Ascletis Pharma Inc. (Ascletis) has selected a fixed-dose combination (FDC) of two in-house oral small-molecule agonists—ASC48 (GIPR) and ASC30 (GLP-1R)—for clinical development as a once-daily treatment for obesity.

ASC48 demonstrated an EC50 of 1 pM in the human GIPR cAMP activation assay, showing higher potency than tirzepatide’s 3 pM. The compound is selective for GIPR, with no observed activity on GLP-1R or GCGR, and exhibited favorable oral bioavailability and a long half-life in both rodent and non-human primate (NHP) studies.

In an eight-day, head-to-head NHP study, the ASC30_48 FDC reduced body weight by 10.5%, versus 6.9% for ASC30 monotherapy and 1.7% for ASC48 monotherapy. The FDC’s relative body-weight reduction was 52% greater than ASC30 alone and 518% greater than ASC48 alone.

Positioned as an oral analogue to tirzepatide—which is administered weekly by injection and projected to exceed USD 30 billion in 2025 sales—the once-daily ASC30_48 tablet targets both GLP-1R and GIPR receptors in a single pill. Ascletis expects to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration in the fourth quarter of 2026.

The company emphasized that the development, manufacturing, and commercialization of ASC30, ASC48, and their combination remain subject to successful clinical progress.