Positive results from a phase 1 first-in-human study of EP262, a highly selective small molecule antagonist of MRGPRX2, suggest high safety and tolerability of the experimental drug for the treatment of mast cell-mediated diseases such as systemic mastocytosis (SM), Escient Pharmaceuticals announced.

“The absence of significant safety findings in this first-in-human study of EP262 is consistent with findings from nonclinical toxicology studies,” said Christian Weyer, MD, MAS, chief medical officer at Escient. “Having pioneered research on MRGPRX2 pharmacology with our proprietary preclinical knock-in model and successfully completed phase 1, we now look forward to evaluating the therapeutic potential of this new target in patients with mast cell-mediated disorders, a first in the field.”

The phase 1, randomized, double-blind, placebo-controlled, study evaluated the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of EP262 in 64 healthy volunteers.

The researchers evaluated 5 single ascending dose levels of EP262, from 50 to 1200 mg, and 3 multiple ascending dose levels of EP262, including 7 daily doses ranging from 50 to 300 mg.

Read more about experimental therapies for SM

According to the results, the experimental drug was safe and well-tolerated at all doses. There were no serious or severe adverse events, no adverse events leading to discontinuation, and no adverse changes in safety laboratory parameters, vital signs, or electrocardiogram parameters. The only treatment-emergent adverse events were mild, with an incidence lower than placebo (33.3% vs 62.5%).

The pharmacokinetic data suggest low variability and once-daily administration of EP262.

The experimental medication blocks the activation of MRGPRX2 and the degranulation of mast cells. It is primarily directed toward chronic urticarias (hives) and atopic dermatitis (eczema).


Escient Pharmaceuticals announces positive results from phase 1 study of EP262, a first-in-class oral MRGPRX2 antagonist for mast cell mediated disorders. News release. Escient Pharmaceuticals, Inc.; June 20, 2023.