Aardvark Therapeutics (AARD) investor relations material

Mechanism of action and therapeutic strategy

• Oral, gut-restricted small molecule targets gut-brain signaling to regulate eating behavior, primarily by releasing gut peptide hormones that suppress hunger rather than appetite.

• Drug activates taste receptors on enteroendocrine cells in the small intestine, triggering hormone release that signals satiety via the vagus nerve to the brain.

• Approach is distinct from central-acting obesity drugs, aiming for a more physiological modulation of hunger pathways.

• Particularly relevant for Prader-Willi syndrome, where hyperphagia is driven by extreme hunger and elevated ghrelin levels.

• Clinical and preclinical data support the drug’s ability to modulate key hormones like ghrelin, GLP-1, and CCK, with evidence of reduced hunger and improved behavioral outcomes.

Clinical data and trial design

• Phase II trial in Prader-Willi syndrome showed nearly 50% reduction in HQ-CT9 scores over 28 days, with rapid onset of effect and strong behavioral changes such as food left on plate and reduced anxiety.

• Secondary endpoints included body composition improvements: 1.5% reduction in body fat and 2% increase in lean mass over 28 days.

• Phase III trial expanded age inclusion to 13+ and aims to further lower the age threshold, with enhanced design to minimize placebo effect by using a second baseline assessment.

• Study is powered for 90% confidence to detect a four-point placebo-adjusted HQ-CT difference, with interim analysis for sample size re-estimation and optionality to increase enrollment if needed.

• Key secondary endpoints in Phase III include CGI score, inflammatory and metabolic biomarkers, gut hormones, and DEXA-based body composition.

Pipeline and future plans

• ARD-201, a fixed-dose combination of ARD-101 and sitagliptin, demonstrated 19% weight loss in diet-induced obese mice, comparable to tirzepatide, with potential for weight maintenance post-GLP-1RA therapy.

• Combination of ARD-201 with a microdose of tirzepatide achieved 30% weight loss in preclinical models, exceeding results from GLP-1RAs alone.

• Clinical studies are planned to validate these findings in humans, aiming for strong efficacy without the nausea associated with injectable GLP-1 therapies.