ASCLETIS-B(01672): Oral small-molecule GLP-1 ASC30 achieved a placebo-adjusted HbA1c reduction of 1.7% at week 12 in a U.S. Phase II study in subjects with diabetes

ASCLETIS-B(01672) announced positive topline results from its U.S. Phase II study (NCT07321678) evaluating the oral small-molecule GLP-1 receptor (GLP-1R) agonist ASC30 for the treatment of type 2 diabetes (T2D). This Phase II study was a 13-week U.S. study designed to evaluate the efficacy, safety, and tolerability of once-daily oral small-molecule GLP-1R agonist ASC30 tablets in 100 subjects with diabetes. The primary endpoint was the reduction in glycated hemoglobin (HbA1c) from baseline at week 12; one of the secondary endpoints was the reduction in body weight from baseline at week 13. ASC30 (40 mg, 60 mg, and 80 mg) met the primary endpoint and all secondary endpoints, achieving significant HbA1c reductions and body weight loss, and improving multiple cardiovascular risk factors. Type 2 diabetes is the second indication under development for ASC30 in addition to obesity. For the primary endpoint, compared with placebo, ASC30 achieved statistically significant and clinically meaningful HbA1c reductions in subjects with diabetes (p < 0.0001). Based on the efficacy estimand, at week 12, the placebo-adjusted HbA1c reductions from baseline (least squares mean) for the 40 mg (n=20), 60 mg (n=29), and 80 mg (n=28) dose groups were 1.7%, 1.6%, and 1.7%, respectively. Subjects' mean baseline HbA1c was 8.3%. For the secondary endpoint of body weight loss, compared with placebo, ASC30 achieved statistically significant and clinically meaningful body weight loss (p=0.001 to 0.003). Based on the efficacy estimand, at week 13, the placebo-adjusted body weight reductions from baseline (least squares mean) for the 40 mg (n=20), 60 mg (n=29), and 80 mg (n=28) dose groups were 4.4%, 3.8%, and 4.0%, respectively, with no plateau observed. Subjects' mean baseline body weight was 93.7 kg. Despite the rapid titration (once weekly) in this study, ASC30 continued to demonstrate good gastrointestinal (GI) tolerability. ASC30 was titrated weekly up to maintenance doses (40 mg, 60 mg, and 80 mg), demonstrating good safety and GI tolerability, with no study discontinuations due to GI adverse events (AEs). The good GI tolerability observed in subjects with diabetes was consistent with findings from studies conducted in subjects with obesity or overweight. GI tolerability is expected to improve significantly further in the Phase III diabetes program when titration is slowed to once every four weeks. There was only 1 study discontinuation due to any adverse event (1/80, 1.3%, hiccup). There were no study discontinuations due to adverse events in the placebo group. In this U.S. Phase II diabetes study of ASC30, all drug-related adverse events were only Grade 1 (mild) and Grade 2 (moderate) in severity. There were no drug-related serious adverse events (SAEs). The overall safety profile of ASC30 in subjects with diabetes was consistent with that observed in another Phase II study (NCT07002905) conducted in subjects with obesity or overweight. No liver safety signals were observed. There were no elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin (TBL) during the treatment period. With respect to all other safety signals, ASC30 demonstrated a good safety profile in subjects with diabetes. "These data indicate that ASC30 has the potential to become a best-in-class oral small-molecule GLP-1 drug for the treatment of diabetes, just as the efficacy and tolerability demonstrated in our U.S. Phase II study in subjects with obesity or overweight show that ASC30 is a best-in-class oral small-molecule GLP-1 drug for the treatment of obesity," said Dr. Jinzi J. Wu, Founder, Chairman of the Board, and Chief Executive Officer of Ascletis. "The combination of significant HbA1c reduction, body weight loss, and good tolerability further strengthens our confidence in advancing ASC30 as a once-daily oral treatment option for patients with type 2 diabetes." ASC30 is a small-molecule GLP-1R full biased agonist independently developed by Ascletis. The global Phase III program of ASC30 for the treatment of obesity includes two pivotal trials (AURORA-1, NCT07743463 and AURORA-2, NCT07743450) being conducted in the United States, Europe, and Canada, and is currently enrolling approximately 4,600 subjects with obesity or overweight. Topline data from the global Phase III clinical program of ASC30 for obesity are expected in the third quarter of 2028, a New Drug Application (NDA) for obesity is expected to be submitted to the U.S. Food and Drug Administration (FDA) by the end of 2028, and a Marketing Authorization Application (MAA) for obesity is expected to be submitted to the European Medicines Agency (EMA) in early 2029. If approved, ASC30 has the potential to become the second oral small-molecule GLP-1 receptor agonist marketed in the United States and Europe.