Evommune has enrolled the first patient in a global Phase 2b trial of EVO756, an orally available MRGPRX2 antagonist, for treating moderate to severe chronic spontaneous urticaria (CSU). The biotechnology company announced positive Phase 2 data showing the drug's potential as a first-in-class treatment for chronic inflammatory diseases.
Novel Mechanism Targets Dual Pathways
EVO756 represents a differentiated therapeutic approach by inhibiting mas-related G-protein coupled receptor X2 (MRGPRX2) on both mast cells and peripheral sensory neurons. This dual mechanism distinguishes it from other therapeutic options currently available for urticaria treatment.
"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," said Luis Peña, President and CEO at Evommune.
Phase 2 Results Demonstrate Clinical Activity
The company reported positive top-line data from its Phase 2 trial in chronic inducible urticaria (CIndU), evaluating 30 patients with symptomatic dermographism. After four weeks of treatment, 30% of patients achieved a complete response, with 50% of these responders having high IgE levels (≥100 IU/ml). Additionally, 41% of patients demonstrated a clinically meaningful response with a ≥2 point reduction in itch numerical rating scale.
The multi-center trial administered EVO756 orally at either 300mg once daily or 50mg twice daily for four weeks. Clinically meaningful responses were consistent across both dosing regimens, with patients serving as their own control during weekly treatment visits.
"As one who treats urticaria, these results suggest that EVO756, if approved, could present a compelling alternative to biologics, especially when we expect continued improvement and more responses with treatment beyond four weeks," commented Edward (Ted) Lain, MD, MBA, a board-certified dermatologist and clinical investigator.
Safety Profile and Development Timeline
EVO756 demonstrated a favorable safety profile in the Phase 2 trial, with no serious treatment-emergent adverse events and no discontinuations due to adverse events. Eugene Bauer, M.D., Chief Medical Officer at Evommune, noted that enrollment of the open-label Phase 2 chronic inducible urticaria trial is nearly complete, and the pharmacokinetic, pharmacodynamic, and safety data support advancing to Phase 2b trials.
The global Phase 2b CSU trial is designed as a Phase 3 enabling study, randomizing approximately 160 patients to receive one of three active dose regimens or placebo. Data from this trial are expected in mid-2026. The company also plans to initiate a separate Phase 2b trial of EVO756 in atopic dermatitis later this year.
Addressing Unmet Medical Need
Chronic spontaneous urticaria affects patients with hives lasting six or more weeks, occurring three to four times per week without known cause. One in five people experience hives at some time during their life. The condition results from mast cell activation in the skin, releasing histamines, leukotrienes, and chemokines that cause itchy hives, swelling, and inflammation that can persist for years or decades.
Current treatment typically involves H1 antihistamines targeting H1 receptors to control symptoms. However, the disease remains uncontrolled despite antihistamine treatment in many patients, leaving some with limited alternative treatment options.
MRGPRX2 is a G-protein-coupled receptor found predominantly on mast cells and peripheral sensory neurons, activated by a broad spectrum of ligands prevalent during inflammation. By targeting this receptor, EVO756 aims to provide a new therapeutic option that reduces inflammation and provides rapid relief of itch while offering the convenience of oral dosing.
