Evommune Advances EVO756 Into Global Phase 2b Trial for Chronic Spontaneous Urticaria

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Evommune, Inc. announced today that it has officially launched its phase 2b clinical trial evaluating EVO756 for chronic spontaneous urticaria (CSU), marking the next step in the development of the novel oral therapeutic aimed at disrupting mast cell-driven inflammation via MRGPRX2 antagonism.¹

The announcement comes on the heels of positive results from the company’s phase 1 proof-of-concept study and ongoing phase 2 trial in chronic inducible urticaria (CIndU), reported by Dermatology Times in September and December 2024.^2-3

With the new trial now enrolling across multiple US sites, Evommune is positioning EVO756 as a potential once-daily oral alternative to injectable biologics.

Targeting a Unique Receptor on Mast Cells

EVO756 is a highly selective small molecule antagonist of the mas-related G-protein coupled receptor X2 (MRGPRX2), a novel target expressed on mast cells and peripheral sensory neurons. MRGPRX2 activation plays a key role in non-IgE-mediated mast cell degranulation, which is increasingly recognized as a central mechanism in both CSU and CIndU.⁴

By inhibiting this receptor, EVO756 aims to disrupt the cascade of histamine release and neurogenic inflammation responsible for symptoms such as hives, pruritus, and angioedema.

In its earlier studies, Evommune demonstrated that EVO756 effectively blocked mast cell degranulation triggered by icatibant, a known MRGPRX2 agonist. Patients showed a reduction in wheal size post-treatment, highlighting the molecule’s pharmacodynamic activity.³

Study Design: CSU Patients Who Remain Symptomatic on Antihistamines

The new phase 2b trial will evaluate the safety and efficacy of multiple dose regimens of EVO756 in patients with CSU inadequately controlled by antihistamines, which are currently the standard first-line therapy.

Participants will receive once-daily oral EVO756 over the course of several weeks, with the primary endpoint focusing on changes in urticaria activity scores and other validated symptom indices.

The randomized, double-blind, placebo-controlled study builds on the company’s existing phase 2 trial in CIndU, which enrolled patients with symptomatic dermographism and cold urticaria. In that study, patients served as their own controls as researchers assessed provocation thresholds to cold and mechanical stimuli.²

In its first-in-human study involving 132 participants, the molecule demonstrated favorable pharmacokinetics, no dose-limiting toxicities, and no serious adverse events.³

Looking Ahead

"Enrollment of our open-label phase 2 chronic inducible urticaria trial is nearly complete, and we believe the pharmacokinetic, pharmacodynamic, and safety data generated on EVO756 warrant the initiation of our phase 2b trial and we look forward to reporting the CSU data in 2026," said Eugene Bauer, MD, chief medical officer at Evommune, in a news release.¹

Beyond urticaria, Evommune is also evaluating the therapeutic potential of MRGPRX2 antagonism in other inflammatory conditions, with a separate phase 2b study evaluating EVO756 in atopic dermatitis beginning later this year.

References

1. Evommune initiates phase 2b trial of MRGPRX2 antagonist, EVO756, in adults with moderate to severe chronic spontaneous urticaria. News release. April 15, 2025. Accessed April 15, 2025. https://www.prnewswire.com/news-releases/evommune-initiates-phase-2b-trial-of-mrgprx2-antagonist-evo756-in-adults-with-moderate-to-severe-chronic-spontaneous-urticaria-302428672.html
2. Evommune initiates phase 2 trial of EVO756, an oral MRGPRX2 antagonist, in chronic inducible urticaria. Evommune. Published September 3, 2024. Accessed April 15, 2025. https://www.evommune.com/wp-content/uploads/2024/09/21_Evommune_EVO756_CindU_Phase_2_Trial.pdf
3. Evommune presents positive clinical results of its MRGPRX2 antagonist (EVO756) at the 7th GA²LEN Global Urticaria Forum. News release. PR Newswire. December 4, 2024. Accessed April 15, 2025. https://www.prnewswire.com/news-releases/evommune-presents-positive-clinical-results-of-its-mrgprx2-antagonist-evo756-at-the-7th-galen-global-urticaria-forum-302322332.html
4. Zhou B, Li J, Liu R, Zhu L, Peng C. The role of crosstalk of immune cells in pathogenesis of chronic spontaneous urticaria. Front Immunol. 2022;13:879754. Published 2022 May 31. doi:10.3389/fimmu.2022.879754