Turning Point Therapeutics, Inc. provided program updates for its four drug candidates and ongoing clinical studies. The emergence of RET solvent-front mutations is an indication of the need for a next-generation RET inhibitor given the limited treatment options for these patients.' PROGRAM UPDATES AND 2020 MILESTONES Repotrectinib Clinical study of repotrectinib continues to progress in the Phase 2 registrational portion of the TRIDENT-1 global study and Phase 1/2 study in pediatric patients. The company announced that repotrectinib has been granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of ROS1-positive advanced non-small cell lung cancer (NSCLC) patients who have been previously treated with one prior line of platinum-based chemotherapy and one prior line of a ROS1 tyrosine kinase inhibitor (TKI). There are currently no approved targeted therapies for TKI-pretreated ROS1-positive NSCLC patients. Following ongoing dialogue with health authorities, the company recently amended the TRIDENT-1 protocol for expansion cohorts 2 and 3 to clarify that ROS1-positive advanced NSCLC patients must have had one prior platinum-based chemotherapy regimen in addition to one prior TKI (cohort 2) or two prior TKIs (cohort 3). This amendment to cohort 2 is in line with the patient population granted fast track designation. Additionally, based on the potential future treatment paradigm, expansion cohort 4 has been amended to enroll only ROS1-positive advanced NSCLC patients with one prior TKI and no prior chemotherapy. This amendment is aimed at expanding enrollment in multiple ROS1-positive advanced NSCLC TKI-pretreated patient populations. TPX-0022 - MET/CSF1R/SRC Inhibitor Study of TPX-0022 continues to progress in a Phase 1 clinical trial in advanced solid tumor patients with MET genetic alterations. The company continues to anticipate reporting early interim data from initial patients during the second half of the year. TPX-0046 - RET/SRC Inhibitor Study of TPX-0046 continues to progress in a Phase 1/2 clinical trial, with early enrollment including multiple RET-positive patients with solvent-front mutations previously treated with other investigational RET inhibitors. In preclinical studies against proxy molecules for other investigational RET inhibitors, TPX-0046 showed comparable or stronger potency against wildtype and certain RET solvent-front mutations. TPX-0131, A Next-Generation ALK Inhibitor. The company announced the advancement of TPX-0131, its next-generation ALK inhibitor candidate, into IND-enabling studies. TPX-0131 has been designed with a compact macrocyclic structure and in preclinical studies has been shown to potently inhibit wildtype ALK and numerous ALK mutations, in particular the clinically observed G1202R solvent-front mutation and G1202R/L1196M compound mutation. ALK-driven tumors are estimated to represent up to 7% of driver oncogenes in NSCLC and of patients who develop a resistance mutation, G1202R has been reported in approximately 42%. 2020 Milestones Key milestones anticipated in 2020 include: Additional TPX-0131 preclinical data during the first half of the year; Present preclinical repotrectinib combination data; Early interim data from initial patients in some of the registrational cohorts of the repotrectinib TRIDENT-1 Phase 2 study during the second half of the year; Early interim data from initial patients treated with TPX-0022 during the second half of the year; and Submitting the IND for TPX-0131 by early 2021.