Ascletis Enters the Obesity Drug Space with Announcement of Two Ongoing U.S. Phase I Clinical Trials Utilizing Its Small Molecule GLP-1R Agonist ASC30 for Both Once-Monthly Subcutaneous Injection and Once-Daily Oral Tablet for the Treatment of Obesity

- ASC30 is the first and only small molecule GLP-1 receptor (GLP-1R) agonist that can be dosed once-monthly subcutaneously and once-daily orally to treat obesity

- ASC30 is two- to threefold more potent, in vitro, than orforglipron and stimulated significantly greater insulin secretion when compared with orforglipron in non-human primates (NHPs)

- ASC30 single dose subcutaneous injection demonstrated sustained weight loss over one month in NHPs supporting once-monthly administration in humans

- ASC30 oral once-daily dosing demonstrated sustained weight loss in NHPs supporting once-daily oral administration in humans

- Topline data from ongoing U.S. Phase I clinical trials of ASC30 once-monthly subcutaneous injection and once-daily oral tablet to treat obesity expected first quarter 2025

- ASC30 has the potential to be a first-in-class and best-in-class small molecule GLP-1R agonist to treat obesity given its superior NHP data, as well as once-monthly and once-daily dosing

HONG KONG, Sept. 17, 2024 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX:1672, "Ascletis") announces today completion of initial dosing in its two recently initiated U.S. Phase I clinical trials for ASC30, the first and only small molecule GLP-1 receptor (GLP-1R) agonist that can be dosed once monthly subcutaneously and once-daily orally for the treatment of obesity. Ascletis received clearance for its Investigational New Drug (IND) applications from the U.S. Food and Drug Administration (FDA) in July 2024 for ASC30 tablets and September 2024 for ASC30 injection. The Company expects topline data from both U.S. Phase I clinical trials in the first quarter of 2025.

ASC30 was discovered and developed in-house at Ascletis as a GLP-1R biased small molecule agonist without β-arrestin recruitment.  ASC30 has unique and differentiated properties that enable the administration of one small molecule as both a once-monthly subcutaneous injection and a once-daily oral tablet. ASC30 has two- to threefold better in vitro potency against GLP-1R when compared head-to-head with orforglipron. In the intravenous glucose tolerant test (IVGTT) in non-human primates (NHPs), ASC30 (1.5 mg/kg dose) stimulated statistically and significantly more insulin secretion when compared head-to-head with orforglipron (6 mg/kg dose).

In animal models, ASC30 injection showed a half-life of up to 25 days, supporting once-monthly injection in humans. In NHPs, a single dose of ASC30 subcutaneous injection demonstrated sustained and favorable weight loss over one month compared to six weekly doses of an antibody-peptide conjugate.

ASC30 once-monthly subcutaneous injection has potentially strong competitive advantages (less frequent injections and/or lower cost of goods) against weekly injected peptide GLP-1 drugs and monthly injected antibody-peptide conjugate drug candidate.

ASC30 once-daily tablets have the potential to be the best-in-class GLP-1R small molecule agonist given its superior 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 dosing. In NHPs, once-daily oral dosing of ASC30 demonstrated significant weight loss. Utilizing Ascletis' proprietary technology, the relative bioavailability of ASC30 tablets was 99% at steady state in animal models. 

"In obesity and diabetes markets, both once-monthly injections and oral once-daily administration are attractive to patients, who may choose to switch from injections to oral drugs or vice versa based on chronic weight management approach, lifestyle and convenience," said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis. "As one small molecule, ASC30 offers both once-monthly injection and once-daily oral dosing options. Furthermore, the ASC30 oral tablet and injection offer same or similar safety profiles to enhance ease of switching between both options."

Dr. Wu continued, "From our research and development efforts over the past three years, we have developed a differentiated small molecule product that is highly competitive in both the subcutaneous obesity treatment market and the oral obesity treatment market. By combining the unique properties of ASC30 and Ascletis' proprietary technology, we have successfully prolonged the half-life of ASC30 injection to 25 days, enabling once-monthly dosing. To date, the data for ASC30 subcutaneous and oral forms supports our belief that it has the potential to be a first-in-class and best-in-class GLP-1R agonist."

Two ASC30 Phase I Clinical Studies for the Treatment of Obesity

The Phase I study of ASC30 once-monthly subcutaneous injection is a randomized, double-blind, placebo-controlled, single ascending dose (5 cohorts) study being conducted in the U.S. to evaluate the safety, tolerability, PK and efficacy of ASC30 in participants with obesity over 16 weeks. In cohort 1, two patients with obesity have been successfully dosed with ASC30 once-monthly injection and demonstrated good safety and tolerability.

The Phase I study of ASC30 once-daily tablets is a randomized, double-blind, placebo-controlled, single ascending dose (6 cohorts) and multiple ascending dose (3 cohorts, 28 daily oral doses) study being conducted in the U.S. to evaluate the safety, tolerability, PK and efficacy of ASC30 in participants with obesity. In cohort 1, all eight obese patients (six on drug and two on placebo) have been successfully dosed with ASC30 tablets and demonstrated good safety and tolerability.

About ASC30

ASC30 is an investigational GLP-1R biased small molecule agonist and has unique and differentiated properties that enable the same small molecule for both subcutaneous injection and oral tablet administrations. ASC30 is a new molecular entity (NME), with U.S. and global compound patent protection until 2044. 

About Ascletis Pharma Inc.

Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), covering the entire value chain from discovery and development to GMP manufacturing. Led by a management team with deep expertise and a proven track record, Ascletis has rapidly advanced its pipeline, focusing on two therapeutic areas with unmet medical needs from a global perspective: metabolic diseases and viral diseases. Ascletis has multiple clinical stage drug candidates in its R&D pipeline.

For more information, please visit www.ascletis.com.

Contact：
Peter Vozzo
ICR Westwicke
443-231-0505 (U.S.)
Peter.vozzo@westwicke.com

Ascletis Pharma Inc. PR and IR teams
+86-181-0650-9129 (China)
pr@ascletis.com
ir@ascletis.com

source: Ascletis Pharma Inc.