Aardvark’s Global Trial Targets Insatiable Hunger in Rare Disease

SAN DIEGO, CA – December 10, 2025 – Aardvark Therapeutics has taken a significant step forward in its quest to treat a rare and devastating genetic disorder. The company announced it has dosed its first patient in Australia for the pivotal Phase 3 HERO trial of its lead candidate, ARD-101. This expansion, coupled with new regulatory clearances in Canada and the United Kingdom, marks a critical milestone in the journey to commercialize a potential new therapy for the relentless, insatiable hunger that defines Prader-Willi syndrome (PWS).

With strong enrollment already underway in the United States, this international progress keeps the San Diego-based biopharma company firmly on track for its anticipated topline data readout in the third quarter of 2026. For investors and industry watchers, this is a clear signal of operational execution on a complex global stage. For the PWS community, it represents tangible progress and renewed hope.

The Unrelenting Grip of Hyperphagia

To understand the significance of Aardvark's progress, one must first grasp the profound challenge of Prader-Willi syndrome. Affecting an estimated 1 in 15,000 births, PWS is a complex genetic disorder that is the leading genetic cause of life-threatening childhood obesity. While the syndrome includes developmental delays, behavioral issues, and hormonal abnormalities, its most defining and distressing feature is hyperphagia—an insatiable, all-consuming hunger that cannot be satisfied by eating.

This is not the common hunger pang felt before a meal; it is a constant, torturous drive that compels individuals to seek food relentlessly. For families, this necessitates extreme measures, including locking refrigerators and cabinets, to prevent life-threatening overeating and obesity. Until recently, the treatment landscape for hyperphagia was barren, with management relying solely on strict environmental controls and behavioral therapy. A major breakthrough occurred in March 2025 with the FDA approval of Soleno Therapeutics' VYKAT™ XR, the first drug specifically sanctioned to treat hyperphagia in PWS. While a landmark achievement, the high unmet need in this population means the door remains wide open for new therapeutic options with different mechanisms and potentially improved profiles.

“Significant unmet needs continue to persist in the PWS community, and many families are eager for a therapy that could ameliorate the relentless hunger that is a hallmark of PWS,” noted Manasi Jaiman, M.D., Chief Medical Officer of Aardvark, in the company's announcement.

A Novel Gut-Brain Strategy

Aardvark’s ARD-101 is not another entrant in the crowded field of systemic metabolic drugs. Instead, it employs a novel and targeted scientific approach. ARD-101 is a gut-restricted small molecule designed to activate specific bitter taste receptors, known as TAS2Rs, located on the surface of enteroendocrine cells within the intestine.

The scientific rationale is elegant. In healthy individuals, eating triggers the release of gut hormones like cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), which signal to the brain to create a feeling of fullness. Research suggests this signaling pathway is impaired in PWS patients. By activating these TAS2R receptors directly in the gut, ARD-101 stimulates the local release of these very hormones, effectively aiming to restore the natural gut-brain communication loop that governs satiety.

Because ARD-101 is designed to be over 99% restricted to the gut with minimal systemic absorption, it holds the potential to avoid the systemic side effects, such as nausea, that are common with other metabolic therapies like injectable GLP-1 agonists. This differentiated mechanism is what has captured the attention of investors and clinicians alike.

Prior clinical data provides a strong foundation for this optimism. In a Phase 2 study, 11 of 12 PWS patients treated with ARD-101 for 28 days showed a reduction in hyperphagia, with an average drop of 7 points on the validated Hyperphagia Questionnaire for Clinical Trials (HQ-CT)—the same primary endpoint being used in the current Phase 3 HERO trial. Some patients even reported a near-complete resolution of hunger, accompanied by beneficial changes in body composition, including decreased fat and increased lean muscle mass.

The Blueprint for a Global Rare Disease Trial

Executing a late-stage clinical trial for a rare disease is a monumental undertaking. Patient populations are small and geographically dispersed, making recruitment a significant bottleneck. Aardvark's strategy to establish trial sites across the US, Australia, Canada, and the UK is a textbook example of how to overcome this challenge and accelerate development timelines.

By going global, the company not only widens its recruitment pool to reach its target of 90 patients but also generates data from a more diverse population, which can strengthen its regulatory submission. The announcement that enrollment is progressing so well that the company may not need to activate previously planned sites in the European Union is a powerful indicator of both operational efficiency and high demand from the patient community.

“We have seen very strong interest in the HERO trial within the patient community, which has been driving enrollment in the United States and in our newly opened Australia sites,” said Tien Lee, M.D., Founder and Chief Executive Officer of Aardvark. This interest is further validated by a crucial metric of potential efficacy: patient retention. Dr. Lee added, “all patients who have completed the 12-week clinical trial to date have enrolled in the Open Label Extension trial, which is an encouraging indicator of patient interest and engagement.”

This is a critical commercialization insight. High retention in an open-label extension, where all participants receive the active drug, strongly suggests that patients and their caregivers are perceiving a tangible benefit that makes continued participation worthwhile. It's a promising, albeit anecdotal, signal that bodes well for the formal data readout.

Building a Financial Fortress for a Pivotal Milestone

Innovation and operational excellence are meaningless without the capital to see a program through to completion. Here, too, Aardvark has executed a robust strategy. The company is well-capitalized to reach its Q3 2026 data milestone, having secured an oversubscribed $85 million Series C financing in May 2024, followed by a successful $94.2 million initial public offering in February 2025.

Notably, the financing rounds included participation from patient advocacy groups such as the Foundation for Prader-Willi Research and the Prader-Willi Syndrome Association – USA. This alignment between the company, investors, and the patient community creates a powerful synergy, ensuring the development program remains laser-focused on the needs of those it aims to serve. With a projected cash runway into 2027, Aardvark has mitigated a key risk for a clinical-stage biotech, allowing management to focus on executing the HERO trial without the near-term pressure of fundraising.

The company’s journey from a promising prototype to a globally recognized Phase 3 asset demonstrates a clear understanding of the path to profit in the rare disease space. By advancing ARD-101, Aardvark is not only targeting the unmet needs of the PWS community but is also validating a scientific platform that could have broader applications in other metabolic diseases. The successful international expansion of the HERO trial is the latest proof point that Aardvark is methodically navigating the complex path from innovation to commercial viability, with all eyes now on the pivotal data expected in 2026.