Ascletis Pharma Inc. (Ascletis) has begun two Phase I clinical studies in the United States to evaluate novel, ultra-long-acting peptide therapies for obesity, following recent Investigational New Drug clearances from the U.S. Food and Drug Administration.
The first study tests ASC36_35FDC, a once-monthly subcutaneous fixed-dose combination that co-formulates ASC36—an amylin receptor peptide agonist—with ASC35, a dual GLP-1R/GIPR peptide agonist. Positioned as a potentially first-in-class therapy targeting three validated metabolic pathways, the trial will enroll 176 adults who are obese (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with weight-related comorbidities. Participants will receive single and multiple ascending doses of two formulation variants (Injection A and Injection B) in a randomized, double-blind, placebo-controlled design.
The second study assesses ASC36, a next-generation amylin receptor agonist formulated for once-monthly to once-quarterly dosing. A total of 144 participants meeting the same BMI criteria will be randomized to receive either of two formulations (Injection A or Injection B) or placebo, also under double-blind, placebo-controlled conditions.
Preclinical data underpinning the human trials include:
• In diet-induced obese rat models, ASC36 monotherapy achieved approximately 91% and 32% greater relative body-weight reduction versus petrelintide and eloralintide, respectively. • The ASC36_35FDC co-formulation delivered about 51% higher relative weight reduction than co-administered eloralintide and tirzepatide. • In non-human primates, ASC36’s Self-Assembling Lipid Depot (SALD) formulation displayed an observed half-life roughly six times longer than eloralintide, supporting monthly to quarterly dosing; ASC36_35FDC showed similarly prolonged exposure for both components.
Both investigational products employ Ascletis’ in-house Artificial Intelligence-assisted Structure-Based Drug Discovery and Ultra-Long-Acting Platform technologies. The low-viscosity SALD formulations are designed for administration with 29-gauge auto-injectors, forming subcutaneous depots that release active pharmaceutical ingredients over at least one month while maintaining chemical and physical stability without aggregation.
Ascletis’ Chairman and CEO, Dr. Jinzi Jason Wu, highlighted the differentiation versus current regimens that may require up to eight injections per month, noting the company’s parallel advancement of three U.S. Phase I peptide programs—ASC35, ASC36 and ASC36_35FDC—alongside a global Phase III trial of oral small-molecule GLP-1 candidate ASC30.
The company cautioned that successful development, manufacturing and commercialization of ASC36_35FDC, ASC35, ASC36 and ASC30 are not guaranteed.