In an interview with PharmaShots, Jonathan Rigby, Group Chief Executive Officer at Revolo Biotherapeutics shared his views on the unique mechanism of ‘1104 and discuss the plan of the company’s clinical studies.
- Revolo reported the US FDA’s approval to initiate a P-II clinical trial evaluating the safety and efficacy of ‘1104 in adults with EoE
- ‘1104 is a naturally derived, first-in-class immune-regulatory peptide for allergic disease. In pre-clinical studies, a single dose of ‘1104 increased cells that control inflammation & reduced levels of eosinophils & other inflammatory cells without immunosuppression, showcasing its unique potential to change the treatment landscape for EoE
- EoE is a progressive rare allergic disease characterized by difficulty swallowing and gastric reflux, because of elevated numbers of inflammatory immune cells in the esophagus wall
Tuba: What is Eosinophilic Esophagitis (EoE)?
Jonathan: EoE is a progressive rare allergic disease characterized by difficulty swallowing and gastric reflux, as a result of elevated numbers of inflammatory immune cells in the esophagus wall. Roughly 180,000 children and adults in the US have EoE, and up to 80% of patients have secondary allergic conditions. Early disease control is critical to avoid the thickening of the tissue of the esophagus.
There are no FDA-approved drug products for EoE, and 50,000 patients are unresponsive to available treatments, including long-term steroids. Patients may take proton pump inhibitors, but chronic frequent dosing often leads to poor compliance.
Tuba: Discuss the MoA of 1104. How will this drug change the treatment landscape for EoE.?
Jonathan: ‘1104 is a peptide that was derived from a natural immune-regulatory protein, Mycobacterium tuberculosis Chaperonin 60.1, that plays a key role in immune system function.
In allergic diseases, such as EoE, the immune system “overreacts” to certain molecules (allergic antigens) that are unknown to the body. This results in the stimulation of inflammatory immune cells and molecules, leading to chronic inflammation and tissue destruction.
Most pharmaceutical solutions currently in use or in development focus on alleviating the overactive immune and inflammatory response after it starts, by targeting downstream processes and leaving many patients with unresolved symptoms.
‘1104 resets the immune response “upstream,” or ahead of the inflammatory cascade, stimulating the production of immune cells that regulate the inflammatory response, thereby preventing the immune system from entering overdrive.
‘1104 has the potential to revolutionize the treatment landscape for EoE by providing long-term disease remission while eliminating the risk of life-threatening immune suppression often seen with the current standard of care.
Tuba: Discuss the P-I results of 1104 that allow you to advance the program to the P-II study.
Jonathan: ‘1104 has already been evaluated in two Phase 1 clinical trials. In the first Phase 1 placebo-controlled clinical trial, administration of ‘1104 intravenously and subcutaneously was safe at clinically relevant doses in 94 healthy volunteers and patients with mild asthma. A second Phase 1 multiple ascending dose studies in 18 healthy subjects found again that ‘1104 given intravenously was safe and tolerable also with no serious adverse events (SAEs) and served as the basis of the selection of the 8 mg dose for a subsequent Phase 2 EoE trial.
Tuba: What motivates you to work on eosinophilic esophagitis?
Jonathan: Until a few years ago, there was little awareness about eosinophilic disorders like EoE. There are no FDA-approved drug products for this debilitating disease and a significant number of patients are left to adapt their diet and take medications without a total response. Given the allergic nature of the disease and the mechanism of action of ‘1104, we believe it has the potential to really change the treatment landscape for these patients and are excited to provide them with the first-ever disease-modifying therapy. We look forward to advancing a Phase 2 trial before the end of the year.
Tuba: Big leaders like GSK, Sanofi or Takeda are also working on EoE. Do you think Revolo’s 1104 can compete with its competitors?
Jonathan: Absolutely. There are others working to develop a therapy for EoE, but what makes our therapy and approach different from all others is that our drug acts before the inflammatory response occur. We don’t focus on targeting individual inflammatory molecules such as cytokines that are produced after the inflammatory response has begun. ‘1104 may prevent the inflammatory response from ever starting, which could drive clinical improvement compared to the current standard of care.
Tuba: How is the company revolutionizing autoimmune and allergic disease treatment?
Jonathan: We are revolutionizing autoimmune and allergic disease treatment by advancing therapies that may achieve superior long-term disease remission, require less frequent dosing, and avoid suppression of the immune system.
Tuba: What are the company’s clinical trial plans for this year and the coming years?
Jonathan: We recently received approval of an investigational new drug application by the FDA to evaluate ‘1104 in a Phase 2 trial for EoE. We also received Clinical Trial Authorization (CTA) from the Medicines and Healthcare Products Regulatory Agency in the UK to evaluate ‘1104 in a Phase 2 allergen sensitivity study. We expect to start enrolling in both studies shortly and anticipate providing updates before the end of next year.
We are also advancing ‘1805, a modified analog of the endogenous binding immunoglobulin protein otherwise known as BiP, which is another key player in immune function. We anticipate initiating two Phase 2 clinical trials evaluating ‘1805, one for moderate-to-severe rheumatoid arthritis and the other for non-infectious uveitis in the near term.
Given the agnostic nature of the mechanism of action of ‘1104 and ‘1805, we believe they have the potential to treat multiple allergic and autoimmune diseases, respectively and we continue to explore additional indications.
Tuba: Are you open to collaborations to develop and commercialize your pipeline products?
Jonathan: We welcome collaborations with strategic partners who are looking to join us in drastically shifting the treatment landscape for allergic and autoimmune diseases. As we advance our clinical pipeline, we will consider every opportunity in order to bring treatments to patients in need as quickly as possible. We have identified many more additional indications for ‘1805 and ‘1104, and we are always willing to discuss partnerships as we explore the endless potential of these platform programs.
About Jonathan Rigby:
He currently serves as the CEO of Revolo Biotherapeutics. Prior to leading the charge at Revolo, Mr. Rigby established SteadyMed Therapeutics Inc. and co-founded Zogenix. He has experience of three decades in the pharmaceutical, biotech, and drug delivery technology industry.