Evommune Launches Phase 2b Trial of Oral MRGPRX2 Antagonist, EVO756, In Adults With Atopic Dermatitis

Evommune, Inc announced enrollment of the first participant in the company's 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).¹

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The company will enroll approximately 120 participants in the 12-week, randomized, multicenter, double-blind, placebo-controlled trial to assess the safety and efficacy of EVO756 at multiple dose levels, according to the August 27 announcement. The primary endpoint will measure the percentage change in the Eczema Area and Severity Index (EASI) from baseline to week 12, with a key secondary endpoint evaluating the effect itch severity using the Pruritus-NRS scale, both changes compared with placebo.¹

“MRGPRX2 is one of the most important new targets in chronic inflammation, and we believe our...candidate, EVO756, has the potential to be a critically needed oral therapeutic for AD," Luis Peña, Evommune CEO said in the statement. According to the company, EVO756 is specifically designed to address the need for a safe and effective oral therapy with disease modulation and fast onset of itch relief of patients with uncontrolled disease.¹

MOA: Mediation of Neurogenic Inflammation

The focus on MRGPRX2 is based on its central role in mediating neurogenic inflammation, according to Evommune. MRGPRX2 is a G-protein-coupled receptor that is predominantly expressed on mast cells and peripheral sensory neurons. These 2 key regulators of immune responses and neuroimmune interactions are particularly active during inflammation. When activated by ligands common in inflammation, the receptor triggers mast cell degranulation and the release of mediators that drive cutaneous inflammation and itch. Greater numbers of mast cells and increased MRGPRX2 ligand activity have been found in AD lesions, supporting MRGPRX2 as a potential therapeutic target.¹

Evommune data from translational studies in chronic inducible urticaria have demonstrated similar findings, according to the company, suggesting potential for application across multiple chronic inflammatory conditions. Top line results from the current trial in AD are expected in the second half of 2026.

Atopic dermatitis (AD), or eczema, is a common chronic inflammatory skin disease marked 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. AD often begins in childhood but also affects 1–3% of adults, making it one of the most prevalent chronic skin disorders.²

“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," Eugene Bauer, MD, Evommune chief medical officer said. "MGPRX2 antagonism is exciting in its potential to change the paradigm as the first target that modulates both mast cells and sensory neurons.”¹

References

1. Evommune initiates phase 2b trial of its oral MRGPRX2 antagonist, EVO756, in adults with moderate to severe atopic dermatitis. News release. Evommune. August 27, 2025. Accessed August 27, 2025. https://www.evommune.com/wp-content/uploads/2025/08/27_Evommune_Initiates_Ph2b_AD_Trial_082725.pdf

2. Atopic dermatitis. National Eczema Association. Reviewed January 27, 2025. Accessed August 27, 2025. https://nationaleczema.org/types-of-eczema/atopic-dermatitis/