Tango Therapeutics, Inc. announced progress updates across its pipeline and recent corporate highlights. Pipeline Progress Updates: TNG908 IND cleared and first-in-human clinical trial expected to start in first half 2022. The U.S. Food and Drug Administration has cleared the Investigational New Drug application for the Company's lead program, TNG908, a synthetic lethal small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5) designed to selectively kill cancer cells with an methylthioadenosine phosphorylase deletion.

MTAP deletions occur in 10% - 15% of all human cancers, including non-small cell lung cancer, mesothelioma, pancreatic cancer and cholangiocarcinoma. Tango expects to initiate a Phase 1/2 clinical trial in the first half of 2022, with preliminary safety and efficacy data expected in the first half of 2023. Enrollment will be limited to patients with confirmed MTAP-deleted tumors.

In preclinical studies TNG908 demonstrated strong selectivity for MTAP-deleted tumors with robust anti-tumor effects in vitro and in vivo. Target 3 inhibition reverses immune evasion in STK11 mutant cancers; development candidate planned for 1H 2022. Target 3, an undisclosed synthetic lethal target, reverses the immune evasion effect of serine-threonine kinase 11 loss-of-function mutations.

Target 3 was discovered using novel in vivo target discovery platform. In syngeneic mice, Target 3 inhibition, in combination with an anti-PD1 antibody, resulted in complete regressions in all treated mice, and the induction of immune memory against re-implantation of tumors in the majority. Tango expects to advance a development candidate in the first half of 2022 and file an IND in 2023.

USP1 development candidate anticipated in 2H 2022. Tango anticipates advancing a development candidate for their ubiquitin-specific protease 1 program, a synthetic lethal target for BRCA1-mutant breast, ovarian and prostate cancer, in the second half of 2022. USP1 inhibition is synergistic with poly (ADP-ribose) polymerase inhibition in BRCA1 mutant cancer cell lines and murine xenograft models.

Clinical trials of the USP1 inhibitor will be conducted both as a single agent and in combination with PARP inhibitors in BRCA1-mutant cancers. Tango expects to advance a development candidate in the second half of 2022 and file an IND in 2023.