Aardvark Therapeutics Conference Call Summary Company Overview - **Company**: Aardvark Therapeutics (NasdaqGS:AARD) - **Lead Program**: ARD-101, an oral small molecule drug targeting gut receptors to manage hunger and eating behavior, particularly in Prader-Willi syndrome, a pediatric rare disease characterized by hyperphagia [2][6][18]. Key Points on ARD-101 - **Mechanism of Action**: ARD-101 is designed to convey gut-brain signaling to reduce hunger and improve metabolic benefits. It specifically targets gut receptors to stimulate gut hormones that regulate hunger and appetite [2][6][7]. - **Clinical Trials**: - Phase 2 data showed promising results with 18 subjects, leading to a Phase 3 HERO trial with expected top-line results in Q3 2026 [2][20]. - The Phase 2 trial reported a significant reduction in hunger, with a -8 reduction in HQCT scores over a short period [20][22]. - The Phase 3 trial will include a higher cutoff for HQCT scores, aiming for a more robust benefit [22][30]. Comparison with Other Treatments - **GLP-1 Class Drugs**: Existing medications like GLP-1s primarily address appetite but not hunger, which is crucial for Prader-Willi patients. ARD-101 uniquely targets hunger-driven mechanisms [4][6][9]. - **Market Opportunity**: Approximately 50% of Prader-Willi patients may not respond adequately to Vycat, indicating a significant market for ARD-101 [60][61]. Secondary Benefits and Biomarkers - **Additional Assessments**: The trial will also evaluate anxiety levels, inflammation markers, and body composition changes, with a noted 1.5% reduction in body fat and 2% increase in lean body mass during Phase 2 [26][28]. - **Glucose Homeostasis**: ARD-101 is expected to improve glucose levels, which is critical for patients prone to hyperglycemia [28]. Obesity Program Overview - **Combination Therapy**: ARD-201 combines ARD-101 with sitagliptin (a DPP-4 inhibitor) to enhance the duration of hormone activity, showing promising preclinical results with significant weight loss [69][72]. - **Clinical Trials**: The POWER trial will assess the efficacy of ARD-201 in patients transitioning from GLP-1 treatments, with data expected in the second half of 2026 [81][85]. Strategic Considerations - **Partnership Opportunities**: Aardvark Therapeutics is exploring partnerships for the obesity asset while retaining control over the Prader-Willi program [86]. Conclusion Aardvark Therapeutics is positioned to address significant unmet needs in the treatment of Prader-Willi syndrome and obesity through innovative mechanisms targeting hunger and metabolic regulation. The upcoming clinical data and strategic partnerships will be critical in shaping the company's future in these therapeutic areas.