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 Dermavant Sciences, 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), food allergy, and asthma.

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 HCPLive during the meeting.

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.

Dermavant Sciences 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.

References

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