ECRIs Potential for Long-Term Disease Modification in CSU, With Geoff Harris, PhD

At the 2025 American College of Allergy, Asthma & Immunology (ACAAI) Annual Meeting in Orlando, Florida, Geoff Harris, PhD, of Excellergy, discussed how allergic effector cell response inhibitors (ECRIs) could influence long-term disease activity in chronic spontaneous urticaria (CSU) and other IgE-mediated conditions.

ECRIs represent a new therapeutic approach that differs from traditional IgE-targeting therapies. While current agents neutralize free IgE to prevent binding to effector cells, ECRIs are designed to address the entire IgE signaling pathway. These agents remove IgE already bound to mast cells and basophils, neutralize circulating IgE, and downregulate the FcεRI receptor on effector cells.

This tri-functional mechanism may provide a broader means of interrupting IgE-driven signaling and chronic allergic activation. According to Harris, this approach could dampen the feedback loop that promotes continued IgE production and rearming of effector cells.

“A wonderful speculation, is: could this indeed be not only treating disease, but can it be disease modifying? I think that's something that we'll find out in the clinic over time. Conceptually, this allows a really comprehensive disarming of the system, such that you may be able to change the trajectory of people's overall underlying immune response that continues to potentiate the production of IGE and the rearming of the system,” Harris told HCPLive during an on-site interview. “This may… be really effective at draining the energy out of that side of the pathophysiology of CSU, and if it does…it could be quite disease modifying.”

Excellergy plans to initiate a phase 1 clinical study in early 2026 to evaluate the safety, exposure, and pharmacodynamic effects of its lead ECRI candidate. The trial will measure changes in basophil and mast cell activation, as well as free and total IgE levels, to assess target engagement and confirm that disarming effects occur without unwanted activation.

Beyond CSU, Excellergy anticipates potential applications in food allergy and certain asthma subsets, where IgE plays a central role. In food allergy, for example, further research may determine whether combining IgE suppression with oral immunotherapy (OIT) enhances tolerance outcomes. Data from early trials will help determine whether ECRIs can achieve consistent modulation of IgE-mediated pathways and inform their role in the future management of allergic disease.

“Until we get into the clinic, we won't know where [this mechanism] falls on a continuum of mostly treating disease versus being profoundly disease modifying, but I think the reality is somewhere in between those two,” Harris said.

References

Harris, G. Validating the trifunctional mechanism of action (MOA) of Effector Cell Response Inhibitors, or ECRIs. Presented at ACAAI 2025 in Orlando, Florida.