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Turning Point Therapeutics Inc (TPTX)
Q3Â 2019 Earnings Call
Nov 4, 2019, 4:30 p.m. ET
Contents:
- Prepared Remarks
- Questions and Answers
- Call Participants
Prepared Remarks:
Operator
Good afternoon, ladies and gentlemen, and welcome to the Turning Point Therapeutics Third Quarter 2019 Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. [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.
Jim Mazzola -- Senior Vice President, Communication and Investor Relations
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.
Athena M. Countouriotis -- President, Chief Executive Officer
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 toward 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 those 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 inhibitor 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 2 trial, called TRIDENT-1 for the treatment of patients with ROS1-positive, advanced non-small cell lung cancer and for patients with ROS1, and TRK or ALK-positive advanced solid tumors.
First, in early September, we announced updated preliminary data from the Phase 1 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 and TRK inhibitor based on both the clinical Phase 1 data and preclinical potency data shown earlier this year.
Since ASCO of last year, each time we have reported data from the Phase 1 TRIDENT-1 study, it has improved and continued to build our confidence in the potential for repotrectinib to be a best-in-class agent in both the front line and later line treatment settings for ROS1-positive non-small cell lung cancer patients and TRK-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 1/2 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 1 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 2 TRIDENT-1 Study and the Phase 1 TPX-0022 study 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 two NTRK-positive advanced solid tumor patients. The results continued 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 three 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 one 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 2 dose of 160 milligrams or above.
Among the crizotinib-pretreated patients with a known solvent-front mutation, the confirmed overall response rate was 43%. We also reported responses in patients previously pretreated with two prior TKIs, showing a confirmed ORR of 29% at the time of the data cutoff. Each of these response rates in patients treated with either one prior or two 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 2 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-naive, 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 2 portion of TRIDENT-1.
Moving now to the Phase 2 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 2 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 six single-arm cohorts, 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, as we continue to activate sites and enroll patients, we will have better visibility on our timeline for enrollment and we'll plan to provide an update on the timeline at a later time. At this early stage, I am pleased with our progress with many sites now activated in the US 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 registrational 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 1/2 single-arm open label study will assess repotrectinib in pediatric patients with ALK and TRK 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 and SRC inhibitor. Our Phase 1 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 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 region. 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 is it's 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 1/2 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 1/2 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 1 dose escalation portion and approximately 300 patients in the Phase 2 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 2 portion of the study to be potentially registrational, taking a similar approach as we did with repotrectinib. Prior to starting the Phase 2 portion, we would plan on having a discussion with health authorities about the registrational path for TPX-0046.
Finally, we continue to make progress toward 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 two INDs and initiating four clinical trials across our pipeline of three molecules. We have made excellent progress toward achieving these goals, often well ahead of our projected timelines. 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 Merck -- excuse me, it was acquired by Merck in July. Prior to Peloton, his role as Chief Medical Officer of 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.
Yi Larson -- Executive Vice President And Chief Financial Officer
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'm 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 headcount we have added. Operating expenses in the third quarter also include $3.5 million in non-cash stock-based compensation expenses.
For the nine months ending September 30, operating expenses were $54.7 million compared to $16.2 million during the prior year period. The increase was also driven by development expenses for our three clinical stage assets, as well as personnel expenses. Included in the year-to-date increase is $8.5 million in non-cash 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 three 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.
Athena M. Countouriotis -- President, Chief Executive Officer
Thank you, Yi.
I am very pleased with the progress we have made to date against our plan for the year. We have 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 two 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 1/2 clinical study of TPX-0046; initiate our Phase 1/2 study of repotrectinib in pediatric patients; nominate a development candidate in our ALK inhibitor program; and continue to focus on our ongoing pre-clinical 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 four quarters, we have grown the company from less than 20 employees to now approximately 90 employees and I'm 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.
Questions and Answers:
Operator
[Operator Instructions] Our first question comes from the line of Michael Schmidt from Guggenheim. Your line is open.
Michael Schmidt -- Guggenheim -- Analyst
Hey, guys, congrats on all the progress, and thanks for taking my questions. I had one on your two more recent pipeline or Phase 1 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 two agents, the RET and the MET inhibitor respectively? And to what degree might this potentially add to potential toxicities as well?
Athena M. Countouriotis -- President, Chief Executive Officer
Yeah, sure. Thanks, Michael, for the question. One of the things in regards to start, I have quite a bit of experience here. I've worked on two prior SRC inhibitors from both quizartinib bosutinib or BOSULIF. I think what has been clearly shown in the past is may be 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 in track, but to be highly selective. And part of that so activity included SRC and the SRC family kinases, which we believe add to some of the benefit of repotrectinib and its ability to tackle bypass mechanisms of resistance through what's called the STK3 bypass pathway. That is where SRC has activity, that is what could potentially also translate into both 022 and 046 and one of the ways that we believe our MET inhibitor and our RET inhibitor differentiate versus those that are ahead of us.
Michael Schmidt -- Guggenheim -- Analyst
Very good, thank you. I guess, that brings me to my next question. So it sounds like the 0022 study is a little bit further along in 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?
Athena M. Countouriotis -- President, Chief Executive Officer
Yeah. 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. 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 the 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 two 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 2 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 in SRC will come through the data, and as we've said, we're guiding toward an update from the Phase 1 in the second half of next year.
Michael Schmidt -- Guggenheim -- Analyst
Great, thanks. Then, one more, maybe on repotrectinib. I know you mentioned the interim analysis of the initial data from the Phase 2 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 1 study, especially when we think about durability of the front-line patient population? Thank you.
Athena M. Countouriotis -- President, Chief Executive Officer
Yeah, sure. So, as you know, and as I said in the prepared remarks, the Phase 2 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 2 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 toward meaningful data timepoints.
And so what we've been saying for not only the Phase 2, but 022 as I just mentioned is an update in the second half of next year. In relation to the Phase 1, 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 2 now is incredibly high based on the data again that we've continued to show, not just within this year, but also the data cut that we showed last year from the Phase 1.
I am putting the team now a 100% focused on trial execution. We are about to have our third and fourth trials in the clinic very soon and the two data timepoints 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 1, but it's not our intention to do another update from that dataset 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.
Michael Schmidt -- Guggenheim -- Analyst
Helpful. Thank you so much and congrats on the progress.
Athena M. Countouriotis -- President, Chief Executive Officer
Thank you, Michael.
Jim Mazzola -- Senior Vice President, Communication and Investor Relations
Thanks, Michael.
Operator
Our next question comes from the line of Paul Choi from Goldman Sachs. Your line is open.
Paul Choi -- Goldman Sachs -- Analyst
Hi, good afternoon, everyone and thanks for taking our questions. 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 combinations 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?
Athena M. Countouriotis -- President, Chief Executive Officer
Yeah. 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 STK3 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.
Paul Choi -- Goldman Sachs -- Analyst
Okay, great. Thank you for that. 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 experience population or is the plan to go at them simultaneously given that you could potentially have launches of two drugs in the category over the near term?
Athena M. Countouriotis -- President, Chief Executive Officer
Yeah. Again, I would say that there is a lot of similarities in regards to what we're doing for both of the Phase 1 programs. Obviously, 022 is further ahead than 046. 022 essentially is a standard dose escalation with the Phase 1 components of escalation and then expansion, where we would be looking at multiple different disease types, whether it's long or GI-oriented diseases such as gastric or hepatocellular. There will be optionality there, based on prior TKI used, yes or no. That is a standard Phase 1.
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 1/2 mirrors what we did with repotrectinib, and again allows quite a bit of optionality. There is a Phase 1 dose escalation component, but as we proceed toward Phase 2, 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 used, prior platinum used, 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 timeline for the RET inhibitor.
Paul Choi -- Goldman Sachs -- Analyst
Got it. Thank you for that. I'll jump back into queue.
Operator
Our next question comes from the line of Andrew Berens from SEB Leerink. Your line is open.
Andrew Berens -- SEB Leerink -- Analyst
Thanks. Congrats guys on the progress. There are a couple of questions on repo. I guess in TRIDENT, what percentage of patients do you think will have brain mets and what's the typical course of a patient with brain mets?
Athena M. Countouriotis -- President, Chief Executive Officer
Yeah. 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 front line setting with all three patients having responses. You 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 incidents.
Andrew Berens -- SEB Leerink -- Analyst
So you're saying in the front-line setting it's 50%, which is higher than in the second, third line?
Athena M. Countouriotis -- President, Chief Executive Officer
It really depends on the dataset that you're looking at. In our hands, again, our data was pretty consistent with what you've seen in the literature, which is about half of the patients.
Andrew Berens -- SEB Leerink -- Analyst
Okay. And how long do those patients typically survive without progression and once they progress, any idea how long they usually will?
Athena M. Countouriotis -- President, Chief Executive Officer
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 NTRK inhib 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 six months ago. Now in the literature may have that, but I don't have that on top of my head.
Andrew Berens -- SEB Leerink -- Analyst
Okay. And then I guess, any idea of how the entrectinib launch is going?
Athena M. Countouriotis -- President, Chief Executive Officer
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 front line. 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.
Andrew Berens -- SEB Leerink -- Analyst
Okay. And then, I guess, on the RET program, just how difficult will it be to enroll patients that have failed 292 or 667, identify them and then enroll them or the [Indecipherable] also aggressively trying to enroll those patients in the trial?
Athena M. Countouriotis -- President, Chief Executive Officer
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 has a tremendous amount of enthusiasm from the investigators to get the trial going because we know patients are waiting.
Andrew Berens -- SEB Leerink -- Analyst
Okay. Thanks a lot. Appreciate it guys. Congrats again.
Athena M. Countouriotis -- President, Chief Executive Officer
Thank you. Thanks a lot, Andy.
Andrew Berens -- SEB Leerink -- Analyst
Sure.
Operator
Our next question comes from the line of Arlinda Lee from Canaccord. Your line is open.
Arlinda Lee -- Canaccord -- Analyst
Hi, guys. 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? Thank you.
Athena M. Countouriotis -- President, Chief Executive Officer
Yeah. 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 we are very comparable in the wild-type setting. The Phase 1 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 are enrolling patients who are TKI-naive.
From the ALK inhibitor characteristic, as you know, repotrectinib does hit out, but 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 mutation, 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.
Arlinda Lee -- Canaccord -- Analyst
Thank you.
Jim Mazzola -- Senior Vice President, Communication and Investor Relations
Thanks, Arlinda. Next question?
Operator
Our next question comes from the line of Jim Birchenough from Wells Fargo Securities. Your line is open.
Yanan Zhu -- Wells Fargo Securities -- Analyst
Hi. Thanks for taking the question. 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, maybe 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? Thanks.
Athena M. Countouriotis -- President, Chief Executive Officer
Yeah. I think it's a very good question. From the resistance perspective of repotrectinib, that data was not captured within the Phase 1 study. It will be captured within the Phase 2. So just to level set, within the Phase 2 study, patients who have, obviously, tumor biopsies evaluated for the presence of their fusions prior to enrollment. In addition, prior to enrollment, they will 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 two to three cycles into treatment and then at the end of treatment or the time of progression. So, we'll have potentially two 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 there about utilizing repotrectinib in front line, 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 is a tremendous amount of enthusiasm for the Phase 2 study and specifically using repotrectinib in front line. 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.
Yanan Zhu -- Wells Fargo Securities -- Analyst
Got it. That's very helpful. Maybe two 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 -- strong concentration of patients. And also, a question on whether you have a better sense of the percentage for ROS1 patients [Indecipherable] that have solvent-front mutations? Thank you.
Athena M. Countouriotis -- President, Chief Executive Officer
Yeah, thanks. So, the historical information that's in their literature that mirrors pretty much what we've shown as well for solvent-front mutation, specifically, the most common G2032R mutation is about 40%. And so, that's -- our dataset is a little bit lower than that, but again our dataset 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 physicians' 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 incident 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.
Yanan Zhu -- Wells Fargo Securities -- Analyst
Got it. Very helpful. Thank you, Athena.
Athena M. Countouriotis -- President, Chief Executive Officer
Thanks very much for all the questions.
Operator
[Operator Instructions] I'm showing no further questions at this time. I would now like to turn the conference back to Jim Mazzola for his closing remarks.
Athena M. Countouriotis -- President, Chief Executive Officer
I'm happy to step in for Jim. This is -- 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.
Operator
[Operator Closing Remarks]
Duration: 42 minutes
Call participants:
Jim Mazzola -- Senior Vice President, Communication and Investor Relations
Athena M. Countouriotis -- President, Chief Executive Officer
Yi Larson -- Executive Vice President And Chief Financial Officer
Michael Schmidt -- Guggenheim -- Analyst
Paul Choi -- Goldman Sachs -- Analyst
Andrew Berens -- SEB Leerink -- Analyst
Arlinda Lee -- Canaccord -- Analyst
Yanan Zhu -- Wells Fargo Securities -- Analyst
