Ascletis Pharma Inc.  announces  positive topline results of its randomized, double-blind, placebo-controlled Phase Ib multiple ascending dose (MAD) study (NCT06680440), conducted in the U.S., of ASC30 oral once-daily tablet in participants with obesity (body mass index (BMI): 30-40 kg/m²). The Phase Ib MAD study consisted of three cohorts, each with a different weekly titration scheme, for a total of four-week treatment and one-week follow up. Scheme 1 (mid starting dose, slow titration: 2 mg, 5 mg, 10 mg, and 20 mg); Scheme 2 (mid starting dose, normal titration: 2 mg, 10 mg, 20 mg, and 40 mg); and Scheme 3 (high starting dose, fast titration: 5 mg, 15 mg, 30 mg, and 60 mg).  Based on single ascending dose (SAD) data in participants with obesity, Schemes 1 and 2 were designed to investigate tolerability and efficacy. All participants with obesity stayed at the clinical site from day 1 to day 2 and from day 27 to day 29. For other days during the study, participants maintained their habitual eating and physical activity patterns as out-patients.

After reviewing the safety and efficacy results of the first two dosing schemes, a third dosing scheme (high starting dose, fast titration: 5 mg, 15 mg, 30 mg, and 60 mg) was designed to help validate the optimal combination of tolerability and efficacy seen in Schemes 1 and 2. Mean body weight reduction from baseline for Scheme 3 was 4.8% (n=7, p=0.0015 vs placebo) after four-week treatment. Placebo-adjusted mean body weight reduction from baseline was 5.0%. The maximum body weight reduction from baseline was 9.3%. In Scheme 3, there were two outliers, each with body weight reduction of 1.8% from baseline, which were not seen in Schemes 1 or 2.  Excluding these two outliers, placebo-adjusted mean body weight reduction from baseline in Scheme 3 was 6.1%, comparable to Scheme 2. The maximum body weight reduction from baseline of Scheme 3 was also comparable to Scheme 2 (9.3% and 9.1%, respectively). Moreover, the GI tolerability observed in Scheme 3 was less than that of Schemes 1 and 2, due to its high starting dose, fast titration design.

For all the above mentioned three schemes, no serious adverse events (SAEs) were reported. There were no Grade 3 or higher AEs including GI-related AEs observed. There were no elevations of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBL) during the treatment. There were no abnormal findings in laboratory tests, vital signs, ECGs (electrocardiograms, including QTc intervals), and physical exams.

Both tolerability and efficacy data from the ASC30 tablet Phase Ib study support a "lower starting dose and slower titration" strategy for a 13-week Phase IIa study design of ASC30 oral once-daily tablet. The 13-week Phase IIa study protocol, which has a low starting dose and slow weekly titration to the desired maintenance doses, has been submitted to the U.S. Food and Drug Administration (FDA) following a preliminary consultation with FDA.  The Company expects to initiate the 13-week Phase IIa study in the U.S. at the beginning of the third quarter of 2025.

ASC30 was discovered and developed in-house at Ascletis as a first and only investigational small molecule GLP-1 receptor (GLP-1R) biased agonist designed to be dosed once daily orally and once monthly subcutaneously for the treatment of obesity.

"We are excited that these topline results from our Phase Ib study demonstrated potential best-in-class characteristics to treat obesity," said Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis. "Results from the Phase Ib study in U.S. informed and provided critical knowledge for our 13-week Phase IIa study design of ASC30 oral once-daily tablet. As a small molecule, ASC30 has the potential to offer both once-daily oral and once-monthly subcutaneous injection dosing options for obesity treatment, if approved."