EVO756 is a highly selective, potent small molecule antagonist of mas-related G-protein coupled receptor X2, designed to block MRGPRX2 activation and degranulation of mast cells
Evommune initiates trial of EVO756 for spontaneous urticaria. (Credit: andreas160578 from Pixabay)
US-based biotechnology firm Evommune has started the Phase I first-in-human study of EVO756 in healthy adults and adults with chronic spontaneous urticaria (CSU).
EVO756 is a highly selective, potent small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2). It is designed to block MRGPRX2 activation and degranulation of mast cells.
The biotech firm claimed that the asset can be the first-in-class oral treatment for multiple mast cell-mediated diseases, including chronic spontaneous urticaria and inflammatory itch.
Evommune chief medical officer Eugene Bauer said: “As a company committed to developing a pipeline of therapeutics to halt the progression of chronic inflammatory diseases, we are excited to dose the first volunteer in our Phase 1 trial of EVO756.
“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.
“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.”
In the Phase I study, adults with chronic spontaneous urticaria will participate in an open-label study and normal healthy adults will take part in a randomised, double-blind, placebo-controlled research using single and multiple ascending doses (SAD and MAD).
The purpose of the study is to evaluate the pharmacokinetics, safety, and tolerability of oral EVO756 administration.
A skin challenge test will be used to evaluate the pharmacodynamic potential of EVO756 on mast cell degranulation. In this test, an intradermal administration of a known X2 receptor ligand will cause detectable skin responses in both healthy people and adults with CSU.
This part of the study will be conducted in association with Sarbjit Saini of Johns Hopkins University.