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Edited Transcript of TPTX.OQ earnings conference call or presentation 6-Aug-19 8:30pm GMT

Q2 2019 Turning Point Therapeutics Inc Earnings Call

Aug 7, 2019 (Thomson StreetEvents) -- Edited Transcript of Turning Point Therapeutics Inc earnings conference call or presentation Tuesday, August 6, 2019 at 8:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Jim Mazzola

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

* Athena Countouriotis

Turning Point Therapeutics, Inc. - President & CEO

* Brian Baker

Turning Point Therapeutics, Inc. - VP of Finance & Administration

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Conference Call Participants

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* Paul Choi

Goldman Sachs - Analyst

* Andrew Berens

SEB Leerink - Analyst

* Michael Schmidt

Guggenheim Securities - Analyst

* Yanan Zhu

Wells Fargo Securities - Analyst

* Arlinda Lee

Canaccord Genuity - Analyst

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Presentation

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Operator [1]

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Good day, ladies and gentlemen, and welcome to the Turning Point Therapeutics second-quarter 2019 conference call. (Operator Instructions). As a reminder, today's conference may be recorded. I would now like to turn the conference over to our host, Jim Mazzola. Sir, the floor is yours.

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Jim Mazzola, Turning Point Therapeutics, Inc. - SVP, Communication & IR [2]

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Thank you and good afternoon, everyone. Following market close today we filed our Form 10-Q for the second quarter and issued a news release with a summary of our results, as well as updated our investor presentation. You may find these documents on the Investor pages of TPtherapeutics.com.

Leading the call will be Turning Point's President and Chief Executive Officer, Dr. Athena Countouriotis, who will [give] you an update on our business results followed by a review of second-quarter financials by Brian Baker, our Vice President of Finance. 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 Countouriotis, Turning Point Therapeutics, Inc. - President & CEO [3]

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Thanks, Jim, and good afternoon to everyone joining us on today's call. I am very proud to lead our first earnings call since our initial public offering in April this year. And excited to outline the tremendous progress that our team made during the quarter against multiple significant goals that we set out to accomplish across our pipeline in 2019.

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-naïve and TKI-pretreated patients.

Our macrocyclic platform enables us to design small and compact kinase inhibitors with the potential to overcome the limitations of conventional TKIs, which was the intent when our Co-Founder and Chief Scientific Officer, Dr. Jean Cui, and her team designed the drug candidates we currently have in our pipeline.

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. (technical difficulty) is the emergence of mutations in an area of the kinase called the solvent-front, which is a common cause of acquired resistance to (technical difficulty) therapies for ROS1, TRK and ALK.

We believe our macrocyclic [formula targets] 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.

Now I would like to highlight a few key achievements from the quarter, starting with our lead drug candidate Repotrectinib, which is being evaluated in the ongoing Phase 1/2 trial called TRIDENT-1 (technical difficulty) patients with ROS1+ advanced non-small cell lung cancer and for patients with ROS1 and TRK or ALK+ advanced solid tumors.

First, following the preliminary data we presented in a total of 33 ROS1+ non-small cell lung cancer patients at an oral presentation at ASCO in May, we have now demonstrated that our lead asset, Repotrectinib, is potentially a best-in-class ROS1 inhibitor with continued improvement in the data as it has matured over time in both the TKI-naïve and TKI-pretreated patient settings.

In addition, we remain encouraged by the clinical activity in NTRK+ advanced solid tumor patients. It is strongly correlated with our preclinical data; albeit in fewer patients than we have treated in ROS1+ on non-small cell lung cancer to date.

Second, we are advancing development of a (technical difficulty) inhibitors in addition to our lead program. We are pleased to have recently initiated the Phase 1 study of our novel MET inhibitor, TPX-0022, after clearance of the IND. We believe TPX-0022 is differentiated from other investigational or approved therapies through its dual inhibition of MET and the known cancer signaling pathways of CSF1R and SRC.

Our third molecule is our novel RET inhibitor, TPX-0046, where our goal continues to be submission of our IND in the second half of this year.

And finally, we completed a (technical difficulty) public offering in April in which we received $175 million in net proceeds. We believe our current cash position of $250 million (technical difficulty) current operations into the second half of 2021, which is past the interim data readouts we project in the second half of 2020.

With that background I will provide a more comprehensive update beginning with Repotrectinib and the results we presented at the end of May at the ASCO annual meeting from the Phase 1 portion of our TRIDENT-1 study. To me there were four important takeaways from ASCO.

First, the preliminary data we presented in patients with ROS1+ non-small cell lung cancer (technical difficulty) multiple dose escalation cohorts demonstrated a consistent safety profile and continued clinical activity in TKI-naïve and TKI-pretreated patients. The clinical data continue to support why we believe Repotrectinib has the potential to be a best-in-class agent in both the front line and later line treatment settings for ROS1+ non-small cell lung cancer patients.

As of the March 2019 data cutoff, in TKI-naïve patients the data showed a confirmed overall response rate by blinded independent center review of 83% at 160 mg daily or above. Equally important for patients is the duration of response. (technical difficulty) more than 16 months of median follow-up we had yet to achieve the median duration of response.

(technical difficulty) activity within the central nervous system is very important for long-term patient benefit. In all three TKI-naïve patients with measurable CNS disease at baseline a confirmed response was achieved in ongoing with durations of 10.9 to 17.6 months.

Overall from our discussions with investigators at ASCO, we believe there was a clear shift in the appreciation of the front-line potential for Repotrectinib based on the continued clinical data in this setting, as well as the preclinical potency that was shown earlier this year at the annual AACR conference.

This (technical difficulty) takeaway from ASCO came from the results we presented in the ROS1+ TKI pre (technical difficulty) cancer patient population, which continued to improve at a dose of 160 mg daily or above. With a median follow-up of 14.6 months, patients treated with one prior TKI showed a confirmed overall response rate by blinded independent central review of 55% with three patients remaining in a response from 1 to 7.6 months at the time of the data cutoff.

In patients with a documented G2032R solvent-front mutation, which has been reported as occurring in up to 41% of patients previously treated with the current approved ROS1 TKI, Crizotinib, the confirmed overall response rate was 40% with both responses occurring at a dose of 160 mg daily. This is clinically meaningful given the limited treatment options in this setting.

Equally encouraging to us was the response we observed in patients with measurable CNS disease at baseline where three of four patients achieved a confirmed response. Overall the Takeaway here was our ASCO data continued to demonstrate the potential of Repotrectinib to address treatment resistance, which was the basis for its design and a key limitation of conventional TKIs that often have very little, if any, efficacy in this patient setting.

The (technical difficulty) away from ASCO was the safety profile and duration of Repotrectinib treatment in the ROS1+ non-small cell lung cancer patient population. At the time of the data cutoff the overall safety profile in a total of 83 patients treated across nine dose escalation cohorts remained consistent with the majority of treatment emergent adverse events being Grade 1 or Grade 2 and the most common being low-grade dizziness, [dyskesia], dyspnea and fatigue.

There were very few Grade 3 treatment-related adverse events, no Grade 4 treatment-related adverse events and no cases of dizziness leading to treatment discontinuation. There were also no new dose limiting toxicities or treatment-related deaths since the prior data cutoff in October of 2018.

Additionally, 45% of patients remained on treatment with 12 of the 15 patients who remained on Repotrectinib for greater than one year and many patients continuing to be treated post radiologic progression.

The final takeaway from ASCO was the enthusiasm from investigators for the Phase 2 registration portion of our TRIDENT-1 clinical study of Repotrectinib, which we (technical difficulty) in June. We are seeing demand for our clinical trial in the ROS1 and TRK cancer settings and we look forward to working closely with our (technical difficulty) investigators activate as many sites as fast as possible.

Just last week we completed our first North America investigator meeting where engagement in the trial was high and the caliber of (technical difficulty) impressive. I could not be more pleased with the group of thought leaders and experts involved in this study.

Since ASCO I am happy to report that the FDA very recently accepted our recommended [phased] dose regimen of Repotrectinib, which is 160 mg daily for the first 14 days after which the dose may be escalated to 160 mg twice per day based on patient tolerability. We are very motivated and now in full execution mode to (technical difficulty) sites and dose patients. This will be our top priority through the end of this year and into next year.

As a reminder, our registrational trial, TRIDENT-1, is an ongoing Phase 1/2 open label of single agent Repotrectinib. The Phase 1 portion is winding down as we move sites towards the Phase 2 portion, which has six individual basket cohorts, three dedicated to ROS1+ non-small cell lung cancer, two dedicated to TRK+ advanced solid tumors, and (technical difficulty) exploratory cohort that will enroll ROS1 or ALK+ patients with advanced solid tumors other than non-small cell lung cancer.

The Phase 2 portion is expected to enroll approximately 110 patients at about 100 sites globally in the United States, Europe and Asia-Pacific regions. Six are on cohort, five may be registrational based on feedback we received from FDA following an end of Phase 1 meeting in late 2018.

In terms of a timeline for our registrational Phase 2 study, we expect to be in a position to provide an update as we make progress with site activations and patient enrollment. At this early stage I would say we are very happy that we initiated the Phase 2 portion ahead of initial estimates, that the FDA accepted our recommended Phase 2 dose regimen, and that patient screening is underway.

It remains our goal to provide early interim results from (inaudible) patients in these studies during the second half of 2020. We are all very encouraged by the response from investigators and sites to the study design. Our team is now focused on activating sites and working with physicians to support enrollment in the registrational study.

While the Phase 2 is our top priority, we also plan to initiate a study of Repotrectinib in pediatric patients during the second half of the year. This Phase 1/2 single arm open label study is planned for multiple sites within the US (technical difficulty) and Asia-Pacific regions to assess (technical difficulty) in pediatric patients with ROS1 and TRK or ALK+ advanced solid tumors. We will provide more information on study design, endpoints and timelines as we move closer to this initiation later this year.

Finally, we continue to evaluate [potential] (technical difficulty) combinations with Repotrectinib for future clinical studies. We are working closely with our key opinion leaders and anticipate providing an update on next steps later this year.

To close on Repotrectinib, we recently were notified that our abstract for an interim Phase 1 data update has been [lifted] by the European Society for medical (inaudible) for presentation at the [annual] Congress in Barcelona Spain. The presentation will be a poster with a poster discussion session to follow on September 28 and will be based on interim data from the Phase 1 portion of TRIDENT-1 that will primarily focus on additional follow-up since the last data cutoff in March with a limited number of new patients.

With that summary of our development plans for Repotrectinib I want to transition to our pipeline, beginning with TPX-0022, our MET CSF1R and SRC inhibitor. We recently initiated our Phase 1 open label study in patients with advanced solid tumors, [heart or genetic] alterations in MET. This goal was achieved just 2.5 months after our IND clearance in May, which was a great achievement for the team.

The study will be a standard dose escalation design starting at 20 mg daily to determine the maximum tolerated dose, overall safety profile and preliminary efficacy of TPX-0022. Upon determination of the recommended Phase 2 dose, the study would then evaluate multiple dose expansion cohorts for targeted enrollment of approximately 120 patients at sites in the US, Europe and Asia-Pacific regions. We look forward to beginning enrollment with the goal of being in a position to provide an initial clinical data update during the second half of 2020.

Next in our pipeline is TPX-0046, our novel RET inhibitor. We recently were informed that our submitted abstract was accepted for a poster presentation at ESMO. This will be our first time to showcase our RET inhibitor and the presentation will build on the preclinical work we have shown against proxy molecules with new preclinical potency data. In addition to ESMO we look forward to submitting our IND for TPX-0046 and, pending clearance, initiating our planned clinical study.

Finally, we are making good progress towards candidate selection for our next-generation (technical difficulty). (technical difficulty) our candidate later this year for (technical difficulty) enabling studies.

As we remain focused on executing against (technical difficulty) to submit two INDs, initiate four clinical trials across our pipeline of three molecules. We continue to build out our chemistry, biology and preclinical teams to support further research and discovery efforts. We believe the discovery of new targeted molecules is a key strength of our Company and will be an area for continued development.

In addition, we continue to strengthen our executive team, including hiring our General Counsel, Annette North, during the quarter and more recently Yi Larson as our Chief Financial Officer who will start with us later this month. As our lead banker and a managing director at Goldman Sachs, I worked very closely with Yi for over a year as we prepared for and executed our IPO.

Each of these key hires add new dimension to our growing team and add tremendous value to Turning Point as we continue our efforts to progress our pipeline, explore additional discovery efforts and identify new targets.

In addition to key members of management we have also added two accomplished independent directors to our Board. Both Patrick Machado and Carol Gallagher are 20-plus year biotech leaders and Board members who have been part of several successful clinical stage companies. I am very happy to welcome them to our Board.

With that operational update, I will turn it over to Brian to discuss our financial results.

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Brian Baker, Turning Point Therapeutics, Inc. - VP of Finance & Administration [4]

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Thank you, Athena, and good afternoon, everyone. Operating expenses for the second quarter were $18.5 million, an increase of $4.4 million sequentially from the first quarter and $13.3 million from the second quarter of 2018.

The (technical difficulty) year increase was primarily driven by the investments we have made to develop Repotrectinib and the rest of our pipeline (technical difficulty) we have added. The year-over-year increase also includes approximately $3.1 million in noncash stock-based compensation expenses.

Given the cash flow on the balance sheet, net cash used in operating activities in the quarter was $16.9 million, bringing our year-to-date net cash used in operating activities to $27.1 million.

Our cash, cash equivalents and marketable securities at June 30 were $250.2 million compared to $90 million as of March 31. The increase (technical difficulty) by net proceeds from the April IPO which, as a reminder, were approximately $175 million. We currently project our cash position will fund current operations [into] the second quarter of 2021.

Looking ahead to our spending for the second half of the year, we expect expenses to continue to increase as we activate sites in the Phase 2 registrational study and the Phase 1 study of TPX-0022 and prepare to initiate two additional clinical trials, the Phase 1/2 study of Repotrectinib in (technical difficulty) patients and the Phase 1 study of TPX-0046. And with that let me turn the call back to Athena (technical difficulty).

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

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Thank you, Brian. Our goal (technical difficulty) 2019 completion of our IPO, submission of 2 INDs and initiation of four clinical trials across our pipeline of three molecules. I am very pleased with the progress we have made to date against this plan and I look forward to the milestones we anticipate for the second half of the year.

As a reminder, let me reiterate a few (technical difficulty). Number one, two presentations at ESMO, including an interim [update] from the Phase 1 portion of TRIDENT-1, as well as new preclinical data for our RET inhibitor, TPX-0046.

Number two, submission of our IND for TPX-0046 and pending clearance initiation of the Phase 1 [clinical efficacy].

Number three, nomination of a development candidate in our ALK inhibitor program and, finally, initiation of (technical difficulty) study of Repotrectinib in pediatric patients with advanced solid tumors with NTRK, ALK or ROS1 alterations.

I want to close by thanking our great Turning Point team for all they accomplished during the quarter and year to date. We set big goals for ourselves during the first half of 2019 and I am proud of how this team delivered often ahead of projected timelines.

I also want to acknowledge the impressive group of people who have joined us during the past few months. They will make us stronger as we work to execute against our goals for the second half of 2019 and into the future. 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). Paul Choi, Goldman Sachs.

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Paul Choi, Goldman Sachs - Analyst [2]

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Congratulations on all the progress. Athena, maybe if we could start with the upcoming Phase 1 update at the ESMO meeting. Can you maybe frame for us how many additional new patients we'll see? And also how many are potentially at the go-forward Phase 2 dose? And what will be the data cut off or median follow-up that you will be able to present to us?

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

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One thing I'd just say is we don't want to front run the abstract. At this point the titles are currently out, so we've been mindful of that fact. What I will say is that we have two presentations, both of which will be Saturday, September 28. The first will be a Phase 1 update for TRIDENT-1 with a focus, as you mentioned, on additional follow-up.

Just as a reminder, we used March as our data cutoff for ASCO, and so we had always anticipated trying to bring four to five additional months of follow-up. Much more than that I won't share at this time again (technical difficulty) run that abstract. The number of additional patients will be small, it will be primarily focused on ROS1 pretreated patients, but we do anticipate a small number of TRK additional patients as well.

I think it's important thought to put the abstract in context in that we do believe, again, to continue to support the story of Repotrectinib (technical difficulty) class ROS1 inhibitor, continuing to show progress in terms of duration of treatment as well as duration of response is clinically important. And so, that's the focus of that presentation.

The second presentation is in relation to our RET inhibitor and we're very excited. This is the first time we will show this data in a scientific forum. These are the first presentations we will actually show outside of the US. And for the RET update this will primarily focus on additional preclinical potency data against proxy molecules which add on to data we've all already shown in different investor forums.

And just to get to the question you also asked, Paul, about which doses the patients would (technical difficulty) maybe just for further clarity. What we have continued to enroll are those last two cohorts we showed at ASCO, which would (technical difficulty) cohorts that are consistent with the Phase 2 (inaudible).

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Unidentified Analyst [4]

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Thank you for that. Maybe pivoting to the Phase 2 registrational portion of the trial, can you maybe provide us a rough timeline as to when you think you'd get all the centers up and running in the US and other geographies? And what is the rough timeline for when you expect to complete the trial enrollment for the 310 patients that you mentioned?

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

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Maybe [to step back] a second, because we are very excited that the FDA accepted our recommended Phase 2 dose. We just received that feedback (technical difficulty). It was always the intention to wait for that feedback prior to dosing. So as of now we are essentially moving the sites from Phase 1 to Phase 2, all seven sites that participated in the Phase 1 are going to participate in the Phase 2.

We have multiple sites that are now activated as well and multiple patients that are in screening. We've also started to utilize our clinical trial assay, our companion diagnostic to (technical difficulty) presence of the fusion. And we are eagerly anticipating dosing.

In regards to overall timelines, at this point it's premature. We just initiated the trial at the end of June. We are just now actively screening patients. And our goal is once we have a meaningful additional number of sites activated and have a good line of sight on our enrollment curve, that we will then start to potentially guide towards timelines for completion of the trial.

What we are trying to guide you towards, though, are meaningful milestones, which at this point is an early interim update from the Phase 2 data set, at least the cohorts within the second half of 2020.

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Unidentified Analyst [6]

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Then with 022, can you maybe just help us think about what would be the next meaningful update for that program in terms of when we might see some next set of data or some more mature data from that asset? Thanks.

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

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Sure. First, again, excitement that this is our second molecule that is now in the clinic. It was a very bold plan to submit two INDs and initiate four clinical trials prior to the end of the year and we are essentially halfway there now with initiating both our Phase 2 and the MET inhibitor. And so, again, we have multiple sites now activated. We are looking for patients to screen.

The goal here, again, is not to announce the first patient dose. We are taking the approach that we will continue to announce initiations. So, we've recently initiated that trial. It is posted on clinicaltrials.gov. We will go through the standard dose escalation cohorts (technical difficulty) again would be to present data in the second half of 2020 and we haven't guided yet in terms of the medical forum that we would show that data set.

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Operator [8]

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Andrew Berens, SEB Leerink.

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Andrew Berens, SEB Leerink - Analyst [9]

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I appreciate the PowerPoint deck, very helpful. Thanks are putting that together. Maybe a question on the dosing protocol. Can you give us a little color -- I guess most of the presentations were the 160 QD and above that were presented. How is the escalation beyond that going to be determined in the trial? And I guess if there's any color you could give us on the clinical experience to date at the b.i.d., how much more efficacy was there and what did the safety tolerability profile look when you went up to b.i.d. dosing?

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

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Let me back up just a second from a reminder perspective. From the Phase 1 we enrolled nine dose escalation cohorts of which four of those cohorts either started at 160 mg daily or 160 mg b.i.d. In addition, we looked at the patients that not only started at 160 mg b.i.d., but also those that intra patient dose escalate. And that's actually over half of the patient population.

So, that's why we are confident in 160 mg daily as the starting dose looking at the overall totality of the efficacy, the safety and the PK. The reason we chose the regimen that we chose, which is a dose titration -- it's not a forced escalation to b.i.d. Essentially patients will all start at 160 mg daily. And after 14 days the patients can move up to b.i.d. dosing if they're tolerating the drug well, which essentially means they're not having high grade treatment-related adverse events or dizziness or lab abnormalities.

And we did this, again, rather than taking a different approach, which is potentially starting too high and requiring dose interruptions and reductions, this is an approach I've done before with titrating up based on tolerability, and it's not uncommon with tyrosine kinase inhibitors to do that. But it really does allow physicians to have flexibility.

Primarily to the question that you're asking, which is the data that (technical difficulty) TKI naïve population is very similar. The efficacy is essentially in the 80% to 85% range whether you (technical difficulty) 60 mg daily, or if you are looking at higher than 160 mg daily. But when you look at the pretreated patient population, this is where the data down not as subtle in the sense that it is quite stark the difference.

The overall response rate by blinded independent central review for patients that had one prior TKI, it is 55% for patients that had 160 mg daily or above compared to 14% if they were treated at less than 160 mg daily. So again, that is why we were always leaning in the direction of having 160 mg daily as our starting dose.

From a safety perspective, as you know, TRK on target toxicity, predominantly dizziness, is what we have seen with Repotrectinib, nearly all cases being Grade 1. And what we have seen is a very similar percentage, whether they were at 160 mg and higher or lower. It's a slightly higher percentage if they were at 160 and above, but it's very similar in both camps.

So, I would say from an overall totality looking at the benefit risk, the efficacy, the safety, as well as target saturation and PK, this is why we chose 160 mg QD as the starting dose. And then the FDA accepted the ability for physicians to have flexibility to dose up to b.i.d. And we do think that will be predominantly for patients who are pretreated, potentially who have resistant mutations and/or those that have CNS disease.

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Andrew Berens, SEB Leerink - Analyst [11]

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Okay, thanks for all that color, that's great. Do you have -- and obviously I think this would be speculation, but maybe you might have an idea from the Phase 1 experience. What percentage of the patients do you think will actually be able to go up to the b.i.d. dose?

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

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Yes, it's a really good question. In the Phase 1 we had about 25% that went up to the b.i.d. dose. Now appreciate, again, that was based on just seven centers. And also at that time we didn't have a dose titration cohort that was as enrolled as much as it is now. So, we have already explored this.

The last cohort that (technical difficulty) was 160 mg QD, but it [was dose] escalation up to b.i.d. And despite the fact that it was forced and actually at seven days, there were no dose limiting toxicities there. So again, this will be some of the data we will bring to ESMO.

But I think with more support, physician engagement and more education that (technical difficulty) escalation to b.i.d. may be more common than 25%. But again, that's not the intent. The intent here was to allow flexibility for the physicians, especially in the TKI naïve setting (technical difficulty) may need a b.i.d. dose.

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Andrew Berens, SEB Leerink - Analyst [13]

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Okay. And then maybe to follow up on Paul's question, I know you said you don't want to preempt the ESMO presentation, but I just wanted to clarify I think -- because you gave us some color before about what we could expect with the next update.

The naïve patients, the 11 patients that were the sample presented at ASCO, I think you told us not to expect many more patients in that cohort because those would be enrolled in the Phase 2. And there might be more patients in the pretreated group, but certainly both groups would have more duration. Is that a proper way for us to think about what we might see at ESMO?

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Athena Countouriotis, Turning Point Therapeutics, Inc. - President & CEO [14]

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Yes, I'm trying to be (technical difficulty). Again, I don't know the data. We just recently cut the data set. We go through blinded independent central review now. But I am trying to guide you (technical difficulty) of the update will be in ROS1 non-small cell lung cancer patients that are pretreated and potentially with two or more TKIs. Because again, we were holding some patients for the Phase 2 to go into screening.

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Andrew Berens, SEB Leerink - Analyst [15]

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Okay. And then maybe a question on the RET program. I know we are hearing that there are patients failing 292 that are out there now. I was wondering if you guys have any idea of what the genetic profile of those patients may look like. Is it going to be a solvent front mutation that renders them resistant or is there something else that could be causing the resistance?

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Athena Countouriotis, Turning Point Therapeutics, Inc. - President & CEO [16]

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We've obviously been monitoring the information regarding both of the investigational agents. What I will say is that we are very excited about our molecule (technical difficulty) and different in the way it was built.

Again, this is another macrocycle similar to Repotrectinib. It is smaller in regards to [weight]. It will hopefully continue to fit within the ATP binding pocket despite the presence of resistant (technical difficulty). And we've already shown strong preclinical data to support efficacy not only in the wild type setting but also against solvent-front mutations.

When we look at the structures of the other investigational agents we predict they might develop solvent-front mutations, but we appreciate that that's information that hasn't been shared yet. So, at this point that's our hypothesis. But again, our molecule is novel and different and we believe will differentiate based on its potency specifically against the [G810] series of solvent-front mutations.

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Andrew Berens, SEB Leerink - Analyst [17]

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Okay, thanks for all the color, Athena, and congrats on the progress. Appreciate it.

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Operator [18]

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(Operator Instructions). Michael Schmidt, Guggenheim.

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Michael Schmidt, Guggenheim Securities - Analyst [19]

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I had a question regarding the TRIDENT-1 Phase 2 trial portion specifically on the TKI-pretreated cohort. And I guess the question I had was whether there's any reason to believe that patients that have received either Xalkori or Entrectinib have different types of mutations, and whether it is non-(inaudible) works differentially depending on what type of TKI they were receiving previously.

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Athena Countouriotis, Turning Point Therapeutics, Inc. - President & CEO [20]

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No, very good question. What we know and what has been published in the literature is about 40% of patients post-Crizotinib have developed a specific G2032R solvent-front mutation. There is less in the literature to support Entrectinib, but we do not believe there would be a difference, again looking at the (technical difficulty) structures, the fact (technical difficulty) very different than the structure of Repotrectinib.

We've obviously treated much fewer Entrectinib patients than Crizotinib patients, but at this point our prediction would be that (technical difficulty) and that's also based on feedback that we've heard from investigators as well.

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Michael Schmidt, Guggenheim Securities - Analyst [21]

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Okay, perfect. And then maybe just one follow-up on the RET inhibitor, 0046. Just big picture wise, I know you say you planned the IND submission this year. The Phase 1 study, will there be a traditional 3+3 or will you do -- an intra-patient dose escalation like your competitors have done in the past, which could potentially be a faster way to get to maximum dose?

Then how do you think about development plans or path to market longer-term? Will you initially just focus on a pretreated patient population or would you go into a front-line indication right from the get-go?

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Athena Countouriotis, Turning Point Therapeutics, Inc. - President & CEO [22]

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Very good questions. First of all, we are always watching our competitors in this space. We also appreciate that we want to get the molecule as fast to patients as possible. I don't want to guide too much prior to IND submission because obviously you submit your protocol with the initial IND.

So, without going into too much detail, Michael, I think everything that you've just outlined is on the table because the goal here is to optimize the drug in terms of its drug development to get to patients as fast as possible. So, nothing is off the table in terms of thoughts of how we will design that trial. But without guiding to specifics at this point prior to submission and obviously clearance of the IND.

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Michael Schmidt, Guggenheim Securities - Analyst [23]

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I appreciate it and congrats on all the progress this year.

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Operator [24]

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Jim Birchenough, Wells Fargo.

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Yanan Zhu, Wells Fargo Securities - Analyst [25]

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This is Yanan dialing in for Jim. Most of my questions have been asked. Perhaps I just have a quick one on the kind of investigator interest that you are seeing between treatment ROS naïve versus ROS pretreated patients, to have a sense of, relatively speaking, the naïve cohort and the pretreated cohorts, which one might have faster enrollment.

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

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Thank you for the question. I attended the investigator meeting that was in New York recently where we had over 30 participants in the room. I will just reiterate what I heard, which is, again, the paradigm of using the most potent molecule in the front line setting has already been established for both ALK inhibitors as well as EGFR inhibitors. And so, I do really believe that that's the shift that occurred at ASCO for Repotrectinib for ROS1.

We've also discussed previously that we have enrolled a TKI-naïve TRK patient and those patients are consented, appreciating that there is now a commercially available option for them. But they are consented by physicians who use (technical difficulty) as the rationale for why they should participate in a clinical trial, which is, again, the most molecules should be utilized upfront.

And so, without trying to predict too much how enrollment will go, I've always said I think the pretreated patient populations will enroll the fastest because there are many patients that are out there that unfortunately have developed resistant mutations potentially or other mechanisms of resistance that now have very few treatment options.

And as you know, we have a very strong data set at over 50% response rate post-Crizotinib. And we are the only drug that has shown clinical activity to date against solvent-front mutation.

And so, I do think that story will continue to resume in terms of enrollment, but equally so the front-line data for both ROS1 and obviously to a lesser extent TRK because it's more rare in terms of the patient population (technical difficulty) believe that the most potent molecule should be utilized upfront. And I'm hopeful that with this cohorts, naïve and pretreated, will enroll very well.

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Operator [27]

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Arlinda Lee, Canaccord Genuity.

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Arlinda Lee, Canaccord Genuity - Analyst [28]

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Back to the KOLs preferring to use the most potent drug upfront, do you think -- what do you think are the key criteria for that? Obviously activity in last line therapy, but kind of curious what in particular you guys are looking for in your drugs that are entering the clinic in the later part of this year, both the RET and the MET (inaudible).

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

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Let me start with just what I've heard from Repotrectinib, to reiterate what I just said, Arlinda. And thank you for the question; I look forward to seeing you this week. What I've heard, again, from key investigators that have enrolled many patients within the Phase 1 is, again, the way they consent patients who are TKI naïve -- and this is both for TRK patients as well as our Korean [investigative] consenting patients in the ROS1 space -- is continuing to use the preclinical potency data that we showed at AACR.

In addition, now they have the (technical difficulty) very strong response rate of over 80% at 83% and median DOR not yet met. And so, it's a strong data set to support the story for utilizing Repotrectinib in a front line setting for ROS1 and hopefully also translates to TRK.

And again, if you believe the idea of the macrocycle overcoming treatment resistance and potentially prolonging duration of response, then that story should also be applicable to both of our additional pipeline molecules that are (technical difficulty). The MET inhibitor is already now there and then inevitably our RET inhibitor after IND submission and clearance.

And so, I do believe the story that we've already established with Repotrectinib will translate into the other two pipeline molecules based on, again, the way they were rationally designed.

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Brian Baker, Turning Point Therapeutics, Inc. - VP of Finance & Administration [30]

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Any other questions, operator?

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Operator [31]

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At this time I'm showing no additional questioners in the queue. I will turn the program back over to you for any additional or closing remarks.

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Athena Countouriotis, Turning Point Therapeutics, Inc. - President & CEO [32]

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Thank you very much (technical difficulty), again, for your interest and support of Turning Point Therapeutics to everybody on the call. I look forward to seeing many of you at upcoming banking and medical conferences throughout August and September and providing additional updates as we execute against our second half agenda. Thank you very much.

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Operator [33]

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