Revolo Biotherapeutics is developing '1104, a first-in-class peptide derived from Mycobacterium tuberculosis Chaperonin 60.1, with the potential to revolutionize the treatment of allergic diseases by resetting the immune system. '1104 acts upstream in the inflammatory response, targeting antigen-presenting cells (APCs) and shifting the immune system from a pro-inflammatory state to a homeostatic one, potentially offering remission for allergic conditions.
Mechanism of Action
In allergic diseases, APCs identify and present antigens to the immune system, triggering inflammatory signals like interleukin 4 (IL-4) and IL-13. '1104 binds to a novel receptor on APCs, reducing IL-4 and IL-13 signaling by activating SHP-1, a molecule that helps turn off these inflammatory signaling pathways. This prevents the activation of T and B effector cells and reduces the effects of Th2 inflammatory cells. Additionally, '1104 increases the number of activated regulatory T and B cells, modulating the immune response and maintaining immune tolerance.
Comparison with Traditional Therapies
Traditional therapies for allergic diseases, such as corticosteroids, antihistamines, or biologics, primarily target inflammation after it has already set in, addressing only the downstream effects. This can lead to inadequate long-term effectiveness and potential side effects. In contrast, '1104 restores immune homeostasis by uniquely influencing both the effector and regulatory components of the immune response, without suppressing the immune system.
Preclinical and Clinical Findings
Preclinical studies have validated '1104's mechanism of action, demonstrating its effectiveness in treating eosinophilic esophagitis (EoE) and other Th2 allergic diseases such as asthma and atopic dermatitis. A short course of '1104 treatment effectively prevents inflammatory cell infiltration and cytokine release, with effects lasting for several weeks. In a Phase IIa clinical trial for EoE, '1104 reduced eosinophil counts in the esophagus, increased regulatory B cells (Bregs) and T regulatory cells (Tregs), and significantly reduced pro-inflammatory CD4+ and CD8+ T cells. The treatment also normalized 15 key EoE-related genes affecting inflammation, cell adhesion, and epithelial lining. Safety assessments revealed no safety signals, serious adverse events or drug discontinuations, and treatment resulted in a significant improvement in clinical symptoms, including patient-reported dysphagia, compared to placebo.
Potential Beyond EoE, Asthma, and Atopic Dermatitis
Given its antigen-agnostic nature and immune resetting mechanism, '1104 has the potential to address unmet needs in allergic diseases beyond EoE, asthma, and atopic dermatitis, such as food allergies and other eosinophilic gastric disorders. By acting upstream in the inflammatory cascade, '1104 can broadly modulate immune responses, leading to better symptom control and potentially fewer flare-ups with less frequent administration compared to current therapies.
Woody Bryan, CEO of Revolo Biotherapeutics, expressed excitement about advancing '1104 for the treatment of multiple diseases, both internally and in collaboration with partners, citing its significant potential to meet the large unmet needs in Th2-driven diseases.
