Turning Point Therapeutics, Inc.

Good day and thank you for standing by and welcome to the Turning Point Therapeutics second quarter 2021 conference call. At this time, all participants are in a listen-only mode. After the speaker's remarks, 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, Jim Mazzola. Head of Investor Relations, please go ahead.

Okay, thank you, and good afternoon, everyone. Following market close today, we filed our Form 10-Q and issued a news release with a summary of our results for the second quarter of 2021. We also updated our investor presentation. You may find these documents posted on the investor pages of tptherapeutics.com. Leading the call today will be Turning Point's President and Chief Executive Officer, Dr. Athena Conturiadis, 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 will be joined by 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, Jim, and good afternoon to everyone joining us on today's call. I am pleased to be joined by Mohamed and our newly hired CFO, Paolo, who brings tremendous financial experience supporting commercial organizations, which is critical as we advance our current pipeline. Our growing Turning Point team of now more than 200 employees has continued to make excellent progress against many important milestones for 2021. Since our last quarterly update, we have received two regulatory designations from the FDA for TPX0022 and began dosing in our FORGE-1 study of our fourth clinical candidate, TPX0131, bringing our total number of ongoing studies to five, with two additional clinical trial initiations planned in the second half. Overall, we continue to advance our four clinical stage next-generation tyrosine kinase inhibitors that target genetic drivers of cancer, and I look forward to sharing today initial information about our ongoing discovery work and our anticipated timelines to potentially new development candidates. As always, I will start with our lead program, Repetrectinib, which is a next-generation ROS1 and TREC TKI with three fast-track designations for ROS1-positive TKI-naive and pretreated non-small cell lung cancer patients and N-TREC-positive TKI-pretreated patients. as well as breakthrough therapy designation for patients with ROS1-positive TCAT-naive non-small cell lung cancer. Reprotrectinib 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. As of last week, we now have approximately 300 patients enrolled in the combined Phase 1 and 2 portions of the Trident 1 study. This total includes approximately 200 patients in the Phase 2 portion of the study, and more than 50 in the ROS1-positive TK-naive advanced non-small cell lung cancer cohort, or EXP1. We have continued steady enrollment across all five additional cohorts within TridentOne, and we were pleased to see our partner XyLab dose initial patients in the study in China. This triggered milestones of $5 million, which we recognized in the second quarter. In June, we reached our target enrollment in eXp1 and have continued to enroll patients in this cohort based on strong momentum and to provide continued treatment access to new patients. As we announced last quarter, based on feedback from a Type B meeting with the FDA, we plan to discuss the top-line blinded independent central review results from eXp1 with the FDA when responders have been followed for at least six months past onset of response. which we continue to anticipate in the first quarter of 2022. We plan to provide further guidance on the potential registration timeline upon completion of the FDA meeting. Turning to the second half Trident One clinical data update, we currently anticipate providing updated efficacy data across multiple ROS1 and NTRK cohorts by physician assessment at the AACR NCI EORTC annual conference in early October. We expect this update at the A&E meeting will also include safety data from approximately 300 patients. And at that time, we will be in a better position to provide next steps on other Trident 1 cohorts beyond EXP1. Our development plan for Reprotrectinib includes two additional studies beyond Trident 1. The first is our Phase 1-2 care study in pediatric and young adult patients with advanced malignancies harboring ROS1, NTRK, or ALK alterations. We are pleased that our first clinical data has been accepted for oral presentation at the International Society of Pediatric Oncology Conference this October. The second is our Phase 1B-2 Trident-2 Combination Study of Repotrectinib and Trematinib, which we plan to initiate in the third quarter. The Trident-2 study will examine safety, tolerability, pharmacokinetics, and any early signals of efficacy of the combination in patients with KRAS G12D mutated advanced solid tumors with the potential to add additional cohorts to the study over time. 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. During the quarter, we received orphan drug designation for TPX0022, for patients with gastric cancer, including gastroesophageal junction adenocarcinoma. In addition, just last week, we received fast-track designation for TPX0022 for patients with MET-amplified advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma after prior chemotherapy. As a reminder, there are no currently approved MET-targeted therapies in gastric cancer. We believe we have multiple opportunities to differentiate O2-2, including in exon 14 indications, as well as both met amplified gastric and non-small cell lung cancer. Last fall, our preliminary data for TPX0022 in the first 21 patients treated showed objective responses across several tumor types with a generally well-tolerated safety profile in a heavily pretreated patient population. Since then, we have continued enrollment across multiple different dosing cohorts, and based on the available PK, safety, and preliminary efficacy data, we have selected our likely recommended Phase 2 dose and began dosing in the Phase 1 dose expansion. This is an important milestone for the program, as the patient populations within Shield 1 will now be further refined, with less heavily treated patients enrolled into individual cohorts, based on tumor type, including exon 14, and met amplified non-small cell lung cancer, and met amplified gastric cancer. We are preparing for an end of phase one meeting with the FDA this quarter, and pending FDA feedback, including agreement on the recommended phase two dose, our goal is to revise the study into a potentially registrational phase one-two, and proceed into the multi-cohort phase two portion of the SHIELD-1 study. Our proposed phase two study designs is similar to the phase one dose expansion, which is currently ongoing and focuses on four main patient populations, including met exon 14 skipping non-small cell lung cancer, both treatment naive and pretreated, and both met amplified non-small cell lung cancer and gastric cancer. We plan to share more details on the FDA feedback and the phase two design after the end of phase one meeting. In addition to our TridentOne data update at the A&E meeting in October, We also anticipate providing a clinical data update in patients with MET alterations across multiple tumor types from the phase one dose finding portion of the SHIELD-1 study. This update will focus on PK, safety, and preliminary efficacy data supporting our recommended phase two dose. Last, for O2-2, we continue to anticipate initiation of our combination study with an EGFR targeted therapy later this year. We plan to provide guidance regarding the details of the study once the IND is filed. Next in our pipeline is TPX0046, our RET inhibitor, currently being studied in our ongoing Phase I-II SORD1 study in patients with advanced solid tumors determined to be RET fusion or mutation positive. The Phase I dose-finding portion of SORD1 continues to enroll patients, where we are evaluating multiple doses and schedules to further characterize the pharmacokinetics, safety, and efficacy profile before determining the recommended Phase 2 dose. We will outline plans for our next data update from this program in early 2022. Last in our pipeline is TPX0131, our CNS penetrant ALK inhibitor, where the Phase 1-2 FORGE-1 study is actively enrolling, and we are currently opening additional sites in the U.S. and Australia. We are excited to advance 0131 given the potency we have seen preclinically, which was recently published in Molecular Cancer Therapeutics. 0131 is a selective ALK inhibitor that is highly potent in a wide array of cellular and in vivo tumor models. Against the G1202RL1196M compound mutation, which harbors both solvent front and gatekeeper mutations, TPX0131 had substantially higher cellular activity than approved ALK targeted therapies. In in vivo xenograft tumor studies, 0131 demonstrated complete tumor regression in an ALK-dependent model harboring the G1202R solvent front mutation and models harboring compound mutations. While there are several ALK inhibitors currently approved, we believe 0131 could have great potential initially in TKI pre-treated patients who often develop single or compound ALK mutations. Shifting focus now, the progress and investments we continue to make in our discovery programs are all directed towards advancing our vision to be the leader in precision oncology. Since the company was founded, Turning Point's core discovery methodology has been anchored by deep structure-based drug design expertise to deliver highly potent and differentiated small molecules. This approach has enabled us to successfully advance four candidates into clinical development, with our lead asset now in an ongoing registrational study. Moving forward, our goal is a research portfolio that can support at least one new IND every year beginning in 2023. Today, I will share two of the four discovery targets our team is pursuing and our potential timeline to future development candidates. Our focus in selecting new targets begins with the following criteria. First, addressing areas of high unmet medical need for patients. Second, leveraging our deep expertise in fragment and structure-based drug design. Third, the strength of the biology supporting the target. And finally, the potential market opportunity. Each of our four new programs have been established around targets that play large roles in aberrant GTPase activity and signaling known to drive genomically defined cancers with significant unmet medical need. Each program is underpinned with a fully-enabled structural platform, providing real-time protein ligand co-crystal structures used to prospectively guide designs. We are focused both on validated targets as well as novel first-in-class opportunities within oncology. Today, I will share initial information on the two most advanced programs. The first program targets KRAS G12D. Mutant KRAS is present in approximately 30% of all cancers and is an attractive therapeutic target for its role in modulating RAS, RAS, MEK signaling pathways. While there is now an approved KRAS G12C therapy in Lumicrast, there have been very few advances in the G12D space, and it remains an area of high unmet medical need in multiple tumor types, including pancreatic, colon, and non-small cell lung cancers. Our goal is to nominate a development candidate in the second half of 2022. Our second program targets the P21-activated kinase, or the PAC family. This target represents a multi-tumor opportunity with a selective inhibitor of PAC1 and PAC4, which are key signaling nodes in subsets of breast and ovarian cancers, melanoma, and non-small cell lung cancer. Our goal is to differentiate this program with dual inhibition of amplified PAC-1 and PAC-4, which we believe has potential as a single agent and in combination. We are also targeting a development candidate in the second half of 2022 for this program. Overall, we are excited by these early pipeline programs and look forward to sharing more detail in future investor and medical forums. Now let me turn the call over to Paolo to provide an update on our financial results.