Aardvark Therapeutics Reports Positive Phase II Clinical Data for ARD-101

• ARD-101 shows strong efficacy signals including reduction of hunger and body fat composition in the treatment of Prader-Willi Syndrome, a rare genetic disease characterized by unabating hunger and extreme overeating.
• The effect on hunger differentiates ARD-101 from other programs for obesity since, in addition to the release of other beneficial gut peptide hormones, ARD-101 increases the release of cholecystokinin (CCK) from enteroendocrine I-cells. Reported in Nature Biotechnology Article.
  https://www.nature.com/articles/s41587-023-01818-4
• ARD-101 did not demonstrate appreciable nausea or diarrhea that is common among the GLP-1 drugs currently being marketed.
• ARD-101 shows a positive impact on hunger scores in general obesity subjects and post-bariatric surgery patients.
• In obese patients, ARD-101 demonstrated, in spite of the short study duration, increased weight control when compared to placebo.

SAN DIEGO, June 12, 2023 /PRNewswire/ -- Aardvark Therapeutics, Inc., a clinical stage biopharmaceutical company, today reported positive clinical data from three Phase II trials for its lead program ARD-101, an oral small molecule bitter taste receptor (TAS2R) agonist. 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).

General Obesity:  This was a placebo-controlled study in 20 subjects.  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, with a p-value of 0.015.

Prader-Willi Syndrome:  This was an open label study where 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 behavior. Four of the twelve subjects had a near complete resolution of hunger symptoms.

Post-bariatric Surgery:  This was an open label study in 11 subjects that continued to gain weight after surgery. There was a consistent reduction in hunger scores, as well as cravings for sweets, and for savory foods.

ARD-101 is differentiated from other treatment options.

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 signaling. The selective local secretion avoids the off-target side effects seen with approaches using systemic exposure of artificial CCK analogue molecules. 

Appetite is the desire to eat driven by neurological "reward", whereas hunger is a negative sensation driving the need to eat. While the neural pathways regulating these sensations overlap, 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. 

About ARD-101

Aardvark's lead product, ARD-101, is a first-in-class oral composition that has shown promising activity in reducing hunger and promoting weight loss in pre-clinical studies. Phase I studies demonstrated safety and tolerability in healthy human volunteers; three Phase II studies have demonstrated an impact on hunger suppression with associated metabolic benefits. ARD-101 is substantially gut-restricted with minimal systemic exposure yet conveys systemic effects via activation of gut peptide hormone secretion, including CCK.

About Aardvark Therapeutics, Inc.

Aardvark Therapeutics is a clinical stage biopharmaceutical company focused on developing novel small molecule therapeutics to activate innate homeostatic pathways for the treatment of metabolic diseases, inflammation, and other indications. Founded in 2017, the company has now advanced ARD-101 to Phase II clinical trials. Aardvark has multiple other programs in its pipeline.

For more information visit www.aardvarktherapeutics.com.

SOURCE Aardvark Therapeutics, Inc.