Evommune Reports Positive Trial Results for MRGPRX2 Antagonist EVO756

Evommune, Inc., a biotechnology company based in Palo Alto, California, has announced promising results from its initial human proof-of-concept study of EVO756, a novel drug designed to treat immune-mediated inflammatory diseases. EVO756 is a highly selective small molecule antagonist of the MRGPRX2 receptor, which plays a significant role in a variety of mast cell-mediated diseases. The results suggest that EVO756 could become a first-in-class oral treatment targeting these conditions.

The clinical trial, which was randomized, double-blind, and placebo-controlled, aimed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of EVO756 in healthy adults. Participants received ascending doses of the drug, ranging from 1 mg to 500 mg, across seven cohorts. The results were positive, showing that the drug was well tolerated at all doses.

One of the key findings of the study was the excellent safety profile of EVO756, which was well tolerated even at higher doses. Pharmacokinetic data further indicated that the drug supports once-daily oral dosing. According to Eugene Bauer, M.D., Chief Medical Officer at Evommune, the data surpassed expectations, prompting plans to initiate several clinical trials, including a Phase 2b study in chronic spontaneous urticaria (CSU) patients in early 2025.

The study also explored the pharmacodynamic potential of EVO756 by assessing mast cell degranulation through a skin challenge test. In this test, icatibant, a known ligand of the MRGPRX2 receptor, was administered intradermally, resulting in measurable skin responses. This method helped evaluate the drug's target engagement and activity under controlled conditions, simulating its potential impact against inducible urticarias. The results indicated that blocking the MRGPRX2 receptor could effectively treat the root causes of inflammation, potentially offering greater relief than current treatments.

Sarbjit Saini, M.D., Professor of Medicine at Johns Hopkins University, remarked on the potential of EVO756, noting its excellent safety profile and the feasibility of once-daily oral dosing. He highlighted that the data supports the hypothesis that blocking the MRGPRX2 receptor could treat inflammation at its root cause, offering significant advantages over existing treatments.

EVO756's mechanism of action involves blocking the activation of the MRGPRX2 receptor, which is predominantly found on mast cells and peripheral sensory neurons. These receptors can trigger IgE-independent activation, leading to a range of symptoms depending on the affected tissue. Pre-clinical data from Evommune supports the idea that by inhibiting the activation of MRGPRX2 and subsequent mast cell degranulation, EVO756 could serve as a pioneering oral treatment for various mast cell-mediated diseases. Additionally, due to its unique action on peripheral sensory neurons, EVO756 may offer rapid relief from itch associated with inflammatory diseases like atopic dermatitis.

Evommune, Inc. is dedicated to creating innovative therapies for immune-mediated inflammatory diseases. The company's efforts focus on discovering, developing, and delivering treatments that not only alleviate symptoms but also halt disease progression. With the promising results from the EVO756 study, Evommune is set to advance its clinical trials, potentially revolutionizing the treatment landscape for inflammatory diseases.