Ascletis reveals positive interim results from first two cohorts of MAD study of small molecule oral GLP-1R agonist ASC30

Ascletis Pharma has revealed positive interim results from the first two cohorts of its randomised, double-blind, placebo-controlled Phase Ib multiple ascending dose (MAD) study conducted in the US of ASC30 oral once-daily tablet in patients with obesity.

ASC30 is an investigational GLP-1R biased small molecule agonist and has unique and differentiated properties that enable the same small molecule for both oral tablet and subcutaneous injection administrations.

The Phase Ib MAD study consists of 3 cohorts, with eight patients in each cohort on ASC30 tablets and two patients in each cohort on matching placebo. Cohort 1 had four dose levels (2mg, 5mg, 10mg and 20mg). Patients in cohort 1 received each dose level of ASC30 or placebo for seven days in a sequential manner. The average daily dose over the 28-day treatment period was 9.25 mg ASC30 for cohort 1. Cohort 2 had four dose levels (2mg, 10mg, 20mg and 40mg). Patients in cohort 2 received each dose level of ASC30 or placebo for seven days in a sequential manner. The average daily dose over the 28-day treatment period was 18 mg ASC30 for cohort 2.

Mean body weight reductions from baselines were 4.3% and 6.3% for MAD cohorts 1 and 2, respectively, after 28-day treatment with ASC30 oral once-daily tablets. Placebo-adjusted mean body weight reductions from baselines were 4.2% and 6.2% for MAD cohorts 1 and 2, respectively.

ASC30 was generally well tolerated in MAD cohorts 1 and 2, with a favorable safety profile. There were no serious adverse events (SAEs). All gastrointestinal (GI)-related adverse events (AEs) were mild (grade 1) or moderate (grade 2). Weekly titrations of ASC30 improved GI tolerability. In MAD cohort 1, there were no incidences of vomiting. No clinically significant changes in liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBL) were observed. There were no clinically significant findings in laboratory tests, vital signs, ECGs (electrocardiograms, including QTc intervals), and physical exams.

"We are excited that these interim results from our Phase Ib MAD study demonstrated potential best-in-class characteristics to treat patients with obesity," said Dr Jinzi Jason W, Founder, Chairman and CEO of Ascletis. "As a small molecule, ASC30 has the potential to offer both once-daily oral and once-monthly subcutaneous injection dosing options for patients, if approved."

ASC30 is a new chemical entity (NCE), with US and global compound patent protection until 2044. Detailed results will be presented at a future medical conference.