Aardvark Therapeutics FY Conference Summary Company Overview - **Company**: Aardvark Therapeutics (NasdaqGS:AARD) - **Focus**: Development of oral small molecule drugs targeting obesity and rare diseases, specifically Prader-Willi syndrome Core Product Information - **Drug**: ARD-101 - **Mechanism**: Activates gut-brain signaling via the vagus nerve, engaging GPCR on enteroendocrine cells to release gut peptide hormones that regulate hunger [6][11] - **Formulation**: Gut-restricted with minimal systemic absorption, designed to avoid taste perception [31] Product Variants - **Single Agent**: ARD-101 for rare diseases - **Combination Agent**: ARD-101 with Sitagliptin for general obesity - **Sitagliptin**: A DPP-4 inhibitor that prolongs the action of gut hormones, enhancing weight loss effects [7][12] Clinical Data and Trials - **Phase 2 Study**: - **Results**: 1.3 kg weight loss in obese patients over 28 days without diet/exercise [29][30] - **Comparison**: Semaglutide (2.4 mg) resulted in approximately 1.6 kg weight loss in a similar timeframe [29] - **Preclinical Data**: - **Combination Therapy**: 19% body weight loss in high-fat-fed mice within 30 days, comparable to Tirzepatide's 20.5% [21] - **Upcoming Trials**: - **HERO Trial**: Phase 3 trial for Prader-Willi syndrome, with top-line data expected in Q3 2026 [32] Primary Endpoint - **Hunger Measurement**: HQ-CT9 score, focusing on hyperphagia rather than weight loss as the primary outcome [33][34] Competitive Landscape - **Competitor**: ViCat (diazoxide choline) - **Differentiation**: Aardvark's drug does not have renal insufficiency exclusions and may improve insulin sensitivity [39] - **Endpoint Similarity**: Both drugs use the HQ-CT9 score for measuring hyperphagia [40] Additional Insights - **Mechanistic Insights**: The combination therapy is believed to invoke multiple gut peptide hormone releases, enhancing therapeutic benefits beyond single-agent effects [53] - **Exploratory Endpoints**: Addressing hyperanxiety, systemic inflammation, and gut transit issues in Prader-Willi patients [52] Conclusion - Aardvark Therapeutics is positioned to address significant unmet needs in obesity and rare diseases with its innovative drug formulations and ongoing clinical trials, showing promising early results and a clear differentiation strategy against competitors.