• ASC30 oral tablet demonstrated dose-proportional pharmacokinetic (PK) properties and a long half-life (t_1/2) up to 60 hours in the single ascending dose (SAD) study of patients with obesity, supporting once-daily or less frequent oral dosing.
• ASC30 oral tablet was generally safe and well tolerated. All adverse events (AEs) were mild (grade 1) or moderate (grade 2), and most of the AEs were gastrointestinal (GI)-related. There were no grade 3 or higher AEs as well as no serious AEs (SAEs). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other liver enzymes were in normal ranges.
• ASC30 oral tablet is stable at room temperature. Relative oral bioavailability of ASC30 tablet is 99% in animal models.
• Data from the animal models utilizing a new tablet formulation of ASC30 support up to once-weekly oral dosing.
• Topline results, including weight loss, safety and PK, from the U.S. Phase Ib multiple ascending dose (MAD) study of ASC30 oral tablet, once daily, in obese patients are expected by the end of March 2025.

Ascletis Pharma Inc. announces positive topline results from its U.S. single ascending dose (SAD) study  (NCT06680440) of ASC30 oral tablet in patients with obesity (body mass index (BMI): 30-40 kg/m²). The SAD study consists of five cohorts (2 mg, 5 mg, 10 mg, 20 mg and 40 mg) with a total of 40 patients with obesity under fasting conditions.

ASC30 oral tablet demonstrated dose-proportional pharmacokinetic (PK) properties and a long half-life (t_1/2) up to 60 hours in the SAD study of patients with obesity, supporting once-daily or less frequent oral dosing. Cross-trial comparison indicates that in humans, drug exposure (area under the curve, "AUC") of 5 mg ASC30 single dose is 2.2-fold of that of 6 mg orforglipron single dose ^[1]. ASC30 oral tablet demonstrated superior PK properties (including a longer t_1/2 and higher AUC) to other small molecule oral GLP-1 receptor (GLP-1R) agonists in development ^[1-3], suggesting ASC30 oral tablet has the potential to be a best-in-class small molecule GLP-1R agonist to treat obesity.

In Cohort 5, 40 mg ASC30 oral tablet single dose was given orally to patients with obesity under both fasting and fed conditions. The data indicated that ASC30 oral tablet's PK properties including AUC and t_1/2 were essentially identical in the absence or presence of food, suggesting that ASC30 oral tablet can offer patient-friendly, once-daily oral dosing without food and water restrictions.

ASC30 oral tablet was generally safe and well tolerated in the Phase Ia SAD study.  All adverse events (AEs) were mild (grade 1) or moderate (grade 2), and most of the AEs were gastrointestinal (GI)-related. There were no grade 3 or higher AEs, as well as no serious AEs (SAEs). GI-related safety profiles of ASC30 oral tablet were consistent with or better than other small molecule oral GLP-1R agonists in development ^{[1, 3, 4]} (Table 1). Furthermore, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other liver enzymes were in normal ranges.

Table 1. All GI-related AEs of ASC30 oral tablet were mild (grade 1) or moderate (grade 2) 

ASC30 oral tablet formulation, which is stable at room temperature, was developed using Ascletis' proprietary technology and has a relative oral bioavailability of 99% at steady state in animal models. Data from the animal models utilizing a new tablet formulation (stable at room temperature) of ASC30 support up to once-weekly oral dosing.

ASC30 was discovered and developed in-house at Ascletis as a GLP-1R biased small molecule agonist without β-arrestin recruitment.  ASC30 has unique and differentiated properties that enable the administration of one small molecule as both a once-monthly subcutaneous injection and a once-daily oral tablet. ASC30 has two- to three-fold better in vitro potency against GLP-1R when compared head-to-head with orforglipron. In the intravenous glucose tolerant test (IVGTT) in non-human primates (NHPs), ASC30 (1.5 mg/kg dose) stimulated statistically and significantly more insulin secretion when compared head-to-head with orforglipron (6 mg/kg dose).

ASC30 is the first and only small molecule GLP-1R biased agonist that can be dosed once monthly subcutaneously and once daily orally for the treatment of obesity. ASC30 oral tablet has the potential to be a best-in-class GLP-1R small molecule agonist given its PK and safety profiles as well as potency against GLP-1R.

"We are excited that the results from our Phase Ia SAD trial of ASC30 oral tablet, once daily in patients with obesity demonstrated potential best-in-class characteristics. With superior PK properties observed in the SAD study, we are looking forward to sharing efficacy, safety, and PK data from Phase Ib 28-day multiple ascending dose (MAD) trial of patients with obesity by the end of March this year," said Dr. Jinzi Jason Wu, Founder, Chairman and CEO of Ascletis, "As one small molecule, ASC30 potentially offers both once-daily oral and once-monthly subcutaneous injection dosing options."