ImCyse plans first-in-human-therapy(FIHT) with disease-modifying vaccine to treat multiple sclerosis

Belgian-based ImCyse, a spin-off originally from the Catholic University of Leuven (KUL), but now established at both KUL and University of Liège (ULg), was founded in July 2010 by Prof. Jean-Marie Saint-Remy to valorize discoveries made by his team in the field of fundamental and applied immunology, believes it has a promising first-of-its-kind, disease-modifying vaccine to treat multiple sclerosis( MS). ImCyse CEO, Dr Jean-Louis Poplavsky has recently announced that the company plans to start it’s first-in-human-therapy (FIHT) with the product in October 2014, enrolling 18 patients with relapsing-remitting MS. The company completed a milestone-setting round of funding in November 2012, raising €7 million ($9,5 million) minimum with a first installment of €2.2 million. In addition, ImCyse is receiving support from the Wallonia region for work carried out in its Liège-based facility, whilst maintaining an operational facility in Leuven.

Even though treatment options for patients with multiple sclerosis have considerably improved in recent years, there is still no cure for the debilitating disease. Today’s next-generation drugs (dimethyl fumarate-based) only treat symptoms of the progressive disorder, rather than halt or reverse the course of the disease. In response to the need of both the patient and the pharmaceutical industry a product that could actually cure the disease would be a greatly welcomed breakthrough.

Targeting cells with potential to modify immune system

Imcyse is targeting CD4+ T-cells, which trigger an immune reaction and are implicated in autoimmune diseases such as MS, “If we can act on an early event, we could modulate the immune system,” explained chief scientific officer and founder, Jean-Marie Saint-Remy. Imcyse’s vaccine effectively switches off the immune response, in part by converting pathogenic CD4+ cells to beneficial cytolytic CD4+ cells. Dr Saint-Remy believes that unlike other approaches, Imcyse’s product doesn’t cause blanket immunosuppression, so should not lead to the same side-effects as other MS drugs such as immune deficiency.

In addition, the vaccine could also have an anti-inflammatory effect. According to the company, preliminary animal results suggest that this anti-inflammatory effect could lead to myelin sheath regeneration around the damaged nerve fibers caused by MS.

If this holds true in humans, this means that, as well as potentially halting disease progression, the vaccine could also reverse damage already done. However, this still remains to be tested, with Dr Saint-Remy describing the upcoming 30-patient clinical trial as being “quite a challenge”.

How it differs from current technologies

ImCyse’s platform technology, in contrast to conventional biotherapies, allows interference with the initial step of immune response, (when the antigen is presented to T cells), permitting suppression an ongoing immune response by a triple action: conversion of naïve and pathogenic T cells into “beneficial” T cells (cytolytic CD4+), elimination of the antigen-presenting cell by apoptosis (programmed cell death) followed by elimination (by apoptosis) of activated bystander pathogenic CD4+ T cells engaged with recognition on the same antigen-presenting cell.

Other advantages the ImCyse technology has in comparison to current technologies used for immune-mediated disorders include :

• A treatment that offers the possibility of curing diseases, whereas current therapies are only symptomatic;

• An ability to provide an antigen-specific approach, with no side effects such as those related to current non-specific immunosuppressive therapies;

• The possibility of being administered in either a preventive or suppressive setting,( most current therapies use only suppressive applications);

• A treatment effective for pathologies that are among the most frequent and chronic with an ongoing increasing incidence;

• Production costs that would be minimal for short synthetic modified peptides;

• Easy identification of suitable peptides for modification and therapy since they contain natural T cell epitopes of pathological interest.

In addition to development of this treatment for MS, ImCyse is developing its platform in several other applications: cancer, allergic asthma, graft rejection, gene therapy, and other autoimmune diseases such as type 1 diabetes. In fact, the company is already in collaboration with GlaxoSmithKline, and hopes to start a first clinical trial for diabetes in 2016. In parallel to these ongoing developments, several preclinical animal proof-of-concept experiments are currently being conducted in a variety of indications.

Although well on its way in terms of growth and development, ImCyse is still a young company and is seeking additional funding, and perhaps partners**, in order to keep progressing in its effort to not only stop and potentially reverse diseases such as MS but to develop its other applications as well.

**The company is currently seeking research partners, which would help establishing preclinical evidence on efficacy, safety and mechanism of action in fields such as infectious diseases, tumors and veterinary applications and R&D partners wishing to invest in fields such as gene therapy and gene vaccination as well as development of therapeutic agents (e.g. monoclonal antibodies) with non-immunogenic potential.