Ascletis Reports Positive Topline Results From U.S. Phase Ib Trial Of Oral GLP-1R Agonist ASC30 And Submits 13-Week Phase IIa Study Plan To FDA

Ascletis Pharma Inc. has announced encouraging topline results from its Phase Ib multiple ascending dose (MAD) study of ASC30, an oral, once-daily tablet developed for the treatment of obesity. The randomized, double-blind, placebo-controlled study (NCT06680440) was conducted in the United States in adults with a body mass index (BMI) between 30 and 40 kg/m².  

The trial included three separate dosing schemes over a four-week treatment period, followed by one week of monitoring. The first two schemes, which started at a mid-dose with slower and moderate titration, were based on earlier single-dose data. Scheme 1 included doses of 2 mg, 5 mg, 10 mg, and 20 mg, while Scheme 2 used 2 mg, 10 mg, 20 mg, and 40 mg. In both groups, participants showed significant weight loss without reaching a plateau. 

Scheme 1 achieved an average weight reduction of 4.3% (n=7, p=0.0002 vs placebo), and Scheme 2 showed a 6.3% reduction (n=8, p<0.0001 vs placebo). The placebo group experienced a slight weight gain of 0.2% (n=6). The placebo-adjusted weight reductions were 4.5% and 6.5% for Schemes 1 and 2, respectively. The greatest individual weight reductions in these groups were 7.6% and 9.1%. ASC30 was found to be safe and well tolerated, with mild and temporary gastrointestinal (GI) side effects, and no vomiting reported in Scheme 1.

Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis, said in a statement, “We are excited that these topline results from our Phase Ib study demonstrated potential best-in-class characteristics to treat obesity. Results from the Phase Ib study in the 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.”

Based on the outcomes from the first two groups, a third scheme was introduced with a higher starting dose and faster titration: 5 mg, 15 mg, 30 mg, and 60 mg. This group showed an average weight reduction of 4.8% (n=7, p=0.0015 vs placebo), with a maximum reduction of 9.3%. However, tolerability was reduced in this group, likely due to the more aggressive dosing schedule. Two outliers in Scheme 3 had minimal weight loss, which impacted the average; excluding them, the placebo-adjusted weight reduction rose to 6.1%, comparable to Scheme 2. Across all three schemes, ASC30 demonstrated a strong safety profile. There were no serious adverse events (SAEs), no Grade 3 or higher side effects, and no signs of liver enzyme abnormalities. 

Participants also had normal results in lab tests, vital signs, ECGs, and physical exams. Based on these findings, Ascletis plans to move forward with a 13-week Phase IIa study using a low starting dose and gradual titration approach. The study protocol has already been submitted to the U.S. FDA after preliminary discussions and is expected to begin in the third quarter of 2025. ASC30 is an internally developed GLP-1 receptor (GLP-1R) biased agonist designed to be taken either once daily by mouth or once monthly via subcutaneous injection. It is currently the only known investigational small molecule of its kind aimed at treating obesity.