1682-P: ID110521156, a Novel Oral Small-Molecule GLP-1RA: Evidence of Favorable Safety Profile and Dose-Dependent Reduction in Body Weight and Glycemic Control after 28 Days of Treatment

Introduction and Objective: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) treat type 2 diabetes mellitus (T2DM) and obesity; however, gastrointestinal (GI) tolerability and dose titration remain challenges. ID110521156 is a novel oral small-molecule GLP-1RA under development. This study evaluated safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of ID110521156 in healthy participants. Methods: A randomized, double-blind, placebo-controlled, multiple ascending dose study was conducted (NCT06635226). Participants were assigned to 3 cohorts (50, 100, and 200 mg). Each cohort included 12 participants randomized (10:2) to once-daily ID110521156 or placebo for 28 days without titration. Results: ID110521156 was well tolerated across all doses, with mild GI adverse events. A reversible, dose-dependent increase in indirect bilirubin resolved within 2 days after the last dose; other liver function parameters were within normal ranges. Systemic exposure (AUCτ,ss) increased dose proportionally (4,648.89, 8,246.40, and 21,486.75 μg·h/L for 50, 100, and 200 mg) with no accumulation. Plasma concentrations were sustained throughout the dosing interval, supporting once-daily dosing. After 28 days, dose-dependent reductions in body weight were observed (-5.50, -6.89, and -9.88% for 50, 100, and 200 mg) versus placebo (-3.1%). Glucose exposure after OGTT (ΔAUGC0-4) decreased dose dependently (-90.16, -102.44, and -124.69 mg·h/dL for 50, 100, and 200 mg) versus placebo (-15.21 mg·h/dL). CGM showed persistent reductions in mean daily glucose through 28 days. Conclusion: ID110521156 showed favorable tolerability, dose-proportional PK, and clinically meaningful PD effects after 28 days dosing. Robust, dose-dependent body-weight reduction and improved glycemic control, PK profile supporting once-daily regimen, and satisfactory tolerability without titration justify further clinical development of ID110521156 for T2DM and obesity. Disclosure S. Lee: None. K. Kim: None. Y. Kyoung: Employee; Current; YUNOVIA Co., Ltd. S. Yoo: None. S. Lee: None. J. Park: None.