EVO-756

PALO ALTO, CA, USA I September 3, 2024 I Evommune, Inc., a clinical stage biotechnology company discovering and developing new ways to treat immune-mediated inflammatory diseases, today announced the enrollment of the first patient in a Phase 2 trial of EVO756 in adults with CIndU. EVO756 is a potent, highly selective small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2) and represents a new, targeted approach with the potential for once-daily oral administration without the serious side effects observed with other therapies. “As we continue to execute on our clinical development plans for EVO756, we are commencing this Phase 2 trial in 15 study sites across the United States. CIndU patients have limited treatment options, and we believe a novel, highly potent, selective agent, that can be orally administered once daily, could provide patients with major therapeutic benefit,” said J. Mark Jackson, MD, Vice President, Clinical Development at Evommune. The multi-center trial is designed to evaluate the safety and efficacy of EVO756 in approximately 30 patients with either symptomatic dermographism or cold urticaria, the two most common forms of CIndU. Efficacy endpoints include changes from baseline in disease specific provocation thresholds that are used as objective markers to quantify disease severity and response to treatment. EVO756 will be administered orally, once daily, for four weeks, and will be evaluated for safety and efficacy at weekly visits during treatment, with patients serving as their own control. “Initiation of this trial marks another important milestone in dedication to delivering the therapeutic potential of MRGPRX2 antagonism to patients in a broad range of mast cell-mediated disorders,” said Daniel J. Burge, M.D., Senior Vice President, Clinical Development at Evommune. “Following the success of our proof-of-concept study with EVO756 earlier this year, we are also on track to initiate a Phase 2b trial in chronic spontaneous urticaria in the second quarter of 2025.” About Chronic Urticaria Chronic urticaria, defined as urticaria persisting for more than 6 weeks, is a substantial burden for patients, their families and careers, the healthcare system, and society. Chronic urticaria manifests with very itchy hives that may vary in size and can result in sleep deprivation, anxiety, depression, lack of energy, and social isolation which can result in a significant deterioration in the quality of life. 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. Chronic urticaria is a mast cell-driven disease. Activated mast cells release histamine along with other mediators, such as platelet-activating factor and cytokines, resulting in sensory nerve activation, vasodilation, plasma extravasation, and recruitment of cells to the urticarial lesion. About EVO756 EVO756 is a potent, highly selective small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2). MRGPRX2 is most abundantly found on mast cells and peripheral sensory neurons. MRGPRX2 can trigger IgE-independent activation (degranulation) via multiple ligands, which can lead to a variety of symptoms depending on the tissue that is affected. Evommune’s pre-clinical data demonstrates that by blocking activation of MRGPRX2 via all disease relevant ligand categories, EVO756 can prevent the degranulation of mast cells. EVO756 has the potential to be a first-in-class oral treatment for a variety of mast cell mediated diseases. In addition, due to its unique function on peripheral sensory neurons, EVO756 could provide fast relief of itch associated with inflammatory diseases, such as atopic dermatitis. About Evommune, Inc. Evommune, Inc., a Palo Alto based biotech company, is creating game-changing science to treat immune-mediated inflammatory diseases by discovering, developing, and delivering therapies that address symptoms and halt progressive disease. For more information, please visit www.evommune.com . SOURCE: Evommune

PALO ALTO, Calf., July 16, 2024. Evommune, Inc., a clinical stage biotechnology company discovering and developing new ways to treat immune-mediated inflammatory diseases, today announced positive results of its first-in-human proof-of-concept study with EVO756. By blocking MRGPRX2 activation and degranulation of mast cells, EVO756 has the potential to be a first-in-class oral treatment for a variety of mast cell-mediated diseases. Evommune is planning to present a comprehensive data set of this trial at a peer-review scientific meeting in the fall of 2024. "The data from our proof-of-concept trial exceeded our expectations, and we now plan to initiate multiple clinical trials of EVO756, including a Phase 2b study in chronic spontaneous urticaria (CSU) patients during the first half of 2025," said Eugene Bauer, M.D., Chief Medical Officer at Evommune. "We believe we have a novel, highly potent and selective agent that can be orally administered once daily, with broad opportunity for patients suffering from various mast-cell mediated diseases." The proof-of-concept study is a randomized, double-blind, placebo-controlled single and multiple ascending dose (SAD and MAD) study in normal healthy adults and assessed the safety, tolerability, pharmacokinetics and pharmacodynamics/target engagement of orally administered EVO756. Doses from 1 mg to 500 mg were administered in ascending order across 7 cohorts of 8 subjects each (6 active, 2 placebo). In the MAD cohorts completed to date, ascending doses of 10 mg, 30 mg, 100 mg and 240 mg BID have been administered across 4 cohorts of 16 subjects each (12 active and 4 placebo). The pharmacodynamic potential of EVO756 on mast cell degranulation was assessed in a skin challenge test, in which icatibant, a known ligand of the MRGPRX2 receptor, was administered intradermally, resulting in measurable skin responses in all MAD participants. Multiple experimental methods have determined that mast cell degranulation caused by icatibant is representative to changes associated with MRGPRX2 disease-relevant endogenous ligands. This portion of the study allowed for an evaluation of target engagement and activity in a highly controlled setting and had the benefit of mimicking the potential impact of EVO756 versus placebo in inducible urticarias. "EVO756's excellent safety profile and potential for a once daily oral dosing provide continued excitement around this new class of therapies in inflammatory diseases. As expected, these data further support the hypothesis that blockade of the MRGPRX2 receptor and its subsequent downstream effect has the potential to treat the root cause of inflammation, offering greater relief than currently available treatments," commented Sarbjit Saini, M.D., Professor of Medicine at Johns Hopkins University in Baltimore, Maryland. About EVO756 EVO756 is a potent, highly selective small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2). MRGPRX2 is most abundantly found on mast cells and peripheral sensory neurons. MRGPRX2 can trigger IgE-independent activation (degranulation) via multiple ligands, which can lead to a variety of symptoms depending on the tissue that is affected. Evommune's pre-clinical data demonstrates that by blocking activation of MRGPRX2 and degranulation of mast cells, EVO756 has the potential to be a first-in-class oral treatment for a variety of mast cell mediated diseases. In addition, due to its unique function on peripheral sensory neurons, EVO756 could provide fast relief of itch associated with inflammatory diseases, such as atopic dermatitis. About Evommune, Inc. Evommune, Inc., a Palo Alto based biotech company, is creating game-changing science to treat immune-mediated inflammatory diseases by discovering, developing, and delivering therapies that address symptoms and halt progressive disease. For more information, please visit Evommune.com. SOURCE Evommune, Inc Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.