Selvita is developing an immunoncology platform, currently focused on two protein targets: GCN2 and STING .
GCN2 (general control non-repressed 2) kinase is a metabolic checkpoint of T-cell differentiation and a key effector signaling element for IDO1/IDO2/TDO. GCN2 is a serine/threonine-protein kinase that senses amino acid deficiency through binding of uncharged transfer RNA (tRNA). It plays a key role in modulation of amino acid metabolism in response to nutrient deprivation. Selvita is focusing on the discovery of small molecule selective inhibitors of GCN2 as an immunotherapy aimed at preventing immune escape of tumor cells. Therapy should offer single agent efficacy in solid/liquid tumors with IDO1/IDO2/TDO overexpression as well as combination potential with other immune checkpoint inhibitors. It can also be applied in direct treatment of cancer cells under nutrient stress.
A transmembrane adaptor protein STING (Stimulator of interferon genes) is a natural sensor of cytosolic DNA and type I interferon signaling in response to pathogen invasion. Activation of STING signaling pathway in tumor-resident antigen-presenting cells leads to MyD88/TRAF6-independent production of IFNβ and promotes spontaneous anti-tumor CD8+T cell priming.
STING agonists promote patient immune response to facilitate malignancy recognition and elimination, offering highly personalized treatment.
Selvita focuses on development of small molecule STING agonists of unique chemotype with fine-tunable ADME properties. They will serve as a next-generation anticancer regiment which directly kills cancer cells and in parallel converts them into a malignant-specific therapeutic vaccine, preventing spreading, invasion and providing long-term immunological memory.
Additionally, STING agonists may be a therapeutic solution for poorly immunogenic tumors to overcome a weak point of currently investigated immunotherapies. This approach offers a great potential for combination to sensitize resistant tumors to checkpoint blockade release and T-cell priming treatment options.