Tango Therapeutics is advancing its PRMT5 inhibitor, TNG462, into combination trials after promising early data from its Phase 1/2 clinical trial. The drug has shown clinical activity across multiple tumor types, including non-small cell lung cancer (NSCLC) and pancreatic cancer.
TNG462: A Potential Best-in-Class PRMT5 Inhibitor
The ongoing Phase 1/2 trial of TNG462, an MTA-cooperative PRMT5 inhibitor, has demonstrated an objective response rate (ORR) of 43% in cholangiocarcinoma (n=7). The trial also indicates substantive durability and a good safety and tolerability profile. Tango Therapeutics anticipates providing the next clinical update in 2025.
Barbara Weber, M.D., President and Chief Executive Officer of Tango Therapeutics, stated, "We have made great progress with our PRMT5 development program, including positive data from the TNG462 phase 1/2 clinical trial that showcase the best-in-class potential of TNG462 in multiple tumor types, including pancreatic and non-small cell lung cancers (NSCLC)."
Combination Studies with TNG462
Tango Therapeutics plans to initiate multiple combination studies with TNG462, pairing it with RAS(ON) multi-selective and RAS(ON) G12D-selective inhibitors from Revolution Medicines, as well as with osimertinib (AstraZeneca) and pembrolizumab (Merck). Enrollment for these studies is expected to begin in the first half of 2025.
The company has entered a clinical collaboration with Revolution Medicines to evaluate the efficacy and safety of TNG462 in combination with RMC-6236, a RAS(ON) multi-selective inhibitor, and RMC-9805, a RAS(ON) G12D-selective inhibitor. Revolution Medicines will supply RMC-6236 and RMC-9805 to Tango, with Tango acting as the sponsor for any combination trials. Both companies will retain commercial rights to their respective compounds, and the agreement is non-exclusive.
TNG908 and TNG456 Updates
TNG908, an MTA-cooperative brain-penetrant PRMT5 inhibitor, has shown clinical activity and is well-tolerated across non-CNS cancers in its Phase 1/2 clinical trial. Among nine evaluable pancreatic cancer patients, two achieved partial responses (ORR 22%), and five had stable disease as their best response. The five ongoing pancreatic cancer patients have been on the study for an average of 24 weeks, with the longest duration being 72 weeks.
However, TNG908 did not demonstrate activity in glioblastoma (n=23 at active doses), likely because CNS exposure did not meet the required exposure threshold for clinical efficacy. Enrollment for TNG908 is being stopped to fully resource TNG462, based on TNG462's longer time on treatment (24 weeks and increasing) compared to TNG908 (16 weeks), superior target coverage, and safety and tolerability profile.
Tango is also developing TNG456, a next-generation brain-penetrant MTA-cooperative PRMT5 inhibitor that is 55-fold selective for MTAP deletion with 20 nM potency. Preclinical studies suggest that TNG456's central nervous system exposure has the potential to be sufficient for meaningful efficacy in glioblastoma and brain metastases. The company expects to begin enrolling patients in the planned Phase 1/2 trial during the first half of 2025.
Financial and Business Highlights
As of September 30, 2024, Tango Therapeutics held $293.3 million in cash, cash equivalents, and marketable securities, which the company expects will be sufficient to fund operations into the third quarter of 2026, including additional planned TNG462 and TNG456 clinical trials.
Tango's research and development expenses were $33.3 million for the three months ended September 30, 2024, compared to $27.1 million for the same period in 2023. This increase is attributed to increased spending related to the advancement of TNG462, preclinical programs, and personnel-related costs to support research and development activities.
