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.

Financial Data and Key Metrics Changes - Aardvark Therapeutics recently completed its IPO in February 2025, raising approximately $150 million, which is expected to fund operations until 2027 [2][3] Business Line Data and Key Metrics Changes - The company is focusing on three indications: Prader Willi syndrome, hypothalamic obesity, and general obesity, with ongoing clinical trials for these conditions [11][12] - A pivotal phase three trial for Prader Willi syndrome is currently enrolling patients, with additional trials for hypothalamic obesity and general obesity expected to start in 2025 or 2026 [11][12] Market Data and Key Metrics Changes - The market for Prader Willi syndrome is estimated to have around 25,000 patients in the U.S., with a potential multibillion-dollar market opportunity, especially following the pricing of a competitor's product at $450,000 per year [12] Company Strategy and Development Direction - Aardvark Therapeutics aims to address the hunger axis of calorie intake through its drug, which targets the dysfunctional hunger signal in patients [10][11] - The company is also exploring a combination product that includes a DPP-4 inhibitor to enhance weight loss and metabolic benefits [37][48] Management's Comments on Operating Environment and Future Outlook - Management believes that the regulatory benchmark for weight loss approval remains at 5% placebo-adjusted weight loss, which aligns with the health benefits observed in patients [58] - The company is confident in its unique mechanism of action compared to GLP-1 drugs, suggesting potential for synergistic effects when used in combination [58] Other Important Information - The company has a clean safety profile from its phase one studies, with no adverse events reported, indicating a low risk of side effects due to the drug's localized action in the gut [18][19] - Aardvark is implementing strict controls in its phase three trial design to mitigate the impact of external factors on study outcomes [27][28] Q&A Session Summary Question: What is the current status of the regulatory outlook regarding placebo-adjusted weight loss? - The FDA has confirmed that a 5% weight loss is the benchmark for approvability, as it correlates with significant health benefits [58] Question: How does Aardvark's drug compare to GLP-1 drugs? - Aardvark's management emphasizes that their drug operates through a different mechanism and may be used synergistically with GLP-1 drugs, focusing on achieving the 5% weight loss benchmark while ensuring a better safety profile [58]

Core Viewpoint - Aardvark Therapeutics, Inc. has announced the appointment of key leadership members to enhance its expertise and strategic insight as it progresses with its Phase 3 HERO study of ARD-101 for treating hyperphagia associated with Prader-Willi Syndrome [2] Leadership Appointments - Timothy Kieffer, Ph.D., appointed as Chief Scientific Officer, brings extensive experience in diabetes mechanisms and translational medicine, having previously served as Chief Scientific Officer at ViaCyte Inc. and Fractyl Health [2][3] - Danny Villeneuve appointed as Chief Commercial Officer, has over 20 years of commercial leadership experience in the biopharmaceutical industry, including a successful tenure at Ironshore Pharmaceuticals [3] - Terrie Kellmeyer, Ph.D., appointed as Senior Vice President, Regulatory Affairs, has nearly 30 years of regulatory strategy and clinical development expertise, contributing to multiple successful New Drug Applications [4] - Christian Zapf, J.D., appointed as General Counsel, has over 20 years of legal and transactional experience in biotechnology, previously serving at Abpro Corporation and NantWorks [5] Company Overview - Aardvark is a clinical-stage biopharmaceutical company focused on developing small-molecule therapeutics to suppress hunger for treating Prader-Willi Syndrome and metabolic diseases, with its lead compound ARD-101 in Phase 3 clinical development [8] - The company is also developing ARD-201, a fixed-dose combination of ARD-101 with a DPP-4 inhibitor, aimed at addressing limitations of current GLP-1 therapies for obesity [8] Inducement Grants - On May 16, 2025, Aardvark granted options to purchase an aggregate of 137,500 shares of common stock to two new employees, with an exercise price of $9.89, the closing price on the grant date [7]

Aardvark Therapeutics (AARD) Conference Call Summary Company Overview - Aardvark Therapeutics is a publicly traded company based in San Diego, California, focusing on developing oral small molecule drugs targeting bitter taste receptors to influence gut-brain signaling pathways related to hunger and appetite [2][3] Clinical Programs - The most advanced program is for Prader Willi syndrome, currently in a pivotal phase three trial with expected readout in early 2026 [4] - Plans to initiate a phase two program for hypothalamic obesity and advance another formulation, ARD 201, for general obesity [4][18] Drug Mechanism and Differentiation - Aardvark's drug targets hunger rather than appetite, differentiating it from GLP-1 drugs, which primarily suppress appetite [5][7] - The drug works through gut-brain pathways, reducing ghrelin levels, which is contrary to the effect of GLP-1 treatments that can increase ghrelin [8][20] - The company believes that CCK deficiency contributes to symptoms of Prader Willi syndrome and general obesity, which their drug aims to address [9] Clinical Data and Efficacy - In the phase two trial for Prader Willi syndrome, patients showed an average reduction of 30% in hyperphagia scores (HQCT) over a 28-day dosing period [12][14] - A subgroup of patients with similar features to those expected in the phase three trial experienced a 48% reduction in HQCT, indicating a high probability of success for the upcoming trial [15] - The drug has shown a favorable safety profile, with no adverse events exceeding grade two reported in over 70 patients dosed [11] Future Trials and Endpoints - The phase three trial will include a randomized, placebo-controlled design with primary endpoints focused on HQCT scores at week twelve [15][16] - Secondary endpoints will assess clinical global impression, body composition, inflammatory biomarkers, and ghrelin levels [16] Additional Programs - The hypothalamic obesity program is set to leverage similarities with Prader Willi syndrome, targeting patients with overactive hunger due to prior interventions [17] - The ARD 201 program aims to combine ARD 101 with a TPD4 inhibitor, enhancing its efficacy for general obesity while being cautious of its use in Prader Willi syndrome due to potential risks [18] Market Potential - There are approximately 10,000 to 25,000 patients in the U.S. with Prader Willi syndrome, with a global occurrence rate of 1 in 15,000 live births, suggesting a significant market opportunity [10] - The company aims to demonstrate additive benefits of their drug on top of existing GLP-1 therapies, potentially appealing to a broader patient population [20][22] Summary - Aardvark Therapeutics is strategically positioned with a unique approach to treating hunger-related conditions, backed by promising clinical data and a robust pipeline of programs targeting rare and general obesity [22]

Financial Performance - The company has incurred significant net losses, with an accumulated deficit of $67.6 million as of March 31, 2025, and net losses of $9.3 million and $2.2 million for the three months ended March 31, 2025, and 2024, respectively [103]. - The total operating expenses for the three months ended March 31, 2025, were $10.5 million, compared to $2.2 million in 2024, resulting in a loss from operations of $10.5 million [125]. - The company reported a net loss of $9.3 million in Q1 2025, compared to a net loss of $2.2 million in Q1 2024 [138]. - The accumulated deficit as of March 31, 2025, was $67.6 million, with expectations of continued losses for the foreseeable future [133]. Funding and Capital - The company completed its IPO in February 2025, raising approximately $87.5 million from the sale of 6,120,661 shares at an IPO price of $16.00 per share [104]. - The company raised a total of $129.1 million in gross proceeds from the sale of convertible preferred stock prior to its IPO in February 2025, which generated net proceeds of $87.5 million from the sale of 6,120,661 shares at an IPO price of $16.00 per share [130]. - Net cash provided by financing activities was $88.9 million in Q1 2025, primarily from proceeds of $91.1 million from the IPO [140]. Cash and Investments - As of March 31, 2025, the company had cash, cash equivalents, and short-term investments totaling $151.3 million, which is expected to fund operations into 2027 [104]. - The company had cash, cash equivalents, and short-term investments of $151.3 million as of March 31, 2025, which is expected to fund operations into 2027 [131]. - Net cash used in operating activities increased to $11.4 million for Q1 2025 from $2.2 million in Q1 2024, primarily due to a reported net loss of $9.3 million [138]. - Net cash used in investing activities was $112.6 million in Q1 2025, mainly due to the purchase of short-term investments [139]. Research and Development - The company has no products approved for sale and does not expect to generate revenue until regulatory approval is obtained for its product candidates [105]. - The lead product candidate, ARD-101, is currently in a Phase 3 clinical trial for hyperphagia associated with Prader-Willi Syndrome, with topline data anticipated in early 2026 [96]. - The company has focused on developing small-molecule therapeutics targeting Bitter Taste Receptors (TAS2Rs) to alleviate hunger, with ongoing research into additional product candidates [96]. - The company plans to continue its development of ARD-101 and other candidates, conduct ongoing clinical trials, and expand its clinical management and regulatory capabilities [107]. - Research and development (R&D) expenses for the three months ended March 31, 2025, were $7.8 million, a $6.5 million increase from $1.2 million in the same period of 2024, primarily due to increased external costs related to ARD-101 [126]. - The company anticipates substantial increases in R&D expenses as it continues ongoing R&D activities and clinical trials for its product candidates [116]. Operational Strategy - The company relies on third parties for the manufacture of its product candidates and plans to maintain this strategy to focus on research and development [106]. - The company expects to incur significant commercialization expenses if regulatory approval is obtained for its product candidates [103]. Economic and Market Conditions - Macroeconomic conditions, including inflation and geopolitical conflicts, may negatively impact the company's financial position and growth prospects [110]. - The impact of foreign currency costs on operations has been negligible, with no formal hedging program in place [146]. - Inflation has not had a material effect on the company's results of operations during the periods presented [147]. Future Outlook - Future capital requirements are uncertain and depend on various factors, including the costs and timing of clinical trials and regulatory approvals [134]. - The company does not believe that a hypothetical 100 basis point change in interest rates would have a material impact on its financial statements [145]. - There have been no material changes to contractual obligations and other commitments as of March 31, 2025 [141]. - The company continues to evaluate its critical accounting estimates and policies, with no material changes reported [144].

Financial Performance - Aardvark Therapeutics raised $97.9 million in gross proceeds from its IPO, with net proceeds of approximately $87.5 million[3]. - The net loss for Q1 2025 was $9.3 million, compared to a net loss of $2.2 million in Q1 2024[7]. - Total operating expenses for Q1 2025 were $10.5 million, significantly higher than $2.2 million in Q1 2024[11]. - The weighted-average shares used in the net loss per share calculation for Q1 2025 were approximately 13.2 million[11]. Cash and Investments - As of March 31, 2025, Aardvark had cash, cash equivalents, and short-term investments totaling $151.3 million, sufficient to fund operations into 2027[6]. - Total assets as of March 31, 2025, were $157.0 million, up from $77.5 million at the end of 2024[13]. Research and Development - Research and development expenses increased to $7.8 million for Q1 2025, up from $1.2 million in Q1 2024, reflecting a $6.6 million increase[6]. - Aardvark's lead candidate, ARD-101, is in Phase 3 clinical development for treating hyperphagia associated with Prader-Willi Syndrome, with data readout expected in early 2026[5]. - Aardvark is also developing ARD-201, a fixed-dose combination aimed at addressing limitations of current GLP-1 therapies for obesity[8]. General and Administrative Expenses - General and administrative expenses rose to $2.7 million in Q1 2025, compared to $0.9 million in Q1 2024, marking a $1.9 million increase[6].

Core Viewpoint - Aardvark Therapeutics is focused on developing innovative small-molecule therapeutics aimed at activating innate homeostatic pathways to treat metabolic diseases, with a particular emphasis on addressing hunger signaling in rare metabolic diseases and obesity [2][5]. Business Highlights - Aardvark completed its initial public offering (IPO) in February 2025, raising $97.9 million in gross proceeds, resulting in approximately $87.5 million in net proceeds after expenses [3]. - The company's stock began trading under the symbol "AARD" on February 13, 2025 [3]. Financial Highlights - As of March 31, 2025, Aardvark reported cash, cash equivalents, and short-term investments totaling $151.3 million, which is expected to support operations into 2027 [6][7]. - Research and development expenses for the first quarter of 2025 were $7.8 million, a significant increase from $1.2 million in the same quarter of 2024, primarily due to higher development costs related to ARD-101 [7]. - General and administrative expenses rose to $2.7 million in the first quarter of 2025 from $0.9 million in the same quarter of 2024, attributed to increased professional fees and costs associated with being a public company [7]. - The net loss for the first quarter of 2025 was $9.3 million, compared to a net loss of $2.2 million in the first quarter of 2024 [7][10]. Clinical Development - Aardvark's lead candidate, ARD-101, is in Phase 3 clinical development for treating hyperphagia associated with Prader-Willi Syndrome (PWS), with data readout expected in early 2026 [6][2]. - The company is also developing 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 [5].

Core Viewpoint - Aardvark Therapeutics, Inc. is actively engaging in presenting its clinical developments and strategies at various conferences in May 2025, highlighting its focus on novel therapeutics for metabolic diseases [1][4]. Company Overview - Aardvark Therapeutics is a clinical-stage biopharmaceutical company that develops small-molecule therapeutics aimed at suppressing hunger, particularly for conditions like Prader-Willi Syndrome (PWS) and other metabolic diseases [2]. - The lead compound, ARD-101, is currently in Phase 3 clinical development for treating hyperphagia associated with PWS and is also being studied for hypothalamic obesity [2]. - Aardvark is developing ARD-201, a combination of ARD-101 and a DPP-4 inhibitor, to address limitations of existing GLP-1 therapies for obesity and related conditions [2]. Upcoming Presentations - Aardvark will present at the following conferences: - Bank of America Global Healthcare Conference on May 15, 2025, at 12:35 p.m. ET [4]. - H.C. Wainwright 3rd Annual BioConnect Investor Conference on May 20, 2025, at 3:30 p.m. ET [4]. - RBC Capital Markets Global Healthcare Conference on May 21, 2025, at 2:35 p.m. ET [4]. - Live webcasts of these presentations will be available on the company's website, with archived recordings accessible for approximately one month post-presentation [1].

Clinical Trials and Product Development - The company has initiated a Phase 3 clinical trial for its lead product candidate, ARD-101, targeting hyperphagia associated with Prader-Willi Syndrome (PWS), with topline data expected in early 2026[16]. - In a completed Phase 2 clinical trial for ARD-101 in subjects with PWS, 12 subjects showed an average decline of approximately 8 points in the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score after 28 days[18]. - The company plans to conduct a Phase 2 clinical trial for hyperphagia associated with hypothalamic obesity (HO), referred to as the HONOR trial, expected to initiate in the second half of 2025[19]. - ARD-201, a fixed-dose combination of ARD-101 and a DPP-4 inhibitor, is being developed to address obesity and obesity-related conditions, with a Phase 2 EMPOWER trial planned for the second half of 2025[20]. - The Phase 2 clinical trial of ARD-101 demonstrated well-tolerated results with limited systemic absorption, reducing potential systemic toxicity[18]. - The Phase 3 HERO trial for ARD-101 in subjects with hyperphagia associated with PWS was initiated in December 2024, with results expected in early 2026[61]. - The Phase 3 HERO trial for ARD-101 is designed to treat subjects with PWS-associated hyperphagia over 12 weeks, with topline data expected in early 2026[101]. - The company plans to conduct the Phase 3 trial in multiple countries, including the United States, the United Kingdom, and South Korea[101]. - The company plans to initiate the Phase 2 clinical trial for ARD-101 in hyperphagia associated with hypothalamic obesity (HO) in the second half of 2025, with topline data expected in the first half of 2026[111]. - In Phase 2a clinical trials, ARD-101 demonstrated a 2.51-fold greater reduction in hunger rating compared to placebo, with a statistically significant p-value of 0.015[136]. - The company has completed Phase 2a clinical trials of ARD-101, which showed no dose-limiting safety issues or serious adverse events (SAEs)[113]. - The second part of the Phase 2 trial involved dose escalation from 400 mg to 800 mg BID, with all patients experiencing benefits and mild adverse events[90]. Financials and Funding - The company raised $129.1 million prior to its IPO in February 2025, including $85.0 million from a Series C financing in May 2024, and net proceeds from the IPO were approximately $87.5 million[25]. - The estimated cost of obesity-related healthcare in the U.S. was $261 billion in 2016, emphasizing the financial burden of obesity on the healthcare system[116]. - The global market for branded anti-obesity drugs is projected to reach over $100 billion by 2030, driven by an estimated increase in global obesity prevalence to over 50% by 2035[116]. Regulatory and Compliance - The company must submit annual progress reports and safety reports to the FDA, detailing any serious adverse reactions or significant risks identified during trials[177]. - The regulatory process for drug candidates requires substantial time and financial resources, with potential delays due to non-compliance leading to administrative or judicial sanctions[170]. - The FDA's review process for New Drug Applications (NDAs) aims for a standard review within 10 months and priority review within 6 months, depending on the product's significance[183]. - The FDA requires satisfactory completion of pre-approval inspections of manufacturing facilities to ensure compliance with current Good Manufacturing Practices (cGMP)[173]. - The company is subject to numerous regulatory authorities in the U.S., including the FDA and CMS, impacting manufacturing, sales, and marketing activities[200]. - Non-compliance with regulatory requirements can lead to severe consequences, including criminal prosecution, fines, and product recalls[202]. - The FDA allows for 505(b)(2) NDAs, enabling applicants to use existing studies not conducted by them, which can expedite the approval process[204]. - The FDA's fast track designation program aims to expedite the review of drugs intended for serious conditions, with a determination made within 60 days of the request[191]. - Priority review can shorten the review timeframe to six months for products that significantly improve safety and effectiveness compared to existing therapies[192]. - Accelerated approval may be granted for products that show meaningful advantages over existing therapies, but requires post-approval confirmatory studies[193]. - Post-approval, manufacturers must comply with ongoing FDA regulations, including monitoring adverse experiences and maintaining cGMP compliance[198]. Product Characteristics and Market Need - ARD-101 is an oral gut-restricted small-molecule that is approximately 99% restricted to the gut with minimal systemic exposure, leading to local elevation of gut peptide hormones like CCK and GLP-1[33]. - The hypothalamic obesity condition affects approximately 5,000-10,000 people in the United States, highlighting the unmet need for effective treatments[19]. - The incidence of Prader-Willi Syndrome (PWS) is approximately 1 in 15,000 births globally, with an estimated 10,000 to 20,000 patients in the U.S.[51]. - ARD-101 aims to address the limitations of current GLP-1 therapies by stimulating local secretion of CCK to reduce hunger without significant side effects[42]. - ARD-101 has shown potential in preclinical studies to decrease food intake and body weight without treatment tachyphylaxis, indicating sustained efficacy[62]. - The treatment with ARD-101 led to a mean placebo-adjusted weight loss of approximately -1% at 28 days without chronic nausea, a common issue with GLP-1 receptor agonists[136]. - The company aims to leverage its expertise in TAS2R targeting to expand its pipeline across metabolic, inflammatory, and other adjacent indications[26]. Competition and Market Strategy - The company faces competition from major pharmaceutical companies and biotechnology firms in the obesity treatment market, including Eli Lilly and Novo Nordisk[154]. - The commercial strategy for product candidates is still under evaluation, with potential use of strategic partners or establishing a commercial sales force[159]. - The company plans to selectively evaluate strategic collaborations to enhance the development and commercialization of its product candidates[26]. Intellectual Property - The patent portfolio includes 22 distinct patent application families, with 17 issued U.S. patents and 72 pending applications as of March 12, 2025[161]. - ARD-101 has received orphan drug designation for the treatment of Prader-Willi Syndrome (PWS), which could provide seven years of marketing exclusivity upon approval[162].

Financial Performance - Aardvark Therapeutics reported a net loss of $20.6 million for the year ended December 31, 2024, compared to a net loss of $7.2 million in 2023, representing an increase of 186%[10] - Research and development expenses increased to $17.4 million in 2024 from $4.5 million in 2023, marking a rise of 184%[10] - General and administrative expenses rose to $5.3 million in 2024, up from $2.2 million in 2023, reflecting an increase of 141%[10] - Cash, cash equivalents, and short-term investments totaled $73.7 million as of December 31, 2024, excluding IPO proceeds[10] - As of December 31, 2024, total assets were reported at $77.5 million, a significant increase from $10.5 million in 2023[15] Clinical Trials and Development - The lead candidate ARD-101 showed a meaningful reduction in hyperphagia of up to 16 points in a Phase 2 trial for Prader-Willi Syndrome, with an average reduction of approximately 8 points among compliant subjects[5] - The ongoing Phase 3 HERO trial for ARD-101 is expected to generate topline data in early 2026[6] - Aardvark plans to initiate the Phase 2 HONOR trial for ARD-101 in the second half of 2025, targeting hyperphagia associated with acquired hypothalamic obesity[10] - The company is also set to begin the Phase 2 EMPOWER trial for ARD-201 in the second half of 2025, focusing on obesity and obesity-related conditions[10] IPO and Funding - Aardvark completed its IPO in February 2025, raising $97.9 million in gross proceeds to support ongoing and future pipeline development[6]