Evommune Initiates Phase 2b Trial of MRGPRX2 Antagonist, EVO756, in Adults with Moderate to Severe Chronic Spontaneous Urticaria

• Novel mechanism of action (MOA) inhibits MRGPRX2 on both mast cells and peripheral sensory neurons - a key differentiator to other therapeutic options
  
  
• Potential first- and best-in-class safety and efficacy profile for patients suffering from a broad range of chronic inflammatory diseases
  
  
• Global Phase 2b trial is Phase 3 enabling, with data expected in mid-2026

PALO ALTO, Calif., April 15, 2025 /PRNewswire/ -- Evommune, Inc., a clinical stage biotechnology company discovering and developing new ways to treat immune-mediated inflammatory diseases, today announced the enrollment of the first patient in a global Phase 2b trial of EVO756, an orally available, highly potent and selective small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2), in adults with moderate to severe chronic spontaneous urticaria (CSU).   

"The dual mechanism of EVO756, which has been shown in preclinical studies to address MRGPRX2 activation on both mast cells and peripheral sensory neurons, represents a promising new therapeutic approach for CSU and a broad range of other inflammatory diseases for which new treatments are urgently needed. Building upon these studies and our previously disclosed EVO756 clinical proof-of-concept data, we are pleased to have the Phase 2b CSU trial now underway. In addition, we are planning to initiate a separate Phase 2b trial of EVO756, in atopic dermatitis, later this year," said Luis Peña, President and CEO at Evommune.

"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, M.D., Chief Medical Officer at Evommune.  

EVO756 is being evaluated in a global, multi-center, Phase 2b randomized, double-blind, placebo-controlled, dose-ranging study evaluating the efficacy and safety in adults with moderate to severe CSU. Approximately 160 patients will be enrolled and patients will be randomized to receive one of three active dose regimens or placebo.

About Chronic Spontaneous Urticaria (CSU)

Chronic spontaneous urticaria (CSU) is the name for hives (urticaria) that are chronic, lasting six or more weeks, three to four times per week, and have no known cause (spontaneous). One in five people will get hives at some time during their life. The activation of the mast cells in the skin (release of histamines, leukotrienes, chemokines) results in episodes of itchy hives, swelling, and inflammation of the skin that can persist for years or even decades. CSU is typically treated with H1 antihistamines, medicines that target H1 receptors on cells to control symptoms of urticaria. However, the disease remains uncontrolled despite antihistamine treatment in many patients, some of whom are left with limited alternative treatment options.

About MRGPRX2 and EVO756

MRGPRX2, is a G-Protein-Coupled-Receptor (GPCR) found on mast cells (MC) and sensory neurons. It facilitates potent degranulation in MCs, and on sensory neurons, driving neurogenic inflammation and sensations such as cough, pain, and itch. The receptor is activated by a broad spectrum of ligands that are prevalent during inflammation. Targeting MRGPRX2 may have potential across an array of MC-mediated diseases and in mitigating neurogenic inflammation.

EVO756 is a small molecule antagonist of MRGPRX2 that is being developed as a first-in-class, best-in-class oral treatment for mast cellmediated diseases including chronic spontaneous urticaria (CSU) and atopic dermatitis (AD), with additional possible applications in neuroinflammation. Both the CSU and AD markets are underserved by current treatment options, and alternative therapies offering improved efficacy, safety, and the convenience of oral dosing are needed to fill the unmet need in these patients.

About Evommune

Evommune, Inc. is a clinical-stage biotechnology company discovering and developing new ways to treat immune-mediated inflammatory diseases. The company is creating game-changing science with the goal of delivering therapies that halt disease progression and address disease symptoms. For more information, please visit www.evommune.com or follow us on LinkedIn.

SOURCE Evommune, Inc