143-OR: NA-931, a Novel Quadruple IGF-1-1, GLP-1, GIP, and Glucagon Receptor Agonist Reduces Body Weight without Muscle Loss

Introduction and Objective: NA-931 is a quadruple agonist of the insulin-like growth hormone- (IGF-1), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon receptor agonist for the potential treatment of metabolic disorders such as obesity. Methods: This is a randomized, double-blind, placebo-controlled, dose escalation, study to assess the safety and tolerability, pharmacokinetics, and pharmacodynamics of NA-931 when administered as single and multiple-ascending doses in overweight/obese participants. ClinicalTrials.gov ID NCT06615700 Results: Body Weight Reductions: In the 28-day study, subjects receiving NA-931 (n=74) demonstrated dose-dependent reductions in mean body weight from baseline, ranging up to 6.4%. For doses ≥60 mg, placebo-adjusted reductions in mean body weight were maintained or improved at Day 35, seven days after the last dose of NA-931 was administered, ranging up to 5.3% relative to placebo. An exploratory assessment of the proportion of subjects achieving at least 5% weight loss after 28 days demonstrated that up to 63% of NA-931-treated subjects achieved ≥5% weight loss, compared with 0% for placebo. Safety and Tolerability: Among subjects receiving NA-931, emergent adverse events (TEAEs) were reported to date have been insignificant or mild. All observed gastrointestinal (GI) adverse events have been reported as insignificant or mild, with the majority (84%) reported as insignificant. Mild nausea and vomiting were not reported among any NA-931-treated subjects. Diarrhea was reported in one subject (2.3%) receiving NA-931 compared with two subjects (10%) receiving placebo. No muscle loss was observed. No clinically meaningful differences were reported for GI-related adverse events among subjects treated with NA-931 compared with placebo. Conclusion: We are conducting a Phase 2 trial with the oral formulation of NA-931 for the possible treatment of obesity. Disclosure L.L. Tran: None.