top of page

Aardvark reveals positive data for ARD-101 in treating obesity or other metabolic conditions

Aardvark Therapeutics has reported positive clinical data from three Phase II trials for its lead product ARD-101, an oral small molecule bitter taste receptor agonist. According to the company, these early results suggest a promising future for a new class of pharmaceuticals that could benefit people afflicted with obesity or other metabolic conditions, particularly those associated with hunger, which is a prominent feature of the rare genetic condition Prader-Willi Syndrome (PWS).

ARD-101 is a first-in-class oral composition of chemical compounds with an extremely bitter taste, which target specific receptors in the mouth and also in the gut, where they trigger appetite-suppressing hormones like GLP-1, GIP, PYY and cholecystokinin. Aardvark’s taste receptor type 2 (TAS2R) agonist acts and stays, almost exclusively in the gut. ARD-101 is a salt of denatonium, a bitter chemical used in antifreeze and other products to prevent ingestion. The compound also reduces the inflammation associated with obesity, which GLP-1 agonists do not address.

ARD-101 is shown to be safe and substantially gut-restricted; yet it conveys systemic effects via activation of gut peptide hormone secretion, including GLP-1, GLP-2, and cholecystokinin (CCK).

CCK has long been recognized as an interesting pharmaceutical target because its release is triggered with food and helps suppress feelings of hunger. ARD-101 stimulates the release of the body's natural CCK, but primarily targets vagal nerve afferents located near the gut; this in turn induces positive effects on hunger, metabolism, and inflammation through gut-brain signalling. The selective local secretion avoids the off-target side effects seen with approaches using systemic exposure of artificial CCK analogue molecules.

In summary, the three studies from unpublished data demonstrate that in:

  • A placebo-controlled study in 20 patients with general obesity, using the Control of Eating Questionnaire (COEQ), patients treated with ARD-101 experienced a 2.51-fold greater reduction in hunger rating compared to those receiving placebo (p=0.015).

  • In an open label study with Prader-Willi Syndrome patients, 11 of 12 patients showed a reduction in hyperphagia in only 28 days using the HQ-CT (Hyperphagia Questionnaire for Clinical Trials) assessment with an average reduction of 7 points and demonstrating often beneficial changes to behaviour. Four of the twelve subjects had a near complete resolution of hunger symptoms.

  • In an open label post-bariatric surgery study in 11 subjects who continued to gain weight after surgery, there was a consistent reduction in hunger scores, as well as cravings for sweets and savoury foods.

Overall, ARD-101 did not demonstrate appreciable nausea or diarrhoea that is common among the GLP-1 drugs currently being marketed.

While the neural pathways regulating these sensations overlap, according to the company ARD-101 is thought to be the only drug in development with a significant impact on the hunger axis. This is particularly relevant to individuals with Prader-Willi Syndrome (PWS) who have a lifelong insatiable hunger and have inhibited ability to release their endogenous CCK. Thus far, no drug has been approved by the FDA to address the hyperphagia in PWS.


bottom of page