Ascletis Announces Two U.S. Phase I Trials for Obesity Drug ASC30

HONG KONG, Sept. 17, 2024. Ascletis Pharma Inc. ("Ascletis") has successfully completed the initial dosing in two U.S. Phase I clinical trials for ASC30, a novel small molecule GLP-1 receptor (GLP-1R) agonist. This molecule is unique in that it can be administered either via a subcutaneous injection once a month or orally once a day, aimed at treating obesity. The U.S. Food and Drug Administration (FDA) granted clearance for the Investigational New Drug (IND) applications for ASC30 tablets in July 2024 and for ASC30 injection in September 2024. Ascletis expects to release topline data from both Phase I trials in the first quarter of 2025.

ASC30 was internally developed at Ascletis as a GLP-1R biased small molecule agonist that avoids β-arrestin recruitment. This novel compound showcases distinctive properties allowing its use as both a once-monthly subcutaneous injection and a once-daily oral tablet. In vitro studies reveal that ASC30 exhibits two to three times higher potency against GLP-1R compared to orforglipron. Moreover, in intravenous glucose tolerance tests (IVGTT) conducted on non-human primates (NHPs), ASC30 at a 1.5 mg/kg dose significantly stimulated more insulin secretion compared to orforglipron at a 6 mg/kg dose.

Animal model trials have demonstrated that ASC30 injection has a half-life of up to 25 days, supporting the feasibility of once-monthly injections in humans. In NHPs, a single dose of ASC30's subcutaneous injection resulted in sustained and favorable weight loss over a month, outperforming six weekly doses of an antibody-peptide conjugate.

The monthly subcutaneous injection of ASC30 presents notable advantages over weekly peptide GLP-1 drugs and monthly antibody-peptide conjugate drug candidates by reducing the frequency of injections and potentially lowering the cost of goods. The once-daily tablet form of ASC30 is also promising, given its better pharmacokinetic (PK) profile and greater potency against GLP-1R. In animal models, ASC30 tablets had a half-life of up to 36 hours, supporting once-daily oral administration. Additionally, in NHPs, daily oral dosing resulted in significant weight loss. Using Ascletis' proprietary technology, the tablets achieved 99% relative bioavailability at steady state in animal models.

Dr. Jinzi J. Wu, Founder, Chairman, and CEO of Ascletis, highlighted the benefits of ASC30, emphasizing its advantageous options for both monthly injections and daily oral intake, which cater to the varying needs and preferences of patients managing chronic weight issues. Dr. Wu noted that “the ASC30 oral tablet and injection offer similar safety profiles, facilitating easy transition between the two forms based on patient convenience.”

Dr. Wu further elaborated on Ascletis' research efforts, stating that over the past three years, the company has developed this competitive small molecule product for both subcutaneous and oral obesity treatments. The prolonged half-life of the ASC30 injection, achieved through their proprietary technology, enables monthly dosing. The current data for both forms of ASC30 supports their potential as first-in-class and best-in-class GLP-1R agonists.

Regarding the Phase I clinical trials, the study for the monthly subcutaneous injection of ASC30 is a randomized, double-blind, placebo-controlled, single ascending dose study spanning five cohorts. This trial will assess the safety, tolerability, PK, and efficacy of ASC30 over 16 weeks in obese participants. In the first cohort, two patients have successfully completed dosing with positive safety and tolerability results.

The Phase I study for the daily oral tablets of ASC30 follows a similar randomized, double-blind, placebo-controlled format. This trial includes single ascending dose (six cohorts) and multiple ascending dose (three cohorts, 28 daily doses) studies to evaluate safety, tolerability, PK, and efficacy in obese participants. In the first cohort, all eight patients, including six on the drug and two on placebo, have completed dosing with favorable safety and tolerability outcomes.

ASC30, protected under U.S. and global patents until 2044, is a significant addition to Ascletis' pipeline. The company continues to make strides in the biotech industry, focusing on addressing unmet medical needs, particularly in metabolic and viral diseases.