Blueprint Medicines Corp

NASDAQ:BPMC

Earnings Call Transcript 2018-Q3

[Operator]

Good day, ladies and gentlemen, and welcome to the Blueprint Medicines Third Quarter 2018 Financial and Operating Results 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 is being recorded.

I would now like to introduce your host for today's conference, Kristin Hodous. Ma'am, you may begin.

[Kristin Hodous, Senior Manager, IR]

Thank you, Operator. Good morning. This is Kristin Hodous of Blueprint Medicines and welcome to Blueprint Medicines third quarter 2018 financial and operating results conference call.

This morning, we issued a press release which outlines the topics we plan to discuss today. You can access the press release as well as the slides that we will be reviewing today by going to the Investors Section of our website at www.blueprintmedicines.com.

Today on our call, Jeff Albers, our Chief Executive Officer, will discuss Blueprint Medicines' third quarter 2018 business highlights; Dr. Andy Boral, our Chief Medical Officer, will provide a regulatory update for BLU-667; Dr. Marion Dorsch, our Chief Scientific Officer, will discuss our foundational preclinical data for BLU-782; and Mike Landsittel, our Vice President of Finance, will review our third quarter 2018 financial results. We will then open the call for your questions.

Before we get started, I would like to remind everyone that statements we make on this conference call will include forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the Risk Factors section of our most recent Quarterly Report on Form 10-Q filed with the SEC and any other filings that we may make with the SEC.

In addition, any forward-looking statements made on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements.

Now, here is our CEO, Jeff Albers.

[Jeff Albers, CEO]

Thanks, Kristin, and good morning, everyone.

Today we plan to share important updates across our portfolio that demonstrates the growing strength and breadth of our business.

At Blueprint Medicines, our mission is to deliver transformation precision therapies to patients with cancer and rare diseases. By leveraging our scientific platform, we aim to rapidly and reproducibly design highly selective kinase medicines with improved potency and safety with an increased probability of clinical success. We focus our development efforts on core areas of expertise including genomically defined cancers, rare diseases, and cancer immunotherapy. Ultimately, we aim to build an integrated biopharmaceutical company capable of delivering precision medicine to patients worldwide.

This morning, we'll share a number of key updates to take us closer to this vision. Across these updates will focus on four key themes. First, we're quickly advancing towards potential approvals for avapritinib and BLU-667 in multiple patient population. As previously announced, we have completed enrolment of registration and study cohorts for PDGFRα GIST and fourth-line GIST earlier this year.

This morning, we announced that we received FDA breakthrough therapy designation for avapritinib for the treatment of patients with Advanced Systemic Mastocytosis, and also that we have initiated patient screening in our pivotal advanced SM study called PATHFINDER. We believe the breakthrough designation and FDA feedback reinforce our plans to expedite development of avapritinib in both advanced and indolent systemic mastocytosis.

We also announced this morning that we've received FDA written feedback on our proposed registration strategy for BLU-667 in RET-altered cancers. We believe, we now have a clear path for expedited development in multiple patient populations based on our ongoing ARROW study and we plan to submit an NDA for BLU-667 in the first half of 2020. Andy will discuss these plans in more detail later on the call.

Taken all together in addition to the completed PDGFRα and fourth-line GIST study, we expect to have registration enabling studies ongoing for five additional patient populations by the end of the year.

Second, we're building a global commercial enterprise with a focus on delivering a portfolio of medicine to patients. Yesterday was great to announce the appointment of two key leaders who will spearhead this effort. Christy Rossi joined Blueprint Medicines as Chief Commercial Officer from Sanofi Genzyme, where she most recently served as the Multiple Sclerosis Business Unit Head for North America. She has 20 years of commercial experience in specialty biopharmaceuticals including expertise in building from scratch and leading an integrated commercial organization. In the new role, Christy will join our executive team and lead all of our commercial efforts.

In addition, we announced the appointment of Paul Beresford, as General Manager, International. Paul joined us from Shire where he was Vice President and Global Product Strategy Lead for rare diseases. He has 25 years of experience launching innovative specialty and oncology products, including international commercial operations and market access experience. Paul is based in Switzerland and will lead our efforts to build out European and international operations.

Our third theme is the continued realization of our research vision with the rapid and reproducible design of novel targeted therapies. In September, we presented foundational preclinical data for BLU-782 which we expect to soon become our fourth clinical phase therapeutic candidate. These data show that BLU-782 potently inhibits mutant out to the underlying cause of fibrodysplasia ossificans progressiva, a devastating rare bone disease. In a few moments, Marion will walk through these data and our plans to initiate clinical development of BLU-782 next year.

By the end of 2018 we expect to have up to nine research programs including that the five programs under our cancer immunotherapy collaboration with Roche, which is progressing nicely. As these programs continue to mature, we look forward to sharing the next phase of our portfolio plan.

Finally, as a fourth theme today, we expect to have important catalysts before the end of 2018, and continuing throughout 2019. Next month we will report updated data from the NAVIGATOR study in advanced GIST at the Connective Tissue Oncology Society Annual Meeting. There we anticipate sharing a robust update on patients with PDGFRα driven GIST and fourth-line GIST. Importantly we'll focus on response rates and duration of response in these population as we anticipate these end points will be the basis for a potential accelerated approval in the U.S.

In addition we'll share a preliminary data for patients with second-line and third-line GIST. Given the proximity to the conference and corresponding Investor Call, we'll limit responses to any GIST-related questions on the call today.

We also recently learned that NAV abstract for avapritinib in advanced SM was accepted for oral presentation at ASH in December. We look forward to sharing more information on that data once the abstract is publicly available.

In 2019, we expect to share additional data across all of our clinical stage programs including BLU-554. Under our collaboration with CStone Pharmaceuticals, we recently submitted an IND for BLU-554 to the Chinese health authorities and we continue to focus on operationalizing the collaboration across all three lead clinical programs.

Overall, we believe these update showed significant progress towards building long-term value across our portfolio. And as we prepare to enter the critical year we're accelerating our efforts. In particular, we're focused on executing five registration enabling studies, building a commercial infrastructure to deliver our medicine to patients, and continuing to advance in the next-generation of precision therapies.

I'll now turn the call over to Andy to provide more detail on our BLU-667 clinical program. Andy?

[Andy Boral, CMO]

Thanks, Jeff, and good morning everyone.

I'm excited to share an update on our BLU-667 program, including recent FDA feedback on potential registration strategies. BLU-667 is precision therapy designed for potent and selective targeting of oncogenic RET alterations including resistance mutations. RET-fusions have been identified in about 1% to 2% of non-small cell lung cancer, and about 10% to 20% of papillary thyroid cancer. Activating RET mutations have been seen up to 90% of patients with advanced medullary thyroid cancer.

In addition, published data have shown that RET alterations occur at low frequencies across a wide range of other tumor types.

In April, we reported initial results from the ARROW study of BLU-667. These data were from the dose escalation portion of the trial and the overall response rate was 53% in patients with RET-fusion positive non-small cell lung cancer and papillary thyroid cancer and it was 40% in patients with RET medullary thyroid cancer.

Earlier this month, we reported new data for BLU-667 at the American Thyroid Association Annual Meeting with a focus on thyroid cancer patients. These data showed a strengthening of clinical activity as more patients were treated with the recommended Phase 2 dose for longer durations. 90% of patients have tumor shrinkage across all dose levels. The response rate was 62% in medullary thyroid cancer patients in the 300 and 400 milligram dose once daily dose groups who were treated for at least 24 weeks. In addition, all responders and all patients treated with the recommended Phase 2 dose remains on treatment as of the date of cutoff.

Consistent with these results, we expect to see further strengthening of the data over time. Supported by these data, we are rapidly enrolling the ARROW study at clinical sites worldwide with a goal of generating registration enabling datasets consistent with the recent FDA feedbacks. With this goal in mind, we plan to report updated data from the ARROW trial in the first half of 2018.

Over the last several months, we have engaged with regulatory authorities on potential registration pathways for BLU-667 and we received written feedback from the FDA. Based on this feedback, today we are announcing plans to submit a new drug application for BLU-667 in the first half of 2020.

With additional data from the ongoing ARROW study, we anticipate that the NDA filing will include several indications, including patients with RET-fusion positive non-small cell lung cancer, RET-fusion positive papillary thyroid cancer, and RET-fusion medullary thyroid cancer, all with progressions following prior systemic therapy.

We believe the key clinical endpoints will include overall response rate and duration of response with sufficient follow-up, which is consistent with regulatory precedent for expedited approvals based on single-arm oncology studies.

Importantly, we also intend to explore longer-term development opportunities for BLU-667. These may include the frontline treatment of patients with RET-altered lung cancer and medullary thyroid cancer, a tumor agnostic indications across all RET-altered cancers, and combination therapy for treatment-resistant EGFR-mutant lung cancer with an acquired RET-fusion.

Altogether we think there are significant short and long-term opportunities for BLU-667 to improve outcomes across a broad population of patients with RET-altered cancers.

Now I will turn the call over to Marion to review the updated preclinical data for BLU-782. Marion?

[Marion Dorsch, CSO]

Thank you, Andy.

Before I share an update on BLU-782, let me start by discussing our overall research strategy. As you know, all our lead therapeutic candidates were internally discovered and developed at Blueprint Medicine, using our scientific platform and resource capabilities that are core to our strategic vision.

Key to our success is our proprietary library that was assigned by Blueprint Chemist to provide product kinam coverage. Upon identification of genetic kinase drivers of disease, we leverage our library to identify starting points for the kinase of interest. We then tap into our extensive expertise in structure based design and Medicinal Chemistry to optimize the starting points into drug candidates. This approach has worked very well for us as evidenced by the rapid clinical proof of concept achieved with our highly selective precision therapies. Building on our expertise, we expect to have up to nine ongoing research programs by the end of this year, including up to five cancer immunotherapy programs under our Roche collaboration.

This is the same strategy we applied to BLU-782 which we designed to target mutant activin-like kinase-2 or ALK2, the underlying cause of Fibrodysplasia Ossificans Progressiva or FOP. FOP is a severely disabling ultra rare disorder of the connective tissue characterized by the abnormal transformation of skeletal muscle ligaments and tendons into bone, either spontaneously or as a result of physical trauma. Beginning in early childhood, patients experience loss of joint function, progressive disability, and ultimately premature death. While mutant ALK2 has long been recognized as the underlying cause of FOP, prior efforts to develop a selective ALK2 inhibitor has failed due to persistent technical challenges.

Specifically, it has proven difficult to selectively target ALK2 without inhibiting other members of the ALK family which has the potential to drive off-target toxicity. Our proprietary compound library and expertise in structure guided Medicinal Chemistry have allowed us to overcome these historic challenges and we were pleased to present foundational preclinical data at ASBMR that speak to the tremendous potential of BLU-782 in this disease.

On this Slide we show some of the top-line data included in the BLU-782 presentation at ASBMR. In vitro studies showed BLU-782 was more than 100 to almost 1,000 fold selective for ALK2 compared to other kinases in the ALK family including ALK1, ALK3, and ALK6. Additional in vitro data showed that BLU-782 inhibited ALK2 regardless of the activating ligand, including Activin A, B, or BMP6.

In vivo studies showed BLU-782 potently inhibits a band bone formation in a genetically accurate FOP mouse model. This activity was shown in models of muscle injury and bone surgery.

In particular I would like to draw your attention to the video that clearly showed in addition of Heterotopic Ossification upon treatment with BLU-782. We also were pleased to see the repair of the bone fracture and multi tissue following injury. We think these data are incredibly encouraging because they validate ALK2 inhibition as a potentially important therapeutic strategy for FOP and strongly support initiating clinical development of BLU-782. Importantly, we plan to pursue a continuous dosing regimen in patients with the goal of preventing disease progression.

We think this approach offers advantages over acute intervention following a disease flare up particularly because Heterotopic Ossification may not always be associated with a flare.

Right now, we are working to submit an IND application for BLU-782 by year-end. Subject to approval of the IND by the FDA, we plan to initiate a Phase 1 clinical trial in healthy volunteers in the first quarter of 2019.

In addition, we are accelerating plans to initiate a potential Phase 2 trial of BLU-782 in patients with FOP with the goal of identifying opportunities to expedite global development.

As we continue to make progress, we look forward to providing updates on BLU-782 and other emerging programs across our research stage portfolio.

I will now turn the call over to Mike to review our financial results for the third quarter.

[Mike Landsittel, VP, Finance]

Thanks, Marion.

We continue to operate from a position of financial strength which allows us to continue investing resources in our growing clinical pipeline, while also building the infrastructure to support the potential commercialization of our product candidates.

We ended the third quarter with cash of $559.6 million compared to $673.4 million as of December 31, 2017. The decrease in fair cash was primarily related to cash used in operating activities partially offset by the $40 million upfront payment received in connection with entering into the CStone collaboration, and the $10 million milestone payment achieved under the Roche collaboration, both of which occurred in June of 2018.

We continue to believe that this provides us the necessary capital to fund our operations into the second half of 2020.

Turning to the P&L, we recognized $1.1 million of collaboration revenues in the third quarter of 2018 compared to $8.1 million for the third quarter of 2017. This decrease was primarily due to the termination of the Alexion agreement in 2017.

With respect to operating expenses, we incurred $64.6 million in R&D in the third quarter of 2018 compared to $39.3 million for the same period in the prior year. This increase in R&D expense was primarily driven by increased clinical and manufacturing expenses associated with advancing avapritinib and BLU-667 further through clinical trials as well as increased personnel-related expenses.

G&A expenses were $12 million for the third quarter of 2018 compared to $7.4 million for the third quarter of 2017. This increase in G&A expense was largely due to increased personnel-related expenses and increased professional fees including pre-commercial planning activities.

This is an exciting time for Blueprint as we now have five ongoing or planned registrational studies. We are actively preparing for a first NDA filing in the first half of 2019 and we are laying the groundwork for our commercial infrastructure in both the U.S. and Europe.

As we've guided before, we expect that our operating expenses will continue to increase in future quarters as we devote additional resources towards these important activities and prepare for the transition to becoming a fully integrated biopharmaceutical company.

With that, I will now turn the call over to the operator for questions. Operator?

[Operator]

Thank you. [Operator Instructions].

Our first question comes from Terence Flynn with Goldman Sachs. Your line is now open.

[Terence Flynn, Goldman Sachs]

Hi, thanks for taking the question. Congrats on the progress. I was just wondering with respect to the avapritinib second and third line GIST data that's coming at CTOS, just wanted to confirm that the trial enrolled All-Comers there and assuming that that's the announced that CTOS will present and then any more details you can share at this point Jeff or Andy on the Phase 3 second-line GIST trial design? Thanks.

[Jeff Albers, CEO]

So this is Jeff. I’ll take that question. So the second and third line data as I've mentioned in the opening prepared remarks will focus any updated detailed questions around that at the Investor Call while we're at CTOS. We will point out second and third line and when you say All-Comers I'm assuming you mean KIT-driven as well as PDGFRα, we will likely exclude the PDGFRα or call them out separately.

And then, in terms of development plans, we will provide that update on that Investor Call at CTOS.

[Operator]

Thank you. And our next question comes from Andrew Berens with Leerink Partners. Your line is now open.

[Andrew Berens, Leerink Partners]

Thanks and congrats on the progress guys. Just a question I guess on 667 and I hate to say the glass is half empty but what's the -- you had given us an update on after regulatory discussions and honestly Loxo has a breakthrough designation in the same indication. So can you just give us some color on that potential for 667?

[Jeff Albers, CEO]

Sure. This is Jeff. I will start with that. So as we have with avapritinib, we always start with the most important piece of information from our perspective be it establishing an accelerated path to approval. So we start with those conversation and then we view breakthrough therapy designation as the tool to ensure consistent and regulatory feedback around that path. So now with the announcement that we have the written feedback from FDA on a potential accelerated path, breakthrough therapy designation would be something that we could explore to help ensure effective execution of that plan. So whether we take it as a glass half full or glass half empty, we think this is very consistent with what we've done in other programs and we found that it works well.

[Andrew Berens, Leerink Partners]

Okay. And then this is a question I guess for Andy, you've mentioned that 667 has activity of the Gatekeeper Mutation, can you just give us some insights as to what that means and what you’ve seen?

[Andy Boral, CMO]

Sure. So one of the things that we think is very -- is unique about the 667 is truly has equally potent activity against the range of fusions, the activin point mutations as well as the expected resistance mutations at the Gatekeeper across various several variance. And now our hope is that this will translate into prolonged durations of response. So we think that -- so with the multi-kinase inhibitor, Gatekeeper Mutations will be the primary cause of resistance, they could come up quickly, this could apply to other broader range of RET inhibitors as well and by inhibiting that off that, we think that will -- should pan out to longer durations of response but first we have to show that clinically.

[Andrew Berens, Leerink Partners]

Would it also potentially allow you to use 667 sequentially as the patient develops the resistance to another RET inhibitor?

[Andy Boral, CMO]

No, I mean I think that our perspective on 667 is that is a very potent selective RET inhibitor and that be best used as the first RET inhibitor.

[Operator]

Thank you. And our next question comes from Joseph Thorne with Cowen & Company. Your line is now open.

[Joseph Thorne, Cowen & Company]

Hi there and thank you for taking my question and congrats on the progress. Just a couple on the regulatory filings for PDGFRα and fourth-line GIST for AVA I guess what remain to be done before you can file that application, simply just waiting for additional follow-up from the ongoing studies in these patient subsets or is there additional information that's needed there. And when we look ex-U.S. is there plan to go ex-U.S. yourselves or how -- what the thought process on that and will you need results from the Phase 3 study in order to file in Europe?

[Jeff Albers, CEO]

So this is Jeff. I will take that question and Andy can add color as necessary. So on the first part of the question of what remains to be done for our plan first half filing of an NDA in the U.S. for PDGFRα and fourth-line GIST. As we previously announced we fully enrolled that in the first half of this year and so as with any accelerated approval, one of the components is sufficient follow-up and data around response rates and duration of response. So just accumulating that but then it’s a process, then it's -- the next step is then pulling all that together for the filing.

So we’re in the midst of all of that and then again importantly the presentation at CTOS in a few weeks will include all of that data from a recent cutoff or as of a recent cutoff that will give you a better sense of what we're looking at and why we're -- what data will be the basis of the filing.

And then the second component is international plans, so it's always been our plan I think we’ve announced previously that we will first file the NDA but then certainly plan to file an MAA soon thereafter within Europe.

[Operator]

Thank you. And our next question comes from Laura Chico with Raymond James. Your line is now open.

[Laura Chico, Raymond James]

Good morning, thanks for taking the question. I have one for you on BLU-667, I think Jeff, Andy we refer to use the terms annoyingly similar before with regard to 667 and 292. And now with the regulatory update today it sounds like you're heading down a similar path, so I guess if you could just elaborate a little bit on what you see as the key point of differentiation emerging and kind of what you’ll see there as we progress? And then secondarily you just mentioned on the last question accelerated approval requiring physician follow-up, is that the primary gating factor to submission for 667 or are there other elements that will be necessary to complete?

[Jeff Albers, CEO]

All right. Andy why don't you take that?

[Andy Boral, CMO]

So Laura thanks for the question. So as we've shown in the past, we have a very potent selective rate inhibitor in BLU-667 and are very happy with the data that is evolving so far. We do think that the two compounds are on similar regulatory path and if there are differences, they will be small in terms of what is needed for accelerated approval or to build out the accelerated approval data set, it really is focusing on continuing to conduct our study, enroll patients rapidly as possible at the maximum tolerated dose and recommended Phase 2 dose as we initiated around the time of the ACR meeting and then the main focus really is enrolling study in patients and the follow-up there aren't any other specific, I think limitations that we see at this time.

[Laura Chico, Raymond James]

Okay, thank you. And if I could just sneak one quick one in on the FOP program, Clementia recently moved towards well they will be moving towards an NDA submission in the second half of 2019. I guess would that move suggest a rapid path to market also exist for you? And then, also how should we be thinking about the route of administration of potential therapies for FOP?

[Andy Boral, CMO]

So yes, so we've always understood that Aloe Vera team is -- would be likely be ahead of us and actually we think it's good to see multiple agents being developed for a rare disease such as FOP. I will say that Clementia actually deserves some credit for helping define important -- playing an important role in defining some of the regulatory paths but we do see that -- we do think that by selectively targeting out to which is the underlying cause of disease, BLU-782 has the potential to offer very potent clinical activity that we think could differentiate it from other various agents being developed.

BLU-782 will be an oral compound -- is an oral compound and I think one thing that we think is very important for as we think about treatment for FOP and the approach we're taking for BLU-782 is that we're really focused on developing it as a continuous treatment with the goal of preventing disease progression and as we learn about the disease, I think it's particularly important because Heterotopic Ossification clearly progresses in between flares not just with flares. I think, so we think it's important to treat chronically and not with acutely in setting flares only. We think that will be an important distinction.

[Operator]

Thank you. [Operator Instructions].

Our next question comes from Michael Schmidt with Guggenheim Securities. Your line is now open.

[Unidentified Analyst]

Hi Etzer Darout [ph] calling in for Michael. I got a couple questions on mastocytosis [indiscernible]. First within mastocytosis specifically would begin to lent [ph] in a smoldering constellation, in your view what type of symptom improvements would be sufficient to be clinically significant and what the delivery process look like in reality to particular end points?

[Andy Boral, CMO]

Yes, so maybe I'll step back. So we're developing avapritinib in both advanced and indolent systemic mastocytosis. In advanced systemic mastocytosis the primary endpoint is response rate using the IWG criteria. And of course we have developed a disease specific patient reported outcome tool that will be an important secondary end point in that study but we don’t expect to be the primary driver of approval and that’s in contrast to indolent systemic mastocytosis where we have developed again a similar but slightly different patient reported outcome tool specific to indolent disease that will be the primary -- the primary end point for approval in the indolent population.

I mean in that case we are -- we have -- the tool is validated and we will be kicking off that study in indolent disease in the latter part of the year which we do anticipate to be a registration enabling study. Here we haven’t really gone into details publically about what differences we would expect or we think would be needed for approval. But the comparison will be to placebo and we would be targeting significant differences. Sorry, did I miss the second part?

[Unidentified Analyst]

No, that's helpful. And also now regarding the BLU-667, how would you evaluate the potential with that [indiscernible] product within let's say the frontline systemic treatment as well as in thinking you mentioned that entering in a [indiscernible] what about other RET-altered tumors now with an existed [indiscernible]?

[Andy Boral, CMO]

Yes, so and I think that’s -- I think as we think about the development of highly potent agents against dominant drivers like RET of course from the clinical perspective, we want to move into frontline therapies as quickly as possible. Now the initial registration plan and certainly the fastest path is as an accelerated approval based on single-arm data and in oncology that is generally -- the quickest [indiscernible] there is generally in patients who have received the available standard of care in lung cancer and medullary thyroid cancers that are established standards of care. So in that setting we expect the first and most rapid approval path to be in patients who have received those frontline standards but no we certainly very much developing a development and regulatory path that would then get us into frontline quickly as we can.

[Jeff Albers, CEO]

And then the second part of that question was the tumor agnostic approach and that continues to be part of our ongoing study and as Andy mentioned in the prepared remarks that we’re starting with a focus on non-small cell lung cancer and various types of thyroid cancer but we will continue to evaluate the emerging data in those patients for which -- for those types of cancers for which RET alterations occur at a very low frequency and we are currently enrolling them in our study.

[Unidentified Analyst]

Great. And then one last one on GIST if you don't mind. Just curious how much clinical data do you think you will need in order to make a decision obviously development plan within second-line GIST and do you think will have this information by CTOS?

[Jeff Albers, CEO]

Yes. So we have made that decision, I think we disclosed our intentions to move forward with a trial in second-line GIST. Obviously as you know we have an ongoing randomized third-line GIST trial versus regorafenib that started enrolling at the end of second quarter this year and we'll provide more comprehensive update of those plans in the path forward on the Investor Call at CTOS.

[Operator]

Thank you. And our next question comes from Arlinda Lee with Canaccord. Your line is now open.

[Arlinda Lee, Canaccord]

Hi guys, thanks for taking the questions. On the CTOS data, I know you didn’t want to disclose too much but on the fourth-line dataset, are we going to see that separated out from the PDGFR and might we see progression free survival on some of the surveyor lines evolve, considering you just started the second-line study about a year ago? And then I guess lastly on the breakthrough designation for SMP, can you maybe provide a little bit of information if about how -- what [indiscernible] dataset that prompted additional FDA voice [ph] care?

[Jeff Albers, CEO]

So, this is Jeff. I will take the first question and then Andy I will have you answer the question around breakthrough therapy designation. So at this update, we don’t want to get into all the different cuts that will be providing some of that still being pulled together, currently but it will be a robust update. We’ve said this from early on that we see GIST as a very meaningful opportunity for avapritinib. There is about 9,000 frontline patients that are currently treating, most of them go on to receive multiple lines of therapy over time and so we’ve got a comprehensive development plan and we think this update where we will be showing data from fourth-line GIST from PDGFRα, those patients with PDGFRα regardless of line, third-line GIST, second-line GIST that there will be a lot to that. Obviously, as Andy highlighted in the opening remarks the primary focus for fourth-line will be around highlighting response rate and duration of response because that's what FDA will be looking for in terms of an evaluation of any regulatory approval. So that will be really the cornerstone of the presentation but we'll look to provide additional valuable information as possible.

Specifically to the PFS obviously I think you said this in your question that that will be more preliminary dataset, so we’ll look at a variety of different cut to that but I know that it is early data.

[Andy Boral, CMO]

It’s Andy, on terms of the Mastocytosis datasets for PGD; it was really based on what we showed at EHA which was an incremental update on the data that was at ASH, of course the document that the FDA is a lot cares so there is more detail. But that's the fundamental dataset.

[Operator]

Thank you. And our next question comes from Konstantinos Aprilakis with JMP Securities. Your line is now open.

[Konstantinos Aprilakis, JMP Securities]

Hi guys, thanks for taking my questions. So Andy you mentioned strengthening of the BLU-667 efficacy signal in thyroid cancer presented at ATA. So would you expect to see the same phenomenon in lung cancer when we see more patients driven to go forward dose with 667, when should we expect to see updated data in lung, and I have got two follow-ups.

[Andy Boral, CMO]

Okay. So we were very pleased to see the continued increase and response -- response rate with for the follow-up and higher doses in the thyroid cancer patient population and we think it's important to look at the lung cancer population in a similar way, as when we presented data at AACR which is our last real update of lung that was I think on the call -- on the call -- all on the call, no that was really based on the escalation part of the study with very few patients at the NTD. So we are hopeful to see continued improvement in response rate over time in the lung cancer population. We plan to update on -- to a comprehensive update on that study including thyroid and lung in the first half of the coming year. We always keep the opportunity possibility open for smaller updates at disease specific meetings and so we will keep our eyes out.

[Konstantinos Aprilakis, JMP Securities]

Okay, great. And then with regard to avapritinib when we glass out data from EXPLORE and EHA there were two patients with smouldering SMs, so I’m just wondering if the updated ASH piece of follow-up data on those two patients or any new patients with indolent SM?

[Andy Boral, CMO]

Yes, so we are however excited to be having -- that we have a update an oral update at ASH with avapritinib in SM, it will be an incremental but complete update of the study and so certainly we give additional follow-up on the patients we have reported before and we’re still thinking about what other pieces of information are of interest that we can bring out at that presentation.

[Konstantinos Aprilakis, JMP Securities]

Okay, then one quick one for Jeff. I know you said limit answers to GIST related questions but I was wondering if you could just remind us when the second-line GIST cohort opens for enrolment and maybe confirm the target there, I believe it was 50 patients is that right?

[Jeff Albers, CEO]

Yes. That is correct and that started enrolment I think was late first quarter.

[Operator]

Thank you. And our next question comes from Eun Yang with Jefferies. Your line is now open.

[Eun Yang, Jefferies]

Thank you. I have a general question on GIST, so in second and third line current therapies avapritinib and regorafenib, they give less than 10% of response rate, so anything better than that would be good for avapritinib. However there remains always a challenge when we compare single-arm cost of study comparison, so in your mind one magnitude of response will give you constant stat avapritinib would provide a significant value over current therapy?

[Jeff Albers, CEO]

Yes, Eun, this is Jeff. So I think that falls precisely into the types of commentary that we want to provide with all of the data in hand. As mentioned it’s been a year since we provided update on the study and so we can walk through that type of detail on the Investor Call at CTOS.

[Eun Yang, Jefferies]

Okay. And the second question is on the commercial side, so now you’re on track to file for approval in the first half of next year for GIST. And then 667 in the first half of 2020, so can you kind of comment on what your commercial time [ph] look like by the time your first launch of the product probably toward the end of 2019 or early 2020? Thank you.

[Jeff Albers, CEO]

Sure. So Christy is on day two of the job, so we’re going to let her build out those plans over the coming weeks and months. But I think you hit on a really important piece, so that has always been the vision of Blueprint Medicines to commercialize in a wide array of indications and with several therapeutics and we see that vision coming into focus increasingly, most notably with the fact that we've got one study that could be potentially registration enabling, fully enrolled, and by the end of this year, we expect to have five additional registration enabling studies ongoing several with FDA guidance on a potential accelerated path.

And so when you get into that that array of indication that on one hand is a very attractive opportunity and it also will add complexity. And so if you go back to the founding vision of Blueprint Medicines, there was a notion that in targeted therapies in oncology and in rare genetic diseases, small companies can effectively build-out commercial infrastructure in a thoughtful and efficient manner which focuses on identifying the patients and then educating physicians on how to maintain longer-term treatment and so those guiding principles will really be the focus as we're building out the team in a step-wise fashion as multiple indications move forward.

[Operator]

Thank you. This concludes today’s Q&A session. I would now like to turn the call back over to Jeff Albers for closing remarks.

[Jeff Albers, CEO]

Thanks, Operator, and thanks everyone on the call for taking time to join us this morning and for your continued support Blueprint Medicines. We look forward to updating you further in the coming week as we unveil new clinical data for avapritinib and GIST and systemic mastocytosis. Thanks a lot and good bye.

[Operator]

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program. You may all disconnect. Everyone have a great day.