Ascletis Pharma Initiates Phase I Study for Oral Obesity Treatment ASC36

Ascletis Pharma Inc. has initiated a Phase I clinical trial in the United States for its oral amylin receptor peptide agonist, ASC36, as a potential treatment for obesity. This marks the company's fourth Phase I study of a peptide this year, highlighting its commitment to developing innovative therapies for metabolic diseases.

The new trial, designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ASC36, will involve 86 participants with obesity (body mass index (BMI) ≥ 30.0 kg/m²) or overweight (BMI ≥ 27.0 kg/m²). The study aims to assess the efficacy and safety of ASC36 oral tablets, which have shown promising results in preclinical studies.

In non-human primate (NHP) studies, ASC36 oral tablets achieved an absolute oral bioavailability of 6% to 8% at steady state, utilizing Ascletis' proprietary Peptide Oral Transport ENhancement Technology (POTENT). At a 10 mg dose, ASC36 oral tablets reduced mean body weight by up to 13.2% from baseline after a seven-day once-daily dosing regimen. Moreover, the tablets significantly reduced food intake in NHPs.

Subcutaneous (SQ) injection of ASC36 also demonstrated a significant weight loss advantage over existing therapies. In a head-to-head diet-induced obese (DIO) rat model, ASC36 SQ injection resulted in approximately 32% and 91% greater relative body weight reduction compared to eloralintide and petrelintide injection, respectively. This suggests that ASC36 has the potential to offer a more effective weight management option.

According to Jinzi Jason Wu, Founder, Chairman, and CEO of Ascletis, "ASC36 has shown compelling preclinical weight-loss efficacy, favorable oral bioavailability, and a prolonged half-life. We believe an effective oral amylin receptor agonist could offer a convenient, differentiated option for people with obesity. Combined with our oral small molecule and long-acting injectable programs, ASC36 further strengthens our diversified pipeline addressing the evolving treatment needs of patients with obesity and other metabolic diseases."

The long elimination half-life of ASC36 oral tablets (116 hours to 167 hours) supports once-daily and less frequent oral dosing. Wu continued, "Based on potentially better oral bioavailability and efficacy, ASC36 oral tablets are expected to utilize a lower dose compared to a recently FDA-approved oral GLP-1R peptide agonist. This superior weight loss per milligram of ASC36 peptide may also provide scalability advantages in manufacturing."

ASC36 was discovered and developed in-house utilizing Ascletis' proprietary Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) technology. The oral tablet formulation was optimized by Ascletis' proprietary Peptide Oral Transport ENhancement Technology (POTENT) for delivery of oral peptides. The company's diverse pipeline includes multiple drug candidates, such as its lead program, ASC30, a once-daily oral small molecule GLP-1R agonist for chronic weight management and diabetes, and ASC36, an amylin receptor peptide designed for once-monthly to once-quarterly subcutaneous and once-daily oral administration.

The initiation of the Phase I study in the United States is a significant milestone for Ascletis, further validating the company's proprietary POTENT oral peptide delivery technology and its commitment to addressing the growing burden of obesity and metabolic diseases.