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Comparative Clinical Efficacy Data AOD-9604 Clinical Development History AOD-9604 underwent clinical development by Metabolic Pharmaceuticals (Australia) in the early 2000s: Phase 1: Demonstrated safety and tolerability in healthy volunteers Phase 2a: Showed modest trends toward fat loss in small cohorts Phase 2b (2007): A larger trial of 536 obese participants failed to demonstrate statistically significant weight loss versus placebo after 24 weeks of treatment Development Discontinued: Following Phase 2b failure, clinical development was halted Semaglutide Clinical Evidence The STEP trial program represents the most comprehensive obesity treatment evidence: STEP 1: 14.9% weight loss vs 2.4% placebo at 68 weeks (n=1,961) STEP 2: 9.6% weight loss in type 2 diabetes patients STEP 3: 16.0% weight loss with intensive behavioral therapy STEP 4: Weight maintenance confirmed with continued treatment SELECT: 20% reduction in major cardiovascular events Evidence Quality Comparison The evidence gap is substantial: Semaglutide: Multiple large Phase 3 trials, FDA approval, real-world data, cardiovascular outcomes AOD-9604: Failed Phase 2b, no Phase 3 completion, no regulatory approval for obesity Safety and Tolerability Profile AOD-9604 Safety Profile: Generally Well-Tolerated: Phase 1/2 trials showed favorable safety No Metabolic Disruption: Did not affect blood glucose, insulin, or IGF-1 levels No GH-Related Effects: No fluid retention, joint pain, or tissue growth seen with full GH Limited Data: Lack of Phase 3 and long-term safety information Semaglutide Safety Profile: GI Events: Nausea (44%), diarrhea (31%), vomiting (24%)typically transient Serious AEs: Pancreatitis risk, gallbladder disease (similar to other weight loss) Boxed Warning: Thyroid C-cell tumors (rodent studies

The consequences of NNMT overexpression create a metabolic feedback loop that promotes and maintains obesity

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research-amq-06 Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice