Ascletis Pharma has announced positive topline results from its US single ascending dose (SAD) study of ASC30 oral tablet in patients living with obesity. The SAD study consists of five cohorts (2mg, 5mg, 10mg, 20mg and 40mg) with a total of 40 patients with obesity under fasting conditions.

ASC30 is an investigational GLP-1R biased small molecule agonist and has unique and differentiated properties that enable the same small molecule for both subcutaneous injection and oral tablet administrations.
The ASC30 oral tablet demonstrated dose-proportional pharmacokinetic (PK) properties and a long half-life (t1/2) 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 6mg orforglipron single dose. ASC30 oral tablet demonstrated superior PK properties (including a longer t1/2 and higher AUC) to other small molecule oral GLP-1ra in development, suggesting ASC30 oral tablet has the potential to be a best-in-class small molecule GLP-1R agonist to treat obesity.
In Cohort 5, 40mg 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 t1/2 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 (Table 1). Furthermore, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other liver enzymes were in normal ranges.

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.
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