On February 28, 2022 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported financial results for the fourth quarter and year ended December 31, 2021, and provided operational updates (Press release, Turning Point Therapeutics, FEB 28, 2022, View Source [SID1234609241]).

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"We are encouraged by the progress made during 2021 and into the first two months of 2022," said Athena Countouriotis, M.D., President and CEO. "We look forward to sharing topline ORR and DOR data for our lead investigational therapy repotrectinib in patients with ROS1-positive NSCLC and completing a pre-NDA meeting with the FDA in the second quarter. Supported by our strong financial position, with approximately $1 billion in cash at the end of 2021, we continue to invest in our clinical programs and our research engine, while we also consider opportunities to bring in external innovation where there’s a strategic fit."

Fourth quarter and recent operational highlights include:

REPOTRECTINIB, ROS1/TRK INHIBITOR

Remain on track to report topline blinded independent central review (BICR) data from all of the ROS1-positive non-small cell lung cancer (NSCLC) cohorts from TRIDENT-1 and discuss the BICR data with the FDA at a pre-NDA meeting, as well as share topline ORR and DOR BICR data prior to the pre-NDA meeting, in the second quarter of 2022.
The Chinese Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) granted the company’s Greater China partner, Zai Lab, Breakthrough Therapy Designation for repotrectinib for the treatment of patients with ROS1-positive metastatic NSCLC who have not been treated with a ROS1 tyrosine kinase inhibitor (TKI).
Strong enrollment progress in the Phase 2 registration enabling TRIDENT-1 study across all cohorts during the fourth quarter of 2021 with expansion cohort 4 (EXP-4 — ROS1-positive advanced NSCLC population pretreated with one prior TKI without chemotherapy) now fully enrolled with the targeted 60 patients. Enrollment across all six cohorts of the study remains open and continues to progress steadily.
Updated durability data from ROS1-positive TKI-naïve NSCLC patients in the Phase 1 portion of the TRIDENT-1 trial continues to demonstrate best-in-class potential. Among a total of 7 patients treated at or above the recommended Phase 2 dose (RP2D), 3 patients had a DOR of greater than 30 months, using blinded independent central review (BICR) assessments as of the data cut-off date of July 22, 2019 followed by physician assessments as of the data cut-off date of November 29, 2021. 4 out of 7 patients remained on treatment for greater than 3 years.
Held a Type B meeting with the FDA to discuss potential next steps for repotrectinib in NTRK-positive TKI-pretreated advanced solid tumor patients treated within expansion cohort 6 (EXP-6) of the registrational TRIDENT-1 study.
The FDA guided that a pre-NDA meeting should be requested to discuss the topline BICR results from the Phase 2 TKI-pretreated EXP-6 and TKI-naïve EXP-5 patients, when responders have been followed for at least six months past onset of response.
The FDA noted that data from EXP-5 may be used to support the efficacy data for EXP-6, or potentially could be pooled with data from EXP-6 to support a broader indication.
The company plans to provide guidance on the timing of the pre-NDA meeting for repotrectinib in patients with NTRK-positive advanced solid tumors after completion of enrollment of the targeted 40 EXP-6 patients is achieved.
ELZOVANTINIB (TPX-0022), MET/SRC/CSF1R INHIBITOR

Patient enrollment continues in the SHIELD-1 study at 40 mg QD to 40 mg BID in Phase 1 dose expansion and in parallel elzovantinib is being studied at an intermediate dose level (60 mg QD to 60 mg BID) in Phase 1 dose escalation.
FDA clearance of the Investigational New Drug (IND) Application for the combination of elzovantinib and aumolertinib in EGFR mutant MET-amplified NSCLC. The combination of elzovantinib and aumolertinib will be studied in the SHIELD-2 Phase 1b/2 trial in patients with EGFR mutant MET-amplified advanced NSCLC who have progressed following treatment with osimertinib.
TPX-0046, RET INHIBITOR

Ongoing evaluation of multiple doses and schedules to further characterize the pharmacokinetics, safety, and efficacy profile before determining the RP2D.
TPX-0131, ALK INHIBITOR

Ongoing patient dosing in the Phase 1/2 FORGE-1 study of TPX-0131 in locally advanced or metastatic TKI-pretreated ALK-positive NSCLC. The study endpoints include safety and tolerability, determination of the RP2D, pharmacokinetics, and any early signals of efficacy.
DISCOVERY

Continued advancement of internal discovery programs targeting aberrant GTPase signaling known to drive genomically defined cancers with significant unmet medical need. The most advanced programs target KRAS G12D and the p21 activated kinase, or "PAK" family. The company is targeting nomination of two development candidates in the second half of 2022 with a goal to achieve at least one new IND per year beginning in 2023.
Upcoming Milestones
Key milestones anticipated in 2022 include:

Repotrectinib

Provide topline BICR data from all the ROS1-positive NSCLC cohorts from TRIDENT-1 and discuss the BICR data with the FDA at a pre-NDA meeting in the second quarter of 2022
Provide a clinical data update from the NTRK+ advanced solid tumor cohorts from TRIDENT-1 in the second half of 2022
Elzovantinib

Initiate the Phase 1b/2 SHIELD-2 study of elzovantinib in combination with aumolertinib in mid-2022
Initiate the Phase 2 portion of the SHIELD-1 study in the second half of 2022, pending FDA feedback on data from the intermediate dose level
Provide a clinical data update from the Phase 1 SHIELD-1 study in the second half of 2022
TPX-0131

Provide early interim data from initial patients treated in the dose-finding portion of the FORGE-1 study in the fourth quarter of 2022 or early 2023
Discovery

Nominate 2 development candidates in the second half of 2022
Provide details on the other 2 GTPase signaling discovery programs in the second half of 2022
Fourth Quarter and Full-Year 2021 Financial Results

Revenue: Revenue of $30.8 million for the year was attributable to the company’s licensing agreements with Zai Lab for repotrectinib and elzovantinib in Greater China.

R&D Expenses: Research and development expenses were $58.2 million for the fourth quarter compared to $34.3 million for the fourth quarter of 2020, and $193.0 million for the year compared to $113.4 million for the year ended December 31, 2020. Primary drivers of the year-over-year increase were investments made to develop repotrectinib, elzovantinib, TPX-0046, TPX-0131, discovery efforts and personnel expenses.

G&A Expenses: General and administrative expenses were $20.5 million for the fourth quarter compared to $13.7 million for the fourth quarter of 2020, and $75.9 million for the year compared to $73.4 million for the year ended December 31, 2020. G&A expenses in 2020 included a one-time non-cash stock-based compensation charge of $31.4 million associated with the modification of the vesting and expected term of the outstanding stock options pursuant to a transition agreement with our scientific founder.

Net Loss: Net loss was $78.4 million for the fourth quarter compared to net loss of $47.4 million for the fourth quarter of 2020, and $236.6 million for the year compared to $157.3 million for the year ended December 31, 2020.

Cash position: Cash, cash equivalents and marketable securities at December 31 totaled $981.6 million, reflecting a net decrease of $140.9 million from December 31, 2020. Turning Point projects its cash position is sufficient to fund current operations into the second half of 2024.