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Edited Transcript of BPMC earnings conference call or presentation 30-Oct-18 12:30pm GMT

Q3 2018 Blueprint Medicines Corp Earnings Call

CAMBRIDGE Jan 22, 2019 (Thomson StreetEvents) -- Edited Transcript of Blueprint Medicines Corp earnings conference call or presentation Tuesday, October 30, 2018 at 12:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Anthony L. Boral

Blueprint Medicines Corporation - Chief Medical Officer

* Jeffrey W. Albers

Blueprint Medicines Corporation - CEO, President & Director

* Kristin Hodous

Blueprint Medicines Corporation - Senior Manager of IR

* Marion Dorsch

Blueprint Medicines Corporation - Chief Scientific Officer

* Michael Landsittel

Blueprint Medicines Corporation - VP of Finance

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Conference Call Participants

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* Andrew Scott Berens

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

* Arlinda Anna Lee

Canaccord Genuity Limited, Research Division - Analyst

* Joseph John-Charles Thome

Cowen and Company, LLC, Research Division - Associate

* Konstantinos Nikolaos Aprilakis

JMP Securities LLC, Research Division - Senior Analyst

* Kyung Yang

Jefferies LLC, Research Division - MD & Senior Equity Research Analyst

* Laura K. Chico

Raymond James & Associates, Inc., Research Division - Senior Research Associate

* Terence C. Flynn

Goldman Sachs Group Inc., Research Division - MD

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Presentation

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Operator [1]

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Good day, ladies and gentlemen, and welcome to the Blueprint Medicines Third Quarter 2018 Financial and Operating Results Conference Call. (Operator Instructions) As a reminder, this conference call may be recorded.

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

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Kristin Hodous, Blueprint Medicines Corporation - Senior Manager of IR [2]

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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'll 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.

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [3]

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Thanks, Kristin, and good morning everyone. Today, we plan to share important updates across our portfolio that demonstrates a growing strength and breadth of our business. At Blueprint Medicines, our mission is to deliver transformative precision therapy 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 medicines to patients worldwide. This morning we'll share a number of key updates that take us closer to this vision. Across these updates we'll focus on 4 key themes; first, we're quickly advancing towards potential approvals for avapritinib and BLU-667 in multiple patient populations. As previously announced, we completed enrollment of registration and study cohorts for PDGFR-alpha 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've 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 PDGFR alpha and fourth-line GIST study, we expect to have registration enabling studies ongoing for 5 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 medicines to patients. Yesterday was great to announce the appointment of 2 key leaders who will spearhead this effort. Christina 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 her 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 joins 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 stage therapeutic candidate. These data show that BLU-782 potently inhibits mutant ALK2, the underlying cause of fibrodysplasia ossifcans progressiva, a devastating rare bone disease. In a few moments, Marion will walk through these data and our plans to initiated clinical development of BLU-782 next year. By the end of 2018 we expect to have up to 9 research programs including up to 5 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'll 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 PDGFR-alpha driven GIST and fourth-line GIST. Importantly, we'll focus on response rates and duration of response in these populations as we anticipate these endpoints will be the basis for a potential accelerated approval in the U.S.

In addition, we'll share 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 an 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 publically 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 3 lead clinical programs.

Overall, we believe these updates show significant progress towards building long-term value across our portfolio and as we prepare to enter a critical year we're accelerating our efforts. In particular we're focused on executing 5 registration enabling studies building a commercial infrastructure to deliver our medicines to patients and continuing to invest in the next generation of precision therapies.

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

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [4]

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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 in 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 was 40% in patients with RET mutant 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 at the recommended Phase II dose for longer durations. 90% of patients had 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 are treated for at least 24 weeks.

In addition, all responders and all patients treated at the recommended Phase II dose, remained on treatment as of the data cutoff. Consistent with these results, we expect to see further strengthening of the data over time. Supported by these data, we're rapidly rolling the ARROW study at clinical sites worldwide with the goal of generating registration enabling datasets consistent with the recent FDA feedback. With this goal in mind, we plan to report updated data from the ARROW trial in the first half of 2019.

Over the last several months, we've 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 mutant medullary thyroid cancer. All with progression 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 the 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 front-line treatment of patients with a RET-altered lung cancer and medullary thyroid cancer; a tumor agnostic indication across all RET-altered cancers and combination therapy for treatment-resistant EGFR mutant lung cancer with required -- 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'll turn the call over to Marion to review the updated preclinical data for BLU-782. Marion?

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Marion Dorsch, Blueprint Medicines Corporation - Chief Scientific Officer [5]

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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 Medicines using our scientific platform and research capabilities that are core to our strategic vision. Key to our success is our proprietary library that was designed by Blueprint chemists to provide broad kinome 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 and 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 9 ongoing research programs by the end of this year including up to 5 cancer immune therapy 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 ultrarare disorder of the connective tissue characterized by the abnormal transformation of skeletal muscle, ligaments and tendons into bone, either spontaneously or as the result of physical trauma. Beginning in early childhood, patients experience loss of joint function, progressive disability and ultimately, premature death.

While mutant ALK2 has now 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 have the potential to drive off-target toxicity. Our proprietary compound library and expertise in structure-guided medicinal chemistry has allowed us to overcome these historical challenges, and we are pleased to present foundational pre-clinical 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 a hundred to almost a thousandfold selective for up to -- 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 show that BLU-782 potently inhibits a 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 shows inhibition of heterotopic ossification upon treatment with BLU-782. We also -- we're pleased to see the repair of the bone fracture and muscle tissue following injury.

We think this 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're 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 I clinical trial in healthy volunteers in the first quarter of 2019. In addition, we are accelerating plans to initiate a potential Phase II 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.

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Michael Landsittel, Blueprint Medicines Corporation - VP of Finance [6]

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Thanks, Marion. We continued to operate from a position of financial strength which allows us to continue investing in 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. This decrease in 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 precommercial planning activities.

This is an exciting time for Blueprint as we now have 5 ongoing or planned registrational studies. We are actively preparing for our 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?

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from Terence Flynn with Goldman Sachs.

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Terence C. Flynn, Goldman Sachs Group Inc., Research Division - MD [2]

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I was just wondering with respect to the avapritinib second and third-line GIST data that's coming at CTOS, I just wanted to confirm that the trial enrolled all-comers there and assuming that that's the analysis you guys will present. And then any more details you can share at this point, Jeff or Andy, on the Phase III second-line GIST trial design?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [3]

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So this is Jeff, I'll take that question. So the second and third-line data, as I mentioned in the opening or prepared remarks, we'll focus any updates or detailed questions around that at the investor call while we're at CTOS. But we'll break out second and third-line and when you say all-comers, I'm assuming you mean kit driven as well as PDGFR-alpha. We will likely exclude the PDGFR-alpha or call them out separately. And then in terms of developing plans, we'll provide that update on that investor call while at CTOS.

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Operator [4]

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And our next question comes from Andrew Berens with Leerink Partners.

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Andrew Scott Berens, Leerink Partners LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst [5]

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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 the breakthrough designation and the same indication. So, can you just give us some color on that potential for 667?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [6]

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Sure, this is Jeff. I'll start with that. As we have with avapritinib, we always start with the most important piece of information from our perspective is establishing an accelerated path to approval so we start with those conversations 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 had the written feedback from the 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 you take it as a glass half full or a glass half empty, we think this is very consistent with what we've done in other programs and we've found that it works well.

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Andrew Scott Berens, Leerink Partners LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst [7]

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And then this is a question, I guess, for Andy. You've mentioned that 667 has activity at the gatekeeper mutation. Can you just give us some insights about what that means and what you've seen?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [8]

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

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Andrew Scott Berens, Leerink Partners LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst [9]

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Would it also potentially allow you to use 667 to potentially -- if a patient developed a resistance to another RET inhibitor?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [10]

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So I mean, I think that our perspective on 667 is that is a very potent selective RET inhibitor and that it will be best used as the first RET inhibitor.

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Operator [11]

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And our next question comes from Joseph Thome with Cowen and Company.

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Joseph John-Charles Thome, Cowen and Company, LLC, Research Division - Associate [12]

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Just a couple on the regulatory filing for PDGFR-alpha and fourth-line just for ava. I guess what remains 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 at ex-U. S., is it still the plan to go ex U.S. yourselves or how was the thought process on that and will you need results from the Phase III study in order to file in Europe?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [13]

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So this is Jeff, I'll 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 planned first half filing of an NDA in the U.S. for PDGFR-alpha and fourth-line GIST. As we previously announced, we fully enrolled that in the first half of this year and so as with an accelerated approval, one of the components is sufficient follow-up -- a follow-up and data around response rates and duration of response. So it's just accumulating that but then it's -- the next step is then pulling all of 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 will first follow the NDA but then we'll certainly plan to file an MAA soon thereafter within Europe.

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Operator [14]

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And our next question comes from Laura Chico with Raymond James.

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Laura K. Chico, Raymond James & Associates, Inc., Research Division - Senior Research Associate [15]

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I have one for you on BLU-667. I think Jeff, Andy, we've heard you use the terms annoyingly similar before with regards to 667 and 292. 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 points 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 sufficient follow-up. Is that the primary gating factor to submission for 667 or are there other elements that will be necessary to complete?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [16]

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Andy, why don't you take that.

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [17]

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So Laura, thanks for the question. So as we've shown in the past, we have a very potent selective RET inhibitor in BLU-667 and are very happy with the data as it's evolving so far. We do think that the 2 compounds are on similar regulatory paths 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 dataset, it really is focusing on continuing to conduct our study and enroll patients as rapidly as possible at the maximum tolerated dose and recommended Phase II dose as we initiated around the time of the ACR meeting and the main focus really is enrolling the study treatment patients and the follow-up. There aren't any other specific, I think, limitations that we see at this time.

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Laura K. Chico, Raymond James & Associates, Inc., Research Division - Senior Research Associate [18]

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Okay. And if I could just make 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 exists for you? And then also, how should we be thinking about the route of administration of potential therapies for FOP?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [19]

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Yes, so we've always understood that Palovarotene is -- would 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 to find important -- playing an important role in defining some of the regulatory paths but we do see that I -- we do think that by selectively targeting ALK2, 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 -- the other various agents being developed. The BLU-782 will be an oral, or 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 as a continuous treatment with the goal of preventing disease progression. And as we learn about the disease, we think this is particularly important because heterotopic ossification clearly progresses in between flares not just with flares. So I think it was -- so, we think it's important to treat chronically and not with -- acutely in the setting of flares only. We think that will be an important distinction.

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Operator [20]

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Our next question comes from Michael Schmidt with Guggenheim Securities.

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Unidentified Analyst, [21]

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(inaudible) calling in for Michael. We've got a couple of questions on mastocytosis (inaudible). First within mastocytosis, specifically within the indolent and smoldering constellation, in your view, what type of symptom improvements would be sufficient to be clinically significant and what would the regulatory process look like to validate particular end point for the rest of the (inaudible)?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [22]

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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 endpoint 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 to slightly different patient-reported outcome tool specific to indolent disease that will be the primary endpoint for approval in the indolent population. Given that case, we have -- the tool is valid and we'll 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. We haven't really gotten into details publically about what differences we would expect or where we think would be needed for approval but the comparison will be to placebo and we would be targeting significant differences. Did I miss the second part?

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Unidentified Analyst, [23]

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No, that's helpful and also now regarding BLU-667, how would you evaluate the potential (inaudible) product within, let's say, the frontline systemic treatment as well as -- and I think (inaudible) you mentioned that it is doing it in a (inaudible) entity. What about other RET-altered tumors not (inaudible)?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [24]

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Yes. So no 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 therapy as quickly as possible. Now, you know, the initial registration plan is certainly the fastest path is as an accelerated approval based on single-arm data and in oncology that is generally the quickest path forward there is generally in patients who have received the available standard of care in lung cancer and in medullary thyroid cancers there 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've certainly very much developing a -- development and regulatory path that would then get us into frontline as quickly as we can.

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [25]

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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.

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Unidentified Analyst, [26]

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

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [27]

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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 the second quarter this year and we'll provide a more comprehensive update on those plans in the path forward on the investor call at CTOS.

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Unidentified Analyst, [28]

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Understood.

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Operator [29]

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And our next question comes from Arlinda Lee with Canaccord.

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Arlinda Anna Lee, Canaccord Genuity Limited, Research Division - Analyst [30]

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On the CTOS dataset 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 earlier lines as well considering you just started the second line study about a year ago? And then I guess lastly, a couple of breakthrough designations for SMP, can you maybe provide a little bit of information if -- about how -- what (inaudible) was there?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [31]

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So this is Jeff, I'll take the first question and then Andy I'll have you answer the question around breakthrough des -- breakthrough therapy designation. So, at this update we don't want to get into all of the different cuts from -- that will be providing some of that, is still being pulled together currently, but it will be a robust update and we have said this from early on that we see GIST as a very meaningful opportunity for avapritinib. There's about 9000 frontline patients we 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'll be showing data from fourth-line GIST from PDGFR-alpha, those patients with PDGFR-alpha 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 will look to provide additional valuable information as possible specifically to the PFS, obviously I think you said this in your question, that will be more preliminary datasets. So we will -- we'll look at a variety of different cuts of that but I'll note that it is early data.

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [32]

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It's Andy. In terms of the mastocytosis dataset supporting 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 goes to the FDA is a lot thicker so there's more detail but that's the fundamental dataset.

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Operator [33]

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Our next question comes from Konstantinos Aprilakis from JMP Securities.

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Konstantinos Nikolaos Aprilakis, JMP Securities LLC, Research Division - Senior Analyst [34]

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So Andy, you mentioned strengthening of the BLU-667 efficacy signal and thyroid cancers presented at ATA, so would you expect to see the same phenomenon in lung cancer when we see more patients receiving the go-forward dose for 667? When should we expect to see updated data in lung and I've got 2 follow-ups.

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [35]

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So yes, we were very pleased to see the continued increase in response and response rate with further follow-up and at 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 ACR which was our last real update of lung that was, as I think, all on the call know that was really based on the escalation part of the study with very few patients at the MTD. So we are hopeful to see continued improvement in response rate over time in lung cancer. We plan to update on -- do a comprehensive update on that study including thyroid and lung in the first half of the coming year. But we always keep the opportunity, possibility, open for smaller updates at disease-specific meetings and so we'll keep our eyes out.

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Konstantinos Nikolaos Aprilakis, JMP Securities LLC, Research Division - Senior Analyst [36]

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Okay, great. And then with regard to avapritinib, when we last out data from EXPLORE at EHA there were 2 patients with smoldering SM, so I'm just wondering if the updated ASH feature follow-up data on those 2 patients or any new patients with indolent SM?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [37]

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Yes, so we're 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've reported before and we're still thinking about what other pieces of information are of interest that we can bring out at that presentation.

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Konstantinos Nikolaos Aprilakis, JMP Securities LLC, Research Division - Senior Analyst [38]

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

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [39]

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

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Operator [40]

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And our next question comes from Eun Yang with Jefferies.

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Kyung Yang, Jefferies LLC, Research Division - MD & Senior Equity Research Analyst [41]

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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 what magnitude of response will give you confidence that avapritinib would provide a significant value over current therapy?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [42]

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

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Kyung Yang, Jefferies LLC, Research Division - MD & Senior Equity Research Analyst [43]

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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 team would look like by the time your first launch of the product, probably toward the end of 2019 or early 2020?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [44]

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Sure. So Christy is on day 2 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, it 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 1 study that could be potentially registration enabling, fully enrolled, and by the end of this year we expect to have 5 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.

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Operator [45]

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

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [46]

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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 goodbye.

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Operator [47]

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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.