Our lead drug candidate, repotrectinib, is an orally administered TKI (tyrosine kinase inhibitor) being evaluated in an ongoing registrational Phase 1/2 trial called TRIDENT-1 for both TKI-naïve and TKI-pretreated patients with ROS1+ advanced non-small cell lung cancer (NSCLC) and NTRK+ advanced solid tumors.

Designed to be Different.

Repotrectinib is a small (low molecular weight), macrocyclic tyrosine kinase inhibitor of ROS1, TRK and ALK. Repotrectinib was designed to efficiently bind with the active kinase conformation and avoid steric interference from a variety of clinically resistant mutations. The compact and rigid structure is believed to enable repotrectinib to precisely and efficiently bind deep into the ATP binding pocket of the kinase, and potentially circumvent the steric interference that results in resistance to bulkier kinase inhibitors, especially the solvent-front and gatekeeper mutations of ROS1, TRK and ALK kinases.

The Patient Need

In 2020, lung cancer was the leading cause of cancer-related deaths globally, including many forms of oncogenic driven NSCLC. Despite new targeted therapies for the treatment of NSCLC, there continues to be a growing number of acquired resistant mutations in patients with previously treated TKIs, particularly solvent-front mutations. Existing TKIs can show susceptibility to acquired mutations, and toxicities that can limit duration of treatment. There continues to be a high unmet medical need to develop novel therapies that overcome intrinsic and acquired resistance, treat brain metastases, and prolong duration of response, with a more tolerable overall safety profile.

Repotrectinib’s Development Designations

  • Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have not been treated with a ROS1 tyrosine kinase inhibitor (TKI-naïve).

  • Three Fast Track designations by the FDA in ROS1-positive NSCLC patients who are TKI-naïve, ROS1-positive NSCLC patients who have been previously treated with one prior platinum chemotherapy and one prior ROS1 TKI, and NTRK-positive patients with advanced solid tumors who have progressed following treatment with at least one prior line of chemotherapy and one or two prior TRK TKIs.