Q3 2019 Earnings Call

At this time, all participants are in that listen only mode.

Later, we will conduct a question and answer session and instructions will follow at that time.

If anyone should require assistance during the conference. Please press Star then zero on you touched on telephone.

As a reminder, this conference call is being recorded I would now like to turn the conference over to your host Mr., Jim Mitchell The senior Vice President. Please go ahead.

Okay. Thank you everyone. 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 the all of these document posted on the investor pages that TP therapeutics Dot com, leading our call today will be turning points president.

Chief Executive Officer Dr., the in a country Otis who will provide an overview and update on our business results followed by a review of third quarter financial but you 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 act.

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 perspectives and quarterly filings now let me turn the call over to a piano. Thank you Jim and get out.

Turning to everyone joining us today I am happy to be joined by our Chief Financial Officer. He Larsen on today's call.

I'm 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 29 team and as of today I'm very pleased with the progress towards accomplishing.

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.

A turning point, we had internally discovered and developed our wholly owned pipeline of next generation tyrosine kinase inhibitors or <unk>. The target numerous genetic drivers of cancer, namely Ross one track ALC, Matt and ready for use in those pecan naive and Sicad pretreated patients.

Our MACRA cyclical platform has enabled us to design multiple small incontact kinase inhibitors with the potential to overcome the limitations of conventional teekay <unk>.

One of the limitations that conventional teekay <unk>, it's a pervasive challenge of intrinsic and acquired resistance, but often limits their response rate and durability of response with existing therapies.

One challenge is the emergence of mutations in an area of the kidney called the solvent phone, which is a common cause it acquired resistance to currently approved therapies for Ross one track and al.

In addition, we believe folding carton stations will arise from current approved an investigational ret inhibitors and that our macro cyclical platform has generated two carriers that are potentially best in class based on their rational design their potency and their ability to buying for their targets.

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 repo trucking, it which is being evaluated in a registrational phase two trial called tried one for the treatment of patients with Ross one positive advanced non small cell lung cancer and for patients with was one and truck or l.

Positive advanced solid tumors.

First in early September we announced updated preliminary data from the phase one portion of try didn't work, 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 repositrak that have to be a best in class Ross, one and Trk inhibitor based on both the clinical phase one data and preclinical potency data showed earlier this year.

Since October of last year. Each time, we have reported data from the phase one tried it warrants study it has improved and continue to build our confidence in the potential for reap attracting them to be a best in class agent in both the frontline and later line treatment settings for walks one positive non small cell lung cancer pain.

Sure and truck positive advanced solid tumor patients.

The second key achievements 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 unclear the I envy for our novel retina, Hibbett or PBX 0046, and expect very soon to initiate our phase one two study in patients with ret altered non small cell lung thyroid and other advanced cancers.

We also continued to make progress and the ongoing phase one study of our novel met inhibitor TDX is your with your Q2.

A key milestone we said at the time of our IPO in April what's to submit and clear the I. Indeed for both PBX zero zero to Q and PBX 0046, and initiate both studies prior to the end of year.

I'm 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 and net proceeds.

With our cash position at September Thirtyth of $424 million. We believe we are sufficiently funded beyond 2021, which is passed the early data read outs from both our fees to try to at one study and the phase one TPS zero zero to two study that we project in the second half of 2020.

With that background I will provide a more comprehensive update on repo trucking there from the data we reported in a total of 93 patients.

Including 40 efficacy of valuable lost one positive non small cell lung cancer patients and to end truck positive advanced solid tumor patients.

The results continue to demonstrate it consistent safety profile and showed repo truck and it was generally well tolerated with clinical activity in both TTR naive anti pretreated patients.

As of the July 22nd data cut off a 91% confirmed overall response rate by blinded independent Central review was achieved in T.I. naive Ross one positive non small cell lung cancer patients.

With the median follow up time of 20.1 month. The median duration of response was not yet mature with 50% of responders without an event at the time any analysis and responses ranging from 3.7 plus to 23.3 plus mark.

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 at 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 T.I. naive patients with measurable CNS disease that baseline confirmed responses were achieved good durations of 14.8, plus 23.1 month at the time of the data cut off.

In patients treated with one prior to <unk>, a 39% confirmed overall response rate was achieved across all devices.

In a 55% confirmed or our was shown in these patients treated at the phase two 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 creek treated with two prior Teekay <unk>.

Showing it confirmed our our of 29% at the time of the data cut off.

Each of these response rate in patients treated with either one prior or two prior T.I.s are quite encouraging given the limited treatment options for pre treated patients.

Additionally, these populations represent individual Ross one positive non small cell lung cancer cohorts within the ongoing piece to Registrational tried at one study.

In addition to the data in Ross one positive non small cell lung cancer, we remain encouraged by the clinical activity of Repositrak and they interact positive advanced solid tumor patients.

We had previously reported a durable response in a patient with a truck see solving front mutation who was previously treated with Crizotinib entrectinib.

And in September reported our first response in a T.K. naive thyroid cancer patient.

We remain encouraged by our initial activity within T.I. naive and pretreated truck patients. Both patient populations also represented in the phase two portion of tried at one.

Moving now to the phase two registration portion for tried at one.

So 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 with high.

The key theme, we continue to hear from investigators is that the most potent Ross one or track Teekay <unk> should be utilized in the frontline setting, which we believe is very positive for reef attracting them.

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, that these two portion to try didn't want is expected to enroll approximately 310 patients at about 100 sites globally in the United States, Europe , and Asia Pacific region.

The six single arm cohorts five maybe registrational based on feedback we receive from <unk> all in end of Phase one meeting in late 2018.

In terms of a timeline for our Registrational phase two 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 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 Registrational cohorts during the second half of 2020.

Lastly for reap attracting and we're on track to initiate our study in pediatric patients very soon.

This phase one two single arm open label study Wasatch, we've attracted in pediatric patients with al and track or Ross positive advanced solid tumors.

This is an important study to evaluate we've attracted to it and patients under the age of 12.

Additionally, we continue to evaluate multiple potential combinations with repo truck and they've for future clinical study I'm excited about the potential here based on our ongoing preclinical and translational research and the potential you see in Repositrak in a beyond Ross one and truck.

I look forward to providing an update on next steps early next year.

With that summary of our development plans to Recontracting, if I want to transition to our pipeline beginning with PBX zero zero to two hour met CSF one are in stark inhibitor.

Our phase one open label study in patients with advanced solid tumors harboring genetic alterations in Matt is progressing well, we sites now screening and enrolling patients.

As a reminder, that study as a standard dose escalation design, starting at 20 milligrams daily to determine the maximum tolerated dose.

Overall safety profile and preliminary efficacy of TPS zero zero to two.

Upon determination of the recommended phase two dose. The study would then evaluate multiple dose expansion cohorts for targeted enrollment of approximately 120 patients at sites in the U.S., Europe and Asia Pacific region.

Remains our goal to provide an initial data update during the second half of 2020.

Next in our pipeline is TPS 0046, our novel Red Star inhibitor. We are encouraged by the potential for TPS 0046 based on its preclinical potency against wild type <unk> five be ret, which has shown at ESMO is comparable to proxy compounds for loxo to nine two and blue.

667.

With stronger potency against all the front mutations, including G 810 are.

We believe they key differentiator for all four six if its compact design and the targeting of both ret and Sark as the inhibition of SAR has the potential to reduce recruitment of multiple receptor tyrosine kinase is involved in bypass weed resistance.

It wasn't active quarter of progress for over four six as we showcased preclinical data in September at ESMO submitted in cleared the I, Andy and expect very soon to initiate our phase one two study, which will be a huge achievement by our team to accomplish this so soon after I'd clearance, which occurred just on.

September Thirtyth.

We're working with our investigators to activate sites.

As possible as we believe there is a clear unmet need that still exists.

The phase one two first in human open label clinical study of O. Four six is designed to enroll patients with ret altered non small cell lung.

Right and other advanced cancers.

Well find the study design in our updated investor presentation posted on our website.

We plan to enroll approximately 50 patients in the phase one dose escalation portion and approximately 300 patients in the phase two 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 threat Teekay naive and pretreated patients.

We designed the phase two portion of the study to be potentially registrational, taking a similar approach as we did with weep attractiveness.

Prior to starting the phase two portion we would plan on having a discussion with health authorities about the Registrational path for TX 0046.

Finally, we continue to make progress toward candidate selection for next generation Alpha inhibitor. Our goal remains to nominate our candidate later this year for I Indy enabling studies.

The plan, we laid out for 2019 included submitting to why in knees and initiating for clinical trials across our pipeline of three molecules.

We have made excellent progress towards achieving these goals often well ahead of our projected timeline.

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 one important note about our growing turning point team.

Today, we announced the hiring and start date for Dr. Mohamad Herman as our Chief Medical Officer.

How many with most recently the Chief Medical Officer for Telecom Therapeutics, which was acquired by Mark Merck Excuse me was acquired by Merck in July .

Prior to Palatine his role as Chief Medical Officer at Medivation, which was acquired by Pfizer in 2017.

Mohamad has a strong background in oncology drug development and will be an important number of our team as we advanced our current clinical studies and further develop our pipeline.

I could not be happier mohamad is joining our team in early December and I look forward introducing him to you in the near future.

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

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 bank or from Goldman Sachs and the turning point IPO.

I decided to join the team given the company leadership encouraging data with we've attracted and the pipeline of additional Teekay I said has rapidly progressing to 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 see more view at upcoming conferences.

Turning to the financial results in 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 2018.

Similar to last quarter expenses are ramping as we initiate our clinical trials in build out our team.

[noise] primary drivers of the year over year increase where investments made to develop we would treximet and the rest of our pipeline.

Including the head count we have added operating expenses in the third quarter also include $3.5 million and noncash stock based compensation expenses.

For the nine months ending September Thirtyth operating expenses were 54.7 million compared to $16.2 million during the prior year period.

Increase was also driven by development expenses for our three clinical stage assets as well as personnel expenses.

Included in any year to date increase is $8.5 million and noncash stock based compensation.

Moving to cash flow in the balance sheet net cash used in operating activities during the quarter with $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 Thirtyth were $423.6 million compared to 250.2 million.

Dollars as of June 30.

The increase was driven by net proceeds for my 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 three clinical stage assets and watch a fourth study in pediatric patients.

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

Thank you he I'm 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 as well funded through key data read outs in 2020.

As I look ahead of the last few months every year, we will continue to focus on delivering against our milestones.

Our goals remain to advance enrollment in each of our clinical trials in.

Initiate our phase one two clinical study a TDX zero three or four six.

Initiate our phase one two study of repo trucking it in pediatric patients.

Nominate a development candidate in our ALC inhibitor program and continue to focus on our ongoing preclinical work to support our combination strategy for reap attracting it.

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 am incredibly humbled by the talent, we continue to attract and what we have as a team accomplished.

We said big goals for ourselves and 2019 and I'm. So proud of how this team continues to deliver operator, you may now open the line for questions.

Ladies and gentlemen, if you have for question at this time. Please press Star and then the number one key on your Touchtone telephone.

If your question that's been answered or you wish to move yourself from the Q. Please press the pound Keith.

Please save 12 week, while the colors Q further questions.

My first question comes from the line of Michael Schmidt from Guggenheim Your line.

Hey, guys. Congrats on all the progress and thanks for taking my questions I had one on your two more recent a pipeline or phase one study entries ofour takes and Hello to too just generally speaking could you remind us how this arc inhibition aspect of those molecules.

Via potential differentiating factors for these two agents.

And the Mets into the respectively and to what degree might this potentially add to potential toxicity.

Yeah sure. Thanks, Michael for the question you know what are they things in regards to circus I have quite a bit of experience here and work on two prior stark inhibitors from both the fattening and the sitting never are both lift I think what has been clearly shown in the past is maybe different than what we're doing here and stark is also a part of Repositrak and it just so you know.

I think that's one of the beauty every protecting it isn't the way that it was design was not to be exclusively specific for Ross, one and track, but couldn't highly selective and part of that selectivity included stark and the Soc family kind nieces, which we believe adds to some of the benefit of Repositrak tonnage in its ability to tackle bypass mechanisms.

Resistance through what's called the Statthree bypass pathway that is where stark has activity that is what could potentially also translate into both 022 and a four six and one of the ways that we believe are met inhibitor and our written inhibitor differentiates versus those that are ahead of us.

Thank you I guess that brings into my next question. So it sounds like the owe to choose study is a little bit further along than the ret inhibitor and you outlined the design on the call. It earlier can you just help us understand how you think about potential positioning of Oh 22 relative to capmatinib longer term I know it's still early.

But how do you think about the novartis comp on here.

Yeah, you know 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 repo tracked and they've been O. Four six I'm very happy to hear your enthusiasm because we have just as much you know gene has been working in that space for over 20 years and this isn't a molecule that she is the most proud of which is auteur.

Two and again to that same theme I said earlier cap not new being more specific I think for where we are hoping to focus OTI to its really again in an area beyond Exxon 14, skipping mutations so any thoughts 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's still isn't unmet medical need for another met inhibitor in the clinic and to the best be benefit as you've been outlining for CSF. One are also with star for our met inhibitor I'm very pleased with enrollment here as I am with the phase two study I definitely been seeing a diversity of the patients that have been enrolled so I do believe.

We've we're starting to show that there is still an unmet medical need for and that inhibitor I think the second component in regard to the benefit of CSF. One on star will come through the data and as we've said we're guiding towards an update from the phase one in the second half of next year.

Great. Thanks, one more maybe on rate will track.

I know you mentioned the interim analysis on any initial data from the phase two portion of the tried and study in a second half of next year, but how should we think about additional follow up data or updates from the ongoing phase one studies specialty when you think about durability of the of the frontline patient population. Thank you.

Yeah sure. So as you know and as I said in her prepared remarks, but these two is by far our top priority for the team I'm pleased with the progress there, making not only with patient enrollment that also investigator engagement as well as site activation in regard to the phase two just see you know and all of our trials, we will not give quarterly.

The 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 point and so what we've been saying for not only the phase two but OTI to as I. Just mentioned is an update in the second half of next year in relation to the phase one as you know weve updated that twice since the IPO and.

On April to ask go the data improved from ask go to ESMO data further improves and my level of confidence in the phase two 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 one.

I'm, putting the team now 100% focused on trial execution, we were about to have our third and fourth trials in the clinic very soon and the two 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 one, 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 month.

Thank you so much and congrats.

Thank you Michael Michael.

Our next question comes from the line haul trucks from Goldman Sachs. Your line Center.

Hi, good afternoon, everyone and thanks for taking your questions.

If you know maybe.

Staying out of rubber truck.

For the plan combination study with degree so can you maybe.

Articulate to us what you think is the lowest hanging fruit in the easier more patient population.

I could potentially help you out 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 for a potential pivotal trial here.

Yeah, I think you further 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 stark and potential activation within the factory bypass pathway is one of the ways that we think we could utilize repositrak name in combination with in Egypt far 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 where we're also looking at quite a few additional combo is and I think we made that the conscious effort on the last call to highlight that weve.

Really been strengthening our internal translational research biology building, our chemistry group to be able to further develop not only the combination strategy with reap attractive but also feature 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 design and we've said that we would give some.

Data in regards to that work early next year.

Okay, great. Thank you for that then turning maybe back to Oh, two to for a moment.

Can you give us maybe as you on trial design and prioritization of either that treatment naive population or the treatment experience poppies population or is the plan to go after them simultaneously given that you could potentially have launches of two drugs in the category all over the near term.

Yeah, No again, I would say that and there's a lot of similarities in regard to what we're doing for both of the phase one programs. Obviously OTI to as further ahead, then ofour six OTI to essentially as a standard dose escalation with a phase one component of escalation and then expansion, where we would be looking at multiple different disease.

These type whether its long or G.I. oriented diseases, such as gastric workout of cellular there will be optionality there based on prior T. I use yes, or no that is a standard phase one the rack is definitely different and as we said in the prepared remarks, we now updated our investigator presentation to show the design.

The rest design, which is a much bigger phase one slashed to mirrors, what we did with repositrak in it and again allows quite a bit of Optionality. There is a phase one dose escalation component, but as we proceed towards the two there were multiple cohorts just like try and at one that would again be disease, driven so long.

Fibroid versus others and options in regard to prior T.K. I used 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 Mac to maximize our timeline for the written have it or.

Got it thank you for that I'll jump back into queue.

Our next question comes from a line if I'm doing parents from SVB Leerink. Your line is open.

Hey.

Congrats guys on the progress maybe a couple questions on repo I guess and try to what percentage of patients.

Well, how brain Mets, what's the typical course, Oh patient Brady mode.

Yes, so one of the things we've been monitoring obviously as the activity in the front line second line as well as intracranial an extra cranial and as you know Andy we have very strong data both in the frontline 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 on our trial and the trial itself for off in 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 set.

Thing, but that's kind of the numbers that we've seen in terms of the incidence.

So you're saying a ma'am the frontline setting, it's 50%, which was higher than and Oh I'm sorry.

Second third line.

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

Okay, and how long do those patients typically survive without progression and once they progress.

How long that usually well.

I don't have the O.S. data in front of needs to be able to answer that Andy I think what you could say from the literature as you see relatively similar rate depending on whether you're looking at the historical Entrectinib data. When they showed response rates, which you don't see is similarities between the duration and.

And or the PFS and so I don't have the west numbers I know there. The recent Crizotinib paper that was presented probably about six months ago now and the literature may have that but I don't have that on top of my had.

Okay.

And then I guess any idea of how the truck or bid launches going.

We have clearly been watching it I think it's early days still clearly I got approved obviously in the beginning of August I think you know again nothing has changed in regards to the way that we believe repo tracking it will eventually be utilized post obviously, a registration path and approval, we still believe based on the fact.

That 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 were we will differentiate as well.

Okay.

And then I guess I'm Oh, the Rep program, just how difficult will be to enroll patients that have failed to not be were six weeks Robyn.

Identify them.

I don't roll them or the walk so when we report also aggressively trying to roll those patients who trial.

You know 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 I, indeed 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 Bill.

For the molecules, you're referring to in terms of proxy compound, but also we clearly heard from multiple investigators that treatment resistance is occurring in a molecule that can overcome some of these resistant mutations is potentially coming to the clinic at the right time.

No I'm not going to protect 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.

Okay. Thanks, a lot appreciate it guys congrats again.

Thank you thanks, a lot Andy.

Sure.

Our next question comes from the line of Arlinda Lee from Canaccord. Your line is something.

Hi, guys congratulations on the process.

I'd like.

Maybe follow up on one of Andy's question.

You talked about some of it as non investigators shared with you about the need for.

Active agent.

Agent factored against resistance.

Curious.

Given that a lot of the long docs talk about using the most potent.

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 ALC inhibitor that you're.

Turning 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.

Yeah sure into thank you here. The one thing I would say is I think it was it's fair and I've said this before establishing efficacy in a pre treated setting may not be uncommon for us to do here with <unk> for six or ret inhibitor. It's exactly what we did with repo tracked in it but from a potency perspective as we showed at ESMO. We believe that we are very comparable and.

A wild type setting the phase one design allows all kinds of flexibility in terms of patients can be enrolled with and without prior ret Tiki I 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 route to move into the clinic and that's.

All the 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 we're enrolling patients who are kicking naive from the ALC inhibitor characteristics. As you know we protractive does hit ALC. It does not hit ALC as quickly as it does Ross one and two.

Correct clearly one of the areas that gene and team have been focused on is our series a candidates for now contributor that can address not only the most common gtwo to our solvents aren't mutation, but also a compound mutation where there really is no current available therapy I think equally they're very big difference.

As between our safety profile for reap attractive and for Latin live and so again, if we can translate some of that safety difference into a new ALC inhibitor I think that would be incredibly encouraging as well, but we're just the candidate nomination. So I think ideally what we're looking for something that can address fill in on that medical need that it's not addressed by low Latin is in its.

Especially if that agent moved up to the front line clearly there will continue to be a need in the second line setting.

The.

Next question.

Your next question comes from the line as Jim Birchenough from Wells Fargo Securities. Your line is open.

Hi, Thanks for taking the questions. This is a young and Oh for Jim.

So do you have a suit just first question is on potential resistance mutations to report every protracted. So do you have something from the clinical trial data im, particularly interested in whether patients.

Yes, I'll report Trust me, maybe resistant to other Ross mutations since people talking about the very compact threed structure.

Possible that resistant mutations that crude throughput track New me also automatically preclude other inhibitors with larger footprint and whether that will.

Impact a weather.

I want to using.

First line or not thanks.

Yeah, I know anything it's very good question from their resistance perspective of Repositrak in its not data was not captured within the phase one study it will be captured within the phase two so just to level set within the phase two study patients will have obviously tumor biopsies evaluated for the presence of their fusions 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 onto Repositrak nib. 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 repo tracking that I do not have that today I think the point that you made though about utilizing reap attractive in front line I do not know that that's going to be dictated by resistance mutation for me for truck enough 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 enthusiasm for the phase two study and vividly using reap attractive in front line. Obviously crizotinib is now approved there and reimbursed, but given the phase.

Back that it is so much more potent that is the key driving factor for investigators to utilize it upfront.

Got it that's very helpful. Maybe two more quick ones could you talk about the distribution of Rosslyn patients and how comes from created a that is and if youre pivotal study.

Youre targeting centers that have a strong strong a concentration of patients and also a question on whether whether you have a better sense of the percentage for Ross one patient failing gel Corey that have a solvent slots mutation. Thank you.

Yes, I think so the historical information this in their literature that mirrors pretty much what we've shown as well for solving front mutation specifically the most common G two or three to our mutation is about 40% in so that that's Burke, our dataset is a little bit lower than that but again. Our dataset is is 40 patients now not all of them that had prior.

Crizotinib, but that's the data that's in the literature to supports prevalence of sovereign fragmentation in regards to Ross one distribution, maybe just let me step back and say we have approximately 100 sites that will participate within this trial, but those sites, where methodically chosen based on not only the incidence of the diseases, but also.

The physician experience in the space and their experience with other T.I.s that are obviously ahead in terms of their development in 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 literature for Ross one, but we were very mindful in our site selection for phase two.

Got it very helpful. Thank you.

Thanks, very much for all the questions.

Again, ladies and gentlemen, if you have question at this time. Please press the Star then the number one key on your Touchtone telephone.

I'm showing no further questions at this time I would now like to turn the conference back to Jim Mitchell enough for his closing remarks.

I'm happy to step in for Jim.

Is that Sina alright, 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 use that have dialed in I look forward to see many of you at upcoming banking conferences throughout November and December operator, you can now close the call.

Ladies and gentlemen. This concludes today's conference. Thank you for participation thing and have a wonderful day you may all disconnect.