Ascletis Begins U.S. Phase I Trials for ASC30 Obesity Drug

Ascletis Pharma Inc. has announced the completion of initial dosing in its two Phase I clinical trials in the United States for ASC30, a groundbreaking small molecule GLP-1 receptor (GLP-1R) agonist designed for the treatment of obesity. ASC30 is notable for being the first and only small molecule GLP-1R agonist that can be administered both as a once-monthly subcutaneous injection and a once-daily oral tablet. The U.S. Food and Drug Administration (FDA) cleared Ascletis’ Investigational New Drug (IND) applications for ASC30 tablets in July 2024 and for ASC30 injection in September 2024. The company expects to release topline data from these trials in the first quarter of 2025.

Discovered and developed internally by Ascletis, ASC30 is characterized as a GLP-1R biased small molecule agonist that does not involve β-arrestin recruitment. Its unique properties make it possible to administer the same small molecule as either a once-monthly subcutaneous injection or a once-daily oral tablet. Laboratory comparisons show that ASC30 is two- to threefold more potent in vitro against GLP-1R compared to orforglipron, another GLP-1R agonist. In non-human primate (NHP) tests, ASC30 at a dose of 1.5 mg/kg significantly stimulated more insulin secretion than orforglipron at a 6 mg/kg dose.

In animal models, a single subcutaneous injection of ASC30 showed a half-life of up to 25 days, supporting its potential for once-monthly human administration. Additionally, this single dose demonstrated sustained weight loss in NHPs over one month, as opposed to six weekly doses of an antibody-peptide conjugate.

The once-monthly subcutaneous injection of ASC30 may present competitive advantages over existing weekly injected peptide GLP-1 drugs and monthly injected antibody-peptide conjugate drug candidates, potentially including less frequent injections and lower costs. The once-daily oral tablets of ASC30 also have the potential to stand out as the best-in-class GLP-1R small molecule agonist due to their superior pharmacokinetic profile and greater potency against GLP-1R. In animal studies, the tablets exhibited a half-life of up to 36 hours, supporting once-daily dosing. In NHPs, the once-daily oral administration of ASC30 resulted in significant weight loss. The tablets also demonstrated a relative bioavailability of 99% at steady state in animal models.

The dual administration options of ASC30, both as a once-monthly injection and as once-daily oral tablets, could be particularly appealing to patients managing chronic weight issues, as they may switch between the two forms based on lifestyle and convenience. Dr. Jinzi J. Wu, Founder, Chairman, and CEO of Ascletis, stated that the company’s research and development efforts have led to a highly competitive small molecule product in both the subcutaneous and oral obesity treatment markets. Dr. Wu also highlighted the prolonged half-life of ASC30 injection, which enables once-monthly dosing.

Two Phase I clinical studies are being conducted for ASC30's treatment of obesity. One study involves the once-monthly subcutaneous injection and is a randomized, double-blind, placebo-controlled, single ascending dose study comprising five cohorts. This study is evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of ASC30 over 16 weeks in obese participants. In the first cohort, two obese patients received the once-monthly injection, showing good safety and tolerability.

The second Phase I study focuses on the once-daily oral tablets and is also randomized, double-blind, and placebo-controlled. It consists of single ascending dose (six cohorts) and multiple ascending dose (three cohorts, with 28 daily oral doses) assessments. This study aims to evaluate the safety, tolerability, PK, and efficacy of ASC30 in obese participants. In the first cohort, eight obese patients (six on the drug, two on placebo) received the ASC30 tablets and demonstrated good safety and tolerability.

ASC30 represents a novel molecular entity with potential U.S. and global patent protection until 2044. Ascletis Pharma Inc., listed on the Hong Kong Stock Exchange, focuses on innovative research and development across the entire drug development value chain, particularly targeting metabolic and viral diseases.