ASCLETIS-B(01672): Positive results achieved in the US Phase Ia single dose escalation study of ASC30, a small molecular oral GLP-1R agonist, and provided project progress updates.

ASCLETIS-B (01672) announced that the ASC30 oral tablet achieved positive top-line results in the United States Single Ascending Dose (SAD) study (NCT06680440) for the treatment of patients with obesity (BMI: 30-40 kg/m2). The SAD study consisted of 5 cohorts (2 mg, 5 mg, 10 mg, 20 mg, and 40 mg) with a total of 40 obese patients, conducted in a fasting state. In the SAD study conducted in obese patients, ASC30 oral tablet demonstrated dose-proportional pharmacokinetic (PK) characteristics, with a half-life of 60 hours, supporting once-daily or lower frequency oral administration. Cross-trial comparisons showed that in humans, the drug exposure of a single dose of 5 mg ASC30 (area under the curve, "AUC") was 2.2 times that of a single dose of 6 mg forglipron. Compared to other investigational small molecule oral GLP-1 receptor (GLP-1R) agonists, the ASC30 oral tablet showed superior PK characteristics (including longer half-life and higher AUC), indicating that ASC30 has the potential to be the best-in-class small molecule GLP-1R agonist for the treatment of obesity. In Cohort 5, obese patients received a single dose of 40 mg ASC30 oral tablet in both fasting and fed states. Data showed that the PK characteristics of ASC30 oral tablet (including AUC and half-life) were similar in fasting and fed states, indicating that ASC30 oral tablet is convenient for daily oral administration, unaffected by food and water intake. Overall, the safety and tolerability of ASC30 oral tablet in Phase Ia SAD study was good. All adverse events (AE) were mild (Grade 1) or moderate (Grade 2), with most AE related to gastrointestinal (GI) issues. There were no Grade 3 or above AEs, and no serious adverse events (SAE). The GI-related safety profile of ASC30 oral tablet was consistent with or better than other investigational small molecule oral GLP-1R agonists. In addition, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other liver enzymes were within normal ranges. ASC30 oral tablet was developed using Ascletis' proprietary technology, stable at room temperature, with a relative oral bioavailability of 99% in animal models. Data from animal models support less frequent oral dosing with the new stable ASC30 tablet (room temperature), possibly once weekly. ASC30 is a small molecule GLP-1R biased agonist developed by Ascletis without -arrestin recruitment. ASC30 has unique and differentiated properties, allowing for once-monthly subcutaneous injection and once-daily oral administration. Through head-to-head comparisons, ASC30 showed 2 to 3 times higher in vitro potency on GLP-1R compared to forglipron. In Intravenous Glucose Tolerance Test experiments conducted in non-human primates (NHPs), ASC30 (dose: 1.5 mg/kg) stimulated more insulin secretion compared to forglipron (dose: 6 mg/kg) with statistically significant differences. ASC30 is the first and only small molecule GLP-1R agonist for the treatment of obesity that can be administered once monthly subcutaneously or once daily orally. Based on its PK and safety profile, as well as its agonistic effects on GLP-1R, ASC30 oral tablet is expected to be the best-in-class small molecule GLP-1R agonist.