TNG-348

“While disappointing, we believe this is the right decision given the data at hand,” Tango's CEO said. Tango Therapeutics has discarded one of its cancer drugs on the dancefloor after the USP1 inhibitor was linked to reports of liver toxicity in a phase 1 trial. The biotech had been testing the safety and efficacy of the candidate, dubbed TNG348, in a phase 1/2 study in patients with BRCA1/2-mutant and other HRD+ cancers. The plan had been to add AstraZeneca’s and Merck & Co.’s PARP inhibitor Lynparza into the mix as a combo treatment, but the study never made it that far. Instead, Tango has decided to end the trial—and the TNG348 program entirely—after grade 3/4 “liver function abnormalities” were observed in patients who continued on the study for longer than eight weeks. A grade 4 event is considered life-threatening.  “Patient safety is always our first priority and based on emerging data from the TNG348 dose escalation study, we have made the decision to discontinue further development of this molecule due to liver toxicity experienced by patients in the trial,” Tango’s CEO Barbara Weber, M.D., said in the May 23 release. “While disappointing, we believe this is the right decision given the data at hand,” Weber added. USP1, a deubiquitinating enzyme that regulates DNA damage response, is one of a number of emerging targets for synthetic lethality, an approach to killing cancer cells that PARP inhibitors such as Lynparza have helped put on the map over the past decade. While PARP inhibitors have validated the concept, they are unable to trigger responses in all patients and are vulnerable to resistance even when they are initially effective. Last year, Roche inked a deal to secure an exclusive global license to KSQ Therapeutics’ early-phase USP1 inhibitor. With Tango’s own USP1 ambitions up in smoke, Weber said the company will focus resources on its remaining portfolio, which is headed up by a PRMT5 program. The lead candidate, TNG908, is being assessed in a phase 1/2 in patients with MTAP-deleted tumors. Another PRMT5 drug, TNG462, is also in phase 1/2 development for various tumor types. “We remain committed to and confident in our ability to deliver a comprehensive clinical update on TNG908 and TNG462 in the second half of this year,” Weber said. Tango also has a dance partner in the form of Gilead, with a long-standing collaboration that stretches to 15 immuno-oncology targets. The biotech's shares were trading down premarket by 5.3% to $7 as of 7:12 am ET on Thursday morning.

Just months after starting a Phase I/II trial of its solid tumour candidate TNG348, Tango Therapeutics said Thursday that it will discontinue development of the USP1 inhibitor because several participants experienced liver toxicities.The study enrolled patients with BRCA1/2-mutant and other homologous recombination deficient cancers and dosed the first participant with TNG348 in January. According to Tango, grade 3/4 liver function abnormalities were observed in patients who remained on the study for more than eight weeks. “Patient safety is always our first priority and based on emerging data from the TNG348 dose escalation study, we have made the decision to discontinue further development of this molecule due to liver toxicity experienced by patients in the trial,” CEO Barbara Weber said in a statement. TNG348 was in-licensed in 2020 from Medivir, who was eligible for development and commercial milestones on the programme, as well as royalties.The company’s portfolio now includes three clinical assets in Phase I/II studies for cancer: TNG908 and TNG462, which both inhibit PRMT5; and TNG260, a highly selective CoREST complex inhibitor.