Type 1 diabetes (T1D) is the immune mediated form of diabetes that results from the body’s destruction of insulin producing pancreatic beta-cells. Immune cells, particularly T and B cells, contribute to the killing of insulin producing beta-cells. A lack of sufficient insulin production prevents tissues from using glucose and leads to high blood sugars. Currently, T1D is treated with life-long insulin administration by an insulin pump or multiple daily injections. Genetic risk for T1D development is predisposed by the HLA-DQ8 gene. People with this gene are ~11 times more likely to develop T1D than those that do not have the gene, and 50-60% of all patients with T1D have the HLA-DQ8 gene.
IMT’s approach to T1D is to develop an oral small molecule drug that effectively starves the autoimmune process by blocking the function of HLA-DQ8 bearing cells to activate T-lymphocytes. In 2018, the company founders published an IND-exempt proof of concept study using an FDA-approved tool drug that had been validated as a hit using our drug screening strategy. Results of the study (Michels et al., Journal of Clinical Immunology, 2018) showed that HLA-DQ8 activity is significantly inhibited by the drug in antigen (insulin) presentation to T cells in adult patients with newly diagnosed type 1 diabetes. Moreover, the study demonstrated that the HLA-DQ8 inhibition extended to presentation of α-gliadin showing promise of this approach for treating celiac disease. The findings successfully elucidated the company’s innovative small molecule approach, basic science and mechanistic action in people.
Our lead drug in development, IMT-002, occupies the peptide binding groove of HLA-DQ8 on the surface of antigen presenting cells to block the binding of insulin and other beta-cell proteins and subsequent activation of CD4 T-cells. When HLA-DQ8 is blocked, the immune system will no longer attack insulin producing beta-cells, and thus modify the disease course to keep patients making their own insulin. In July 2021, we announced positive results from a Phase 1b study of IMT-002 in T1D. The study, a first for the industry, demonstrated the safety and tolerability of IMT-002 in people with T1D preselected for the HLA-DQ8 gene. There were no serious adverse events and adverse events were similar between placebo and treatment and did not increase with dose. Additionally, the drug demonstrated mechanism of action as engagement with HLA-DQ8 in an ex vivo cell-based assay to assess inhibition of self-peptide presentation (insulin and gliadin as autoantigens for T1D and celiac disease, respectively).
