Aardvark Therapeutics (AARD) Evercore ISI 8th Annual HealthCONx Conference summary

Technology overview

• Oral small molecule drug is gut-restricted, activating gut-brain signaling via the vagus nerve to regulate hunger by inducing gut peptide hormone release.

• Single agent (ARD-101) targets rare disease; combination with sitagliptin is for general obesity, leveraging mechanistic rationale for both.

• ARD-101 engages bitter taste receptors in the gut, stimulating enteroendocrine cells to release hormones that suppress hunger.

• Combination with sitagliptin prolongs the activity of gut hormones by inhibiting DPP-4, enhancing anti-appetite effects.

• Drug formulation avoids taste issues by releasing contents only in the gut.

Clinical data and development status

• Monotherapy phase II obesity study showed a 1.3 kg placebo-adjusted weight loss over 28 days without diet or exercise.

• Combination therapy has preclinical data showing 19% body weight loss in high-fat-fed mice in 30 days, nearly matching tirzepatide.

• Phase III HERO trial in Prader-Willi syndrome began dosing in Q2 2024, with top-line data expected in Q3 2026.

• Primary endpoint in HERO is hyperphagia score (HQ-CT9), not weight loss; body composition and other endpoints will also be tracked.

• Phase II data showed a 1.5% reduction in body fat and 2% gain in lean mass over 28 days.

Competitive landscape and differentiation

• VYKAT (diazoxide choline) is a recent competitor, but has exclusions for renal insufficiency and risk of hyperglycemia.

• The new therapy does not have renal exclusions and may improve insulin sensitivity.

• Both drugs use the same HQ-CT9 endpoint for hyperphagia.

• Clinically meaningful reduction in HQ-CT can be as little as one point, especially if safety is favorable.

• Drug may address additional Prader-Willi symptoms such as anxiety, inflammation, and constipation, with exploratory endpoints for these effects.