Paper Title
NA-931, A NOVEL QUADRUPLE IGF-1, GLP-1, GIP AND GLUCAGON RECEPTOR AGONIST REDUCES BODY WEIGHT WITHOUT MUSCLE LOSS

Abstract
We are presenting the topline results from a Phase I clinical study evaluating the safety and tolerabilityof a once-daily, oral medicine NA-931, in participants with obesity, with or without type 2 diabetes. NA-931 is a quadruple IGF-1, GLP-1, GIP and Glucagon receptor agonist. The study demonstrated that NA-931 achieved a clinically meaningful weight loss of -6.4% or -5.1% relative to placebo after 28 days of treatment, and up to -12.7%, or -10.4% relative to placebo after 12 weeks. Importantly, NA-931 showed no significant gastrointestinal-related adverse events and no muscle loss, positioning it as a well-tolerated and promising option for weight management. Body Weight Reduction: The Phase I trial was a randomized, double-blind, placebo-controlled study conducted in participants who were overweight or obese, including those with type 2 diabetes. NA-931, a small molecule quadruple receptor agonist, is being developed for the treatment of both type 2 diabetes and obesity. Results from the 28-day multiple ascending dose (MAD) study showed dose-dependent reductions in body weight. Participants treated with NA-931 experienced mean weight reductions of up to 6.8% , or 5.1% relative to placebo (p < 0.001). Following this 28-day period, participants entered an 8-week open-label extension, extending the total treatment duration to 12 weeks. During this 12-week MAD study, participants receiving 150 mg of NA-931 daily achieved a body weight reduction of up to 12.7%, or 10.4% relative to placebo. Safety and Tolerability: 28-Day Study: NA-931 was well tolerated, with all reported treatment-emergent adverse events (TEAEs) rated as insignificant or mild. Of these, 85% were considered insignificant. Mild nausea was reported in 8.3% (1 of 12) of participants at the highest dose (150 mg/day) and in 3.7% (2 of 54) of participants overall. No vomiting occurred, even at the highest dose of 150 mg/day. Diarrhea was reported in 8.3% (1 of 12) of participants at the highest dose, and in 3.7% (1 of 54) of participants overall. 12-Week Study: During the 12-week study, 78% of TEAEs were insignificant or mild. Mild nausea was reported in 16.6% (2 of 12) of participants at the highest dose and 6.8% (3 of 44) of participants overall. No vomiting occurred, and diarrhea was reported in 8.3% (1 of 12) of participants at the highest dose, and in 4.5% (2 of 44) of participants overall. Pharmacokinetic Profile: Pharmacokinetic data supports a once-daily dosing regimen for NA-931. Blood levels of the drug remained consistent regardless of fasting or after a high-fat meal, suggesting that NA-931 can be taken without regard to meal timing, offering greater flexibility for patients. Conclusion and Next Steps: The Phase I study results indicate that NA-931 not only holds promise for weight loss but also for glycemic control in individuals with type 2 diabetes. A Phase 2 clinical trial of NA-931 for obesity treatment is currently underway, with topline results expected in the first quarter of 2025. Keywords - Obesity, Weight loss, NA-931, Diabetes, Phase 1