Why would a new immunotherapy approach be cause for researchers to reconsider Type 1 diabetes and its treatment? Perhaps a novel modified synthetic peptide-based technology platform known as Imotopes™ could pave the path for new classes of therapies that block improper autoimmune responses. This new approach comes from the team at Imcyse, SA, a small biotech operating in the Walloon Region of Belgiumm which is actually originally a spin-off from Belgium’s KU Leuven. Known as Imcyse, they have raised over $40 million and now gear up for an important Phase 1/2 clinical trial in Belgium and the UK.
The Challenge Addressed
As recently shared in Open Access Government, growing autoimmune diseases, especially the severe and chronic type, represent extremely difficult and complex immune-system-based indications. It’s not a secret that autoimmune disease continues to rise. Although there are no readily available macro-answers, scientists do know that in these situations where the immune system goes haywire, that is, it mistakenly focuses on healthy cells as external invaders, attacking them in the process. Hence the patient’s immune system essentially seeks to destroy the host’s own tissues: a bad situation that occurs in many different immune diseases.
Type 1 diabetes offers an example: in the pancreas insulin producing beta cells are destroyed by pathogenic T cells. Imotopes evidence the potential to block these deleterious immune responses reports the company.
What are Imotopes™ & How do they Work?
Developed by the Belgium-based Imcyse SA, Imotopes are peptides made up by a thioreductase motif linked to an epitope derived from an auto-antigen targeted by the autoimmune response. Upon injection into the body, the imotope is projected at the surface of the antigen-projecting cell. When Imotopes are presented by the antigen-projecting cell to naïve CD4 T cells in the lymph nodes, the thioreductase motif will direct the maturation of the CD4 T into cytolytic CD4 T cells.
The cytolytic CD4 T cells migrate through the bloodstream to the lymph nodes near the damaged organ. There the cytolytic CD4 T cells will specifically identify, recognize and terminate antigen presenting cells, presenting the exact same epitope as well as all the effector cells, interacting with this antigen presenting cell. This includes those identifying different epitopes participating in the autoimmune response.
This action results in the retraction of the pathogenic activity and hence leads to the cessation of the organ’s destruction. This ultimately leads to a slow down and halting of disease progression. Moving forward, the environment becomes more helpful for actual healing of the damaged organ.
Imcyse suggests this breakthrough translates to significant potential to combat autoimmune diseases, such as Diabetes type 1, multiple sclerosis and rheumatoid arthritis.
Lead Candidate Example
The company’s leading candidate, IMCY-0098, is a novel insulin-derived Imotope developed to intervene at an early stage in the autoimmune response by halting the destruction of beta-cells. Via this intervention, Imcyse declares that IMCY-0098 supports the pancreas and its natural ability to generate insulin.
As described above, this approach, truly unique according to the company, aims to interfere early on in the autoimmune system response that the improper immune response is stopped. Theoretically, from this approach, a patient could actually become cured of the autoimmune disease actually triggered by the mistaken immune response.
Phase 1b Study
In their first Phase 1b safety study, IMCY-0098 was found to be safe and well-tolerated. Study summary:
· Demonstrated an excellent safety profile with no safety issues at any dose and no indication of disease exacerbation.
· Detected CD4+ T cells with cytolytic signatures in IMCY-0098 treated patients.
· Identified certain subgroups of patients with signs of improved clinical responses through the use of artificial intelligence data mining analysis.
· Observed correlations between Imotope™-induced immune responses and clinical improvements.
The IMPACT Study
The company gears up for the IMPACT study. Commencing in October 2020, the study Phase 1b/2a study will test IMCY-0098 for the treatment of type 1 diabetes. Led by Jean Van Rampelbergh, PhD, VP Clinical & Regulatory, the sponsor has included trial sites such as KU Leuven in Belgium and a handful of sites in the UK.
Originally founded in 2010 as a spinoff from the KU Leuven, Belgium, the Liège -based firm called Imcyse has raised about $41 million in a couple rounds of financing. Investors include W.IN.G, SFPI-FPIM, Belfius Bank, LSP BioVentures, Meusinvest (Noshaq) and S.R.I.W. The company currently employs about 30.
The company reports that they have completed numerous proof of concept studies in animal models for type 1 diabetes, multiple sclerosis, myasthenia gravis, allergic diseases, prevention of graft rejection and the blocking of immunogenicity to viral vectors.
They report that two projects will commence clinical investigation in patients. In July, the company was awarded 1.1 million over a 29 month period to support the development of a therapeutic vaccination treatment for Neuromyelitis Optica Spectrum Disorder (MNOSD). NMOSD is a rare and severe autoimmune disease of the central nervous system.
Jean Van Rampelbergh, PhD, VP Clinical & Regulatory