Perlmutter Cancer Center

TNG908 is a potent and selective oral small molecule inhibitor of PRMT5 that binds cooperatively with MTA to inhibit PRMT5 function. Elevated levels of MTA are found in tumor cells that have lost the MTAP gene, conveying exquisite specificity of TNG908 to tumor cells that have lost MTAP over normal tumor cells with intact MTAP gene expression. In vitro data of TNG908 demonstrate strong selectivity for MTAP-deleted cells, and selectivity and potency are demonstrated in MTAP-isogenic cell lines representing multiple cancer lineages. It also induces dose-dependent anti-tumor activity in LN18 MTAP-deleted xenografts and dose-dependent PRMT5 PD modulation consistent with on-target anti-tumor activity in MTAP-deleted cells. This Phase 1/2 study will establish an MTD and/or biologically effective dose, support an RP2D, and evaluate the initial anti-tumor activity and tolerability profile of TNG908 when administered as a monotherapy.