Ascletis receives FDA clearance for Phase I trial of obesity treatment

FDA Clears Ascletis' Once-Monthly ASC35 for Phase I Obesity Trial

Ascletis Pharma has received Investigational New Drug (IND) clearance from the US FDA to initiate a Phase I study for ASC35, a once-monthly subcutaneous glucagon-like peptide-1 receptor/glucose-dependent insulinotropic polypeptide receptor (GLP-1R/GIPR) dual peptide agonist, for the treatment of obesity. The placebo-controlled, randomised, double-blind trial will enroll 84 participants with obesity or overweight with weight-related comorbidities. The study aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ASC35 through single and multiple ascending doses, including a head-to-head comparison with once-weekly tirzepatide in Part B.

• Ascletis Pharma achieved a significant regulatory milestone with FDA IND clearance for ASC35, advancing its peptide pipeline for obesity treatment. ASC35 is a novel once-monthly subcutaneous GLP-1R/GIPR dual peptide agonist, independently discovered and developed using Ascletis’ AI-assisted structure-based drug discovery (AISBDD) platform, highlighting the company's innovative approach to drug development.
• The upcoming Phase I study is designed as a placebo-controlled, randomised, double-blind trial involving 84 participants. The patient population includes individuals with obesity (BMI ≥30.0kg/m²) or those overweight (BMI ≥27.0kg/m²) with weight-related comorbidities, ensuring a relevant cohort for evaluating ASC35's safety, tolerability, pharmacokinetics, and pharmacodynamics.
• The clinical trial features a two-part design, with Part B conducting a head-to-head, multiple-ascending-dose comparison between ASC35’s proprietary once-monthly Self-Assembling Lipid Depot (SALD) formulation and the FDA-approved, once-weekly tirzepatide. The SALD formulation, developed using the ultra-long-acting platform (ULAP) technology, is engineered to provide sustained drug release over one month or longer, potentially offering a more convenient and patient-friendly dosing regimen.

ASC35's Phase I Design: A Head-to-Head Look at Once-Monthly Dosing

The obesity therapeutic landscape has been shaped by a diverse range of trial designs, spanning pharmacological, device-based, behavioral, and dietary interventions across both pediatric and adult populations. Key trials vary considerably in duration, randomization strategy, and primary endpoint selection, reflecting the multifactorial nature of obesity as a disease. The following table summarizes the design parameters and endpoints of the most clinically and strategically relevant trials identified in the literature.

Addressing Key Unmet Needs in the Evolving Obesity Treatment Landscape

The obesity treatment landscape has increasingly shifted toward recognizing heterogeneity in disease burden, with mounting evidence highlighting that unmet needs extend well beyond pharmacological gaps to encompass structural, demographic, and disease-specific dimensions. Across recent literature, several discrete populations and clinical scenarios have emerged as priority targets where current standards of care remain inadequate. The following areas represent the most substantiated unmet needs identified over this period.

• Racial, ethnic, and socioeconomically marginalized communities: Racial and ethnic minorities in the US experience disproportionately higher rates of obesity, hypertension, diabetes, and cardiovascular disease relative to White populations. MASLD prevalence is rising fastest among older adults and Hispanic women, particularly in low-income and rural communities. Historical structural factors — including redlining, underinvestment in social infrastructure, limited green space access, and food deserts — compound genetic risk and perpetuate health disparities that pharmacologic advances alone cannot address. Equitable access to approved pharmacologic therapies remains a critical gap.

• Pediatric and adolescent populations: Children and adolescents with severe obesity represent an underserved clinical population, with early-onset chronic comorbidities requiring earlier intervention thresholds, including timely referral for metabolic and bariatric surgery evaluation. Adolescents aged 12–18 show high rates of suboptimal dietary patterns. Additionally, GLP-1 receptor agonists have demonstrated significant BMI reduction (−1.7, p=0.02) and ALT reduction (−3.0, p=0.01) in youth, though long-term safety data and clinical significance of metabolic improvements remain insufficiently characterized.

• Patients with monogenic obesity (MC4R deficiency): MC4R deficiency — the most common monogenic cause of obesity — presents with severe hyperphagia and early-onset obesity, yet targeted therapeutic approaches remain largely unexplored in pediatric patients. A case report of a 17-year-old with MC4R deficiency treated with tirzepatide demonstrated initial hyperphagia reduction and 20.9% total body weight loss at 37 weeks, but hunger scores rebounded toward pre-treatment levels by week 28, underscoring the need for combination strategies and dedicated pediatric trial data.

• Obese patients with MASH (≤F3 fibrosis) without diabetes: This subgroup carries high risk of progression to advanced liver disease and cirrhosis, yet remains undertreated. An estimated 782,920 obese adults in Italy fall within this target population. Cost-effectiveness analysis of semaglutide 2.4 mg in this group demonstrated an ICER of €22,691 per QALY gained over a 10-year horizon — below accepted Italian willingness-to-pay thresholds — indicating both clinical and economic rationale for targeted intervention in this cohort.

• Patients with sarcopenic obesity: Characterized by concurrent excessive adiposity and reduced skeletal muscle mass with impaired function, sarcopenic obesity requires individualized management across special populations including adolescents, the elderly, and menopausal individuals. Expert consensus (2026 edition) recommends a multidisciplinary approach integrating endocrinology, bariatric surgery, clinical nutrition, and rehabilitation medicine, with combining lifestyle interventions and incretin-based therapies showing meaningful improvements in body composition and muscle function.

• Geographically isolated and indigenous communities: Pacific Island nations — particularly the Republic of the Marshall Islands — face among the highest global rates of obesity-related diabetes and downstream complications, including one of the highest amputation rates worldwide, compounded by minimal healthcare infrastructure, financial barriers, and culturally based hesitancy to seek care. Tribal populations in India similarly present with distinct metabolic-hematologic profiles and elevated risk driven by high illiteracy rates and tobacco and alcohol use, necessitating culturally informed, population-specific prevention frameworks.

• Very preterm-born children in socioeconomically deprived neighborhoods: This often-overlooked population demonstrates substantially elevated risk of overweight or obesity at two years of age (42.8% vs. 35.3%, p=0.004), with disadvantaged neighborhood status independently associated with obesity risk (adjusted OR 1.57; 95% CI 1.10–2.23; p=0.01), reinforcing the need for early, neighborhood-level obesity prevention strategies targeting this high-risk developmental window.