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.

The FDA cleared the Investigational New Drug (IND) application for TNG908 in January 2022, and granted Fast Track Designation to TNG908. Additionally, the FDA granted Orphan Drug Designation for the treatment of MPNST and malignant glioma, including glioblastoma, with TNG908. 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 trial, focusing on the proof-of-mechanism, in the second quarter of 2023.

The clinical development path for TNG462 is expected to be similar to TNG908, evaluating safety and efficacy in multiple tumor types in a Phase 1/2 clinical trial. Glioblastoma will be excluded from the Phase 1/2 trial as TNG462 does not cross the blood-brain barrier in preclinical models. We expect to initiate a Phase 1/2 clinical trial in mid-2023. We are planning to fully evaluate both TNG908 and TNG462 in clinical trials.

The TNG260 clinical development plan will be among the first to combine the power of genetic patient selection and immunotherapy, evaluating patients with STK11 mutant cancers in a trial combining TNG260 and a checkpoint inhibitor. The FDA cleared the IND application for TNG260 in Q1 2023 and we expect to initiate a Phase 1/2 clinical trial in the second half of 2023.

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. We expect to file an IND for this program in mid-2023.