Evommune Initiates Phase 2b Trial of its Oral MRGPRX2 Antagonist, EVO756, in Adults with Moderate to Severe Atopic Dermatitis

• MRGPRX2 antogonism is the only known mechanism of action designed to modulate mast cells and sensory neurons, both key drivers in the neuroimmune interaction that drives lesions and intense itch in atopic dermatitis (AD)
• EVO756 is specifically designed to address the need for a safe and effective oral therapy with disease modulation and fast onset of itch relief of patients with uncontrolled disease
• AD trial is Company's second Phase 2b program evaluating EVO756; highlighting EVO756's broad potential for patients suffering from a range of chronic inflammatory diseases
• Top-line data from the Phase 2b AD trial expected in second half of 2026

PALO ALTO, Calif., Aug. 27, 2025 /PRNewswire/ -- Evommune, Inc., a clinical stage biotechnology company discovering and developing innovative therapies that target key drivers of chronic inflammatory diseases, today announced the enrollment of the first patient in a Phase 2b trial of EVO756, a highly potent and selective orally administered small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2), to assess the efficacy and safety in adults with moderate to severe atopic dermatitis (AD).  

"MRGPRX2 is one of the most important new targets in chronic inflammation, and we believe our industry leading development candidate, EVO756, has the potential to be a critically needed oral therapeutic for AD, as well as a broad range of other inflammatory diseases. We expect to have several potential clinical inflection points in 2026, as we now have two Phase 2 programs underway with EVO756 and EVO301 in AD, and continue to rapidly enroll patients in our chronic spontaneous urticaria Phase 2b trial of EVO756," said Luis Peña, Chief Executive Officer at Evommune.

Translational data generated by Evommune and others have demonstrated the increased presence of mast cells and MRGPRX2 ligands in AD diseased-tissue and lesions.  In a Phase 2 trial with chronic inducible urticaria (symptomatic dermographism) patients, Evommune observed  the role of MRGPRX2 antagonism in modulating neurogenic inflammation and mast cell activation.  Evommune believes these data further support the rationale for the initiation of this trial in AD, a disease where itch and pain phenotypes, driven by neurogenic inflammation and mast cell degranulation, and exacerbated by the itch-scratch cycle, play a key role in disease pathophysiology.

"There is still a significant need for better treatment options for AD patients, particularly for the intense itch which is the primary symptom driving patients to physicians. MRGPRX2 antagonism is exciting in its potential to change the paradigm as the first target that modulates both mast cells and sensory neurons," said Eugene Bauer, M.D., Chief Medical Officer at Evommune.

The Phase 2b trial of approximately 120 patients is a randomized, multi-center, double-blind, placebo-controlled, dose-ranging trial which will assess the efficacy and safety of EVO756 in adult patients with moderate to severe AD. Patients will be randomized to receive EVO756 or matching placebo for 12 weeks. The primary objective of this trial is to characterize the efficacy of multiple dose levels of EVO756 compared to placebo as assessed by the percentage change in Eczema Area and Severity Index (EASI) from Baseline to Week 12. A key secondary endpoint is the evaluation of Pruritus-NRS, a tool used to assess the severity of itching.

About Atopic Dermatitis
AD, commonly referred to as eczema, is one of the most prevalent chronic inflammatory diseases and is characterized by acute flares of itchy, red, exudative papules and persistently dry, scaly skin. The hallmark feature of AD is intense inflammatory itch, known as pruritus, which triggers an inflammatory cascade with mast cells and drives underlying chronic inflammation. For most moderate-to-severe AD patients, the disease significantly impacts patients' quality of life, driven primarily by relentless itch, sleep disruption and visible skin symptoms. The intense itch associated with AD often triggers an itch-scratch cycle, further compromising the epidermal barrier and exacerbating disease. While AD commonly begins in childhood, it is also highly and increasingly prevalent in adults, with about 15 percent to 20 percent of children and one percent to three percent of adults impacted, significantly disrupting their quality of life.

About Mas-related G protein-coupled receptor X2
MRGPRX2 is a G-Protein-Coupled-Receptor (GPCR) found predominantly on mast cells and peripheral sensory neurons. Mast cells are critical regulators of immune response and can be found in most vascularized tissues including skin, lung and the digestive tract. The receptor is activated by a broad spectrum of ligands that are prevalent during inflammation. Targeting MRGPRX2 may have potential across an array of chronic inflammatory diseases and play a role in mitigating neurogenic inflammation. By addressing dysregulated MRGPRX2 activity, a key driver of disease pathogenesis in numerous systemic chronic inflammatory diseases, EVO756 could offer a novel, multipronged mechanism to modulate inflammation.  This transformative therapeutic approach is initially focused on ongoing Phase 2b trials in chronic spontaneous urticaria and moderate-to-severe AD, with the potential for broader applications across many other chronic inflammatory diseases such as asthma, migraine, inflammatory bowel syndrome, interstitial cystitis, and pruritus.

About Evommune
Evommune, Inc. is a clinical-stage biotechnology company discovering and developing innovative therapies that target key drivers of chronic inflammatory diseases. The company's mission is to improve patients' daily lives and prevent the long-term effects of uncontrolled inflammation that are a consequence of the limitations of existing therapies. To achieve this, we are advancing a portfolio of differentiated product candidates that target key drivers of chronic inflammation. For more information, please visit www.evommune.com or follow us on LinkedIn.

SOURCE Evommune, Inc