for clinical development as a potential once-daily treatment for obesity.

The combination therapy, ASC30_48 FDC, is being developed as a potentially first-in-class oral, single-pill regimen targeting both GLP-1R and GIPR, with the aim of providing an alternative to injectable obesity therapies.

ASC48 was discovered using Ascletis' proprietary Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) platform. According to the company, the candidate demonstrated high potency in preclinical studies, with an EC50 of 1 pM in the human GIPR cAMP activation assay, compared with 3 pM for tirzepatide. The molecule also showed selective activity for GIPR, without activation of GLP-1R or glucagon receptors (GCGR).

Preclinical pharmacokinetic studies in rodents and non-human primates demonstrated favourable oral bioavailability, sustained drug exposure and a long half-life, supporting the potential for once-daily oral administration in humans.

In a head-to-head non-human primate study, the ASC30_48 fixed-dose combination achieved approximately 52 percent greater relative body weight reduction than ASC30 monotherapy, indicating the potential benefits of dual receptor activation for obesity management.

Ascletis expects to submit an Investigational New Drug (IND) application for the oral fixed-dose combination tablets to the US Food and Drug Administration (FDA) in the fourth quarter of 2026, paving the way for clinical evaluation.

Commenting on the development, Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis, said the company aims to evaluate the fixed-dose combination as a potentially first-in-class oral therapy for obesity. He added that the programme is intended to address the need for an oral treatment capable of delivering weight-loss efficacy and tolerability comparable to currently available dual agonist injectable therapies.

Ascletis Pharma is a fully integrated biotechnology company focused on developing and commercialising first-in-class and best-in-class therapies for metabolic diseases, leveraging artificial intelligence to accelerate drug discovery and development.