Turning Point Therapeutics, Inc.

Good day and thank you for standing by. Welcome to the Turning Point Therapeutics third quarter 2021 conference call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, Adam Levy. Thank you. Please go ahead.

Thank you, operator. Good afternoon, everyone. First, let me start by saying I'm happy to be on the call today and to be joining the Turning Point team at such an exciting time for the company. I also want to thank Scott Lipman for managing our investor relations activities recently, and I look forward to working with many of you going forward. Following market close today, we filed our form 10Q and issued a news release with a summary of our results for the third quarter of 2021. We also updated our investor presentation. You may find these documents posted on the investors' pages of tptherapeutics.com. Leading the call today will be Turning Point's President and Chief Executive Officer, Dr. Athena Kantouriotis, who will provide an overview and update on our business results before turning the call over to Paolo Tombesi, our Chief Financial Officer, for a review of our financials. We will take questions following our prepared remarks, and we'll be joined by Dr. Mohamed Hermand, our Chief Medical Officer. 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 call over to Athena.

Thank you, Adam, and good afternoon to everyone joining us on today's call. As this is our last quarterly call in 2021, I want to start by highlighting what I believe to be the true strength of our Turning Point team. In the past three years, we have advanced our macrocyclic platform from one phase one clinical stage asset in one ongoing clinical trial to now four clinical stage assets in six ongoing clinical trials. In addition, we have received a total of nine regulatory designations for our pipeline, including two breakthrough therapy designations for our lead asset, Repetrectinib. Our company has scaled rapidly from 2018, when we were fewer than 20 employees, to now over 230 employees with a clear focus on continued innovation with research and discovery, as well as expertise in clinical development and regulatory. With that backbone and our current $1 billion in cash, we believe we are well positioned to advance our pipeline and are looking to the future as we prepare for a potential launch of Repatrectinib with additional growth in our medical affairs and commercial teams. Our current macrocyclic platform was internally developed to design highly potent, small, and compact inhibitors that could potentially differentiate by overcoming treatment resistance or increased durability of response in indications where few therapeutic advancements had been made. Since then, multiple recent launches in the ROS1-TREK, MET, RET, and ALK spaces have occurred. Yet we continue to believe in the potential differentiation of our pipeline. Focusing on Repotrekinib, we believe it to be a potential best-in-class ROS1 inhibitor based on the data we previously reported in the ROS1-positive TKI-naive and TKI-pretreated non-small cell lung cancer. In addition, we are encouraged by the early signal seen in NTRK-positive advanced solid tumor patients and the recent breakthrough therapy designation granted in the TKI-protreated patient population, where there are no currently approved targeted therapies. Moving to our second drug candidate, we believe in the potential of L-zivantanib to show differentiation as it continues in development, especially due to the biologic rationale supporting the co-targeting of CSF1R and SARC. that has the potential to prolong duration of response. We are focused on finalizing our recommended phase two dose and studying L-zivantanib in a less heavily pretreated patient population, where we can further evaluate its potential. Rounding out the pipeline are two additional drug candidates, TPX0046 and TPX0131, continuing phase one dose finding studies. We look forward to sharing our planned milestones for these programs in the first quarter of next year along with updates from multiple upcoming interactions with the FDA for both Repetrectinib and L-Divantinib. Shifting now to recent highlights since our last quarterly call, I am especially pleased with the progress our dedicated and talented Turning Point team made as we received two regulatory designations from the FDA for Repetrectinib, initiated the Trident II combination study of Repetrectinib and Tremetinib in KRAS mutant G12D solid tumors, our sixth clinical study, presented four data updates across our pipeline, and announced the clinical collaboration with EQRx. In addition, we continue to strengthen our executive team, most recently with the hiring of Adam, who joined us yesterday as Senior Vice President of Investor Relations and Corporate Communications. I am pleased to introduce Adam and welcome him to our team. He brings more than 20 years of experience across both large and small biopharmaceutical companies, and I look forward to many of you working closely with Adam over time. Today, I will recap our recent accomplishments and provide more details on our anticipated future regulatory milestones into 2022. Overall, we continue to advance our four clinical stage next-generation tyrosine kinase inhibitors that target genetic drivers of cancer and our ongoing discovery work, where our goal is to nominate two development candidates in the second half of 2022, one targeting KRAS G12D and the other targeting PAK. both known to play large roles in a barren GTP signaling. We specifically chose these targets due to the strong biologic rationale and potential market opportunities given the addressable patient populations and the limited number of competitive targeted agents that are approved and in current clinical development. I will begin with our lead program, Repotrectinib, our ROS1 TREC inhibitor. Repotrectinib is currently being studied in our ongoing multi-cohort registrational Trident 1 study in patients with ROS1-positive advanced non-small cell lung cancer, and NTRK-positive advanced solid tumors. We received our second breakthrough therapy designation granted by the FDA for repotrectinib in early October. VTD was granted for the treatment of patients with advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with one or two prior TRK TKIs with or without prior chemotherapy and have no satisfactory alternative treatments. As a result, we plan on discussing next steps towards registration of Repetrectinib in patients with NTRK-positive TKI-pretreated advanced solid tumors at a Type V meeting with the FDA next month. Having now received BTD for both ROS1 and NTRK patient populations, we are well-positioned to continue to have frequent dialogue with the FDA regarding our registration strategy. In October, we presented three clinical data updates for Repetrectinib, two from the Registrational Trident 1 study, and one from the Phase I-II care study in pediatric and young adult patients. Overall, Repetrekinib continued to demonstrate promising clinical activity, including in the TKI-pretreated ROS1-positive non-small cell lung cancer and NTRK-positive advanced solid tumor settings, where there are currently no approved targeted therapies. Looking into 2022, we plan to discuss the blinded independent center review data from all four of the ROS1-positive non-small cell lung cancer cohorts of Trident 1, with the FDA at a pre-NDA meeting anticipated in the second quarter of 2022. At this meeting, we plan to discuss available BICR data in at least 50 TKI-naive and 50 TKI pretreated patients with at least six months of follow-up for the majority of responders. We plan to report the top-line BICR data from these cohorts in the second quarter of 2022. Now, let me shift to some of the advancements we have made as we prepare to be a commercial organization. Since hiring our chief commercial officer, Andy, last July, we've continued to build out our commercial leadership team. This team is continuing engagement with KOLs and high-volume prescribers in community and academic settings. In addition, our medical affairs team continues to grow and is engaging thought leaders both in the U.S. and globally. Based on our interactions with oncologists, we have continued to refine our understanding of the opportunity for Repetrecnib. The feedback we have received has been consistent across market research, advisory boards, and one-on-one interactions, which is that compared to the two approved therapies, a higher response rate, increased durability, increased progression pre-survival, and or the ability to treat or potentially delay the emergence of resistant mutations could be clinically meaningful in the ROS1 positive TK-naive non-small cell lung cancer setting. As a reminder, we've previously reported a higher response rate and historically reported with our competitors in the ROS1-positive TKI-naive setting from our preliminary Phase II datasets, as well as a median duration of response of 23.1 months and median progression-free survival of 24.6 months in 11 patients previously reported from the Phase I portion of the TRIDENT-1 study utilizing a blinded independent central review analysis. In the ROS1-positive TKI pretreated setting, there are limited options for patients outside of cytotoxic chemotherapy or lorlatinib, which is not approved in this setting and has not demonstrated confirmed responses in patients with the G2032R solvent-front mutation. In addition, our interactions with oncologists have highlighted that the ability to overcome resistant mutations would be clinically meaningful in this setting. As we look at the opportunity in NTRK-positive advanced solid tumor patients, We are encouraged by our preliminary data in this patient population. Based on our data, we believe in Repetrectinib's best-in-class potential in the TKI pretreated setting, where we recently received breakthrough therapy designation, and there are no currently approved targeted therapies. Overall, based on our research and data for Repetrectinib, we continue to be excited about its potential in both the ROS1 and NTRK settings. Next in our pipeline is L-zavantinib, or TTX0022, our MET, STARK, and CSF1R inhibitor, currently being studied in our ongoing Phase I, Shield 1 study in patients with advanced solid tumors harboring genetic alterations in MET. At the AACR NCI EORTC meeting, we were encouraged by the updated preliminary data for L-zavantinib that was reported from the Phase I dose-finding portion of the study. There are no currently approved targeted therapies in MET-amplified non-small cell lung cancer or or gastric cancer, and we believe we have multiple opportunities to differentiate L-divantinib, including in the exon 14 skipping non-small cell lung cancer indication and in both med amplified non-small cell lung cancer and gastric cancer. In the third quarter, we completed an end of phase one meeting with the FDA, focused on next steps for L-divantinib in non-small cell lung cancer. During the meeting, we received guidance on the design of the planned phase two portion of SHIELD1, and feedback on our recommended Phase II dose. We proposed a recommended Phase II dose of 40 milligrams daily to 40 milligrams twice daily based on the available data at the time of the meeting. The FDA recommended that we explore an additional intermediate dose level using the QD titration to BID dosing strategy in at least 6 to 10 patients prior to starting the Phase II portion of the study. Patient screening at the intermediate dose level of 60 milligrams daily to 60 milligrams twice daily is ongoing, and we plan to enroll at least 6 to 10 patients at this dose as quickly as possible. We plan to provide data from this dosing cohort to the FDA when available with the intention of revising the SHIELD-1 study into a potentially registrational Phase 1-2 design and initiating the Phase 2 portion in 2022. While we focus on enrolling the intermediate dose level, we are also continuing to enroll patients in the phase one dose expansion portion of the study at the 40 milligram daily to 40 milligram twice daily titration dose level. In addition, we anticipate feedback on the development path for L-zavantinib for the treatment of MET-amplified gastric cancer next month. Last, as it relates to L-zavantinib, we were excited to announce a clinical collaboration with ETRX to evaluate L-zavantinib in combination with ETRX's EGFR inhibitor in patients with EGFR mutant met amplified advanced non-small cell lung cancer. We are planning to initiate the SHIELD2 combination study in mid-2022, pending clearance of the IND by the FDA in the first half of next year. Rounding out our pipeline are TPX0046, our RET inhibitor, and TPX0131, our CNS penetrant ALK inhibitor. We are currently enrolling patients in the Phase I dose-finding portion of the SWORD1 study for 046, and the Phase 1 dose-finding portion of the FORGE-1 study of 0131. Last, turning to discovery, we have four internal programs that target aberrant G2PA signaling known to drive genomically defined cancers with significant unmet medical needs. Our most advanced programs focus on KRAS G12V and PAC, where we are targeting two development candidates in the second half of 2022. Our goal is to submit one IND per year beginning in 2023. We believe these are potentially meaningful opportunities given the limited number of targeted agents that are approved and in clinical development in these indications. Now, let me turn the call over to Paolo to provide an update on our financial results.