Geoff Harris, PhD

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

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 

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 

 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.

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

Articles

Allergic effector cell response inhibitors (ECRIs) offer a novel therapeutic approach for chronic spontaneous urticaria (CSU) and other IgE-mediated conditions by targeting the entire IgE signaling pathway. Unlike traditional therapies, ECRIs remove IgE from mast cells and basophils, neutralize circulating IgE, and downregulate the FcεRI receptor. This tri-functional mechanism may modify disease activity by disrupting IgE-driven signaling. Excellergy plans a phase 1 clinical trial in 2026 to evaluate ECRIs' safety and efficacy, with potential applications in food allergies and asthma subsets.

At ACAAI 2025, Harris spoke with HCPLive about Excellergy’s ECRI program, exploring IgE modulation, safety goals, and potential long-term effects in CSU.

ECRIs Introduce a Novel Approach to Disarming Allergic Effector Cells, With Geoff Harris, PhD

At the 2025 American College of Allergy, Asthma & Immunology (ACAAI) Annual Meeting

Geoff Harris, PhD, of Excellergy, discussed emerging research on a new therapeutic approach known as allergic effector cell response inhibitors (ECRIs) and how this mechanism could influence the treatment of IgE-mediated diseases such as chronic spontaneous urticaria (CSU), 

Harris explained that ECRIs represent a distinct way of targeting the IgE axis compared with existing agents.

“Instead of just reducing reactivity, you basically make these cells almost unable to respond to allergen,” Harris told 

Existing and investigational therapies primarily target free IgE, intercepting it before it binds to mast cells or basophils through the Fc epsilon receptor. This approach effectively prevents new cell activation but has little impact on cells that are already armed with IgE.

“That's why existing drugs are fairly slow to act for patients and give them clinical benefit,” Harris said.

ECRIs function through a tri-functional mechanism: they remove IgE bound to the surface of effector cells, neutralize free IgE, and downregulate the expression of the FcεRI receptor. By addressing each component of the allergic signaling process, these agents may substantially limit the ability of effector cells to respond to allergens.

“Unlike previous approaches, where people have tried to just block IGE binding to the receptor that drives the arming of mast cells, we looked at it to comprehensively say, ‘How can we not only do that, but systematically disarm that cells?’” Harris said. “And so, an ECRI…an allergic effector cell response inhibitor, is really designed to systematically disarm them.”

A recent publication in the Journal of Clinical Investigation (JCI)

supported this approach, showing that ECRIs could reliably remove IgE from cell surfaces without triggering activation. Harris noted that this validation demonstrates a more comprehensive way to inhibit IgE activity, which may translate to faster and more consistent responses in patients compared with currently available therapies.

Excellergy plans to move its lead ECRI candidate into phase 1 clinical development in early 2026, with a study focused on safety, exposure, and biomarker measures of target modulation.

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At ACAAI 2025, Harris discussed research on novel mechanism known as allergic effector cell response inhibitors.