Undisclosed immune evasion therapeutic

A two-step approach was taken to uncover tumor suppressor gene loss driving immune evasion as step one, and immune sensitizers specifically reversing the immune evasion driven by certain tumor suppressor loss as step two...STK11 mutations are found in ~15% of non-squamous non-small cell lung cancer and have been reported as a predictor of primary resistance to PD-1 blockade. Inhibitors selectively targeting HDAC1 & 2 in combination with anti-PD1 represent a promising therapeutic opportunity for non-small cell lung cancer patients with STK11 mutations.

It reverses the immune evasion phenotype caused by loss of STK11 and induces tumor regressions in an STK11-mutant model in combination with α-PD1. The TNG260 clinical development plan will be among the first to combine the power of genetic patient selection and immunotherapy, evaluating patients with STK11 mutant cancers in a trial combining TNG260 and a checkpoint inhibitor.

STK11/LKB1 and/or KEAP1 genomic alterations are found in ~25% of non-squamous non-small cell lung cancer and have been reported as a major predictor of primary resistance to PD-1 blockade. Together, these data demonstrate that high-throughput in vivo genetic screens can identify tumor cell-intrinsic drivers of immune evasion and establish murine system relevant to the study of primary resistance to PD-1 axis immunotherapy and more generally, tumor cell-intrinsic immune evasion.