ASCLETIS-B (ASX: 01672) has announced the selection of a fixed-dose combination of its potential first-in-class oral small molecule GIPR agonist ASC48 and its oral small molecule GLP-1R agonist ASC30 for clinical development.
The fixed-dose combination of ASC30 and ASC48 (ASC30_48 FDC) targets both GLP-1R and GIPR, aiming to become a pioneering "one-pill, once-daily" oral therapy for obesity.
ASC48 was developed internally using the company's proprietary structure-based AI-assisted drug discovery (AISBDD) technology. In a head-to-head human GIPR (hGIPR) cAMP activation assay, ASC48 demonstrated an EC50 of 1 pM, showing stronger agonist activity than tirzepatide (EC50 = 3 pM). ASC48 is a selective GIPR agonist with no agonist activity on GLP-1R or GCGR.
The compound has shown excellent oral bioavailability, drug exposure, and a long half-life in rodent and non-human primate studies, supporting a once-daily oral dosing regimen in humans.
In head-to-head non-human primate studies, the ASC30_48 FDC demonstrated a weight loss effect approximately 52% greater than that of ASC30 monotherapy. After eight consecutive days of once-daily oral administration, the weight loss effect of the FDC was 52% and 518% greater than that of ASC30 and ASC48 monotherapies, respectively.
The company plans to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for the ASC30_48 FDC oral tablet in the fourth quarter of 2026.
"We look forward to initiating this clinical trial to evaluate the fixed-dose combination of ASC48 and ASC30, aiming to develop a first-in-class oral therapy that has the potential to improve treatment outcomes for patients with obesity," said Dr. Jinzi J. Wu, Founder, Chairman, and CEO of ASCLETIS. "We believe there remains an unmet medical need for an oral drug that, when combined with GLP-1R therapy, can achieve the same weight loss efficacy and tolerability as once-weekly injectable tirzepatide."
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