Aardvark Therapeutics has seen its share price halve in value after the company paused a phase 3 study of its lead metabolic asset over heart-related data.
The San Diego-based biotech has been evaluating a gut-restricted small molecule dubbed ARD-101 in a late-stage Hunger Elimination or Reduction Objective (HERO) study of patients with a rare genetic condition called Prader-Willi syndrome, which makes them feel constantly hungry. Aardvark kicked off the study in December with the aim of enrolling 90 patients across the U.S., Australia, Canada, the U.K. and South Korea.
But the company disclosed Friday that routine safety monitoring in a healthy volunteer study of ARD-101 had identified “reversible cardiac observations at above target therapeutic doses.” As a result, the biotech has paused the HERO study “out of an abundance of caution.”
Aardvark said it is now “conducting a comprehensive review of the data to inform next steps,” but, in the meantime, both the HERO study and an open-label extension trial are being paused.
“The safety of every patient in our clinical studies is our highest priority, so we will thoroughly evaluate the signals seen at higher than therapeutic doses of ARD-101 in a healthy volunteer study,” Aardvark CEO Tien Lee, M.D., said in a release.
“We are committed to advancing the ARD-101 clinical program and we are evaluating optimal therapeutic dosing levels to support its progress,” Lee added.
It means Aardvark has abandoned its ambition of read out top-line data from the HERO study in the third quarter.
Related
William Blair analysts said this morning that the cardiac observations “increase the clinical risk of ARD-101 as it calls into question the therapeutic window of ARD-101.”
“Recent scientific literature suggests bitter taste receptors … are expressed in cardiac tissue and may modulate cardiac contractibility and vascular tone, suggesting the clinical observation could be on-target/mechanism-based,” the analysts added in a March 3 note.
The setback comes a year after Aardvark went public via a $94 million Nasdaq listing, with a chunk of the proceeds used to advance the development of ARD-101. The TAS2R pan-agonist is designed to stimulate enteroendocrine cells of the digestive tract. The aim is to release gut-peptide hormones such as GLP-1—the function of which is a focus of Novo Nordisk and Eli Lilly’s blockbuster weight loss drugs—and the satiety hormone cholecystokinin, thereby activating gut-brain neurologic signaling to reduce feelings of hunger.
Aardvark has previously pointed to ARD-101’s ability to suppress appetite when used alone or in combination with Novo and Lilly’s approved drugs.
Analysts have been most excited by Aardvark’s other clinical-stage asset ARD-201, a combination of ARD-101 and a DPP-4 inhibitor, as a potential obesity treatment. Aardvark has taken ARD-201 into a pair of phase 2 studies, and analysts at William Blair in December suggested this mechanism “could offer an alternative mechanism for addressing obesity” to the current crop of GLP-1 drugs.
Aardvark made no mention of any changes to its ARD-201 plans in this morning’s release, but the disruption to ARD-101 was still enough to plunge the biotech’s stock down 54% in post-market trading Friday to $5.72 from a closing price of $12.49. Aardvark’s shares debuted at $16 back in February 2025.