Escient Pharmaceuticals, Inc.

Efficacy and safety of EP262 to be assessed in a randomized, placebo-controlled study in ~90 patients Second of three clinical proof-of-concept studies to be initiated 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-immune disorders, today announced that the first subject has been dosed in CALM-CSU, a Phase 2 clinical proof-of-concept study of EP262 in subjects with chronic spontaneous urticaria (CSU). 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 (hives) and atopic dermatitis (eczema). EP262 represents a novel, targeted approach to the treatment of these disorders with the potential for once-daily oral administration without the side effects observed with other approaches. “Chronic spontaneous urticaria is a debilitating condition driven by activation of mast cells, and there is growing evidence that non-IgE mediated mast cell activation via MRGPRX2 may play an important role in the disease,” said Christian Weyer, M.D., M.A.S, Chief Medical Officer at Escient. “We are excited to initiate Phase 2 clinical development of EP262 for CSU, as it has the potential to become a much needed, once daily oral treatment option that is safe and able to alleviate the spontaneous occurrence of itchy hives via a novel, highly targeted mechanism.” CALM-CSU is a randomized, double-blind, placebo-controlled Phase 2 study designed to evaluate the efficacy, safety and tolerability, and pharmacokinetics of EP262 in approximately 90 patients with CSU who are inadequately controlled with H1-antihistamines. Patients will be randomized, in a 1:1:1 ratio, to treatment with EP262 50 mg, EP262 150 mg, or placebo, administered orally, once daily for 6 weeks, followed by an off-treatment follow-up period. The primary efficacy endpoint is the change from baseline in the urticaria activity score over 7 days (UAS7), a validated and widely used measure of disease activity. More information about this study is available on (Identifier: NCT6077773). 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 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 to learn more. View source version on businesswire.com: Contacts Aaron Mishel Chief Financial Officer Escient Pharmaceuticals, Inc. ir@escientpharma.com Source: Escient Pharmaceuticals, Inc. View this news release online at:

Pliant Therapeutics is part of a small band of biotechs working to address the unmet need in primary sclerosing cholangitis. Investors are swayed by Pliant Therapeutics’ data. The biotech posted early clinical evidence that its lead drug candidate reduces scarring and itching in a chronic liver disease, sending its share price up around 15%. The phase 2a trial is comparing bexotegrast, an oral, dual-selective inhibitor of two integrins, to placebo in patients with primary sclerosing cholangitis (PSC) and suspected liver fibrosis. PSC, a condition with no FDA-approved therapies, causes scarring of bile ducts and cirrhosis. Through tissue specific inhibition of TGF-β, bexotegrast may block fibrosis, leading Pliant to identify it as a potential treatment for PSC. In the phase 2a trial, participants received one of three doses of bexotegrast or placebo. While the study is primarily designed to assess safety, tolerability and pharmacokinetics, Pliant also looked at exploratory efficacy endpoints such as changes in the fibrosis, biochemistry and imaging of the liver. The exploratory endpoints revealed early signs that bexotegrast may improve outcomes.  After 12 weeks of dosing, the ELF score, a blood test of fibrosis markers, was significantly lower in the high, 160-mg dose cohort than in the placebo group and numerically lower in all the bexotegrast arms. Pliant linked the high dose to an 84% reduction relative to placebo. The reduction was underpinned by significant declines in all three markers that make up the ELF score.  Pliant also reported a significant drop in collagen synthesis and, at the high dose, in the score on an itch scale. Other liver biochemistry and imaging parameters favored bexotegrast, too, giving Pliant data with enough promise to send its share price up around 15% to $16.60 in premarket trading. The data set is small—each arm featured around 20 patients—but the signs of efficacy and lack of safety red flags have encouraged Pliant and its investors. Attention now turns to the anticipated publication of 12-week data on a higher, 320-mg dose, which is scheduled for the first quarter of next year.   Pliant is part of a small band of biotechs working to address the unmet need in PSC, a disease that companies including Gilead Sciences have targeted in the past without delivering a FDA-approved treatment. The current crop of companies going after the liver condition includes Chemomab Therapeutics, Dr. Falk Pharma, Escient Pharmaceuticals, HighTide Therapeutics and Mirum Pharmaceuticals.

First of three clinical proof-of-concept studies to be initiated in second half of 2023 Study will evaluate EP262 in ~30 patients with symptomatic dermographism and cold urticaria using an open-label design and objective endpoints SAN DIEGO--(BUSINESS WIRE)-- Escient Pharmaceuticals, a clinical-stage drug development company advancing novel small molecule therapeutics for systemic neuro-immune disorders, today announced that the first subject has been dosed in CALM-CIndU, an open label Phase 1b clinical proof-of-concept study of EP262 in subjects with chronic inducible urticaria (CIndU). 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 (hives) and atopic dermatitis (eczema). EP262 represents a novel, targeted approach to the treatment of these disorders with the potential for once-daily oral administration without the side effects observed with other approaches. “Chronic inducible urticaria is a debilitating condition driven by activation of mast cells in response to common triggers that are exceedingly difficult to avoid in daily life, resulting in an urgent need for novel therapeutic options,” said Dr. Martin Metz, Professor of Dermatology and Allergy at Charité, Universitätsmedizin in Berlin, Germany. “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.” 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. More information about this study is available on (Identifier: NCT06050928). “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,” said Christian Weyer, M.D., M.A.S, 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.” 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 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 to learn more. View source version on businesswire.com: Contacts Aaron Mishel Chief Financial Officer Escient Pharmaceuticals, Inc. ir@escientpharma.com Source: Escient Pharmaceuticals View this news release online at: