Escient Pharmaceuticals Announces Positive Results from Phase 1 Study of EP262, a First-in-Class Oral MRGPRX2 Antagonist for Mast Cell Mediated Disorders

June 20, 2023 |

4 min read

Escient Pharmaceuticals, a clinical-stage drug development company advancing novel small molecule therapeutics for systemic neuro-inflammatory disorders, announced positive results from a Phase 1 first-in-human study of EP262, a potent, highly selective small molecule antagonist of MRGPRX2.

EP262 was safe and well-tolerated at all doses tested, at exposures several fold above doses required for efficacy in preclinical disease models
Pharmacokinetic (PK) profile supports once-daily oral dosing
Clinical proof-of-concept studies in chronic inducible urticaria, chronic spontaneous urticaria and atopic dermatitis to start in second half of 2023

SAN DIEGO--(BUSINESS WIRE)-- Escient Pharmaceuticals, a clinical-stage drug development company advancing novel small molecule therapeutics for systemic neuro-inflammatory disorders, today announced positive results from a Phase 1 first-in-human study of EP262, a potent, highly selective small molecule antagonist of MRGPRX2.

By blocking activation of MRGPRX2 and degranulation of mast cells, EP262 has the potential to treat mast cell mediated diseases with an initial focus on chronic urticarias (hives) and atopic dermatitis (eczema). EP262 represents a new, targeted approach to the treatment of these disorders with the potential for once-daily oral administration without the serious side effects observed with other approaches.

In the Phase 1 study, which enrolled 64 healthy volunteers, EP262 was safe and well-tolerated at all doses tested, with no serious or severe adverse events, no adverse events leading to discontinuation, and no adverse changes in safety laboratory parameters, vital signs or ECG parameters identified. Treatment-emergent adverse events for EP262 were all mild, with an incidence that was lower than placebo (33.3% vs. 62.5%) and did not increase with dose. The plasma PK of EP262 was consistent with predictions from preclinical studies, demonstrating low variability and supporting once-daily administration in future studies.

“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, M.D., M.A.S, 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 study was a randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of EP262 in healthy subjects. It included five single ascending dose levels of EP262, ranging from 50 mg to 1200 mg, and three multiple ascending dose levels of EP262 (seven daily doses, ranging from 50 to 300 mg), administered orally once a day. The doses were evaluated in cohorts of eight volunteers, including two individuals receiving placebo in each cohort.

About EP262

EP262 is a potent, highly selective once-daily small molecule antagonist of MRGPRX2, a receptor expressed on mast cells that is activated by numerous ligands, including many peptides released from sensory neurons as well as other cell types. In response to MRGPRX2 activation, mast cells release histamine, tryptase, chymase, chemokines and cytokines, which can cause itchy hives, angioedema, type 2 inflammation (through engagement of the adaptive immune system) and chronic pruritus and pain. Escient’s preclinical data demonstrates that, by blocking activation of MRGPRX2, EP262 has the potential to effectively treat a broad range of mast-cell-mediated diseases, with an initial focus on chronic urticarias and atopic dermatitis.

About Chronic Urticaria

Chronic urticaria, defined as urticaria persisting for more than 6 weeks, manifests with very itchy hives that may vary in size and can significantly impact a patient’s quality of life by interfering with sleep and daily activities. Some patients with chronic urticaria may also develop swelling deeper under the skin or in other tissues (angioedema). There are two main forms of chronic urticaria. In chronic spontaneous urticaria (CSU), hives occur spontaneously, without known triggers. In chronic inducible urticaria (CIndU), hives are induced by specific triggers such as cold exposure (cold urticaria) or touch (symptomatic dermographism), among others.

About Atopic Dermatitis

Atopic dermatitis is a chronic inflammatory skin disease characterized by abnormalities in immune regulation and skin barrier function. The disease typically manifests with itchy eczematous skin lesions. Thickening, crusting and cracking of the skin may also develop over time. Hypersensitivity to house dust mites and skin colonization by staphylococcus aureus are present in the majority of patients. And these are among the causative or exacerbating factors thought to contribute to the disease.

About Escient Pharmaceuticals

Escient Pharmaceuticals is a clinical-stage company focused on developing novel therapeutics to address a broad range of neurosensory-inflammatory disorders. The company’s pipeline includes two first-in-class small molecule antagonists targeting MRGPRX2 for the treatment of various mast cell mediated disorders and MRGPRX4 for cholestatic pruritus. Based in San Diego, California, Escient is led by an experienced management and scientific team and funded by top-tier life science investors.

Visit www.escientpharma.com to learn more.