Tango Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for TNG462, a next-generation MTA-cooperative PRMT5 inhibitor for the treatment of patients with MTAP-deleted cancers. The Company also announced that TNG908 was granted Orphan Drug Designation (ODD) for the treatment of malignant glioma and provided additional business highlights. Pipeline Update: TNG462 IND cleared; first-in-human clinical trial initiation expected in mid-2023: The U.S. FDA has cleared the IND application for TNG462, a next-generation methylthioadenosine-cooperative (MTA) inhibitor of protein arginine methyl transferase 5 (PRMT5) for the treatment of cancers with methylthioadenosine phosphorylase (MTAP) deletion; The company expects to initiate a Phase 1/2 clinical trial in mid-2023.

The trial, which will require all patients to have an MTAP deletion, will evaluate cancers including non-small cell lung cancer, mesothelioma and cholangiocarcinoma. Unlike TNG908, glioblastoma will be excluded from the clinical trial as TNG462 does not cross the blood-brain barrier in preclinical non-human primate models; TNG462 has the same mechanism of action as TNG908 with enhanced potency and selectivity in MTAP-deleted xenograft models. In preclinical studies, TNG462 is 45X selective for MTAP-deletions (3-fold greater than TNG908) and 20 times more potent than TNG908, which may provide a wider therapeutic index and stronger target inhibition than TNG908.

TNG908 granted ODD for the treatment of malignant glioma: The FDA has granted Orphan Drug Designation (ODD) to TNG908 for the treatment of malignant glioma. ODD is granted to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the United States. This designation provides for a seven-year marketing exclusivity period upon regulatory approval, as well as certain incentives, including federal grants and tax credits; TNG908, an MTA-cooperative PRMT5 inhibitor designed to selectively kill cancer cells with MTAP deletions, is currently being evaluated in a Phase 1/2 clinical trial.