A Phase 1 Study of ID110521156, a Small Molecule Glucagon-Like Peptide 1 Receptor Agonist, in Healthy Subjects

Introduction and Objective: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as effective therapeutic strategies for type 2 diabetes mellitus and obesity. To address the limitations of peptide-based GLP-1RAs, we developed ID110521156, a novel small-molecule GLP-1RA. In nonclinical studies, ID110521156 exhibited favorable pharmacokinetic property for oral administration and potent glucose-lowering efficacy with wide safety margin. Based on these findings, a first-in-human study was initiated in the Republic of Korea [NCT06063291]. Methods: A randomized, double-blind, placebo-controlled, single-ascending dose (SAD) study was conducted in healthy subjects to evaluate the safety, tolerability, and pharmacokinetics of ID110521156. Eligible subjects in the SAD cohorts (total 24, N=8/cohort) were randomly assigned to receive a single oral dose of ID110521156 or placebo in a 6:2 ratio. Additionally, a food effect study was performed in a separate cohort (N=12) using a randomized, two-sequence, crossover design to assess the effect of food on the pharmacokinetics of ID110521156. Results: During dose escalation, systemic exposures (AUClast ) increased in a dose-proportional manner with a 95% confidence interval of 0.0623-1.0219 for the slope of the regression line. A total of 32 treatment emergent adverse events (TEAEs) were reported by 14 subjects in the SAD cohorts. Commonly reported TEAEs were gastrointestinal-related, including nausea and vomiting. No serious adverse events were observed, and most TEAEs were Grade 2 or lower in severity, recovering without intervention. Food intake had minimal impact on the systemic exposure of ID110521156 with comparable AUClast between the fed and fasted states, whereas Cmax was reduced by 36% following a high-fat meal. Conclusion: These results demonstrate that ID110521156 is an orally available, well-tolerated GLP-1RA with an acceptable safety profile in humans. A phase 1 multiple ascending dose study is currently ongoing [NCT06635226]. Disclosure: I. Je: None. Y. Kyoung: None. S. Yoo: None. E. Hong: None. M. Kim: None. J. Yang: None. H. Won: None. S. Lee: None. J. Park: None.