Phase 2 Trial Begins for EVO756 in Chronic Inducible Urticaria

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Evommune, Inc. announced today the commencement of a phase 2 clinical trial for EVO756, an emerging therapeutic option for Chronic Inducible Urticaria (CIndU). The company stated the first patient has been enrolled in this trial, which marks a step forward in the development of targeted therapies for this challenging condition.¹ Evommune's phase 1 study earlier this year marked the first-in-human study of EVO756.²

EVO756 is a novel, highly selective small molecule antagonist targeting themas-related G-protein coupled receptor X2 (MRGPRX2). According to Evommune, this receptor is predominantly expressed on mast cells and peripheral sensory neurons. Activation of MRGPRX2 has been implicated in a range of mast cell-driven disorders, includingCIndU. By inhibiting this receptor, EVO756 aims to offer a more targeted approach to treatment with the potential for once-daily oral administration, minimizing the severe adverse eventsoften associated with existing therapies.

“As we continue to execute on our clinical development plans for EVO756, we are commencing this phase 2 trial in 15 study sites across the United States. CIndU patients have limited treatment options, and we believe a novel, highly potent, selective agent, that can be orally administered once daily, could provide patients with major therapeutic benefit,” said J. Mark Jackson, MD, vice president, clinical development at Evommune, in a press release.

Trial Design and Objectives

Evommune stated the phase 2 trial will take place across 15 study sites in the US and will involve approximately 30 patients with symptomatic dermographism or cold urticaria, 2 prevalent forms of CIndU. The primary endpoints will measure changes in disease-specific provocation thresholds, which serve as objective markers for disease severity and treatment response. Study participants will receive EVO756 orally once daily for a 4-week period. Weekly evaluations will monitor both safety and efficacy, with each patient serving as their own control to provide comparative data. 

"Initiation of this trial marks another important milestone in dedication to delivering the therapeutic potential of MRGPRX2 antagonism to patients in a broad range of mast cell mediated disorders," said Daniel J. Burge, MD, senior vice president, clinical development at Evommune, in a press release. "Following the success of our proof-of-concept study with EVO756 earlier this year, we are also on track to initiate a phase 2b trial in chronic spontaneous urticaria in the second quarter of 2025."

Understanding Chronic Urticaria

Chronic urticaria symptoms include intense itching, hives of varying sizes, and, in some cases, angioedema, which involves deeper skin swelling. The condition can lead to considerable emotional distress, sleep disruption, and social isolation. Chronic urticaria is classified into 2 main types: chronic spontaneous urticaria (CSU), which occurs without obvious triggers, and CIndU, where symptoms are triggered by specific stimuli such as cold exposure or physical touch.

Mast cells play a central role in both types of chronic urticaria by releasing histamine and other mediators that contribute to the symptoms of the disease. EVO756’s mechanism of action involves blocking MRGPRX2, thereby preventing mast cell degranulation and mitigating these symptoms.In addition, due to its unique function on peripheral sensory neurons, EVO756 could provide fast relief of itch associated with inflammatory diseases, such as atopic dermatitis.

Conclusion

The company stated the development of EVO756 represents a promising advancement in the treatment of CIndU and other mast cell-related disorders. With its targeted approach and potential for improved patient compliance due to its oral administration, EVO756 could offer a significant new option for managing chronic urticaria and enhancing patient quality of life.

References

1. Evommune. Evommune initiates phase 2 trial of EVO756, an oral MRGPRX2 antagonist, in chronic inducible urticaria. Evommune. Published September 3, 2024. Accessed September 3, 2024. https://www.evommune.com/wp-content/uploads/2024/09/21_Evommune_EVO756_CindU_Phase_2_Trial.pdf
2. Evommune. Evommune announces initiation of a phase 1 trial of its MRGPRX2 antagonist for the treatment of chronic spontaneous urticaria. PR Newswire. January 18, 2024. Accessed September 3, 2024. https://www.prnewswire.com/news-releases/evommune-announces-initiation-of-a-phase-1-trial-of-its-mrgprx2-antagonist-for-the-treatment-of-chronic-spontaneous-urticaria-302037378.html#:~:text=PALO%20ALTO%2C%20Calif.%2C%20Jan,adults%20and%20adults%20with%20chronic