ASC48 is a potentially first-in-class oral small molecule GIPR agonist.

- ASC48 demonstrated an EC₅₀ of 1 pM in the hGIPR cAMP activation assay, exhibiting greater potency than tirzepatide (EC₅₀ = 3 pM) and is a selective agonist for GIPR without activity for GLP-1R and GCGR.

- ASC48 demonstrated excellent oral bioavailability and drug exposure as well as long half-life in rodents and non-human primates (NHPs), supporting once-daily oral dosing in humans.

- Fixed dose combination of ASC30 and ASC48 (ASC30_48 FDC) is a potentially first-in-class oral one-pill, once-daily treatment for obesity, targeting both GLP-1R and GIPR.

- ASC30_48 FDC demonstrated approximately 52% greater relative body weight reduction compared to ASC30 monotherapy in a head-to-head NHP study.

- ASC30_48 FDC is a once-daily oral small molecule with the same mechanism of action as tirzepatide, the market leading GLP/GIP once weekly subcutaneous peptide with over $30 billion in sales in 2025.

- Submission of an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) for ASC30_48 FDC oral tablets is expected in the fourth quarter of 2026.

 Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") announces that it has selected a fixed-dose combination of ASC48, a potentially first-in-class oral small molecule GIPR agonist, and ASC30, an oral small molecule GLP-1R agonist, for clinical development. ASC30 and ASC48 fixed-dose combination (ASC30_48 FDC) is a potentially first-in-class oral one-pill, once-daily therapy for obesity, targeting GLP-1R and GIPR.

ASC48 was discovered in-house utilizing Ascletis' Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) technology. In a head-to-head study, ASC48 demonstrated an EC₅₀ of 1 pM in the hGIPR cAMP activation assay, exhibiting greater potency than tirzepatide (EC₅₀ = 3 pM) and is a selective agonist for GIPR without activity for GLP-1R and GCGR. ASC48 demonstrated excellent oral bioavailability and drug exposure as well as long half-life in rodents and non-human primates (NHPs), supporting once-daily oral dosing in humans.

ASC30_48 FDC demonstrated approximately 52% greater relative body weight reduction compared to ASC30 monotherapy in a head-to-head NHP study (Table 1).

Table 1. Once-daily oral administration of ASC30_48 FDC for eight consecutive days produced 52% and 518% greater relative body weight reduction, respectively compared to ASC30 and ASC48 monotherapies

Notes:

PO: oral administration; QD: once daily.

Submission of an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) for ASC30_48 FDC oral tablets is expected in the fourth quarter of 2026.

"We look forward to initiating this trial to evaluate the fixed-dose combination of ASC48 and ASC30 with the aim of developing a first-in-class oral treatment regimen to potentially improve outcomes for people with obesity," said Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis. "We believe there is an unmet medical need for an oral drug that when given in combination with GLP-1R therapy can achieve the same weight loss and tolerability as tirzepatide weekly injections."