Aardvark Therapeutics Investor Webinar Summary Company Overview - **Company**: Aardvark Therapeutics (NasdaqGS:AARD) - **Focus**: Development of therapies for obesity and related metabolic disorders, particularly through innovative drug combinations and mechanisms targeting hunger and appetite regulation Key Points and Arguments Clinical Programs - **ARD201**: A fixed-dose combination of TAS2R agonist (ARD101) and DPP-4 inhibitor (acetagliptin) aimed at treating metabolic obesity, showing promising preclinical results [3][7] - **WE868**: A newly in-licensed program exploring a novel mechanism for obesity, currently in preclinical studies [3][4] - **ARD101**: Currently in the HERO phase 3 study for hyperphagia associated with Prader-Willi syndrome, with expected pivotal data readout in Q3 2026 [5][8] Data Highlights - **ARD201** demonstrated a 19% weight loss in a diet-induced obesity mouse model over 30 days, comparable to high-dose tirzepatide (20.5% weight loss) [10] - **Weight Maintenance**: ARD201 showed preservation of weight loss after discontinuation of GLP-1 therapies, achieving approximately 30% weight loss when combined with a microdose of tirzepatide [11] - **Body Composition**: ARD201 preserved lean mass while reducing fat mass, addressing concerns of lean mass loss associated with GLP-1 therapies [12] - **Glucose Homeostasis**: Improvements in glucose tolerance were observed in mice treated with ARD201, indicating potential benefits for patients with obesity-related diabetes [13] Mechanism of Action - **Gut-Brain Signaling**: ARD101 targets gut peptide hormone release to regulate hunger, contrasting with GLP-1 therapies that primarily focus on appetite signaling [6] - **WE868 Mechanism**: Modulates cellular energy use without mitochondrial uncoupling, leading to increased energy expenditure and weight loss [16] Industry Context - **Obesity Treatment Landscape**: The prevalence of obesity is rising, necessitating effective treatments. Aardvark's approach aims to mimic the effects of bariatric surgery through pharmacotherapy [35][38] - **Emerging Trends**: The development of combination therapies and multi-agonist approaches is seen as a future direction in obesity treatment, with potential for improved efficacy and reduced side effects [44][48] Challenges and Unmet Needs - **Side Effects**: Current GLP-1 therapies are associated with nausea and lean mass loss, highlighting the need for better-tolerated options [47][50] - **Insurance Coverage**: Changes in insurance coverage for GLP-1 therapies in Massachusetts may limit access for patients, emphasizing the need for alternative treatments [56] Additional Insights - **Gut-Brain Axis Research**: Ongoing studies into the gut-brain axis and its role in regulating appetite and glucose homeostasis are critical for understanding obesity mechanisms [21][27] - **Nutrient Sensing**: The interplay between nutrient sensing and gut hormones is crucial for developing effective obesity treatments [33][34] Conclusion Aardvark Therapeutics is positioned to make significant contributions to the obesity treatment landscape through innovative drug development and a focus on understanding the underlying mechanisms of hunger and appetite regulation. The upcoming clinical milestones and ongoing research into new compounds like WE868 could provide valuable insights and therapeutic options for patients struggling with obesity and related metabolic disorders.