Selective modulation of a key mast cell receptor.

MRGPRX2 Antagonist

Mas-related G-protein coupled receptor X2 (MRGPRX2) is most abundantly found on mast cells and may also be expressed on peripheral sensory neurons. Mast cells are the primary effector cells that drive a variety of inflammatory diseases, and targeting mast cells via the selective modulation of MRGPRX2 represents a novel therapeutic approach that may deliver biologic-like efficacy with the accessibility and administration of a small molecule.

Blocking MRGPRX2 has the potential to be a first-in-class oral treatment for a variety of mast cell-mediated diseases, including chronic spontaneous urticaria. In addition, due to its unique function on peripheral sensory neurons, blocking MRGPRX2 could provide fast relief of itch associated with inflammatory diseases, such as atopic dermatitis.

EVO756 is currently being evaluated in several areas of high unmet need:

  • Chronic Spontaneous Urticaria: Driven by underlying mast cell activity, these patients will develop inflamed lesions nearly every day, occurring on any part of their body. Current treatments offer only symptomatic relief. Blockade of the MRGPRX2 receptor and its subsequent downstream effects provide a novel target for the treatment of this pathology.

  • Inflammatory Itch: This type of chronic itch, also known as pruritus, is a major symptom of many chronic inflammatory conditions. Increased understanding in the neuroimmunology of pruritus provides support for MRGPRX2 as a key receptor driving the release of a wide variety of itch-causing cytokines that are highly upregulated in inflammatory conditions. Treatment of pruritus is challenging, and currently, only limited, short-term, symptomatic relief is available to patients.

We have a range of chronic inflammatory disease programs currently in development.