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.

Summary of Aardvark Therapeutics (AARD) Conference Call Company Overview - **Company**: Aardvark Therapeutics (AARD) - **Focus**: Development of ARTOR 101, a therapeutic targeting appetite regulation through gut hormones Key Points Therapeutic Mechanism and Approach - ARTOR 101 was developed to inhibit bitter taste receptors to suppress appetite, initially theorized to reduce calorie intake by using a bitter compound that is non-toxic [3][4] - The drug stimulates the release of gut peptide hormones such as CCK, GLP-1, GLP-2, and possibly PYY, which act locally and are rapidly degraded [5][6] - The distinction between hunger (pain avoidance pathway) and appetite (pleasure-seeking pathway) is emphasized, with ARTOR 101 allowing users to skip meals without feeling hungry [8][9][12] Indication and Market Opportunity - The primary indication is for Prader-Willi syndrome, characterized by hyperphagia, which severely impacts patients and families [18][19] - Recent approval of Celino Therapeutics' drug VICAT (DCCR) for hyperphagia presents competition, but Aardvark believes their approach directly addresses the cause of hyperphagia, offering a significant market opportunity [20][21] Clinical Trials and Data - A phase two trial showed a drop of nine points on the HQCT scale, indicating a robust signal of efficacy [23][24] - The phase three trial design includes dose escalation and stricter inclusion criteria to ensure a more reliable data package [36][39] - The trial aims for a clinically meaningful change of five points on the HQCT scale, with 90% power requiring 32 patients per arm [46][47] Regulatory Pathway - The FDA indicated that one statistically significant study could suffice for submission as a pivotal trial [54][55] - Ongoing safety data collection from open-label extensions and additional trials in hypothalamic obesity and general obesity [55] Competitive Landscape - Aardvark anticipates that ARTOR 101 will replace rather than combine with existing treatments due to pricing and efficacy concerns [57][58] - The company is aware of the challenges faced by existing treatments, with a significant dropout rate observed in Celino's studies, indicating potential limitations in efficacy [58][59] Future Directions - Plans to explore hypothalamic obesity and general obesity, leveraging the drug's mechanism to enhance CCK signaling to the hypothalamus [61][63] - A trial comparing ARTOR 101 with GLP-1 drugs is planned to assess weight loss potential and rebound effects post-treatment [65][66] Additional Insights - The importance of consistent patient rating for HQCT scale assessments was highlighted, as variability can affect data reliability [38] - The potential for ARTOR 101 to suppress ghrelin levels, which rise with GLP-1 treatments, could provide a unique advantage in managing weight rebound [67] This summary encapsulates the key discussions and insights from the Aardvark Therapeutics conference call, focusing on the company's innovative approach to appetite regulation and the clinical and market strategies moving forward.