Q&A: Peptide resets immune system to treat eosinophilic esophagitis

Key takeaways:

• Revolo Biotherapeutics’ ‘1104 is designed to reset the immune system “upstream” before the inflammatory cascade occurs.
• Intraepithelial eosinophil counts fell among patients on ‘1104 compared with placebo.

Patients with eosinophilic esophagitis taking a first-in-class peptide during a phase 2a randomized, double-blind clinical trial safely experienced reductions in esophageal intraepithelial eosinophil count, according to a press release.

The placebo trial involved two groups of adults with eosinophilic esophagitis (EoE) with 12 patients each taking different doses of ‘1104 (Revolo Biotherapeutics) and a third group of 12 patients taking a placebo. All three groups received doses intravenously once a week for 3 weeks, with a full treatment period of 4 weeks or 30 days.

According to Revolo, ‘1104 is derived from mycobacterium tuberculosis chaperonin 60.1, a natural immune-regulatory protein that is involved in resetting the immune system.

The treatment groups had dose-dependent numeric reductions from baseline in their peak intraepithelial eosinophil count compared with the placebo group, in addition to positive results in other biologic measures believed to be key drivers of EoE, Revolo said.

Specifically, Revolo noted increases in regulatory B cells and regulatory T cells that suppress inflammatory immune responses, which have not been reported for any other mechanism in EoE.

An EoE-specific gene expression panel showed positive changes in the expression of key genes related to EoE in the treatment group as well, Revolo continued.

Additionally, there were no serious adverse events or study drug discontinuations due to adverse events, nor was there any increase in overall adverse event rates among the treatment group compared with the placebo group.

Healio spoke with Roly Foulkes, PhD, chief scientific officer at Revolo, to find out more.

Healio: What impact does EoE have on quality of life among patients who have it?

Foulkes: EoE is an allergic inflammatory disease in which eosinophils, a type of white blood cell, are found in the tissue of the esophagus. It is characterized by difficulty swallowing and gastric reflux as a result of the thickening of the esophagus walls. In many cases, patients experience difficulty eating, poor weight gain, heartburn, regurgitation and dysphagia, resulting in a significant negative impact to quality of life. Approximately 80% of patients with EoE also suffer from secondary allergic diseases.

Healio: What is the current treatment for EoE? How does ‘1104 improve upon current treatment?

Foulkes: 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. The first drug for EoE-specific management was recently approved and works to inhibit part of the inflammatory pathway.

Roly Foulkes

What is unique about ‘1104’s mechanism of action is that it works to reset the immune system “upstream” or before the inflammatory cascade has occurred. As a result, ‘1104 is able to act more broadly to reduce inflammation. It has been shown to increase the number of cells that naturally regulate the immune system, thereby avoiding chronic inflammation without suppressing the immune system.

This is key, as EoE is not just caused by eosinophils. The disease pathology is much more complex and involves several additional inflammatory factors, including cytokines, monocytes, B cells, T cells and mast cells. The medical community needs further treatment options that increase efficacy and reduce side effects for patients.

Healio: Could you summarize ‘1104’s treatment safety and effectiveness?

Foulkes: Data from our phase 2 trial in EoE, in addition to previous phase 1 studies with ‘1104, have shown a favorable safety and tolerability profile with no serious adverse events to date. Revolo continues to analyze the full dataset from this proof-of-concept study to identify an array of histological measures known to be key drivers of EoE. The company plans to present specific data around safety and effectiveness at an upcoming scientific meeting later this year.

Healio: What impact do these improved outcomes have on quality of life?

Foulkes: The phase 2a clinical trial in EoE proved that in addition to being safely tolerated, ‘1104 reduced the esophageal intraepithelial eosinophil count and had a positive impact on an array of histological measures of EoE. To truly determine the impact of these improved outcomes on quality of life, further clinical evaluation of ‘1104 is required. That said, based on these initial data, I believe ‘1104 has good potential to positively impact the quality of life for patients.

Healio: The study population was all adults. Do you expect to eventually extend the treatment to children?

Foulkes: The current focus is on the adult population, but there is a large unmet need in children as well, considering EoE occurs in 1 out of 1,500 children. Expansion into this population will be considered in due course.

Healio: What is the next step in this research?

Foulkes: We are currently planning to initiate the next stage of clinical development later this year.

Reference:

• Revolo Biotherapeutics announces positive topline data from phase 2a trial of ‘1104 in adults with active eosinophilic esophagitis. https://revolobio.com/2023/04/19/revolo-biotherapeutics-announces-positive-topline-data-from-phase-2a-trial-of-1104-in-adults-with-active-eosinophilic-esophagitis/. Published April 19, 2023. Accessed April 19, 2023.