Tango Therapeutics has terminated the development of its TNG348 programme after data emerged from the Phase I/II trial showing that the therapy may cause liver dysfunction.
The company was evaluating TNG348 in patients with BRCA1/2-mutant and other homologous recombination deficient (HRD+) cancers in a Phase I/II trial (NCT06065059). Tango decided to end the trial after participants who remained in the study longer than eight weeks showed “grade III/IV liver function abnormalities”.
Following the announcement of trial termination, Tango’s stock was down by 9.2% at market open on 23 May, compared to the market close on the previous day. The company’s market cap stands at $757.5m.
Tango also planned to evaluate its therapy in combination with AstraZeneca’s and Merck & Co’s poly-ADP ribose polymerase (PARP) inhibitor Lynparza (olaparib) but none of the participants had received the combination therapy yet.
TNG348 is an inhibitor of the ubiquitin-specific protease 1 (USP1) enzyme, which regulates DNA damage response. Inhibiting USP1 can impact the repair mechanisms in cancer cells, potentially making them more vulnerable to other treatments, or hindering their ability to metastasise. The company licensed the therapy from Medivir in March 2020.
“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. While disappointing, we believe this is the right decision given the data at hand,” said Barbara Weber, Tango’s president and chief executive officer.
“We will focus resources and capital on our existing portfolio, particularly our PRMT5 ((protein arginine methyltransferase 5) programme. 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.”
PRMT5 is responsible for the upregulation of G1 cyclins / cyclin-dependent kinases and the phosphoinositide 3-kinase / AKT signalling cascade. Tango’s PRMT5 therapies, TNG908 and TNG462, are being evaluated in Phase I/II trials (NCT05275478 and NCT05732831) as a treatment for advanced or metastatic solid tumours with methylthioadenosine phosphorylase (MTAP) deletion.
Other USP1 therapies in development include Debiopharm’s cancer therapy Debio 0432 and Mission Therapeutics’ acute kidney injury treatment, MTX652.
