– New preclinical data further elucidate ‘1805’s mechanism of action in rheumatoid arthritis (RA) –
NEW ORLEANS and CAMBRIDGE, UK, November 7, 2023 – Revolo Biotherapeutics (“Revolo” or the “Company”), a company developing therapies that reset the immune system to achieve superior long-term remission for patients with autoimmune and allergic diseases, today announced that new preclinical data on ‘1805 will be presented via two posters at the American College of Rheumatology Convergence 2023 Annual Conference, which is being held November 10–15 at the San Diego Convention Center in San Diego, CA.
“These preclinical data provide further insights into ‘1805’s differentiated mechanism of action,” said Jonathan Rigby, Revolo’s Chief Executive Officer. “While current RA treatments can in part ameliorate joint destruction, they are limited in the ability to prevent osteoclast-induced bone destruction. These results highlight the capacity of ‘1805 to ‘reset’ a number of metabolic pathways involved in bone resorption, thus addressing the progressive bone and joint destruction that is a hallmark symptom of RA. In addition, ‘1805 normalizes the expression of genes abnormally activated in cells from RA patients, such as those associated with inflammation. Altogether, the data support the clinical potential of ‘1805 and its further clinical evaluation. We look forward to initiating the Phase 2b clinical trial in the future.”
The principal investigator of the preclinical translational studies, Carl Goodyear, Professor of Translational Immunology at the University of Glasgow, UK, said “The insights we have generated from this work, emphasize how powerful it is to harness physiological pathways aimed at regulating the immune system. Not only can ‘1805 fundamentally alter cell fate decisions within the innate immune compartment, but it has a unique ability to modulate cells from individuals whose compartment has been perturbed by systemic inflammation. We now need to take these studies to the next step and clearly demonstrate ‘1805’s clinical potential.”
Poster details:
Title: Biologic IRL201805 Drives Differential Cell-contact and Metabolism Transcriptional Profiles in Monocytes from RA Patients Compared to Healthy Donors
Presenter: Yuriko Yamamura, Research Associate (Immunology & Infection), University of Glasgow
Abstract #: 2149
Date/Time: November 14, 2023, 9:00 a.m. to 11:00 a.m. PT
Session: Poster Session C
Presentation highlights:
- Preclinical and clinical studies to date have demonstrated that ‘1805 interacts directly with monocytes, cells which play a key role in the initiation of inflammation and bone erosion in RA patients.
- Gene expression data from RA-derived monocytes and those from healthy donors indicate that ‘1805 upregulates the expression of genes that are downregulated in RA while simultaneously downregulating the expression of genes that are upregulated in RA, such as those involved in inflammatory pathways.
- The effect of ‘1805 is selective towards “diseased” monocytes, as large gene expression changes were not observed in monocytes from healthy donors.
Title: Novel Biologic IRL201805 Inhibits Osteoclastogenesis in Monocytic Cells from RA Patients
Presenter: Yuriko Yamamura, Research Associate (Immunology & Infection), University of Glasgow
Abstract #: 2150
Date/Time: November 14, 2023, 9:00 a.m. to 11:00 a.m. PT
Session: Poster Session C
Presentation highlights:
- In RA patients, osteoclasts derived from CD14+CD monocytes (pre-osteoclasts) are associated with a risk of progressive bone and joint destruction, which fundamentally impacts quality of life and often requires subsequent orthopedic surgery.
- Data from this study suggest that ‘1805 inhibits osteoclast differentiation and activation via modulation of the RANK/RANKL signaling pathway, a key pathway that regulates osteoclast maturation.
- Evaluation of gene expression showed that exposure of pre-osteoclasts to ‘1805 influenced the expression of multiple other genes involved in osteoclast differentiation.
- Notably, ‘1805 influenced metabolic pathways critical for bone resorption, such as V-ATPases. This is particularly relevant, as antiresorptive drugs that inhibit V-ATPase activity have become an area of therapeutic development.
For more information, or to register for the conference: https://rheumatology.org/annual-meeting
About ‘1805
‘1805 is a modified analogue of the endogenous immune-regulatory binding immunoglobulin protein (BiP), a key player in immune function that resets the immune system for long-term disease remission. Its mechanism of action creates vast optionality across multiple indications and routes of administration.
About Revolo Biotherapeutics
Revolo Biotherapeutics is developing therapies that reset the immune system to achieve superior long-term remission for patients with autoimmune and allergic diseases, without the immune system suppression seen with current therapies. Its two drug candidates, ‘1805 and ‘1104, a protein and a peptide respectively, reset the immune system to prevent the chronic pro-inflammatory immune response that results in autoimmune or allergic disease. ‘1104 is a peptide derived from a natural immune-regulatory protein and has recently completed two Phase 2a clinical trials for patients with eosinophilic esophagitis (EoE) and allergic disease. The disease-agnostic mechanism of action of Revolo Biotherapeutic’s assets provides a potential platform for the development of treatments for multiple autoimmune and allergic diseases.
For further information, please visit www.revolobio.com.
Company Contact
Marylyn Rigby, VP Investor Relations & Marketing
mrigby@revolobio.com
Media Contact
Monica Rouco Molina, Ph.D.
LifeSci Communications
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mroucomolina@lifescicomms.com