Evommune's Oral MRGPRX2 Antagonist EVO756 Fails Phase 2b in Atopic Dermatitis, Program Halted
核心洞察
Evommune's oral MRGPRX2 (搜索) antagonist EVO756 missed both primary and secondary endpoints across all doses in a 121-patient Phase 2b atopic dermatitis (搜索) trial.
The company will not advance EVO756 in atopic dermatitis (搜索) but continues Phase 2b development of the drug in migraine (搜索) prophylaxis, with topline data expected in 2027.
Evommune's IL-18BP fusion protein EVO301, which generated positive Phase 2a proof-of-concept data, becomes the lead atopic dermatitis (搜索) program with a Phase 2b trial planned for mid-2027.
Evommune Inc. (搜索) reported that its oral Mas-related G-protein coupled receptor X2 (MRGPRX2 (搜索)) antagonist EVO756 failed to meet the primary and secondary endpoints of a randomized, double-blind, placebo-controlled dose-ranging Phase 2b trial in adults with moderate-to-severe atopic dermatitis (搜索). Based on the top-line results, the clinical-stage biotechnology company does not plan to advance EVO756 in atopic dermatitis.
The trial enrolled 121 adults with moderate-to-severe atopic dermatitis (搜索) over a 12-week treatment period, with follow-up through week 14. The drug candidate did not achieve its endpoints in any of the doses studied.
"We are disappointed that this clinical trial of EVO756 did not meet its primary endpoint, particularly given the need for new treatment options for patients suffering from atopic dermatitis (搜索)," said Dr. Eugene Bauer, chief medical officer of Evommune. "EVO756 was generally well tolerated with a safety profile consistent with prior studies, supporting its continued evaluation in migraine (搜索) prophylaxis. We are sincerely grateful to the patients, clinicians and administrators who participated in this clinical trial."
Luis Peña, president and chief executive officer at Evommune, framed the result against the company's broader pipeline. "This clinical trial did not deliver the outcome we and the atopic dermatitis (搜索) community were hoping for," he said. "We continue to work towards bringing meaningful clinical benefit to atopic dermatitis patients, and importantly, EVO301, our IL-18BP fusion protein, which recently generated positive phase 2a proof-of-concept data, will enter a phase 2b trial planned for mid-2027. With a strong balance sheet supporting operations into 2029, we remain focused on advancing a portfolio of programs with the stated goal of broadly addressing chronic inflammatory diseases."
Migraine Program Continues
EVO756 is a first-in-class, potent and highly selective oral small molecule antagonist of MRGPRX2 (搜索), a receptor predominantly found on mast cells and peripheral sensory neurons. Evommune has sought to produce the first MRGPRX2-targeted oral treatment for chronic inflammatory diseases.
The company will continue Phase 2b development of EVO756 in migraine (搜索) prophylaxis. In July, Evommune dosed the first patient in that Phase 2b trial, which is evaluating the drug in adults with refractory migraine experiencing six or more migraine days per month. Approximately 330 patients will be randomized across two active dose arms and placebo for 12 weeks of treatment, with daily doses of up to 100 mg explored. Topline data are anticipated in 2027.
EVO301 Becomes Lead Atopic Dermatitis Asset
With the EVO756 setback, EVO301 advances as the company's lead atopic dermatitis (搜索) program following positive Phase 2a proof-of-concept data. EVO301 is a long-acting injectable SAFA-IL-18BP fusion protein designed to neutralize aberrantly upregulated IL-18 (搜索) activity.
According to Evommune, EVO301 facilitates more efficient tissue distribution and improved binding affinity and specificity relative to existing attempts to antagonize or inhibit the IL-18 (搜索) pathway, including traditional monoclonal antibodies. The candidate incorporates selective and high binding affinity of native human IL-18BP, binding to serum albumin, a smaller molecular weight, an extended half-life for the neutralization of IL-18, and lower potential for immunogenicity. The company believes the distinct mechanism and modality of EVO301 provides multiple, potentially synergistic avenues to bring innovative therapeutics to the large, underserved and rapidly expanding population of patients suffering from chronic inflammatory diseases.
Analyst Reaction and Market Response
Analysts were not entirely surprised by the outcome. "We are not surprised by the negative result in AD given the failure of EVO756 in CSU, which we believe had more mechanistic support for the MRGPRX2 (搜索) targeting mechanism of action than AD," William Blair wrote on Wednesday. Analyst Matt Phipps maintains a Market Perform rating on Evommune shares.
Evommune shares were down 10.55% at $11.70 during premarket trading on Wednesday, according to Benzinga Pro data.
Evommune describes its mission as improving patients' daily lives and preventing the long-term effects of uncontrolled inflammation that result from the limitations of existing therapies. To that end, the company is advancing a portfolio of differentiated product candidates targeting key drivers of chronic inflammation.