SAN DIEGO--(BUSINESS WIRE)--Escient Pharmaceuticals, a clinical-stage, Mas-Related G Protein-Coupled Receptor (Mrgpr)-based platform company focused on discovering and developing novel MOA-targeted, first-in-class, oral, once-daily therapies to address serious, unserved medical needs, today announced positive results from a Phase 1 study of EP547, a new chemical entity and potent MrgprX4 antagonist, being developed for the treatment of pruritus associated with cholestasis and uremia. The study found that EP547 was safe and well-tolerated in both healthy volunteers and patients with chronic cholestatic or kidney disease at all doses tested.
“At Escient, we have made discoveries that more clearly defined the biological basis of cholestatic and uremic pruritus and have developed EP547 to specifically target MrgprX4, the receptor in the neurons responsible for the unrelenting and debilitating itch that affects the lives of many patients with various types of chronic liver and kidney diseases,” said Alain Baron, M.D., Chief Executive Officer of Escient. “EP547 has the potential to be a first-in-class targeted treatment for patients living with these pruritic syndromes, and we look forward to its continued clinical development. Building on our deep knowledge of Mrgprs, we have taken a similar approach with our MrgprX2 program and look forward to advancing it into the clinic for the treatment of a number of neurosensory-immune overactivation disorders."
EP547 was found to be safe and well-tolerated with no serious adverse events, no adverse events leading to discontinuation, and no safety signals identified. In healthy volunteers receiving doses up to 675 mg, all adverse events observed were mild and transient. Reported adverse events in more than two participants included headache and diarrhea; these were not dose dependent. The plasma PK of EP547 was consistent with predictions from preclinical studies, demonstrating strong dose linearity and supporting once-daily administration in future studies.
“The excellent safety, tolerability and PK profile in this study provides a strong foundation for further development of EP547 in cholestatic and uremic pruritus,” said Christian Weyer, M.D., M.A.S, President and Chief Medical Officer of Escient. “Our team is now highly focused on advancing EP547 into Phase 2 to establish clinical proof-of-concept in the target patient populations.”
The Phase 1 study employed a randomized, double-blind, placebo-controlled design to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of EP547 in healthy subjects. It included an assessment of five ascending single dose levels of EP547, ranging from 25 mg to 675 mg, and three multiple ascending dose levels of EP547 (seven once-daily doses, ranging from 25 to 225 mg), administered orally once a day. The doses were evaluated in cohorts of eight volunteers, including two individuals receiving placebo in each cohort. The safety, tolerability, and PK of EP547 was also characterized in single-dose and multi-dose administration in patients with chronic cholestatic or kidney disease, with results supporting further development in both patient populations.
About EP547 for Cholestatic and Uremic Pruritus
EP547 is a potent, highly selective small molecule antagonist of MrgprX4, a receptor expressed on sensory itch neurons in the skin that is activated by multiple itch-inducing metabolites (pruritogens) including bile acids, bilirubin and related heme metabolites. These pruritogens can be markedly elevated in many chronic liver and kidney diseases. By blocking these pruritogens from activating MrgprX4, Escient believes EP547 has the potential to effectively treat both cholestatic and uremic pruritus.
Pruritus is a common, often severe and life-altering condition in patients with chronic liver and kidney disease. Pruritus occurs in 30-100% of adult and pediatric patients with various forms of cholestatic disease and in up to 55% of adult patients with chronic kidney disease, including those with end-stage renal disease requiring hemodialysis. Drug development to address cholestatic and uremic pruritus has been hampered by the lack of basic biological understanding of the relevant mechanisms. Current pharmacological treatment options for cholestatic and uremic pruritus are non-specific, only marginally effective, and have significant side effects, creating a significant need for new, targeted treatments that are both safe and effective.
About Escient Pharmaceuticals
Escient Pharmaceuticals is a clinical-stage, Mas-Related G Protein-Coupled Receptor (Mrgpr)-based platform company focused on discovering and developing novel MOA-targeted, first-in-class, oral, once-daily therapies to address serious, unserved medical needs. Our platform is based on the novel biology of eight Human Mrgprs, expressed in various cell types and tissues, chiefly sensory neurons and immune cells, that provide multiple product opportunities across a broad range of therapeutic areas. By antagonizing the Mrgpr of interest, we aim to interrupt the vicious cycle of neurosensory-immune overactivation that characterizes many chronic inflammatory disorders, offering a potentially paradigm changing therapeutic approach - with oral therapeutics that can address multiple high-value indications. Based in San Diego, Calif., Escient is led by an experienced team of biotechnology entrepreneurs with specific expertise in GPCR drug discovery and development and funded by top-tier life science investors, including The Column Group, 5AM Ventures, Sanofi Ventures, Cowen Healthcare Investors, Redmile Group, Perceptive Advisors, Osage University Partners and Altitude Life Science Ventures.
Visit www.escientpharma.com to learn more.