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.

Summary of Aardvark Therapeutics Conference Call Company Overview - Aardvark Therapeutics is a San Diego-based biotech company focused on developing small molecule oral drugs aimed at regulating eating behavior, particularly through gut-brain signaling [2][4] Core Product: ARD-101 - ARD-101 is designed to release gut peptide hormones to suppress hunger rather than appetite, targeting conditions like Prader-Willi syndrome and general obesity [2][5] - The drug is gut-restricted, with 99% remaining in the gut, activating taste receptors on enteroendocrine cells to trigger hormone release that dampens appetite [5][6] Mechanism of Action - The drug targets both reward-based and hunger-driven eating behaviors, with a unique approach of activating anti-hunger pathways [4][5] - Ghrelin levels in Prader-Willi patients can be up to 4 times higher than normal, indicating a strong hunger drive, which ARD-101 aims to address [10] Clinical Data and Phase 2 Study - The Phase 2 study involved 18 subjects with Prader-Willi syndrome over a 28-day treatment period, showing nearly 50% reduction in HQ-CT9 scores [28] - Anecdotal evidence included patients leaving food on their plates and forgetting meal times, which are significant behavioral changes for this population [29][36] - Body composition data indicated a 1.5% reduction in body fat and a 2% increase in lean body mass during the 28-day period [31] Phase 3 Study Design - The Phase 3 study has expanded inclusion criteria to include patients aged 13 and up, with plans to lower the age limit further [43] - The study design aims to mitigate placebo effects by implementing a second baseline assessment [44] - The trial is powered to detect a placebo-adjusted change of 4 points in HQ-CT, with a sample size of 45 patients per arm [45] Other Programs: ARD-201 - ARD-201 is a fixed-dose combination of ARD-101 and sitagliptin, showing promising results in animal models with a 19% weight loss [51] - The combination is expected to enhance the efficacy of ARD-101 by prolonging the action of gut peptide hormones [52] - A microdose of tirzepatide combined with ARD-201 resulted in a 30% weight reduction in diet-induced obese mice, indicating potential for significant weight loss in humans [53] Conclusion - Aardvark Therapeutics is positioned to address significant unmet needs in obesity and related disorders through innovative drug mechanisms and promising clinical data, with ongoing studies expected to provide further insights into the efficacy and safety of their products [54]