Evommune (EVMN) Status update summary

Pipeline and program overview

• Two programs are in phase II development, targeting chronic inflammation and autoimmune diseases, with positive data in MRGPRX2 for urticaria and ongoing trials in chronic urticaria and atopic dermatitis.

• A new trial in migraine is about to be initiated, leveraging the MRGPRX2 antagonist EVO756, with the aim to address a large, underserved chronic migraine population.

• The IL-18 program is advancing into phase IIb, showing compelling phase IIa data and potential broad applicability.

Scientific rationale and unmet need in migraine

• MRGPRX2 is expressed in both mast cells and sensory neurons, playing a key role in neuroimmune communication and inflammation.

• Migraine affects over 75 million people worldwide with a significant unmet need for more effective and tolerable preventive therapies.

• Current CGRP therapies provide only modest benefit, with about 50% of patients achieving a 50% reduction in migraine days, highlighting the need for new targets.

Clinical and mechanistic insights

• MRGPRX2 (X2) is positioned at the intersection of meningeal mast cells and trigeminal sensory neurons, mediating signaling from migraine-associated neuropeptides (PACAP, VIP, Substance P).

• Knockout studies in mice and human data support X2’s functional role in migraine, with PACAP, VIP, and Substance P all inducing migraine-like symptoms.

• Blocking X2 may disrupt the neuroinflammatory cycle underlying migraine, offering a broader mechanism than targeting single ligands.