Familial Dermographism

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:

Following multiple high-profile missteps several years ago, the folks over at Celldex Therapeutics began charting a path to redemption that would take on Roche and Novartis’ blockbuster Xolair franchise. That path got a boost Friday with a data readout the company says positions it well against the pharma giants. Celldex reported results from a Phase Ib study for their monoclonal antibody CDX-0159 to treat two conditions that cause severe and debilitating hives. The Hampton, NJ-based biotech said that among 19 patients who received a full dose of the antibody, 18 achieved a complete response and the 19th saw a partial response. That stands in stark contrast to some of the response rates Celldex says patients see on Xolair, which fall around the 40% to 50% range. Those with such conditions also need to take multiple doses of Xolair, while Celldex’s data come from patients taking only one dose of CDX-0159, CEO Anthony Marucci emphasized. “We’ve been antibody developers for a long time, both in oncology and non-oncology assets,” Marucci told Endpoints News . “Looking at this target and where we believed it worked, naturally the science took us to inflammation. That’s not to say we’ve abandoned oncology … but this target and the way we designed the molecule, to reduce infusion reactions and improve its half life, the data in our minds [are] spectacular even in the early stages.” In the wake of the announcement, Celldex $CLDX shares were up more than 35% in post-market trading Friday evening. The diseases in question are two forms of chronic inducible urticaria. The first, called symptomatic dermographism, makes up more than half of cases. Patients can develop severe hives in response to little stimulation on the skin, such as putting on socks. The second condition, known as “cold urticaria,” makes up 16% of cases and causes hives outbreaks when skin is exposed below certain temperatures. Within the Phase Ib study, nine of the 19 patients had symptomatic dermographism while the other 10 suffered from cold urticaria. Eight of the nine SD patients achieved complete response, including three who had previously been treated with Xolair, and all 10 with ColdU met their complete response. On top of the response rates, Celldex said the treatments proved highly durable. The SD patients maintained their responses at a median of 57 days, and those with ColdU maintained the disease state for a median of 77 days. CDX-0159 works by targeting mast cells by binding the receptor tyrosine kinase KIT. Mast cells mediate inflammatory responses in the body and KIT signaling controls mast cell differentiation. As such, Celldex’s theory involves tamping down on KIT in order to deplete the mast cells in the skin. Celldex is continuing to study the drug in other forms of urticarias, including hives triggered by sweating in warm temperatures or from exercise, as well as urticarias that result in spontaneous hive outbreaks. Both of these datasets in the ongoing Phase Ib trial are expected in the first half of 2022. Should everything turn out hunky dory, the program would mark a sharp turnaround for a biotech that culled multiple late-stage assets from its pipeline after Phase III failures. In 2016, a cancer vaccine program flopped a glioblastoma study, and 2018 brought a Phase IIb disaster in breast cancer — a miss that resulted in Celldex laying off about 40% of its workforce. But now Celldex is engaging in a full court press to get CDX-0159 to patients, and Marucci hopes the company can expand the program into other diseases where mast cells are implicated. Celldex isn’t saying much yet, but researchers are looking at other indications in the respiratory, allergic, ophthalmic and GI areas. Taking a bite out of the Xolair pie is proving to be an opportunity Celldex simply can’t pass up, Marucci said. Xolair netted about $3.3 billion in sales between Roche and Novartis in 2020 and continued to see growth in 2021’s first quarter, and analysts estimate that about $1.5 billion of that total comes from the spontaneous form of the disease.