Ascletis Pharma has announced the commencement of two Phase I clinical trials in the United States for its novel drug candidate, ASC30, a small molecule glucagon-like peptide-1 receptor (GLP-1R) agonist. This molecule is distinguished by its potential for both once-monthly subcutaneous injection and once-daily oral tablet administration, targeting the growing obesity market. The trials aim to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ASC30 in obese participants.
ASC30: A Dual-Action GLP-1R Agonist
ASC30, discovered and developed in-house by Ascletis, is a GLP-1R biased agonist designed to avoid β-arrestin recruitment. This unique property allows for the development of both an injectable and an oral formulation. Preclinical studies have shown that ASC30 exhibits two- to threefold greater in vitro potency against GLP-1R compared to orforglipron. Furthermore, in intravenous glucose tolerance tests (IVGTT) conducted on non-human primates (NHPs), ASC30 (1.5 mg/kg) stimulated statistically significant insulin secretion compared to orforglipron (6 mg/kg).
Preclinical Evidence Supports Clinical Development
Animal models have demonstrated that ASC30 injection has a half-life of up to 25 days, supporting the feasibility of once-monthly administration in humans. In NHPs, a single dose of subcutaneous ASC30 resulted in sustained weight loss over one month, outperforming six weekly doses of an antibody-peptide conjugate. Similarly, ASC30 tablets exhibited a half-life of up to 36 hours in animal models, supporting once-daily oral dosing, and demonstrated significant weight loss in NHPs with once-daily oral administration. Ascletis' proprietary technology has achieved a relative bioavailability of 99% for ASC30 tablets at steady state in animal models.
Clinical Trial Design and Objectives
The Phase I trial for ASC30 subcutaneous injection is a randomized, double-blind, placebo-controlled, single ascending dose study involving five cohorts. It is designed to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of ASC30 over a 16-week period in obese participants. The Phase I trial for ASC30 oral tablets employs a similar randomized, double-blind, placebo-controlled design, including both single ascending dose (six cohorts) and multiple ascending dose (three cohorts, 28 daily doses) arms to evaluate safety, tolerability, PK, and efficacy.
Market Potential and Competitive Advantages
According to Dr. Jinzi J. Wu, Founder, Chairman, and CEO of Ascletis, the availability of both once-monthly injections and oral once-daily administration options is highly appealing to patients in the obesity and diabetes markets. ASC30's potential to offer similar safety profiles in both formulations could facilitate switching between administration routes based on patient preference and lifestyle. Dr. Wu believes that ASC30 has the potential to be a first-in-class and best-in-class GLP-1R agonist, citing its superior NHP data and convenient dosing options.
Anticipated Results
Ascletis anticipates topline data from both U.S. Phase I clinical trials in the first quarter of 2025. These results will provide critical insights into the safety, tolerability, and potential efficacy of ASC30 as a novel treatment for obesity.
