Evommune, Inc. has announced the commencement of a Phase 2 clinical trial for EVO756, a novel therapeutic agent targeting chronic inducible urticaria (CIndU). The first patient has been enrolled in the multicenter study, which will assess the safety and efficacy of the drug in treating this challenging condition.
EVO756: A Targeted Approach to CIndU
EVO756 is a highly selective, small molecule antagonist of the Mas-related G-protein coupled receptor X2 (MRGPRX2). This receptor is primarily expressed on mast cells and peripheral sensory neurons. Activation of MRGPRX2 has been implicated in mast cell-driven disorders, including CIndU. By inhibiting MRGPRX2, EVO756 aims to provide a targeted treatment option with the convenience of once-daily oral administration.
"As we continue to execute on our clinical development plans for EVO756, we are commencing this Phase II trial in 15 study sites across the United States," said J. Mark Jackson, MD, vice president, clinical development at Evommune. "CIndU patients have limited treatment options, and we believe a novel, highly potent, selective agent, that can be orally administered once daily, could provide patients with major therapeutic benefit."
Trial Design and Objectives
The Phase 2 trial will enroll approximately 30 patients with symptomatic dermographism or cold urticaria, two prevalent forms of CIndU, across 15 study sites in the US. The primary endpoints will measure changes in disease-specific provocation thresholds, serving as objective markers for disease severity and treatment response. Participants will receive EVO756 orally once daily for four weeks. Weekly evaluations will monitor safety and efficacy, with each patient serving as their own control.
The trial design incorporates an approach where each patient serves as their own control, allowing for comparative data analysis within individuals.
Understanding Chronic Urticaria and the Role of Mast Cells
Chronic urticaria is characterized by intense itching, hives, and sometimes angioedema. It is classified into chronic spontaneous urticaria (CSU), which has no obvious triggers, and CIndU, where symptoms are triggered by specific stimuli. Mast cells play a central role in both types of chronic urticaria by releasing histamine and other mediators. EVO756's mechanism of action involves blocking MRGPRX2, preventing mast cell degranulation and mitigating symptoms.
In addition, due to its unique function on peripheral sensory neurons, EVO756 could provide fast relief of itch associated with inflammatory diseases, such as atopic dermatitis.
Future Development Plans
Evommune is also planning a Phase 2b trial in chronic spontaneous urticaria (CSU), scheduled to begin in the second quarter of 2025. This trial will further explore the potential of EVO756 in treating mast cell-mediated disorders.
"Initiation of this trial marks another important milestone in dedication to delivering the therapeutic potential of MRGPRX2 antagonism to patients in a broad range of mast cell mediated disorders," said Daniel J. Burge, MD, senior vice president, clinical development at Evommune. "Following the success of our proof-of-concept study with EVO756 earlier this year, we are also on track to initiate a phase 2b trial in chronic spontaneous urticaria in the second quarter of 2025."
