On March 2, 2021Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported financial results and operational updates for the fourth quarter and year ended Dec. 31, 2020 (Press release, Turning Point Therapeutics, MAR 2, 2021, View Source [SID1234575951]).

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"The progress we made during the fourth quarter and in 2020 has set us up for another potentially pivotal year in 2021, with multiple anticipated milestones across our portfolio," said Athena Countouriotis, M.D., president and CEO. "Our growing team continues to execute well as we advance our pipeline of precision oncology drug candidates."

Fourth quarter 2020 and recent highlights include:

REPOTRECTINIB, ROS1/TRK Inhibitor

Progress in the Phase 2 TRIDENT-1 registrational study of lead drug candidate repotrectinib, where the company in January reported updated interim findings in patients with ROS1-positive TKI-naïve non-small cell lung cancer (NSCLC). As of the Dec. 31, 2020 data cutoff date in 15 patients enrolled in the Phase 2 portion of the TRIDENT-1 study, the preliminary efficacy analysis showed a confirmed objective response rate (ORR) by physician assessment of 93% (95% CI: 68-100), and in 22 patients pooled from the Phase 1 (dosed at or above the Phase 2 dose) and Phase 2 portions, the confirmed ORR was 91% (95% CI: 71-99). As of an Oct. 30, 2020 data cutoff date, the interim safety update in a total of 185 patients from the Phase 1 and Phase 2 portions of the study showed repotrectinib was generally well tolerated.

Strong enrollment in the TRIDENT-1 study during the fourth quarter and into 2021, with Turning Point now anticipating enrollment in cohort 1 (EXP-1) to reach 50 patients pooled from the Phase 1 and Phase 2 portions of the study in the second quarter of 2021. The company plans to discuss next steps towards registration of repotrectinib in this patient population at a Type B meeting with the Food and Drug Administration (FDA), also anticipated in the second quarter. In addition, enrollment in the other cohorts within TRIDENT-1 continues to progress, and it is the company’s goal to provide an enrollment and clinical data update for other cohorts in the study in the second half.

Breakthrough Therapy Designation (BTD) granted by the FDA for the treatment of patients with ROS1-positive metastatic NSCLC who have not been treated with a ROS1 tyrosine kinase inhibitor. BTD is granted by the FDA to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition.

Plans to present additional preclinical data highlighting repotrectinib’s combination potential in KRAS-mutant disease at a medical conference in the second quarter of 2021.

Progress toward initiating the first cohort in the multi-arm Phase 1b/2 TRIDENT-2 repotrectinib combination study in KRAS-mutant solid tumors in mid-2021.
TPX-0022, MET/ SRC/CSF1R Inhibitor

Progress in the Phase 1 SHIELD-1 study of TPX-0022, Turning Point’s MET, SRC and CSF1R inhibitor, where initial data reported in October 2020 highlighted preliminary clinical activity, including objective responses across multiple tumor types and a generally well-tolerated safety profile.

The company continues to enroll patients in the Phase 1 study and is currently evaluating multiple doses and schedules to further characterize the pharmacokinetics, safety and efficacy profile before ultimately determining a recommended Phase 2 dose (RP2D), anticipated in the second quarter. Turning Point plans to proceed directly into Phase 1 dose expansion in multiple patient cohorts after determining RP2D.
Additional clinical data update from the Phase 1 dose finding portion of SHIELD-1 planned in the second half of 2021. The company also plans to discuss the ongoing study with the FDA with the goal to modify the study into a registrational Phase 1/2 design and initiate the Phase 2 portion in the second half, pending FDA feedback.

Execution of an agreement with Zai Lab in January 2021 to develop and commercialize TPX-0022 in Greater China.
TPX-0046, RET Inhibitor

Progress in the Phase 1 dose finding study of TPX-0046, a novel RET inhibitor, where the company continues to evaluate multiple doses and schedules to further characterize the pharmacokinetics, safety, and efficacy profile. Turning Point plans to provide preliminary data in the second quarter of 2021, which will focus primarily on safety and any early signals of efficacy from initial patients.
TPX-0131, ALK Inhibitor

Approval by the Australian Ethics Committee of the Phase 1/2 clinical study of TPX-0131 focused on ALK-positive TKI-pretreated advanced NSCLC patients. Study initiation is anticipated in the second quarter of 2021.

IND submission to the FDA on track for March for TPX-0131, Turning Point’s fourth drug candidate, which has a compact macrocyclic structure that has been shown in preclinical studies to potently inhibit wildtype ALK and numerous ALK mutations, and in in-vivo studies has shown significant brain tissue penetration after repeat oral dosing supporting the potential to cross the blood-brain barrier.

Presentation of additional preclinical data highlighting the profile of TPX-0131 at a medical conference in the second quarter of 2021.
Fourth Quarter and Full-Year 2020 Financial Results

Revenue: Revenue of $25 million for the year was recognized during the third quarter in connection with the upfront payment from Zai Lab under the company’s license agreement for repotrectinib in Greater China.

R&D Expenses: Research and development expenses were $34.3 million for the fourth quarter compared to $17.1 million for the fourth quarter of 2019, and $113.4 million for the year compared to $57.9 million for the year ended Dec. 31, 2019. Primary drivers of the year-over-year increase were investments made to develop repotrectinib, TPX-0022, TPX-0046, TPX-0131, discovery efforts and personnel expenses.

G&A Expenses: General and administrative expenses were $13.7 million for the fourth quarter compared to $5.9 million for the fourth quarter of 2019, and excluding a one-time non-cash stock-based compensation charge from the first quarter, non-GAAP G&A expenses were $42 million for the year compared to $19.8 million for the year ended Dec. 31, 2019. The increase was primarily attributable to higher personnel expenses as a result of increased employee head count and professional fees for legal and accounting services.

Net Income/Loss: Net loss was $47.4 million for the fourth quarter compared to net loss of $21 million for the fourth quarter of 2019, and excluding a one-time non-cash stock-based compensation charge from the first quarter, non-GAAP net loss was $125.9 million for the year compared to a loss of $72.1 million for the year ended Dec. 31, 2019.

Cash position: Cash, cash equivalents and marketable securities at Dec. 31 totaled $1.1 billion, compared to $409.2 million as of Dec. 31, 2019, driven primarily by net proceeds from follow-on public stock offerings in May and October of $351.6 and $433.9 million, respectively, partially offset by cash used in operating activities. Net cash used in operating activities during 2020 was $82.8 million. Turning Point projects its cash position funds current operations into 2024.
Upcoming Milestones
Key milestones anticipated in 2021 include:

Repotrectinib

Reach enrollment of 50 patients pooled from the Phase 1 and Phase 2 portions of the TRIDENT-1 study in the ROS1-positive TKI-naïve NSCLC patient cohort (EXP-1) in second quarter

Discuss next steps towards registration of repotrectinib in patients with ROS1-positive TKI-naïve NSCLC at a Type B meeting with the FDA in the second quarter

Initiate the first cohort of a multi-arm Phase 1b/2 TRIDENT-2 combination study in patients with KRAS-mutant solid tumors mid-year

Provide an enrollment and clinical data update in other cohorts of the Phase 2 TRIDENT-1 study in the second half
TPX-0046

Report early interim data from initial patients enrolled in the dose finding portion of the TPX-0046 Phase 1 study in the second quarter
TPX-0022

Provide a clinical data update from the Phase 1 dose finding portion of the SHIELD-1 study in the second half

Initiate the Phase 2 portion of the SHIELD-1 study of TPX-0022, pending FDA feedback, in the second half

Initiate the Phase 1b/2 SHIELD-2 study of TPX-0022 in combination with an epidermal growth factor receptor (EGFR) targeted therapy in the second half
TPX-0131

Submit the IND for TPX-0131 in the first quarter

Initiate the Phase 1/2 clinical study of TPX-0131 focused on ALK-positive TKI-pretreated advanced NSCLC patients in the second quarter
Preclinical/Research

Present multiple preclinical data presentations in the second quarter

Outline research strategy in the second half, including focus and anticipated timeline to development candidates.
Webcast and Conference Call
Turning Point will webcast its Quarterly Update Conference Call today, March 1 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 5683087. A replay will be available through the "Investors" section of www.tptherapeutics.com.