RPT-GCN2i: Stimulating the immune system to act even in the hostile tumor microenvironment
We are developing potent inhibitors of GCN2 (a “RPT-GCN2i”). We believe that the computational analysis of proprietary and public databases will allow us to identify tumor types or a subset of patients with a greater potential to benefit from GCN2 inhibition.
In preclinical studies, RPT-GCN2i restores effector T cell proliferation and function under conditions of nutrient limitation in a dose-dependent manner. Also, incubation of activated CD8 T cells with myeloid-derived supressor cells or MSDCs isolated from healthy volunteers as well as from cancer patients leads to inhibition of T cell proliferation, an effect that is reversed by an RPT-GCN2i in a dose-dependent manner. In a CT26 mouse tumor model, oral administration of an RPT-GCN2i led to reductions in tumor volume when dosed as a single agent. We believe an RPT-GCN2i has the potential to have broad activity in stimulating the immune system in multiple tumor types, either as a single agent or in combination with conventional or immune-based therapies.
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