Revolo Validates Upstream Mechanism and Subcutaneous Use of '1104' with New Data

Revolo Biotherapeutics Limited has announced new data from preclinical studies and completed clinical trials that highlight the mechanism of action (MOA) of their drug candidate, ‘1104. This candidate uniquely influences both the effector and regulatory arms of the immune system, offering significant potential for treating allergic diseases.

The data indicate that ‘1104 binds to a novel receptor by selectively targeting allergic antigen-presenting cells (APCs), leading to a reduction in key proteins in the interleukin 4 (IL-4) and IL-13 signaling pathways through SHP-1 activation. This action results in the rapid upregulation of activated T regulatory (Tregs) and B regulatory cells (Bregs) for several weeks, promoting immune homeostasis and supporting less frequent dosing regimens.

Additional animal studies have demonstrated that a subcutaneous (SC) dosage form of ‘1104 is as effective as intravenous administration. This finding supports the continued development of a differentiated SC commercial formulation, with plans to initiate bridging clinical studies in 2025.

Kari Brown, Executive Vice President of Clinical Development, Operations and Strategy at Revolo, expressed the unmet need for therapies that can effectively translate tissue-level eosinophil reduction into significant clinical responses. She noted that ‘1104’s engagement of upstream signaling pathways shows its ability to interact with both effector and regulatory arms of the immune response, highlighting its potential to treat a variety of allergic diseases.

Woody Bryan, President and CEO of Revolo, emphasized the company's priority in developing a patient-friendly and differentiated product for allergic diseases. He mentioned that SC administration of ‘1104 would improve patient convenience and that the company is also exploring sublingual administration based on promising animal data.

Previously announced positive data from clinical trials underscore the potential of ‘1104. In a Phase 2a trial (RVLO 121-04) involving adults with active eosinophilic esophagitis (EoE), treatment with ‘1104 resulted in a statistically significant improvement in key clinical endpoints and rapid clinical response according to the Dysphagia Severity Questionnaire (DSQ). This evidence suggests that ‘1104’s upstream MOA offers a first-in-class treatment modality that overcomes the limitations of other downstream approaches, which have struggled to show clinical response despite impacting histologic endpoints.

Another Phase 2a trial (RVLO 121-05) involving allergic individuals subjected to nasal and skin allergen challenges demonstrated a rapid reduction in intradermal allergic inflammation by the first day and sustained activation of Tregs and Bregs for at least 28 days, providing further clinical validation of its MOA.

‘1104 is a pioneering peptide aimed at restoring immune balance. Revolo has progressed ‘1104 through two Phase 2a trials, one for patients with eosinophilic esophagitis (EoE) and another for individuals with allergen sensitivity. The company plans to advance a commercially differentiated SC dosage form into clinical studies for EoE and other type 2 allergic conditions.

Revolo Biotherapeutics is committed to developing therapies that operate upstream in the immune cascade for autoimmune and allergic diseases, avoiding the immune suppression characteristic of current treatments. Their two drug candidates, ‘1805 and ‘1104, aim to restore immune homeostasis to prevent chronic pro-inflammatory responses associated with autoimmune or allergic conditions. The disease-agnostic MOA of these assets provides a potential platform for treating multiple autoimmune and allergic diseases.