Evommune has enrolled the first patient in a Phase 2b clinical trial evaluating EVO756, an oral small molecule antagonist targeting Mas-related G protein-coupled receptor X2 (MRGPRX2), for adults with moderate to severe atopic dermatitis (AD). The 12-week, randomized, multicenter, double-blind, placebo-controlled trial will enroll approximately 120 participants to assess the safety and efficacy of EVO756 at multiple dose levels.
Novel Mechanism Targets Neurogenic Inflammation
EVO756 represents a first-in-class approach by targeting MRGPRX2, a G-protein-coupled receptor predominantly expressed on mast cells and peripheral sensory neurons. According to Evommune, MRGPRX2 plays a central role in mediating neurogenic inflammation, making it a promising therapeutic target for chronic inflammatory conditions.
"MRGPRX2 is one of the most important new targets in chronic inflammation, and we believe our industry leading development candidate, EVO756, has the potential to be a critically needed oral therapeutic for AD," said Luis Peña, Chief Executive Officer at Evommune.
When activated by ligands common in inflammation, MRGPRX2 triggers mast cell degranulation and the release of mediators that drive cutaneous inflammation and itch. Research has demonstrated greater numbers of mast cells and increased MRGPRX2 ligand activity in AD lesions, supporting the receptor as a potential therapeutic target.
Trial Design and Endpoints
The Phase 2b trial's primary objective is to characterize the efficacy of multiple dose levels of EVO756 compared to placebo, as assessed by the percentage change in Eczema Area and Severity Index (EASI) from baseline to week 12. A key secondary endpoint evaluates the effect on itch severity using the Pruritus-NRS scale, both changes compared with placebo.
"There is still a significant need for better treatment options for AD patients, particularly for the intense itch which is the primary symptom driving patients to physicians," said Eugene Bauer, MD, Chief Medical Officer at Evommune. "MRGPRX2 antagonism is exciting in its potential to change the paradigm as the first target that modulates both mast cells and sensory neurons."
Addressing Unmet Medical Need
Atopic dermatitis affects 1-3% of adults and is characterized by intense pruritus, recurrent flares, and persistent dryness and scaling. The hallmark itch drives an itch-scratch cycle that worsens barrier dysfunction and inflammation, leading to sleep disruption, visible skin symptoms, and substantial quality-of-life burden.
EVO756 is specifically designed to address the need for a safe and effective oral therapy with disease modulation and fast onset of itch relief for patients with uncontrolled disease. The drug candidate aims to break the itch-scratch cycle by targeting the underlying neurogenic inflammation that drives both the inflammatory response and sensory symptoms.
Broader Development Program
This AD trial represents Evommune's second Phase 2b program evaluating EVO756, highlighting the compound's broad potential across chronic inflammatory diseases. The company is also conducting a Phase 2b trial in chronic spontaneous urticaria and has generated translational data in chronic inducible urticaria demonstrating similar findings.
Evommune believes MRGPRX2 antagonism may have potential across an array of chronic inflammatory diseases, with possible applications in asthma, migraine, inflammatory bowel syndrome, interstitial cystitis, and pruritus. Top-line results from the current Phase 2b AD trial are expected in the second half of 2026.
