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.

Core Insights - Aardvark Therapeutics, Inc. has granted a stock option to a new employee as part of its 2025 Inducement Equity Incentive Plan, which includes 4,881 shares of common stock [1][2] Company Overview - Aardvark Therapeutics is a clinical-stage biopharmaceutical company focused on developing small-molecule therapeutics aimed at activating innate homeostatic pathways for metabolic diseases [1][4] - The company is developing treatments specifically for Prader-Willi Syndrome (PWS) and other metabolic diseases, with its lead compound, ARD-101, currently in Phase 3 clinical development for hyperphagia associated with PWS [4] - Aardvark is also working on ARD-201, a fixed-dose combination therapy, and conducting trials to address limitations of existing GLP-1 therapies for obesity and related conditions [4] Stock Option Details - The stock option granted has an exercise price of $10.44, which is the closing price of Aardvark's common stock on the grant date [3] - The option will vest over four years, with 25% vesting on the one-year anniversary of employment and the remainder vesting monthly thereafter, contingent on continued employment [3]

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.

Core Insights - Aardvark Therapeutics is advancing ARD-201, a novel therapy aimed at improving glucose control and preserving lean mass, addressing challenges in obesity treatment [1][3] - The company plans to initiate two Phase 2 trials for ARD-201, named POWER and STRENGTH, to evaluate its efficacy in preventing weight regain and promoting weight loss [2][13] ARD-201 Obesity Program - ARD-201 is a fixed-dose combination of TAS2R agonist ARD-101 and DPP-4 inhibitor sitagliptin, designed to enhance appetite suppression and metabolic effects [3][10] - Preclinical studies indicate that ARD-201 can reduce fat mass while preserving lean mass, achieving glucose control comparable to high-dose tirzepatide [5][10] - Previous preclinical data showed ARD-201 resulted in approximately 19% weight loss after 30 days, similar to high-dose tirzepatide, and around 30% weight loss when combined with low-dose tirzepatide [5][10] Clinical Development - ARD-201 is set to enter the Phase 2 POWER trial by the end of 2025, focusing on preventing weight regain in subjects who have previously lost significant weight [13] - The STRENGTH trial is planned for the first half of 2026, assessing the potential for placebo-adjusted weight loss and the additive effects of ARD-201 with GLP-1RA therapy [13] Investor Engagement - Aardvark will host an investor webinar on November 5, 2025, to discuss the data presented at ObesityWeek and provide insights into ARD-101, ARD-201, and WE-868 [6][7]

Core Insights - Aardvark Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing small-molecule therapeutics aimed at activating innate homeostatic pathways for metabolic diseases [1][2] - The company will present at two upcoming conferences in November, with live webcasts available on its website [1][4] Company Overview - Aardvark is developing therapeutics designed to suppress hunger, particularly for the treatment of Prader-Willi Syndrome (PWS) and other metabolic diseases [2] - The lead compound, ARD-101, is in Phase 3 clinical development for hyperphagia associated with PWS, characterized by insatiable hunger [2] - Aardvark is also working on ARD-201, a fixed-dose combination of ARD-101 with a DPP-4 inhibitor, to address limitations of current GLP-1 therapies for obesity [2]

Core Insights - Aardvark Therapeutics, Inc. is set to present at ObesityWeek 2025, showcasing its innovative approaches to treating metabolic diseases, particularly obesity [1][2] Presentation Details - Aardvark will present two key studies on November 4, 2025: - The first study focuses on TAS2R Pan-Agonist ARD-101, which has shown to reduce weight gain in mice and decrease hunger in adults with obesity [2] - The second study discusses an isoflavonoid modulator of oxidative metabolism (WE-868) with potential therapeutic applications in obesity and diabetes [2] Investor Engagement - An investor webinar is scheduled for November 5, 2025, where Aardvark will discuss data from ObesityWeek, featuring insights from key opinion leaders in obesity drug development and discussions on ARD-101's application in Prader-Willi Syndrome [3] Product Overview: ARD-101 - ARD-101 is a gut-restricted small molecule that acts as a pan-agonist for bitter taste receptors, stimulating the release of gut-peptide hormones like GLP-1 and CCK, which are crucial for hunger regulation [4] - The FDA has granted ARD-101 Orphan Drug Designation and Rare Pediatric Disease Designation for its use in Prader-Willi Syndrome [4] Product Overview: ARD-201 - ARD-201 is a fixed-dose combination of a DPP-4 inhibitor and ARD-101, designed to enhance the body's natural signals for fullness by prolonging the activity of gut hormones [6] - Aardvark is advancing ARD-201 in two Phase 2 trials: - The POWER trial aims to prevent weight regain in subjects who stop GLP-1RA therapy after significant weight loss [7] - The STRENGTH trial will evaluate the potential for placebo-adjusted weight loss and the additive effects of ARD-201 with GLP-1RA therapy [7] Product Overview: WE-868 - WE-868 is a novel small molecule that modulates mitochondrial energy metabolism and is currently under preclinical evaluation for obesity and diabetes treatment [8] Company Background - Aardvark Therapeutics is focused on developing small-molecule therapeutics to suppress hunger, particularly for conditions like Prader-Willi Syndrome and other metabolic diseases [9] - The company aims to address limitations of existing GLP-1 therapies through its innovative product pipeline [9]

Core Insights - Aardvark Therapeutics has aligned with the FDA on a protocol amendment for its Phase 3 HERO trial, lowering the minimum age for participation from 13 to 10 years old, which aims to include a larger segment of the Prader-Willi Syndrome (PWS) patient population [1][2] Company Overview - Aardvark Therapeutics is a clinical-stage biopharmaceutical company focused on developing small-molecule therapeutics to treat metabolic diseases, specifically targeting hunger suppression in conditions like PWS [5] - The lead compound, ARD-101, is a gut-restricted small molecule that acts as a pan-agonist for bitter taste receptors, stimulating the release of gut-peptide hormones to mediate hunger [3][5] Clinical Development - ARD-101 is currently being evaluated in the Phase 3 HERO trial for hyperphagia associated with PWS, with topline data expected in the third quarter of 2026 [2][4] - The decision to expand the trial's eligibility is supported by historical data indicating that younger patients may benefit more from early intervention [2]

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]

Core Insights - Aardvark Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing small-molecule therapeutics for metabolic diseases, particularly targeting hunger suppression in conditions like Prader-Willi Syndrome [3] Company Overview - Aardvark is developing oral compound ARD-101, currently in Phase 3 clinical development for hyperphagia associated with Prader-Willi Syndrome, a rare disease characterized by insatiable hunger [3] - The company is also working on ARD-201, a fixed-dose combination of ARD-101 with a DPP-4 inhibitor, aimed at addressing limitations of existing GLP-1 therapies for obesity and related conditions [3] Upcoming Events - Aardvark will present at the Stifel 2025 Virtual Cardiometabolic Forum on September 30, 2025, at 9:00 a.m. Eastern time, with a live webcast available on their website [1][2]

Aardvark Therapeutics FY Conference Summary Company Overview - Aardvark Therapeutics is a San Diego-based biotech company focused on developing small molecule oral drugs to manage hunger, with a lead program in phase 3 development for Prader-Willi syndrome [2][4]. Industry Context - Prader-Willi syndrome is a genetic disorder caused by a chromosome 15 abnormality, affecting approximately 10,000 to 20,000 patients in the U.S. and 300,000 to 400,000 worldwide. Patients experience extreme hunger, anxiety, systemic inflammation, and severe constipation [4][5]. Core Product: ARD-101 - ARD-101 is designed to activate taste receptors in the gastrointestinal tract, stimulating the release of hormones like GIP and GLP-1, which convey feelings of fullness and reduce hunger [7][9]. - The drug aims to differentiate itself by effectively managing hunger rather than appetite, addressing a significant unmet need in Prader-Willi syndrome treatment [14]. Clinical Data and Phase 2 Results - In a phase 2 study, 18 patients completed a 28-day treatment with ARD-101, showing a reduction of about 8 points on the HQCT-9 score, a validated measure of hunger in Prader-Willi patients [21][22]. - Anecdotal evidence suggested rapid onset of diminished hunger feelings and reductions in anxiety and inflammation [21][22]. Phase 3 HERO Trial - The HERO trial will compare ARD-101 to a placebo, focusing on the HQCT-9 score at week 12 as the primary endpoint [30]. - The trial will now include patients aged 13 and up, expanding the potential patient population [32]. - Enrollment is progressing well, with strong enthusiasm from investigators [34]. Safety and Tolerability - ARD-101 has a unique safety profile, being 99% gut-restricted, which minimizes systemic exposure and potential side effects [29]. - The drug's mechanism allows for physiological release of hormones, reducing concerns associated with chronic pharmacological levels seen in other treatments [16]. Competitive Landscape - Currently, there is only one approved drug for hyperphagia in Prader-Willi syndrome, indicating a significant market opportunity for ARD-101 [44]. - Aardvark Therapeutics believes its differentiated mechanism and safety profile will allow it to capture a substantial share of the market, particularly among patients who do not respond optimally to existing treatments [44]. Obesity Program: ARD-201 - ARD-201 combines ARD-101 with a DPP-4 inhibitor, aiming to extend the biological half-life of gut hormones and enhance weight loss efficacy [47]. - Preclinical studies showed promising results, including a 19% weight loss in obese mice within 30 days, comparable to GLP-1 receptor agonists [49]. - The POWER trial will explore the prevention of weight regain in patients transitioning off GLP-1 treatments, while the STRENGTH trial will assess prospective weight loss with ARD-201 [56][58]. Financial Position - Aardvark Therapeutics reported $141 million in cash, expected to fund operations into 2027, covering key clinical readouts from the HERO and POWER trials [63]. Macro Considerations - The company is aware of the competitive landscape, particularly with rising biotech innovation in China, but believes its late-stage development and unique safety profile position it well [65]. - Aardvark is leveraging AI in its R&D processes to enhance predictive modeling and study design [68][70]. Conclusion - Aardvark Therapeutics is advancing its innovative treatments for Prader-Willi syndrome and obesity, with promising clinical data and a strong financial position to support its ongoing trials and market entry strategies [63][64].