EXALT - Assessing an innovative Immunotherapy, based on a thioredox peptide antigen, in a Phase I Trial for Type-1 Diabetes

The EXALT program (FP7 EU grant) started off in February 2014. In addition to an extensive preclinical research plan, the final objective of the project is to perform a phase I clinical trial in recent-onset (≤ 6 months) adult T1D patients, using an immunotherapeutic preparation, called Imotope^TM, based on Imcyse technology. The current project is being carried out by a consortium of one SME (Imcyse), three academic collaborators (Inserm, HMGU and QMUL) and a Technology Transfer Office (Inserm-Transfert). The project has a duration of 60 months and EU invests 6 million euro to support it.

Imcyse has developed a new technology based on short synthetic peptides flanked with a thioredox motif, which blocks the pathogenic immune response against auto-antigens in type I diabetes through activation of specific cytolytic CD4+ T-cells (cCD4). Preclinical work with Imotopes^TM in a specific T1D mouse model showed that insulitis, an absolute condition for the development of T1D, is fully prevented (and/or suppressed) upon either active immunisation or passive transfer of GAD65-specific cCD4+ T cells. This was also observed for the prevention of hyperglycaemia.

Approval for the EXALT clinical trial was obtained in 7 EU countries. The study will assess the safety of the Imotope^TM, and generate information on its mechanism of action, and potentially preliminary efficacy data. The first patient was included in October 2017. Currently, the study is recruiting patients for the second dose cohort. The study will include a third dose cohort. No safety issues arose in the first dose cohort. The innovative Imotope^TM is expected to be disease-modifying by stopping the autoimmune-mediated destruction of islet beta cells in the pancreas.