Evommune Reports Positive MRGPRX2 Antagonist Trial Results

Evommune, Inc., a clinical stage biotechnology company located in Palo Alto, California, announced positive outcomes from its first-in-human proof-of-concept study for EVO756. This innovative compound targets mast cell-mediated diseases by blocking MRGPRX2 activation and subsequent mast cell degranulation, positioning EVO756 as a potential first-in-class oral treatment. The company plans to reveal detailed data from this trial at a peer-reviewed scientific meeting in fall 2024.

Dr. Eugene Bauer, Chief Medical Officer at Evommune, expressed satisfaction with the trial results, noting that the data surpassed expectations. Consequently, Evommune aims to launch multiple clinical trials for EVO756, including a Phase 2b study focusing on patients with chronic spontaneous urticaria (CSU) in the first half of 2025. Dr. Bauer highlighted the compound's oral administration capability and its broad potential applications for various mast cell-mediated diseases.

The proof-of-concept study was meticulously designed as a randomized, double-blind, placebo-controlled trial. It involved both single and multiple ascending dose (SAD and MAD) investigations in healthy adult participants to evaluate EVO756's safety, tolerability, pharmacokinetics, and pharmacodynamics. The trial featured ascending doses ranging from 1 mg to 500 mg across seven cohorts, each consisting of eight participants (six receiving the active compound and two receiving a placebo). For the MAD component, ascending doses of 10 mg, 30 mg, 100 mg, and 240 mg were administered twice daily across four cohorts of 16 subjects each (12 receiving the active compound and four a placebo).

A critical element of the study involved assessing EVO756's pharmacodynamic potential through a skin challenge test. In this test, icatibant, a known MRGPRX2 receptor ligand, was administered intradermally to induce measurable skin responses in all MAD participants. The results confirmed the relevance of mast cell degranulation caused by icatibant to changes associated with MRGPRX2 disease-relevant endogenous ligands. This part of the study enabled a thorough evaluation of target engagement and activity under controlled conditions, simulating the potential impact of EVO756 compared to placebo in inducible urticarias.

Dr. Sarbjit Saini, Professor of Medicine at Johns Hopkins University, emphasized the promising safety profile and the potential for once-daily oral dosing of EVO756, expressing optimism for this new class of therapies targeting inflammatory diseases. He noted that the data supports the hypothesis that blocking the MRGPRX2 receptor and its downstream effects could address the root cause of inflammation, offering more significant relief than existing treatments.

EVO756 is a highly selective small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2). This receptor is predominantly found on mast cells and peripheral sensory neurons and can trigger IgE-independent activation through multiple ligands, leading to various symptoms depending on the affected tissue. Pre-clinical data from Evommune shows that blocking MRGPRX2 activation and mast cell degranulation could make EVO756 a groundbreaking oral treatment for various mast cell-mediated diseases. Additionally, its unique effect on peripheral sensory neurons might offer rapid relief from itch associated with inflammatory conditions like atopic dermatitis.

Evommune, Inc. is a pioneering biotech company based in Palo Alto, focused on developing treatments for immune-mediated inflammatory diseases. The company's mission is to discover, develop, and deliver therapies that not only alleviate symptoms but also halt disease progression.