PALO ALTO, Calif., & NEW YORK, July 30, 2026
Evommune announced that the first patient has been dosed in its Phase 2b clinical trial evaluating EVO756, a first-in-class oral MRGPRX2 inhibitor, for the prophylactic treatment of migraine. The investigational therapy is designed to target Mas-related G protein-coupled receptor X2 (MRGPRX2), a receptor expressed in human trigeminal neurons and meningeal mast cells, two key tissues involved in migraine biology. Unlike current preventive therapies that primarily focus on the CGRP pathway, EVO756 is intended to inhibit signaling from three migraine-triggering neuropeptides—PACAP, VIP, and Substance P—through MRGPRX2. The company expects top-line Phase 2b data in 2027, positioning the program as a potential next-generation oral therapy for patients with inadequate response to existing migraine treatments.
Global Phase 2b Study Targets Patients with Refractory Migraine
The Phase 2b trial is a global, randomized, double-blind, placebo-controlled, dose-ranging study designed to evaluate the safety and efficacy of EVO756 in adults with refractory migraine experiencing six or more migraine days per month. Approximately 330 patients will be randomized to receive one of two active dose levels or placebo over a 12-week treatment period, with doses evaluated up to 100 mg once daily. The primary endpoint is the change from baseline in monthly migraine days (MMD), while key secondary endpoints include the proportion of patients achieving 50% or greater and 75% or greater reductions in monthly migraine days, changes in monthly headache days, and reductions in the use of acute migraine medications. The study will also assess migraine biomarkers, patient subtypes, and quality-of-life outcomes through exploratory analyses.
Novel MRGPRX2 Mechanism Expands Beyond Existing Migraine Targets
EVO756 represents a first-in-class oral small-molecule antagonist targeting MRGPRX2, a receptor predominantly found on mast cells and peripheral sensory neurons that plays an important role in neurogenic inflammation. By simultaneously blocking signaling triggered by PACAP, VIP, and Substance P, the investigational therapy aims to interrupt multiple biological pathways involved in migraine initiation and progression. This dual-action mechanism could provide a broader therapeutic effect than currently available CGRP-targeted therapies, particularly for patients who continue to experience frequent migraine attacks despite preventive treatment. The approach also highlights Evommune’s broader strategy of developing innovative therapies targeting key inflammatory pathways across multiple chronic diseases.
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Program Addresses Significant Unmet Need in Migraine Prevention
Migraine affects more than 40 million people in the United States and over 10% of the global population, making it one of the leading causes of neurological disability worldwide. Although preventive therapies have improved treatment options in recent years, many patients continue to experience insufficient symptom control, with nearly half failing to achieve meaningful reductions in migraine frequency and more than 80% discontinuing traditional preventive therapies within one year. Evommune believes EVO756 has the potential to become a front-line oral migraine prevention therapy by offering a differentiated mechanism of action capable of addressing patients who remain inadequately treated with current standards of care. If successful, the program could significantly expand treatment options for individuals living with chronic and refractory migraine.
Source: Evommune ,press release
