Evommune's EVO756 suffers second Phase IIb setback in two months with AD miss

California-based Evommune, Inc. (NYSE: EVMN) revealed EVO756, an oral Mas-related G protein-coupled receptor X2 (MRGPRX2) antagonist, failed to meet its primary endpoint in a Phase IIb atopic dermatitis (AD) trial, the second consecutive Phase IIb failure for the molecule in as many months, ending development in the two inflammatory indications that had driven EVO756’s clinical program.

The randomized, double-blind, placebo-controlled, dose-ranging study in adults with moderate-to-severe AD enrolled 121 patients over a 12-week treatment period. The primary endpoint — percent change in Eczema Area and Severity Index (EASI) score from baseline at Week 12 — was not met at any dose studied, and no secondary endpoints were achieved. Evommune said EVO756 was generally well tolerated, with a safety profile consistent with earlier studies, but confirmed it will not advance the molecule further in AD. No numerical efficacy data were disclosed.

The result follows the Phase IIb failure in chronic spontaneous urticaria (CSU) reported in June 2026, in which EVO756 also missed its primary endpoint across all doses in 160 antihistamine-refractory patients. That failure was followed by a shareholder-law-firm investigation into insider share sales made one week before the disclosure under previously adopted Rule 10b5-1 trading plans. Together, the two failures eliminate the indications that had driven EVO756's clinical development program since Phase I, as distinct from the inducible urticaria setting where EVO756 had shown activity.

EVO756 blocks MRGPRX2, a G protein-coupled receptor found predominantly on mast cells and peripheral sensory neurons, inhibiting IgE-independent mast cell degranulation and neurogenic inflammation. The mechanism had appeared promising after a Phase II study in chronic inducible urticaria reported clinical responses in 93% of patients at four weeks and a 30% complete response rate — data that did not translate into efficacy in the larger, placebo-controlled CSU and AD studies.

Evommune is redirecting EVO756 to migraine prophylaxis, where a Phase IIb trial in adults with refractory migraine experiencing six or more migraine days per month has recently dosed its first patient. The primary endpoint is mean change from baseline in monthly migraine days over 12 weeks, with top-line data expected in 2027. In its atopic dermatitis announcement, the company said its balance sheet supports operations into 2029.

The AD program's lead now passes entirely to EVO301, Evommune's long-acting injectable IL-18 binding protein fusion protein, which reported positive Phase IIa proof-of-concept data in February 2026. That 70-patient trial met its primary endpoint, with a 33% placebo-adjusted EASI improvement at Week 12 after only two intravenous doses, and 23% of patients achieving a validated Investigator's Global Assessment score of 0 or 1. A Phase IIb AD trial using a subcutaneous formulation is planned for mid-2027. The AD field is crowded with approved biologics targeting Th2 pathways, including dupilumab and tralokinumab, and later-stage oral options including JAK inhibitors, meaning EVO301 will need to demonstrate differentiation on efficacy, safety, or patient convenience to establish a commercial rationale.

---

Spot something wrong? Report an issue with this article