Evommune (EVMN) Study Result summary

Study background and rationale

• EVO756 is a potent, selective small-molecule antagonist of the MRGPRX2 (X2) receptor, implicated in chronic inducible urticaria (CIndU) pathogenesis and modulating mast cells and sensory neurons.

• CIndU is a subtype of chronic spontaneous urticaria (CSU), often lasting longer and affecting 0.5% of the population.

• Current treatments, including high-dose H1 antihistamines and off-label Omalizumab, leave 20% of patients symptomatic.

• The X2 receptor is present on both mast cells and sensory neurons, making it a unique therapeutic target for inflammation and itch.

• EVO756 blocks multiple ligands at the X2 receptor, potentially alleviating CIndU symptoms at the cellular level.

Study design and patient characteristics

• Phase II, open-label, multicenter U.S. trial in 30 adults with symptomatic dermographism, a common CIndU subtype.

• Two dosing cohorts: 300 mg QD and 50 mg BID, administered orally for four weeks.

• Patients served as their own control, with both IgE high (≥100 IU/mL) and low at baseline; 20–27% had high IgE.

• Efficacy measured by FricTest (pressure-induced hive response) and pruritus NRS (itch scale); baseline FricTest scores were 3–4, pruritus NRS 4–5.

• Majority were female, mean age mid- to late 40s.

Efficacy results

• Clinical responses observed in 93% of patients at four weeks, with improvements as early as week one.

• 70% showed FricTest score improvement; 41% had a two-point improvement; 30% achieved complete response (no hive lines) in both dosing arms.

• 78% had itch reduction at week four, with 41% experiencing at least a four-point NRS decrease.

• Efficacy was similar regardless of IgE status, supporting broad applicability.

• Rapid onset of action, with improvements seen within one week, including three complete responders.