Turning Point Therapeutics, Inc.

Thank you all for standing by, and welcome to the Turning Point Therapeutics first quarter 2021 conference call. All lines have been placed in listen-only mode until the question and answer session of today's conference. To ask a question over the phone by that time, you may press the star key followed by the number one. I'll now hand the call over to your host, Jim Mazzola. Sir, you may begin.

Okay, thank you, Jesse, and good afternoon, everyone. Following market close today, we filed our Form 10Q, issued an 8K, and issued a news release with a summary of our results for the first quarter of 2021. We also updated our investor presentation, and you may find these documents posted on the investor pages of tptherapeutics.com. Leading our call today will be Turning Point's President and Chief Executive Officer, Dr. Athena Kateriotis, who will provide an overview and update of our business results, as well as a review of our financials. We will take questions following our prepared remarks, and we'll be joined by Dr. Mohammed Hermand, our Chief Medical Officer. Mohammed is in a separate location for today's call, so please bear with us as we manage your questions across both sites. 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. 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. For anyone new to our story, just two years ago, Turning Point had approximately 50 employees, had just completed our initial public offering, and had one clinical stage asset in one ongoing Phase I study. Now, two years later, we have approximately 170 employees. We are advancing four clinical stage assets with our lead asset, Reprotrectinib, with five regulatory designations, including breakthrough therapy designation. And this year, we plan to start our sixth and seventh clinical study of our drug candidates. I am so proud of the tremendous progress our growing team has continued to make as we work to accomplish the many important milestones we have outlined for 2021. Overall, we continue to advance our four clinical stage 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 towards advancing our vision to be the leader in precision oncology. I will start with our lead program, Repotrectinib, which 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 Intrectinib against wild-type ROS1. Reprotrectinib is currently being studied in our ongoing registrational phase two portion of Trident 1 in patients with ROS1-positive advanced non-small cell lung cancer and NTRK-positive advanced solid tumors. We recently completed a Type B meeting with the FDA based on Reprotrectinib being granted breakthrough therapy designation for the treatment of patients with ROS1-positive TKI-naive metastatic non-small cell lung cancer. The purpose of the meeting was to discuss potential next steps as it relates to clinical, manufacturing, and companion diagnostic development of Repotrectinib with a focus on the TCAT-NAIVE ROS1-positive patient cohort within the TRIDENT-1 study. The overall feedback from the meeting was generally supportive. Based on the FDA feedback, we now plan to discuss the top-line blinded independent sensory review results with the FDA when responders have been followed for at least six months past onset of response. This is new guidance, and we believe it to be positive. We plan to provide further guidance on the registration path for the ROS1-positive TK-naive patient population upon completion of the next FDA meeting, which we anticipate having during the first quarter of 2022. Turning now to enrollment in the TRIDENT-1 study, we continue to enroll across all patient cohorts and anticipate reaching our target of 50 patients with TK-naive ROS1-positive non-small cell lung cancer pooled from the Phase I and Phase II portions of the study this quarter. It remains our goal to provide an enrollment and clinical data update from the Phase 2 portion of Trident 1 in the second half of the year. Repetrectinib is also being studied in the Phase 1-2 care study in pediatric and young adult patients with advanced solid tumors harboring ALK, ROS1, or NTRK alterations. We continue to enroll patients in this trial, which is one of our five ongoing clinical studies. We are now planning to share initial data from this study in the second half of this year. In addition to our development of Repetrectinib in the Trident 1 and the Phase 1-2 CARE study, we are pleased to have, within the past months, achieved both our third and fourth IND clearance within the past two years. And as it relates to our first company-sponsored combination study, our team continues to make progress towards the planned initiation of the first cohort of our multi-arm Trident 2 combination study in mid-2021. This planned Phase 1b-2 study in KRAS mutant solid tumors is based on Repatrectinib's preclinical inhibition of JAK2, SARK, and FAC, which is believed to suppress FAT3 and AKT signaling, known mechanisms of oncogenic resistance. At AACR, we showed preclinical data of Repatrectinib in combination with approved MEK inhibitor Tremetinib, which was more effective than single-agent treatment in patient-derived k-aracinib in G12D and V-lung and G12D, V, and R pancreatic cancer models. As we previously announced, the first cohort of the TRIDEN-2 study will examine the safety, tolerability, pharmacokinetics, and any early signals of efficacy of ripotrectinib in combination with trimetinib in patients with KRAS mutant G12D advanced solid tumors. Next in our pipeline is PBX0022, our MET, SARC, and CSF1R inhibitor, currently being studied in our ongoing Phase I SHIELD1 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 approved therapies 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, including MET-amplified non-small cell lung cancer, both as a single agent and in combinations, as well as in 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 several tumor types with a generally well-tolerated safety profile in a heavily pretreated patient population. The Phase 1 study continues to enroll patients, and we are on track with our goal to identify the recommended Phase 2 dose this quarter. Once selected, we plan to proceed directly into the Phase 1 dose expansion in multiple patient cohorts. We anticipate sharing an additional clinical data update from the Phase 1 dose-finding portion of SHIELD1 in the second half of this year. We have multiple updates anticipated in the second half of this year for O2-2, including a potential discussion with the FDA regarding our plans to modify the SHIELD1 study into a registrational Phase 1-2 design. initiation of the Phase II portion of the study, pending FDA feedback, and finally initiation of our combination study with an EGFR-targeted therapy. Next in our pipeline is TPX0046, our RET inhibitor, currently being studied in our ongoing Phase I-II SORD-1 study in patients with advanced solid tumors determined to be RET fusion or mutation positive. 046 is a compact TKI with preclinical potency against wild-type RET and multiple RET mutations. As a reminder, there are currently no approved targeted therapies for patients who have been treated with a prior selective RET TKI. We believe this represents an unmet medical need and opportunity for 046 in addition to potential safety differentiation. We recently presented early clinical data for 046 and are encouraged by the emerging profile. TBX0046 was generally well tolerated with preliminary data showing clinical activity in a heavily pretreated patient population. The phase one dose finding portion of SORD1 continues to enroll patients, and we continue to evaluate multiple doses and schedules to further characterize the pharmacokinetics, safety, and efficacy profile of O46 before determining the recommended phase two dose. We have modified the phase one protocol to include multiple dose expansion cohorts in both TKI-naive and less heavily pretreated TKI pretreated patients. Next in our pipeline is TPX0131, our ALK inhibitor, currently in the phase one portion of the FORGE-1 study in patients with TKI-pretreated ALK-positive non-small cell lung cancer. At AACR, we presented preclinical data demonstrating the potential for O131 to cross the blood-brain barrier. Additionally, we showed O131 has sub-nanomolar potency against wild-type ALK and is more potent in comparison to approved ALK inhibitors against many clinically observed resistant mutations. While there are several ALK inhibitors currently approved, we believe O131 could have great potential initially in TKI-protreated patients who often develop single or compound ALK mutations. Lorbrenna or lorlatinib is the current standard of care in this setting, but given its limited potency against many resistant mutations and its known safety profile, we believe there is an opportunity for 0131 to potentially differentiate based on efficacy and or safety. Lastly, I want to highlight our growing discovery team. This is a core area of focus for us, and as a reminder, in the second half of this year, We plan to outline our research strategy, including our anticipated timeline, to new drug candidates. We are making progress in our programs and look forward to sharing more detail later this year. Now let me turn to our financial results. You will see in our press release and financial tables that we generated $25.2 million in revenue during the quarter, primarily related to the upfront payment from XyLab under our licensing agreement for O2-2 in Greater China. Operating expenses for the first quarter totaled $61.3 million compared to $62.6 million in the first quarter of 2020. Excluding a one-time non-cash stock-based compensation charge in the first quarter of 2020, non-GAAP operating expenses increased by $30 million, driven by an $18.5 million increase in R&D expenses and an $11.5 million increase in G&A expenses. Increased expenses were attributable to the investments we made to develop our current pipeline, as well as in earlier stage discovery and personnel. We continue to expect expenses will increase during the year as we execute across now five clinical trials, initiate two additional new clinical trials, and make investments in our discovery efforts. Net cash used during the quarter totaled $15.7 million, with the revenue we generated from the Xilab agreement partially offsetting cash used. cash, cash equivalents, and marketable securities at March 31st totaled approximately $1.1 billion. We continue to project our current cash fund's current operations into 2024. To close, I will summarize our goals for the rest of the year beginning this quarter with a key anticipated milestone of reaching our target enrollment of 50 patients with TKI-naive ROS1-positive non-small cell lung cancer pooled from the Phase I and Phase II portions of the Trident One study. Moving on to mid-year, we expect to initiate the first cohort of our TRIDENT-2 combination study. And in the second half, we anticipate providing three clinical data updates, including from the ongoing TRIDENT-1 and SHIELD-1 studies, and initial data from the ongoing Phase 1-2 pediatric care study. Additionally, we anticipate providing an enrollment update from the TRIDENT-1 study, initiating the Phase 2 portion of the SHIELD-1 study pending FDA feedback, and initiating the SHIELD-2 combination study. Last, we also plan on outlining our research strategy, including our anticipated timeline to development candidates. With that update, we are now ready to take your questions. Before we do, I want to close by thanking our great and growing Turning Point team for all they have accomplished so far this year. Operator, you may now open the line for questions.