Evommune, Inc. is initiating its Phase 1 first-in-human study, evaluating EVO756 in chronic spontaneous urticaria (CSU).
By blocking MRGPRX2 activation and degranulation of mast cells, EVO756 has the potential to be a first-in-class oral treatment for a variety of mast cell-mediated diseases, including chronic spontaneous urticaria and inflammatory itch.
The Phase 1 study is a randomized, double-blind, placebo-controlled single and multiple ascending dose (SAD and MAD) study in normal healthy adults and an open-label study in adults with CSU. The study is designed to assess the safety, tolerability, and pharmacokinetics, of orally administered EVO756. The pharmacodynamic potential of EVO756 on mast cell degranulation will be assessed in a skin challenge test, in which a known ligand of the X2 receptor is administered intradermally, resulting in measurable skin responses in healthy adults and adults with CSU.
This part of the study will be done in collaboration with Sarbjit Saini, MD, Johns Hopkins University, and allows for an evaluation of patients in a highly controlled setting and has the benefit of mimicking the impact of EVO756 versus a control against inducible urticarias in the healthy adult cohort.
“By targeting mast cells via the selective modulation of MRGPRX2, we aim to deliver a novel therapeutic with the efficacy of a biologic and the potential for once-daily oral administration, without the safety challenges of alternative mast cell depleting options,” says Eugene Bauer, MD, Chief Medical Officer at Evommune, in a news release. “In CSU patients, blockade of the MRGPRX2 receptor and its subsequent downstream effect has the potential to treat the root cause of inflammation, offering greater relief than currently available treatments.”
More About EVO756
MRGPRX2 is most abundantly found on mast cells and peripheral sensory neurons. MRGPRX2 can trigger IgE-independent activation (degranulation) via multiple ligands, which can lead to a variety of symptoms depending on the tissue that is affected. Evommune’s pre-clinical data demonstrates that by blocking activation of MRGPRX2 and degranulation of mast cells, EVO756 has the potential to be a first-in-class oral treatment for a variety of mast cell-mediated diseases. 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.
