In a recent interview, we spoke with Kari Brown, Chief Medical Officer, and Woody Bryan, Chief Executive Officer, from Revolo, about their innovative approach to treating allergic and autoimmune diseases. We discussed their lead candidate, ‘1104, clinical trial outcomes, and the implications for chronic disease management.
Moe Alsumidaie: How does Revolo’s approach reshape treatment for allergic and autoimmune diseases?
Kari Brown: Our approach at Revolo focuses on restoring immune system homeostasis rather than suppressing it. Traditional therapies often target diseases downstream after inflammation has occurred and typically do not affect the regulatory arm of the immune system. This limits opportunities for disease modification or sustained effects post-treatment. The need for broader mechanisms of action is highlighted by the recent trial of Benralizumab in eosinophilic esophagitis (EoE). Benralizumab did not improve patient-reported outcomes despite effectively depleting eosinophils.. Our candidate, ‘1104, acts higher in the immune cascade, offering a more comprehensive impact beyond just eosinophils. Our Phase 2A study in EoE showed a significant reduction in eosinophils in esophageal tissue, our
primary endpoint. Additionally, we saw improvements in patient-reported outcomes using the Dysphagia Symptom Questionnaire, a key measure in EoE trials. This dual impact on histological and patient-reported outcomes is key and promising in this therapeutic area.
Moe Alsumidaie: What does ‘1104’s success in EOE signal for broader applicability?
Kari Brown: We’ve considered this extensively and identified atopic dermatitis as our next target after EoE. Both conditions involve chronic allergic inflammation, and we have positive efficacy data from EoE that we believe will translate well. Additionally, our preclinical data in atopic dermatitis is supportive. The broader impact of ‘1104 on CD8 and CD4 T regulatory and B regulatory cells suggests potential across multiple TH2 diseases. This broad mechanism of action allows us to consider multiple indications, but we chose atopic dermatitis due to its similarities with EoE, both disease involve a compromised epithelial barrier function, and the existing preclinical support. The decision also factors in the current treatment landscape and the clinical development program’s feasibility. We believe that targeting these mechanisms can offer new hope to patients suffering from these chronic conditions.
Moe Alsumidaie: Why focus on dosing flexibility with subcutaneous and sublingual options?
Woody Bryan: Despite being a peptide, ‘1104 can be delivered intravenously, subcutaneously, and sublingually. This flexibility is significant compared to monoclonal antibodies, which are typically limited to subcutaneous delivery due to their size and chemistry. Our subcutaneous formulation shows persistent pharmacodynamic effects, potentially allowing for less frequent dosing, such as bi-weekly or even longer intervals. The sublingual option is particularly exciting for EoE, where oral options are limited to steroids, which have safety concerns with chronic use. While oral JAK inhibitors exist in atopic dermatitis, they come with black box warnings. Our sublingual formulation could offer a safer,
more convenient alternative, potentially improving patient adherence and transforming chronic disease management. This dosing flexibility enhances patient convenience and broadens the potential applications of ‘1104 across various conditions.
Moe Alsumidaie: What excites you most about ‘1104’s research and its potential impact?
Woody Bryan: The ability to broadly impact the immune system while maintaining a clean safety profile is exciting. We’ve treated nearly 150 individuals with ‘1104 without safety signals, even at higher doses. This broad impact and safety are unique in the immune space. The flexibility in dosing also broadens treatment options, potentially setting a new standard in managing these diseases. Unlike steroids, which are effective but come with significant safety concerns, ‘1104 offers a targeted approach with a promising safety profile. This could revolutionize how we approach treatment in allergic and autoimmune diseases, providing effective and safe options for patients. We are optimistic that ‘1104 will set a new benchmark in immunology, offering a novel solution to patients who have long-awaited safer and more effective treatments.
Moe Alsumidaie: How do you select additional indications for ‘1104 studies?
Woody Bryan: We consider scientific and clinical rationale, development timelines, and unmet needs. For instance, as previously discussed, atopic dermatitis is a logical next step due to its similarities with EoE and our supportive preclinical data. We also have promising preclinical data in allergic airway models and IgE-mediated food allergy, suggesting broad potential across TH2 diseases. The current treatment landscape and the feasibility of a clinical development program plays a role in our decision-making process for indication expansion. By carefully evaluating these factors, we aim to maximize the impact of ‘1104 across a range of conditions, ultimately improving patient outcomes.
Moe Alsumidaie: What are the anticipated regulatory milestones and production plans for ‘1104?
Kari Brown: We aim to start a larger Phase 2 trial in EOE next year, focusing on subcutaneous dosing. This trial will explore higher doses and longer treatment durations in a larger cohort, preparing us for a Phase 3 program. We also plan to enter the clinic with atopic dermatitis. For scaling, we’ve improved our peptide synthesis process for better purity and scalability, and our sublingual platform has proven robust in other applications. We’re well-prepared for scaling both drug substance and product, ensuring we can meet the demands of commercialization if and when the time comes. Our proactive approach to scaling and regulatory planning positions us well to bring ‘1104 to market, with the potential to offer new hope to patients with chronic allergic and autoimmune diseases.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.