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Edited Transcript of TPTX.OQ earnings conference call or presentation 4-Nov-19 9:30pm GMT

Q3 2019 Turning Point Therapeutics Inc Earnings Call

Nov 23, 2019 (Thomson StreetEvents) -- Edited Transcript of Turning Point Therapeutics Inc earnings conference call or presentation Monday, November 4, 2019 at 9:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Athena Maria Countouriotis

Turning Point Therapeutics, Inc. - President, CEO & Director

* James S. Mazzola

Turning Point Therapeutics, Inc. - SVP of Corporate Communication & IR

* Yi Larson

Turning Point Therapeutics, Inc. - Executive VP & CFO

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Conference Call Participants

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* Andrew Scott Berens

SVB Leerink LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst

* Arlinda Anna Lee

Canaccord Genuity Corp., Research Division - Analyst

* Kyuwon Choi

Goldman Sachs Group Inc., Research Division - Equity Analyst

* Michael Werner Schmidt

Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD

* Yanan Zhu

Wells Fargo Securities, LLC, Research Division - Associate Analyst

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Presentation

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Operator [1]

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Good afternoon, ladies and gentlemen, and welcome to the Turning Point Therapeutics Third Quarter 2019 Conference Call. (Operator Instructions)

As a reminder, this conference call is being recorded.

I would now like to turn the conference over to your host, Mr. Jim Mazzola, Senior Vice President. Please go ahead.

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James S. Mazzola, Turning Point Therapeutics, Inc. - SVP of Corporate Communication & IR [2]

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Okay. Thank you, Ella, and good afternoon, everyone. Following market close today, we filed our Form 10-Q for the third quarter, issued a news release with a summary of our results and updated our investor presentation. You may find all of 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 Countouriotis, who will provide an overview and update on our business results; followed by a review of third quarter financials by Yi Larson, our CFO. We will take questions following our prepared remarks.

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, including our prospectus and quarterly filings.

Now let me turn the call over to Athena.

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [3]

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Thank you, Jim, and good afternoon to everyone joining us today. I am happy to be joined by our Chief Financial Officer, Yi Larson, on today's call.

I am very proud of the progress our team has made over the past quarter and year-to-date. This year, we outlined multiple important milestones for 2019. And as of today, I am very pleased with the progress towards accomplishing them.

During today's call, I will give you an update on each milestone. Before I get into the details, I want to start by highlighting reasons why we believe Turning Point is a differentiated precision medicine company. At Turning Point, we have internally discovered and developed our wholly owned pipeline of next-generation tyrosine kinase inhibitors, or TKIs, that target numerous genetic drivers of cancer, namely ROS1, TRK, ALK, MET and RET, for use in both TKI-naive and TKI-pretreated patients. Our macrocyclic platform has enabled us to design multiple small and compact kinase inhibitors with the potential to overcome the limitations of conventional TKIs. One of the limitations of conventional TKIs is the pervasive challenge of intrinsic and acquired resistance that often limits the response rate and durability of response with existing therapies.

One challenge is the emergence of mutations in an area of the kinase called the solvent front, which is a common cause of acquired resistance to currently approved therapies for ROS1, TRK and ALK.

In addition, we believe solvent-front mutations will arise from current approved and investigational RET inhibitors, and that our macrocyclic platform has generated TKIs that are potentially best-in-class based on their rational design, their potency and their ability to bind to their targets, with greater precision and affinity than other kinase inhibitors.

I would now like to highlight key achievements from the quarter, starting with our lead drug candidate, repotrectinib, which is being evaluated in a registrational Phase II trial, called TRIDENT-1, for the treatment of patients with ROS1 positive advanced non-small cell lung cancer and for patients with ROS1, NTRK or ALK-positive advanced solid tumors.

First, in early September, we announced updated preliminary data from the Phase I portion of TRIDENT-1, which was then presented at the annual congress of the European Society for Medical Oncology. We believe these results continue to demonstrate the potential of repotrectinib to be a best-in-class, ROS1, NTRK inhibitor based on both the clinical Phase I data and preclinical potency data shown earlier this year.

Since ASCO of last year, each time we have reported data from the Phase I TRIDENT-1 study, it has improved and continue to build our confidence in the potential for repotrectinib to be a best-in-class agents in both the front line and later line treatment settings for ROS1-positive non-small cell lung cancer patients, NTRK-positive advanced solid tumor patients.

The second key achievement for the quarter is that we made strong progress advancing our pipeline of kinase inhibitors, in addition to our lead program. During the quarter, we were pleased to submit and clear the IND for our novel RET inhibitor, TPX-0046 and expect very soon to initiate our Phase I/II study in patients with RET-altered non-small cell lung, thyroid and other advanced cancers. We also continue to make progress in the ongoing Phase I study of our novel MET inhibitor, TPX-0022.

A key milestone we set at the time of our IPO in April was to submit and clear the INDs for both TPX-0022 and TPX-0046 and initiate both studies prior to the end of the year. I am so proud of our team for all they have accomplished and achieved this year.

And last, we completed our first follow-on stock offering in September, in which we raised $189.5 million in net proceeds. With our cash position at September 30 of $424 million, we believe we are sufficiently funded beyond 2021, which is past the early data readouts from both our Phase II TRIDENT-1 study and the Phase I TPX-0022 that we project in the second half of 2020.

With that background, I will provide a more comprehensive update on repotrectinib from the data we reported in a total of 93 patients, including 40 efficacy evaluable ROS1-positive non-small cell lung cancer patients and 2 NTRK-positive advanced solid tumor patients. The results continue to demonstrate a consistent safety profile and showed repotrectinib was generally well tolerated, with clinical activity in both TKI-naive and TKI-pretreated patients.

As of the July 22 data cutoff, a 91% confirmed overall response rate by blinded independent central review was achieved in TKI-naive ROS1-positive non-small cell lung cancer patients. With a median follow-up time of 20.1 months, the median duration of response was not yet mature, with 50% of responders without an event at the time of the analysis, and responses ranging from 3.7-plus to 23.3-plus months. That said, the probability of a response duration of 18 months or greater was estimated at 65% using the Kaplan-Meier method, which is encouraging, given the median duration of response with the approved agent crizotinib is 18.3 months.

In addition, activity within the central nervous system is very important for long-term patient benefit. And in all 3 TKI-naive patients with measurable CNS disease at baseline, confirmed responses were achieved with durations of 14.8-plus to 23.1 months at the time of the data cutoff.

In patients treated with 1 prior TKI, a 39% confirmed overall response rate was achieved across all doses and a 55% confirmed ORR was shown in these patients treated at the Phase II dose of 160 milligrams or above. Among the crizotinib pretreated patients with a known solvent-front mutations, the confirmed overall response rate was 43%. We also reported responses in patients previously treated with 2 prior TKIs, showing a confirmed ORR of 29% at the time of the data cut off. Each of these response rates in patients treated with either one prior or 2 prior TKIs are quite encouraging, given the limited treatment options for pretreated patients.

Additionally, these populations represent individual ROS1-positive non-small cell lung cancer cohorts within the ongoing Phase II registrational TRIDENT-1 study. In addition to the data in ROS1-positive non-small cell lung cancer, we remain encouraged by the clinical activity of repotrectinib in NTRK-positive advanced solid tumor patients. We had previously reported a durable response in a patient with a TRKC solvent-front mutation, who was previously treated with crizotinib and entrectinib, and in September, reported our first response in a TKI-naïve thyroid cancer patients. We remain encouraged by our initial activity within TKI-naive and pretreated TRK patients, both patient populations also represented in the Phase II portion of TRIDENT-1.

Moving now to the Phase II registration portion for TRIDENT-1. Since our last call, we have continued to activate our global sites and enroll patients. Just last week, we completed our Asia Pacific investigator meeting, where engagement in the trial was high. The key theme we continue to hear from investigators is that the most potent ROS1 or TRK TKI should be utilized in the front-line setting, which we believe is very positive for repotrectinib. Our team remains very motivated to get our sites up and running and enrolling patients as quickly as possible. This remains our top priority through the end of this year and into next year.

As a reminder, the Phase II portion of TRIDENT-1 is expected to enroll approximately 310 patients at about 100 sites globally in the United States, Europe and Asia Pacific regions. Of the 6 single-arm cohorts, 5 maybe registrational, based on feedback we received from FDA following an end of Phase I meeting in late 2018.

In terms of a time line for our registrational Phase II study, as we continue to activate sites and enroll patients, we will have better visibility on our time line for enrollment. And we'll plan to provide an update on the time line at a later time. At this early stage, I am pleased with our progress with many sites now activated in the U.S. and Australia and additional sites activating soon. It remains our goal to provide an early interim data readout from initial patients from some of the registration cohorts during the second half of 2020.

Lastly for repotrectinib, we are on track to initiate our study in pediatric patients very soon. This Phase I/II single-arm open-label study will assess repotrectinib in pediatric patients with ALK, NTRK or ROS-positive advanced solid tumors. This is an important study to evaluate repotrectinib in patients under the age of 12.

Additionally, we continue to evaluate multiple potential combinations with repotrectinib for future clinical studies. I am excited about the potential here, based on our ongoing preclinical and translational research and the potential we see in repotrectinib beyond ROS1 and NTRK. I look forward to providing an update on next steps early next year.

With that summary of our development plans for repotrectinib, I want to transition to our pipeline, beginning with TPX-0022, our MET/CSF1R/SRC inhibitor.

Our Phase I open-label study in patients with advanced solid tumors harboring genetic alterations in MET is progressing well, with sites now screening and enrolling patients. As a reminder, the study is a standard dose escalation design, starting at 20 milligrams daily to determine the maximum tolerated dose, overall safety profile and preliminary efficacy of TPX-0022.

Upon determination of the recommended Phase II dose, the study would then evaluate multiple dose expansion cohorts for a targeted enrollment of approximately 120 patients at sites in the U.S., Europe and Asia Pacific regions. It remains our goal to provide an initial data update during the second half of 2020.

Next in our pipeline is TPX-0046, our novel RET/SRC inhibitor. We are encouraged by the potential for TPX-0046, based on its preclinical potency against wildtype KIF5B-RET, which has shown at ESMO, is comparable to proxy compounds for LOXO-292 and BLU-667, with stronger potency against solvent-front mutations, including G810R. We believe a key differentiator for 046 (sic) [TPX-0046] is its compact design and the targeting of both RET and SRC, as the inhibition of SRC has the potential to reduce recruitment of multiple receptor tyrosine kinases involved in bypass resistance.

It was an active quarter of progress for 046, as we showcased preclinical data in September at ESMO, submitted and cleared the IND and expect very soon to initiate our Phase I/II study, which will be a huge achievement by our team to accomplish this so soon after IND clearance, which occurred just on September 30.

We are working with our investigators to activate sites as soon as possible as we believe there is a clear unmet need that still exists. The Phase I/II first-in-human open-label clinical study of 046 is designed to enroll patients with RET-altered non-small cell lung, thyroid and other advanced cancers. You will find the study design in our updated investor presentation posted on our website. We plan to enroll approximately 50 patients in the Phase I dose escalation portion and approximately 300 patients in the Phase II expansion portion with multiple cohorts to assess safety, tolerability, PK and efficacy. The study design allows intra-patient dose escalation based on tolerability in both RET/TKI-naive and pretreated patients. We designed the Phase II portion of the study to be potentially registrational, taking a similar approach as we did with repotrectinib. Prior to starting the Phase II portion, we would plan on having a discussion with health authorities about the registrational path for TPX-0046.

Finally, we continue to make progress towards candidate selection for our next-generation ALK inhibitor. Our goal remains to nominate our candidate later this year for IND-enabling studies.

The plan we laid out for 2019 included submitting 2 INDs and initiating 4 clinical trials across our pipeline of 3 molecules. We have made excellent progress towards achieving these goals, often well ahead of our projected time lines. The funding we raised this year in both our initial public offering in April and in our recent follow-on offering in September, positions us well to continue to deliver against our 2019 goals and to further enrollment in each of our clinical studies in 2020 and beyond.

One final and important note about our growing Turning Point team. Today, we announced the hiring and start date for Dr. Mohammad Hirmand as our Chief Medical Officer. Mohammad, who was most recently the Chief Medical Officer for Peloton Therapeutics, which was acquired by Marck -- Merck, excuse me, which was acquired by Merck in July. Prior to Peloton, his role as Chief Medical Officer at Medivation, which was acquired by Pfizer in 2017. Mohammad has a strong background in oncology drug development and will be an important member of our team as we advance our current clinical studies and further develop our pipeline. I could not be happier Mohammad is joining our team in early December, and I look forward to introducing him to you in the near future.

With that strategic and operational update, I will turn the call over to Yi to discuss our financial results.

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Yi Larson, Turning Point Therapeutics, Inc. - Executive VP & CFO [4]

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Thank you, Athena, and good afternoon, everyone. I'm very happy to be on my first quarterly call since joining Turning Point Therapeutics in August. As you may know, my history with the company dates back to my role as the lead banker from Goldman Sachs on the Turning Point IPO. I decided to join the team, given the company leadership, the encouraging data with repotrectinib and the pipeline of additional TKIs that have rapidly progressed into the clinic. In addition to my role as Chief Financial Officer, I am excited to work with the team on our corporate strategy and to further scale the company and continue to strengthen our discovery and development engine. I have already met many of you and look forward to seeing more of you at upcoming conferences.

Turning to the financial results of the third quarter, operating expenses totaled $22.1 million, an increase of $3.6 million sequentially from the second quarter and compared to $6.1 million in the third quarter of 2018. Similar to last quarter, expenses are ramping as we initiate our clinical trials and build out our teams.

Primary drivers of the year-over-year increase were investments made to develop repotrectinib and the rest of our pipeline, including the head count we have added. Operating expenses in the third quarter also include $3.5 million in noncash stock-based compensation expenses.

For the 9 months ending September 30, operating expenses were $54.7 million (sic) [$54.5 million] compared to $16.2 million during the prior year period. The increase was also driven by development expenses for our 3 clinical stage assets as well as personnel expenses. Included in the year-to-date increase is $8.5 million in noncash stock-based compensation.

Moving to cash flow and the balance sheet. Net cash used in operating activities during the quarter was $16.5 million, bringing our year-to-date net cash used in operating activities to $43.7 million. Our cash, cash equivalents and marketable securities at September 30 were $423.6 million compared to $250.2 million as of June 30. The increase was driven by net proceeds from our follow-on offering in September of $189.5 million. We now project our cash position will fund current operations beyond 2021.

Looking ahead to the fourth quarter, we expect expenses will increase from the third quarter as we continue to invest in the execution of clinical trials for our 3 clinical stage assets and launch a fourth study in pediatric patients.

And with that, let me turn the call back to Athena, who will provide closing comments.

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [5]

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Thank you, Yi. I am very pleased with the progress we have made to date against our plan for the year. We've achieved nearly every milestone we outlined earlier this year, often ahead of schedule and took action to complete our follow-on offering in September to ensure the company is well funded through key data readouts in 2020.

As I look ahead to the last 2 months of the year, we will continue to focus on delivering against our milestones. Our goals remain to: advance enrollment in each of our clinical trials, initiate our Phase I/II clinical study of TPX-0046, initiate our Phase I/II study of repotrectinib in pediatric patients, nominate a development candidate in our ALK inhibitor program and continue to focus on our ongoing preclinical work to support our combination strategy for repotrectinib. We look forward to sharing progress against each of these goals in 2020.

I want to close by thanking our great Turning Point team for all they accomplished during the quarter and year-to-date. Looking back at the past 4 quarters, we have grown the company from less than 20 employees to now approximately 90 employees, and I am incredibly humbled by the talent we continue to attract and what we have as a team accomplished. We set big goals for ourselves in 2019, and I am so proud of how this team continues to deliver.

Operator, you may now open the line for questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from the line of Michael Schmidt from Guggenheim.

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Michael Werner Schmidt, Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD [2]

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Congrats on all the progress. I had one on your 2 more recent pipeline or Phase I study entries, 0046 and 0022. Just generally speaking, could you remind us how the SRC inhibition aspect of those molecules could be a potential differentiating factors for these 2 agents, the RET and the MET inhibitor, respectively? And to what degree might this potentially add to potential toxicities as well?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [3]

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Yes. Sure. Thanks, Michael, for the question. One of the things in regards to SRC is, I have quite a bit of experience here. I've worked on 2 prior SRC inhibitors from both bosutinib and -- bosutinib or Bosulif. I think what has been clearly shown in the past is maybe different than what we're doing here. And SRC is also a part of repotrectinib, just so you know. And I think that's one of the beauties of repotrectinib is in the way that it was designed was not to be exclusively specific for ROS1 and TRK, but to be highly selective. And part of that selectivity included SRC in the SRC family kinases, which we believe add to some of the benefit of repotrectinib in its ability to tackle bypass mechanisms of resistance, to what's called the STAT3 bypass pathway. That is where SRC has activity, that is what could potentially also translate into both 022 and 046 (sic) [TPX-0022 and TPX-0046] and one of the ways that we believe are MET inhibitor and our RET inhibitor differentiates versus those that are ahead of us.

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Michael Werner Schmidt, Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD [4]

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Very good. And I guess that brings you to my next question. So it sounds like the 0022 study is a little bit further along than the RET inhibitor, and you outlined the design on the call earlier. Can you just help us understand how you think about potential positioning of 0022 relative to capmatinib longer term? I know it's still early, but how do you think about the Novartis compound here?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [5]

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Yes. When I look at 022, and it's interesting that these are the first questions coming, I would say that I think most of the focus has been on repotrectinib and 046. So I'm very happy to hear your enthusiasm because we have just as much. Jean has been working in the MET space for over 20 years. And this is a molecule that she is the most proud of, which is 022. And again, to that same theme, I said earlier, capmatinib being more specific. I think for where we are hoping to focus 022 is really, again, in an area beyond exon 14 skipping mutations. So I think that's the relevance in terms of the comparison to the compound you're mentioning. I really do believe there are 2 things we have to prove here. I think one is that there still is an unmet medical need for another Met inhibitor in the clinic. And two, the benefit, as you've been outlining, for CSF1R also with SRC for our MET inhibitor. I'm very pleased with enrollment here as I am with the Phase II study. I've definitely been seeing a diversity of the patients that have been enrolled. So I do believe we're starting to show that there is still an unmet medical need for a MET inhibitor.

I think the second component in regards to the benefit of CSF1R SRC will come through the data. And as we've said, we're guiding towards an update from the Phase I in the second half of next year.

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Michael Werner Schmidt, Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD [6]

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Great. Then one more, maybe on repotrectinib. And I know you mentioned the interim analysis or the initial data from the Phase II portion of the TRIDENT study in the second half of next year. But how should we think about additional follow-up data or updates from the ongoing Phase I study, especially when we think about durability of the frontline patient population?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [7]

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Yes. Sure. So as you know, and as I said in the prepared remarks, the Phase II is, by far, our top priority for the team. I'm pleased with the progress they're making, not only with patient enrollment, but also investigator engagement as well as site activations. In regards to the Phase II, just so you know, in all of our trials, we will not give quarterly updates. That's not going to be our standard practice in terms of enrollment numbers, but rather try to guide you towards meaningful data time points. And so what we've been saying for not only the Phase II, but 022, as I just mentioned, is an update in the second half of next year.

In relation to the Phase I, as you know, we've updated that twice since the IPO. And from April to ASCO, the data improved. From ASCO to ESMO, the data further improved. And my level of confidence in the Phase II now is incredibly high based on the data, again, that we've continued to show, not just within this year, but also the data cuts that we showed last year from the Phase I. I am putting the team now 100% focused on trial execution. We are about to have our third and fourth trials in the clinic very soon, and the 2 data time points that we're reading out to next year in the second half of the year. So at this point, obviously, the team is continuing to follow the patients in the Phase I, but it's not our intention to do another update from that data set because, again, the encouraging information we've already shared is that with a median amount of follow-up of over 20 months, the median duration of response was not yet mature. And I think that's incredibly encouraging, again, knowing the number for crizotinib at 18 months.

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Operator [8]

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Our next question comes from the line of Paul Choi from Goldman Sachs.

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Kyuwon Choi, Goldman Sachs Group Inc., Research Division - Equity Analyst [9]

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Athena, maybe staying on repotrectinib. For the planned combination study with Tagrisso, can you maybe articulate to us what you think is the lowest hanging fruit in the EGFR patient population that could potentially help you leapfrog some of the other combination studies that are being pursued by competitors? And then what would you look for as sort of the go or no-go decision for a potential pivotal trial here?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [10]

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Yes. Thank you for the questions, Paul. First of all, we're looking at quite a few combinations. We've obviously discussed previously, as I said before, the benefit of having SRC and potential activation within the STAT3 bypass pathway is one of the ways that we think we could utilize repotrectinib in combination with the EGFR inhibitor. We're still evaluating that as we are evaluating other novel combinations. So at this point, it's a little too early to talk about go/no-go decisions in regards to that trial design. Again, it's something we're still looking at. But we're also looking at quite a few additional combos. And I think we made the conscious effort on the last call to highlight that we've really been strengthening our internal translational research biology, building our chemistry group to be able to further develop not only the combination strategy with repotrectinib, but also future discovery efforts. So it's a little early to give go/no-go because we're still looking at multiple options in terms of combo designs. And we said that we would give some data in regards to that work early next year.

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Kyuwon Choi, Goldman Sachs Group Inc., Research Division - Equity Analyst [11]

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Okay. Great. Then turning maybe back to 022 for a moment and the RET. Can you give us maybe as you -- your thoughts on trial design and prioritization of either the treatment-naive population or the treatment-experienced population or is the plan to go at them simultaneously, given that you could potentially have launches of 2 drugs in the category over the near term?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [12]

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Yes. Again, I would say that there's a lot of similarities in regards to what we're doing for both of the Phase I programs. Obviously, 022 is further ahead than 046. 022 essentially is a standard dose escalation with the Phase I component of escalation and then expansion, where we would be looking at multiple different disease types, whether it's lung or GI-oriented diseases such as gastric or hepatocellular. There will be optionality there based on prior TKI use, yes or no. That is a standard Phase I. The RET is definitely different. And as we said in the prepared remarks, we've now updated our investigator presentation to show the design. The RET design, which is a much bigger Phase I/II mirrors what we did with repotrectinib, and again, allows quite a bit of optionality. There is a Phase I dose escalation component. But as we proceed towards Phase II, there are multiple cohorts, just like TRIDENT-1 that would again be disease driven, so lung, thyroid versus others and options in regards to prior TKI use, prior platinum use, yes or no. I think we've tried to take some of the lessons learned there from the other investigational agents that are ahead of us and potentially look at ways we could maximize our time line for the RET inhibitor.

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Operator [13]

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Our next question comes from the line of Andrew Berens from SVB Leerink.

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Andrew Scott Berens, SVB Leerink LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst [14]

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Congrats, guys, on the progress. Maybe a couple of questions on repo. I guess, in TRIDENT, what percent of your patients do you think will have brain mets? And what's the typical course of a patient with brain mets.

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [15]

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Yes. So one of the things we've been monitoring, obviously, is the activity in the front line, second line as well as intracranial and extracranial. And as you know, Andy, we have very strong data, both in the frontline setting with all 3 patients having responses who had intracranial measurable disease as well as 75% in the pretreated setting. Our estimates are somewhere, and it depends on the literature, but it does mirror what we saw in our trial, and the trial itself for us is somewhere around -- it really depends on the patient population, but around half of the patients. Most of the literature supports a higher incidence for patients potentially in the upfront setting versus pretreated setting. But that's kind of the numbers that we've seen in terms of the incidence.

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Andrew Scott Berens, SVB Leerink LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst [16]

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So you're saying, in the front-line setting, it's 50%, which is higher than in the second and third line?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [17]

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It really depends on the data set that you're looking at. In our hands, again, our data was pretty consistent with what you see in the literature, which is about half of the patients.

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Andrew Scott Berens, SVB Leerink LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst [18]

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Okay. And how long do those patients typically survive without progression? And once they progress, any idea how long they usually live?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [19]

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I don't have the OS data in front of me to be able to answer that, Andy. I think what you could say from the literature is that you see relatively similar rates, depending on whether you're looking at the historical entrectinib data, when they showed response rates. What you don't see is similarities between the duration and/or the PFS. And so I don't have the OS numbers. I know the recent crizotinib paper that was presented, probably about 6 months ago now in the literature, may have that. But I don't have that on the top of my head.

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Andrew Scott Berens, SVB Leerink LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst [20]

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Okay. And then, I guess, any idea of how the entrectinib launch is going?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [21]

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We've clearly been watching it. I think it's early days still, clearly. It got approved, obviously, in the beginning of August. I think, again, nothing has changed in regards to the way that we believe repotrectinib will eventually be utilized post, obviously, a registration path and approval. We still believe, based on the fact that it is the most potent agent, that it will be best-in-class for frontline. As you know, entrectinib is not approved and does not have activity in patients who have resistance. So that's clearly an area we will differentiate as well.

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Andrew Scott Berens, SVB Leerink LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst [22]

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Okay. And then I guess on the RET program, just how difficult will be to enroll patients that have failed 292 or 667, identify them and then enroll them? Are the Loxo, Lilly and Blueprint also aggressively trying to enroll those patients in the trial?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [23]

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The one thing I would say, is this is the one where I would give the team incredible amounts of credit that they've completely knocked it out of the park. We came out of ESMO incredibly motivated. The IND cleared. And basically, what we saw at ESMO was investigator enthusiasm, not only for our data, which was for the first time, head-to-head versus both of the molecules you're referring to in terms of proxy compounds. But also, we clearly heard from multiple investigators that treatment resistance is occurring. And a molecule that can overcome some of these resistant mutations is potentially coming to the clinic at the right time. I'm not going to predict too much in terms of future enrollment, except to say that obviously, we're initiating the trial very soon, and there's a tremendous amount of enthusiasm from the investigators to get the trial going because we know patients are waiting.

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Operator [24]

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Our next question comes from the line Arlinda Lee from Canaccord.

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Arlinda Anna Lee, Canaccord Genuity Corp., Research Division - Analyst [25]

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Congratulations on the progress. I'd like to maybe follow-up on one of Andy's questions. You talked about some of the ESMO investigators shared with you about the need for active agents -- agents active against resistance. Curious, given that a lot of the lung docs talk about using the most potent drug upfront, how that might fit into what they've been talking to you about? And then as well, can you talk a little bit about the ALK inhibitor that you're planning to decide on a go-forward molecule with what kinds of characteristics are you looking for in that molecule versus what you have in the clinic already?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [26]

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Yes. Sure, Arlinda, thanks. The one thing I would say is, I think it was -- it's fair, and I've said this before, establishing efficacy in a pretreated setting may not be uncommon for us to do here with 046, our RET inhibitor. It's exactly what we did with repotrectinib. But from a potency perspective, as we showed at ESMO, we believe that we are very comparable in the wildtype setting. The Phase I design allows all kinds of flexibility in terms of patients can be enrolled with and without prior RET TKI use. So I think it really will be determined based on the investigator. At this point, the conversations we've been having clearly is about an unmet medical need for another RET to move into the clinic, and that's probably where I'll leave it. I want all of that information to be captured within our database, and then clearly, we'll start talking more about what types of resistance are occurring from those other agents and/or if we're enrolling patients who are TKI naive. From the ALK inhibitor characteristics, as you know, repotrectinib does hit ALK, it does not hit ALK as potently as it does, ROS1 and TRK. Clearly, one of the areas that Jean and the team have been focused on is our series of candidates for an ALK inhibitor that can address not only the most common G1202R solvent-front mutations, but also a compound mutation where there really is no current available therapy. I think, equally, there are very big differences between our safety profile for repotrectinib and for lorlatinib. And so again, if we can translate some of that safety difference into a new ALK inhibitor. I think that would be incredibly encouraging as well. But we're just a candidate nomination. So I think ideally, what we're looking for is something that can address still an unmet medical need that is not addressed by lorlatinib. And especially, if that agent moves up to the front line, clearly, there will continue to be a need in the second-line setting.

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Operator [27]

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Our next question comes from the line of Jim Birchenough from Wells Fargo Securities.

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Yanan Zhu, Wells Fargo Securities, LLC, Research Division - Associate Analyst [28]

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This is Yanan on for Jim. So do you -- so just first question is on potential resistant mutations to repotrectinib. So do you have some sense from the clinical trial data? In particular, I'm interested in whether patients who progress repotrectinib, may be resistant to other ROS mutations? Since repotrectinib has a very compact 3D structure, is it possible that resistant mutations that preclude repotrectinib may also automatically preclude other inhibitors with larger footprint? And whether that will impact -- whether doctors want to use it in first-line or not?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [29]

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Yes. No, I think it's a very good question. From the resistance perspective of repotrectinib, that data was not captured within the Phase I study. It will be captured within the Phase II. So just to level-set, within the Phase II study, patients will have, obviously, tumor biopsies evaluated for the presence of their fusion prior to enrollment. In addition, prior to enrollment, they'll have a baseline liquid tumor biopsy to evaluate presence of resistant mutations prior to coming on to repotrectinib. They will also have another liquid tumor biopsy, approximately 2 to 3 cycles into treatment and then at the end of treatment or the time of progression. So we'll have potentially 2 opportunities to capture the answer to the question of what resistant mutations are occurring with repotrectinib. I do not have that today.

I think the point that you made, though, about utilizing repotrectinib in frontline, I do not know that, that's going to be dictated by resistant mutation for repotrectinib. I think that story has already been shown in regards to its potency. And the fact that, obviously, our response rate is over 90%.

And so to me, I think the -- what I just came back from Asia at a very large team meeting, and there's a tremendous amount of enthusiasm for the Phase II study and specifically using repotrectinib in frontline. Obviously, crizotinib is now approved there and reimbursed. But given the fact that it is so much more potent. That is the key driving factor for investigators to utilize it upfront.

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Yanan Zhu, Wells Fargo Securities, LLC, Research Division - Associate Analyst [30]

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Got it. That's very helpful. Maybe 2 more quick ones. Could you talk about the distribution of ROS1 patients and how concentrated that is? And if your pivotal study -- you're targeting centers that have a strong concentration of patients. And also, a question on whether you have a better sense of the percentage of ROS1 patients failing Xalkori that have solvent-front mutations?

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [31]

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Yes. I think -- so the historical information that's in their literature that mirrors pretty much what we've shown as well for solvent-front mutations, specifically, the most common, G2032R mutation, is about 40%. And so that's -- our data set is a little bit lower than that. But again, our data set is 40 patients, not all of them have had prior crizotinib. But that's the data that's in the literature to support prevalence of solvent-front mutations. In regards to ROS1 distribution, maybe just let me step back and say, we have approximately 100 sites that will participate within this trial. But those sites were methodically chosen based on not only the incidence of the diseases, but also the physician's experience in the space and their experience with other TKIs that are obviously ahead in terms of their development.

And so again, I think the incidence what we've seen is anywhere between 2% to 3%. I've seen numbers up to 2.6% presented in the literature for ROS1, but we were very mindful in our site selection for Phase 2.

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Operator [32]

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(Operator Instructions) I am showing no further questions at this time. I would now like to turn the conference back to Jim Mazzola for his closing remarks.

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Athena Maria Countouriotis, Turning Point Therapeutics, Inc. - President, CEO & Director [33]

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I'm happy to step in for Jim. It's Athena. All right. Well, thank you, everybody, obviously, for participating in the call. I really want to say thank you to the team. You have done a tremendous job this year. And for all of you that have dialed in, I look forward to seeing many of you at upcoming banking conferences throughout November and December.

Operator, you can now close the call.

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Operator [34]

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Ladies and gentlemen, this concludes today's conference. Thank you for your participation, and have a wonderful day. You may all disconnect.