Pipeline
‘1104
Potential Platform to Treat Allergic Diseases
‘1104 is a novel linear peptide, derived from a natural immune-regulatory protein, Mycobacterium tuberculosis Chaperonin 60.1, involved in resetting the immune system. It may provide remission for many allergic diseases. ‘1104 engages a novel target on macrophages and is a first-in-class modulator of the macrophage response. This response engages not only the effector arm of the immune system, but the regulatory arm as well.
We are developing ‘1104 for the treatment of patients with eosinophilic esophagitis (EoE) and other Th2 allergic diseases, including asthma and atopic dermatitis.
Eosinophilic Esophagitis
EoE is a progressive allergic disease characterized by difficulty swallowing (dysphagia) and gastric reflux as a result of elevated numbers of inflammatory immune cells, including eosinophils, in the walls of the esophagus. Roughly 180,000 children and adults in the US have EoE1, and up to 80% of patients have secondary allergic conditions.2 Early disease control is critical to avoid thickening of the tissue of the esophagus, associated with disease progression.
Current treatment options include dietary management and medications, such as steroids and biologics, that target inflammatory pathways after the immune system has been overactivated. Steroid treatments require frequent dosing and are often associated with unwanted side effects, such as immune suppression. While some existing treatments are able to reduce eosinophil levels and improve symptoms, they do not address the complex physiopathology of EoE and don’t work for everyone, leaving many patients in need of other options.
A Phase 2a clinical trial evaluating ‘1104’s efficacy, safety and tolerability showed a statistically significant improvement in patient-reported dysphagia symptoms compared to placebo. It also met its primary endpoint with a reduction in the eosinophil cell counts in the walls of the esophagus.3 The data confirmed ‘1104’s broad mechanistic effect across a range of key immune cell types associated with EoE, a key differentiator from other therapies. ‘1104 led to an increase in regulatory B cells (Bregs) and T regulatory cells (Tregs), which are key immune cells associated with immune suppression and self-tolerance. Additionally, ‘1104 caused a statistically significant reduction in pro-inflammatory CD4+ and CD8+ T cells and a normalization of 15 key EoE genes considered to affect remodeling, eosinophil and mast cell count, inflammation, cell adhesion, and the epithelium lining. Safety assessment showed no serious adverse events and there were no study drug discontinuations due to drug-related adverse events.
A Phase 2b trial investigating ’1104 in EoE is anticipated to begin in 2024.
Allergic Diseases
People with allergic diseases often experience symptoms even during treatment with currently available products. For more than 50 years, the number of people with allergic diseases has been rising and continues to climb.4
Recent clinical research across multiple allergic diseases has underscored the significance of targeting upstream pathways in the immune cascade, rather than focusing solely on single cytokines or immune cell types like eosinophils.
Given ‘1104’s immune resetting mechanism, antigen-agnostic nature, and clinical data observed in trials to date, we believe ‘1104 has the potential to work across a number of allergic disease indications beyond EoE.
- Asthma: There is a significant unmet need for the more than 25 million patients living with asthma in the U.S., including 1 million with uncontrolled moderate to severe Th2 and non-Th2 forms of the disease.5,6
- Food Allergy: Approximately 26 million people in the US7 are affected by food allergies, highlighting the critical demand for new advancements and readily available treatments.
- Atopic Dermatitis: An estimated 9 million individuals live with atopic dermatitis in the U.S.8,9, with many patients remaining untreated. Novel upstream mechanisms are crucial for addressing the needs of this patient population.
- Other Eosinophilic Gastric Disorders: There is a pressing need for innovative treatments for the large number of patients suffering from other eosinophilic gastric disorders beyond EoE, many of whom are thought to be undiagnosed.
- Other Th2 Diseases: Beyond asthma and atopic dermatitis, the development of novel therapies is essential for addressing the spectrum of Th2-driven diseases. This includes conditions such as chronic rhinitis with nasal polyps, chronic spontaneous urticaria, and prurigo nodularis.
A proof-of-concept Phase 2 study in an additional Th2 allergic indication will be started in 2024.
‘1104 Publications
REFERENCES
- Moawad FJ. Eosinophilic esophagitis: incidence and prevalence. Gastrointest Endosc Clin N Am. 2018;28(1):15-25.
- Wechsler JB, Bryce PJ. Allergic mechanisms in eosinophilic esophagitis. Gastroenterol Clin North Am. 2014;43(2):281-296.
- Company press release: https://revolobio.com/2023/07/18/revolo-biotherapeutics-announces-additional-data-from-phase-2a-trial-of-1104-in-adults-with-active-eosinophilic-esophagitis/
- Pawankar R, Canonica GW, Holgate ST, Lockey RF, Blaiss MS, eds. WAO White Book on Allergy: Update 2013. Executive Summary. Milwaukee, WI: World Allergy Organization; 2013. https://www.worldallergy.org/UserFiles/file/ExecSummary-2013-v6-hires.pdf. Accessed May 4, 2021.
- Centers for Disease Control and Prevention. Uncontrolled Asthma in Adults. Accessed on February 6, 2024: https://www.cdc.gov/asthma/asthma_stats/uncontrolled-asthma-adults.htm
- Holgate S, Wenzel S, Postma D, et al. Asthma. Nat Rev Dis Primers. 2015;1:15025.
- Gupta RS, Warren CM, Smith BM, et al. Prevalence and Severity of Food Allergies Among US Adults. JAMA Netw Open. 2019;2(1):e185630. doi:10.1001/jamanetworkopen.2018.5630
- Asthma and Allergy Foundation of America (AAFA) AD Prevalence study. Accessed January 30, 2024. https://aafa.org/wp-content/uploads/2022/08/Atopic-Dermatitis-in-America-Study-Overview.pdf
- Endpoints News. Regeneron has a winner in Dupixent and big sales hopes. Accessed February 6, 2024. https://endpts.com/regeneron-has-a-winner-in-dupixent-and-big-sales-hopes-so-why-are-so-few-patients-taking-it/