By blocking activation of MRGPRX2 and degranulation of mast cells, EP262 has the potential to effectively treat multiple mast cell mediated diseases with an initial focus on chronic urticaria and atopic dermatitis.

The first patient has been dosed in Escient Pharmaceuticals CALM-CIndU, an open label Phase 1b clinical proof-of-concept study of EP262, a first-in-class oral MRGPRX2 antagonist for chronic inducible urticaria.

By blocking activation of MRGPRX2 and degranulation of mast cells, EP262 has the potential to effectively treat multiple mast cell mediated diseases with an initial focus on chronic urticaria and atopic dermatitis. 

“MRGPRX2 antagonism with EP262 is an exciting and promising therapeutic approach in that it targets a novel pathway to specifically block non-IgE-mediated mast cell activation with once-daily oral dosing,” says Dr. Martin Metz, Professor of Dermatology and Allergy at Charité, Universitätsmedizin in Berlin, Germany, in a news release.

CALM-CIndU is an open-label Phase 1b study designed to evaluate the safety, tolerability and pharmacodynamics of EP262 in approximately 30 patients with either symptomatic dermographism or cold urticaria, the two most common forms of CIndU. Pharmacodynamic assessments include changes from baseline in disease-specific provocation thresholds that are used as objective markers both diagnostically and pharmacodynamically to quantify disease severity and response to treatment. EP262 will be administered orally, once daily, at a 150 mg dose for 4 weeks, followed by an off-treatment follow-up period. 

“Initiation of the CALM-CIndU study marks another important milestone in our quest to evaluate and harness the therapeutic potential of MRGPRX2 antagonism in a broad range of mast cell-mediated disorders,” adds Christian Weyer, MD, MAS, Chief Medical Officer of Escient. “Following the successful completion of our Phase 1 first-in-human study earlier this year, our team is on track to initiate additional clinical proof-of-concept studies in chronic spontaneous urticaria and atopic dermatitis in the coming months.”