On May 12, 2020 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 first quarter ended Mar. 31 and provided operational updates, including measures taken by the company in response to the COVID-19 pandemic (Press release, Turning Point Therapeutics, MAY 12, 2020, View Source [SID1234564374]).
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"In reflecting on the past quarter of events, I want to acknowledge and thank the dedicated health care providers worldwide who have been treating patients during this unprecedented time," said Athena Countouriotis, M.D., president and chief executive officer. "As we have adapted to manage our business, we are appreciative of their efforts for the health and well-being of patients.
"Despite a very challenging environment in the first quarter, I am pleased with our recent Fast Track designation for repotrectinib based on Phase 1 TRIDENT-1 ROS1+ TKI Naïve NSCLC data which included an update to the duration of response, duration of treatment, and new progression free survival data; and the progress our team made advancing our programs, including our global registrational Phase 2 clinical study of repotrectinib. Site activations continued, with enrollment progressing across our four ongoing clinical trials.
"As it relates to COVID-19, we took action during the first quarter to implement multiple steps in response to the pandemic, including remote site activation and data monitoring; enabling patients to have routine tests conducted closer to home and allowing sites to evaluate certain patients remotely, in compliance with their local procedures. We are also evaluating additional sites for participation in our TRIDENT-1 study.
"Despite these interventions, we have more recently started to experience delays in trial site initiations and patient enrollment within the Phase 2 TRIDENT-1 study. We are also closely watching the progress in our other studies and believe the extent of the impact on our pipeline will depend on the continued duration and severity of the pandemic.
"We continue to anticipate providing data updates from our registrational Phase 2 TRIDENT-1 and TPX-0022 trials in the second half of 2020. For TRIDENT-1, we are currently monitoring the overall study conduct and data collection to be in a position to potentially provide this update in the third quarter. We anticipate the update will include preliminary efficacy and safety data from approximately 30 to 40 patients across multiple Phase 2 cohorts, including registrational and exploratory cohorts. For TPX-0022 we anticipate our update will be primarily a safety update as well as any early efficacy signals as we continue through our dose escalation cohorts."
First quarter and recent highlights include:
The company announced today 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 not been previously treated with a ROS1 tyrosine kinase inhibitor (TKI). In January, repotrectinib was granted Fast Track designation for the treatment of ROS1-positive advanced NSCLC patients who had been previously treated with one prior line of platinum-based chemotherapy and one prior line of a ROS1 TKI, a setting where there are currently no approved targeted therapies.
Fast Track Designation granted in ROS1+ TKI-naive patients. In the Phase 1 portion of TRIDENT-1, utilizing the 22 July 2019 data cut-off date with a median follow-up of 20.1 months (range: 5.3 to 24.9+), repotrectinib demonstrated a confirmed overall response rate (ORR) by blinded independent central review (BICR) of 91 percent (N=11, 95% CI: 59–100) in patients with ROS1+ advanced NSCLC who are ROS1 TKI-naïve. Repotrectinib demonstrated a median duration of response (DOR) of 23.1 months (95% CI: 5.6–NR) (based on Kaplan-Meier estimation). The probability of patients with a DOR ≥ 9 months, ≥ 12 months and ≥ 18 months was 78 percent, 65 percent, and 65 percent, respectively. Also, repotrectinib showed a median progression-free survival (PFS) of 24.6 months (95% CI: 7.2–NR). With an additional 8.5 months of follow-up as of 6 April 2020, 4 of the 5 responding patients remained in a PR (partial response) per physician assessment data since the 22 July 2019 data cutoff and the duration of treatment ranged from 9.2 to 34.2+ months with 7 of the total 11 (64%) patients remaining on repotrectinib.
All 7 (64%) remain on treatment for more than 17 months,
6 (55%) on treatment for more than 24 months, and
3 (27%) on treatment for more than 30 months at the time of the analysis
Repotrectinib has demonstrated CNS activity among patients with ROS1+ advanced NSCLC who are ROS1 TKI-naïve, with an intracranial objective response rate (IC-ORR) of 100% (3 of 3 patients, 95% CI: 29–100) with durations of response, as of the 22 July 2019 data cut-off, of 14.8+, 17.6+ and 23.1 months. All three of these patients remain on treatment, as of 6 April 2020, for 26.0+, 28.5+ and 34.2+ months.
Ongoing site activations and enrollment in the Phase 2 registrational portion of the TRIDENT-1 study of repotrectinib, with approximately 50 percent of planned sites now active in 11 countries. The study is now planned at up to 120 global sites with enrollment of approximately 320 ROS1-positive advanced non-small cell lung cancer (NSCLC) and NTRK-positive advanced solid tumor patients.
Ongoing progress in the Phase 1/2 open-label study to assess repotrectinib in pediatric patients with ALK-, NTRK- or ROS1-positive advanced solid tumors; the Phase 1 study of TPX-0022, Turning Point’s MET/CSF1R/SRC inhibitor; and Phase 1/2 study of TPX-0046, Turning Point’s RET/SRC inhibitor. Both the TPX-0022 and TPX-0046 trials continue dose escalation based on real time pharmacokinetic data evaluation and enrollment includes both TKI-naïve and -pretreated patients across both studies.
Acceptance of multiple abstracts for poster presentations at the ASCO (Free ASCO Whitepaper) and AACR (Free AACR Whitepaper) virtual annual meetings. The ASCO (Free ASCO Whitepaper) presentation is expected to highlight preclinical data for TPX-0046 and the AACR (Free AACR Whitepaper) presentations are planned to highlight preclinical repotrectinib combination data and TPX-0131 preclinical data.
Recent publication in the AACR (Free AACR Whitepaper) journal Clinical Cancer Research of repotrectinib preclinical data and patient case studies from the Phase 1 portion of TRIDENT-1. The publication highlighted potent antitumor activity of repotrectinib in treatment-naïve and solvent-front mutation ROS1-rearranged NSCLC. In addition, repotrectinib demonstrated significant reduction of brain lesions in an intracranial tumor model.
First Quarter Financial Update
Operating expenses for the first quarter totaled $62.6 million, which included $38.4 million in non-cash stock-based compensation expense. The non-cash stock-based compensation expenses included a one-time charge of $31.4 million associated with previously disclosed modifications to the vesting of existing stock options, pursuant to the transition agreement with the company’s scientific founder. Excluding this one-time charge, non-GAAP operating expenses in the first quarter totaled $31.2 million compared to GAAP operating expenses of $14.1 million in the first quarter of 2019 and $23.1 million in the fourth quarter of 2019. Primary drivers of the year-over-year increase were investments made to develop repotrectinib, TPX-0022 and TPX-0046, as well as personnel expenses.
Cash, cash equivalents and marketable securities at Mar. 31 totaled $380.8 million, a decrease of $28.4 million from Dec. 31, 2019. The company projects its cash position funds current operations into 2022.
Upcoming Milestones
Key milestones anticipated through 2020 include:
Presenting preclinical data for TPX-0046, the company’s novel RET/SRC inhibitor, as a poster presentation during the ASCO (Free ASCO Whitepaper) virtual annual meeting on May 29.
Presenting preclinical repotrectinib combination data and preclinical data for TPX-0131, the company’s novel ALK inhibitor, during the AACR (Free AACR Whitepaper) virtual annual meeting in late June.
Early interim data from initial patients in the TRIDENT-1 Phase 2 study during the second half of the year. The company anticipates this update will include preliminary efficacy and safety data from approximately 30 to 40 patients across multiple Phase 2 cohorts, including registrational and exploratory cohorts.
Early interim data from initial patients treated with TPX-0022 during the second half of the year.
Submitting the IND for TPX-0131 by early 2021.
Webcast and Conference Call
Turning Point will webcast its Quarterly Update Conference Call today, May 12 at 4:30 p.m. ET/1:30 p.m. PT. Dr. Countouriotis will host the call, which will be accessible through the "Investors" section of tptherapeutics.com or by dialing (877) 388-2118 (in the United States) or (470) 495-9489 (outside the U.S.) using conference ID 6135289. A replay will be available through the "Investors" section of www.tptherapeutics.com.