Turning Point Therapeutics, Inc.

Ladies and gentlemen, thank you for standing by and welcome to the Turning Point Therapeutic Fourth Quarter 2020 Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star one on your telephone. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Mr. Jim Bezola, Head of Investor Relations. Thank you, sir. Please go ahead.

Okay, thank you. Good afternoon, everyone. Following market close today, we filed our Form 10-K and issued a news release with a summary of our results for the fourth quarter and full year 2020. We also updated our investor presentation, and you may find these documents posted on the investor pages of tbtherapeutics.com. Leading the call today will be Turning Point's President and Chief Executive Officer, Dr. Athena Conturiatis, who will provide an overview and update of our business results. Athena's remarks will be followed by a review of our financials by our CFO, Yee Larson. We will take questions following our prepared remarks. The three of us are in separate locations today, so please bear with us as we manage the call remotely. Before Athena begins, I want to remind you that during this conference call, we will be making forward-looking statements. The company's actual results may differ materially from those expressed in or indicated by such forward-looking statements. And for a description of risk factors associated with investing in Turning Point Therapeutics, please refer to our recent filings with the Securities and Exchange Commission. Now, let me turn the update over to Athena.

Thank you, Jim, and good afternoon to everyone joining us on today's call. Today, I want to briefly recap our progress in 2020, share a number of updates across our programs, and focus on our goals for 2021. Overall, we continue to make progress in developing our four internally discovered next-generation tyrosine kinase inhibitors that target genetic drivers of cancer. In addition, we are investing in a discovery engine with the goal of establishing a pipeline for long-term growth. The progress and investments we have made are all directed toward advancing our vision to be the leader in precision oncology. Starting with our lead program, Repetrectinib, in 2020 and in January 2021, we reported encouraging preliminary data from our Registrational Phase 2 Trident 1 study. Repetrectinib is a next-generation ROS1 and TREC TKI with greater than 90-fold higher preclinical potency than crizotinib and greater than 50-fold higher preclinical potency than intractinib against wild-type ROS1. Reprotractinib has been granted several key regulatory designations, including breakthrough therapy designation in the United States for the treatment of patients with ROS1-positive TK-naive metastatic non-small cell lung cancer. To recap our clinical data updates, which we believe support a potential best-in-class profile, As of a December 31st, 2020 data cutoff date, in 15 ROS1-positive TKNAs advanced non-small cell lung cancer patients who had at least two post-baseline scans in phase two portion of the Trident One study, the confirmed objective response rate by physician assessment was 93%, or 14 of 15 patients, with a 95% confidence interval of 68 to 100. At the time of the data cutoff, the one non-responder remained on treatment with a 13% tumor reduction. In 22 patients pooled from the Phase I and Phase II portions of Trident 1, the confirmed overall response rate was 91%, with a 95% confidence interval of 71 to 99. For historical reference, both Zalkori and Rosletrek are approved in this patient population with confirmed overall response rates of 66% and 67% by blind and independent central review, respectively. Equally important is the duration of treatment, and in the pool phase one patients, the duration of treatment ranged from 10.9 to 37.3 months, with a median of 30.9 months, which we find encouraging, given it compares favorably to the published data for Zalcori, with a median duration of treatment of 22.4 months. Turning to the preliminary safety profile, as of an October 30th, 2020 data cutoff date, in a total of 185 patients in the phase one and phase two portions of the study, Reprotrectinib was generally well tolerated. In addition to the recent update from our ROS1-positive TKI-naive non-small cell lung cancer patients within TridentOne, last August in 2020, we reported early encouraging data from multiple other cohorts of the Phase II TRIDENT-1 study in TKI pre-treated patients with ROS1-positive non-small cell lung cancer or NTRK-positive solid tumors. We look forward to sharing more data from the ongoing TRIDENT-1 study in the second half of this year. I want to now share an enrollment update. First, we continue to be pleased with enrollment in patients with ROS1-positive TK-naive non-small cell lung cancer which is cohort one of the current study. In the second quarter, we now anticipate reaching 50 patients pooled from the phase one and phase two portions and plan to discuss next steps with the FDA during a type B meeting, which was requested based on our recent breakthrough therapy designation being granted. We hope to be in a position to discuss our path to potential registration following this meeting. As it relates to the other cohorts of the study, We continue to steadily enroll patients in the TKI pretreated, ROS1 positive, and NTRK positive cohorts, and it is our goal to provide an enrollment and clinical data update in other cohorts of the Trident 1 study in the second half of the year. In addition to our development of repotrectinib in the Trident 1 study, our team continues to make progress towards the planned initiation of the first cohort, of our multi-arm TRIDENT2 combination study in mid-2021. This planned phase 1B-2 study in KRAS mutant solid tumors is based on Repetrectinib's inhibition of JAK2, SARK, and FAK, which is believed to suppress STAT3 and AKT signaling, known mechanisms of oncogenic resistance. We will provide further details of the study design closer to initiation. and plan to present additional preclinical data highlighting Repetrectinib's combination potential in KRF mutant disease at an upcoming medical conference in the second quarter. Next in our pipeline is TPX0022, our MET, SARC, and CSF1R inhibitor, currently being studied in our ongoing Phase 1 Shield 1 study in patients with advanced solid tumors harboring genetic alterations in MET. MET-driven cancers represent a heterogeneous population across multiple tumor types, as was reflected in our early clinical data update last October. While there are now two therapies approved for MET exon 14 skipping non-small cell lung cancer, we continue to believe we have the potential to expand the development of O2-2 and focus on MET-amplified non-small cell lung cancer both as a single agent and in combinations. as well as GI tumors. Additionally, we believe there is room for improvement in the exon 14 space, given the limited duration of response and safety profile of the two approved agents. As a reminder, our preliminary data update last year showed objective responses across multiple tumor types with a generally well-tolerated safety profile in a heavily pretreated patient population. The Phase 1 study continues to enroll patients, including those with MET amplification and MET exon 14 skipping alterations. Similar to how we approached the Phase 2 dose for Repetrectamib, we are evaluating multiple doses and schedules for O2-2 to further characterize the pharmacokinetics, safety, and efficacy profile before determining a recommended Phase 2 dose. We are currently enrolling patients in the Phase 1 dose finding portion of SHIELD-1, with the goal of selecting the recommended phase two dose in the second quarter, after which we anticipate proceeding directly into the phase one dose expansion in multiple patient cohorts. The dose expansion will include select patient populations, including patients who are both TKI naive or TKI pretreated. We have multiple updates anticipated in the second half of this year in our O2-2 program, including an additional clinical data update from the Phase 1 dose-finding portion of SHIELD1, a planned discussion with the FDA to potentially modify the SHIELD1 study into a registrational Phase 1-2 design, initiation of the Phase 2 portion of the study pending FDA feedback, and finally, initiating our combination study with an EGFR-targeted therapy. Lastly, I want to highlight that in January, we signed our second licensing agreement with XyLab, similar to our licensing agreement for Repetrectinib, The latest agreement included rights for Zylab to develop and commercialize O2-2 in greater China. There is a significant unmet need in met amplified cancer in China, particularly in gastric cancer, where 40% of the world's cases are diagnosed and are often advanced at the time of diagnosis. Next in our pipeline is our RET inhibitor, TPX0046. 0046 has demonstrated preclinical potency against wild-type RET and RET solvent-front mutations. In the dose-finding portion of our ongoing study, we continue to evaluate multiple doses and schedules to further characterize the pharmacokinetics safety and efficacy profile. We plan to provide a preliminary data update in the second quarter, which will focus primarily on safety and any early signals of efficacy from initial patients. We anticipate approximately 15 to 20 patients across multiple doses in this data update. Lastly in our pipeline is TPX0131, our fourth drug candidate. Patients with ALK-positive disease comprise approximately 3 to 5 percent of non-small cell lung cancer, and sales of approved therapies were estimated to be approximately $2 billion globally in 2020. While there are several ALK inhibitors currently approved, we believe TPX0131 could have great potential initially in TKI pretreated patients. Lorbrenna is the current standard of care in this setting, yet O131 is considerably more potent preclinically against many clinically observed resistant mutations, including with sub-nanomolar potency against the most common G1202R solvent-front mutation, L1196M gatekeeper mutation, and multiple compound mutations. PBX0131 has been designed with a compact macrocyclic structure and in preclinical in vivo studies has shown significant brain tissue penetration after repeat oral dosing, supporting its potential to cross the blood-brain barrier in humans. We are excited to have already received approval by the Australian Ethics Committee and plan to submit our IND to the FDA later this month and anticipate initiating our Phase 1-2 clinical study in the second quarter. We also look forward to presenting additional preclinical data highlighting the profile of O131 at a medical conference in the second quarter. Now let me turn the call over to Yi for an update on our financial results.