Pipeline

Our Phase 1/2 first-in-human trial to evaluate TNG908 in patients with MTAP-deleted tumors is being conducted in two parts. The dose escalation phase will evaluate safety, efficacy, pharmacokinetics and pharmacodynamics in patients with locally advanced or metastatic cancer of any histology with an MTAP deletion. After determining the optimally-effective dose for TNG908, we will further evaluate safety and efficacy in multiple tumor types in specific cohorts, including malignant peripheral nerve sheath tumor (MPNST – a rare sarcoma), non-small cell lung cancer, mesothelioma, cholangiocarcinoma, and glioblastoma.  In parallel, we will enroll a histology-agnostic arm to evaluate all other tumor types with MTAP deletion. Given that MTAP deletion occurs in approximately 10-15% of human cancers, we may open other histology-specific arms based on activity observed in the trial.

Patients are being actively enrolled in the Phase 1/2 clinical trial. We expect to provide an update on the ongoing dose escalation portion of the Phase 1/2 trial in 2024.

TNG462 is in the dose-escalation portion of a Phase 1/2 trial, and the clinical development path is similar to TNG908, evaluating safety and efficacy in multiple tumor types. Glioblastoma will be excluded from the Phase 1/2 trial as TNG462 does not cross the blood-brain barrier in preclinical models.

The TNG260 clinical development plan will be among the first to combine the power of genetic patient selection and immunotherapy. TNG260 is in the dose escalation portion of a Phase 1/2 trial, being evaluated in combination with pembrolizumab for the treatment of STK11-mutant cancers.

We are developing TNG348, a novel allosteric inhibitor of USP1 for treatment of BRCA1 and BRCA2-mutant and other HRD+ cancers. In vivo preclinical studies for TNG348 have shown single agent efficacy and combination benefit with PARP inhibitors in BRCA1, BRCA2-mutant and other HRD+ cell-line and patient derived xenografts, including those that are intrinsically resistant to PARP inhibition. These preclinical data further demonstrate that TNG348 is synergistic with PARP inhibition across a panel of human ovarian and breast cancer cell lines, including both PARP inhibitor sensitive and resistant models. Clinically, we expect TNG348 to have single agent activity in PARP inhibitor-naïve and PARP inhibitor-resistant BRCA1/2 mutant and other HRD+ cancers, and to synergize with PARP inhibitors. The U.S. Food and Drug Administration (FDA) cleared the Investigational New Drug (IND) application for TNG348 in September 2023.