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Edited Transcript of BPMC earnings conference call or presentation 13-Feb-20 1:30pm GMT

Q4 2019 Blueprint Medicines Corp Earnings Call

CAMBRIDGE Feb 14, 2020 (Thomson StreetEvents) -- Edited Transcript of Blueprint Medicines Corp earnings conference call or presentation Thursday, February 13, 2020 at 1:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Anthony L. Boral

Blueprint Medicines Corporation - Chief Medical Officer

* Christina Rossi

Blueprint Medicines Corporation - Chief Commercial Officer

* Jeffrey W. Albers

Blueprint Medicines Corporation - CEO, President & Director

* Kristin Hodous

Blueprint Medicines Corporation - Senior Manager of IR

* Michael Landsittel

Blueprint Medicines Corporation - CFO

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Conference Call Participants

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* Andrew Scott Berens

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

* Arlinda Anna Lee

Canaccord Genuity Corp., Research Division - Analyst

* Christopher Joseph Raymond

Piper Sandler & Co., Research Division - MD & Senior Research Analyst

* Dane Vincent Leone

Raymond James & Associates, Inc., Research Division - Research Analyst

* Eun Kyung Yang

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

* George Farmer

BMO Capital Markets Equity Research - Analyst

* Joseph John-Charles Thome

Cowen and Company, LLC, Research Division - VP of Healthcare

* Reni John Benjamin

JMP Securities LLC, Research Division - MD & Senior Research Analyst

* Salveen Jaswal Richter

Goldman Sachs Group Inc., Research Division - VP

* Yue-Wen Zhu

Guggenheim Securities, LLC, Research Division - Associate

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Presentation

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Operator [1]

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Ladies and gentlemen, thank you for standing by, and welcome to the Fourth Quarter 2019 Blueprint Medicines Conference Call. (Operator Instructions)

And I would now like to hand the conference over to your speaker today, Kristin Hodous. Thank you, and please go ahead, ma'am.

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

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Thank you, operator. Good morning, everyone. This is Kristin Hodous of Blueprint Medicines, and welcome to Blueprint Medicines' Fourth Quarter and Full Year 2019 Financial and Operating Results Conference Call. This morning, we issued a press release which outlines the topics that 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' fourth quarter and full year 2019 business highlights; Dr. Andy Boral, our Chief Medical Officer, will review our recent clinical progress; Christy Rossi, our Chief Commercial Officer, will provide an update on the initial launch of AYVAKIT; and Mike Landsittel, our Chief Financial Officer, will review our fourth quarter and full year 2019 financial results.

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 SEC filings. 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's our CEO, Jeff Albers.

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

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Thanks, Kristin.

This morning, in addition to financial results for 2019, we'll highlight key value drivers for Blueprint Medicines in 2020, discuss top line pralsetinib data in RET fusion-positive lung cancer and share initial insights on our early launch experience with AYVAKIT.

2020 is a pivotal year for Blueprint Medicines as we complete our evolution into a fully integrated global biopharmaceutical company. This transformation will be defined by 3 key themes. The first is an increasing focus on commercializing avapritinib and pralsetinib. We were obviously excited to kick off the year with the FDA approval of avapritinib, which is now under the brand name AYVAKIT, for the treatment of patients with PDGFRA exon 18 mutant GIST. AYVAKIT's the first precision medicine for GIST and the only highly effective treatment for patients with PDGFRA mutations. With this launch, we're building the foundation and momentum for additional planned launches of AYVAKIT and pralsetinib across multiple indications and geographies.

The second theme is an expanded strategic focus on systemic mastocytosis and other KIT-driven mast cell disorders. As we highlighted at our recent R&D day, we believe there's a tremendous medical need across a large systemic mastocytosis population, which includes up to 75,000 patients in major markets. We're uniquely positioned to address this need through avapritinib's potent inhibition of D816V mutant KIT, which is the primary genetic driver in the vast majority of patients with systemic mastocytosis. This year, we'll continue to advance avapritinib towards regulatory filings for advanced SM in the second half of 2020 and then indolent SM in 2021. Additionally, we'll initiate a Phase I healthy volunteer trial in the first half of this year for BLU-263, which is our next-generation KIT inhibitor, with the goal of reaching even more patients with indolent SM as well as other KIT-driven mast cell disorders.

Our third theme is the continued strengthening of our early-stage research pipeline. In January, we nominated a first-in-class development candidate for triple mutant EGFR-positive non-small cell lung cancer. This program combines potent inhibition of treatment-resistant triple mutant EGFR, with selectivity over the wild-type kinase, highlighting the strength of our scientific platform to prosecute exceptionally challenging target product profiles. The triple mutant EGFR program is just the first of up to 3 new development candidates we plan to nominate in 2020. So with these areas of focus, we aim to create substantial therapeutic value for patients and health care providers. The cadence of potential commercial launches could be as quick as 1 per quarter over the next 1.5 years. And importantly, with a strengthened balance sheet on the heels of our recent capital raise, we now have the runway to execute on our strategy as we begin to realize meaningful product revenue.

This morning, we'll highlight several of the early 2020 milestones we've already achieved that are setting us off on a strong path forward. So Andy will start by reviewing the top line pralsetinib data in RET fusion-positive lung cancer. 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. In early January, we announced top line data from our Phase I/II ARROW trial of pralsetinib in patients with RET fusion-positive lung cancer and we initiated a rolling NDA submission to the FDA. This morning, I want to take a few moments to share additional perspective on the highly encouraging top line data.

First, let me provide some background on why we think this data set is so strong, we have the potential to position pralsetinib as a best-in-class RET inhibitor. The top line pralsetinib data were centrally reviewed by blinded and independent radiologists, which is the standard required by FDA and EMA to support approval. In addition, all patients were treated at a proposed indicated dose of 400 milligrams once daily. This is important because the data demonstrate both efficacy and safety at the dose expected to be used in the commercial setting. Top line results showed continued strengthening as we've treated a broader population of patients for longer durations. In patients previously treated with platinum-based chemotherapy, the objective response rate was 61%. In treatment-naive patients, the objective response rate was 73%. The data also showed a deepening of response that was striking. In treatment-naive patients, 15% achieved complete resolution of measurable target tumors and 12% achieved the even higher bar of complete response by RECIST 1.1.

In addition, the median duration of response was not reached in patients treated with the 400-milligram dose regardless of prior therapy. This evidence of prolonged durability is consistent with preclinical data we've long highlighted, showing that pralsetinib is uniquely equal potent against RET gatekeeper mutations predicted to be the most likely drivers of resistance. Importantly, safety results were consistent with the previously reported data and no new safety signals were observed. We're excited to see these data, which have further instilled in us a sense of urgency to deliver pralsetinib to patients as quickly as possible. Looking forward, we have several important clinical development milestones on the horizon.

On March 14, we'll present updated Part I data from the PIONEER trial of avapritinib in patients with indolent systemic mastocytosis at the American Academy of Allergy, Asthma & Immunology or the AAAAI Annual Meeting. In this presentation, we plan to share a robust data set, including patient-reported outcomes, quantitative measures of mast cell burden and safety, which we'll use to guide the registration-enabling Part II of the trial. Following that, we anticipate the decision from the FDA on our NDA for avapritinib for fourth-line GIST in the second quarter. As expected, we received a 3-month PDUFA date extension from the FDA last week. This will allow us to provide top line data from the Phase III VOYAGER trial to the FDA early in the second quarter and enable the agency to take action on the fourth-line GIST NDA by the May 14 PDUFA date.

With that, I'll turn the call over to Christy to share an update on the commercial launch of AYVAKIT in PDGFRA GIST. Christy?

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Christina Rossi, Blueprint Medicines Corporation - Chief Commercial Officer [5]

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Thanks, Andy. Good morning, everyone. It's a pleasure to be with all of you this morning to share initial insights on the launch of AYVAKIT for PDGFRA exon 18 mutant GIST. Of course, our approval occurred after the close of Q4, so we will not be reporting any sales results on today's call. Instead, we'll focus on some early accomplishments from the first few weeks of launch that highlight the urgency of our team as well as the strong initial reception from health care providers and payers to the approval.

On January 9, we were thrilled to receive our first FDA approval of AYVAKIT, 5 weeks ahead of the February 14 PDUFA date. At the time of approval, we were well prepared to initiate our commercial launch, continuing the ongoing engagement and dialogue we've been having with the GIST community. As we've previously shared, over the course of last year, we defined a nimble go-to-market strategy, balancing a focus on the specific needs of patients with PDGFRA exon 18 mutant GIST and an ability to scale over time with additional approvals. With this approach, we built an integrated field team, including about 40 area business managers as well as focused groups of precision medicine and market access experts. These teams are fully trained and actively engaging with health care providers and key accounts around the country.

Within hours of the approval, our product website and initial marketing materials were available and the YourBlueprint patient support program was open to receive patient and health care provider inquiries. Within 1 week of the approval, our specialty pharmacies had product on hand and had processed the first payable prescription. We've been very pleased with the initial receptivity of health care providers to the approval, and we are encouraged to see prescribing interest beyond our trial investigators. In addition, our market access team has been out in the field meeting with commercial and government payers to secure appropriate coverage for AYVAKIT. These early discussions have gone well, and we're confident we'll achieve broad coverage for AYVAKIT.

As we reported last week, we were pleased to learn that the National Comprehensive Cancer Network or NCCN has added AYVAKIT to its clinical practice guidelines for soft tissue sarcoma. The FDA guidelines now include AYVAKIT as a frontline treatment for patients with PDGFRA exon 18 mutant GIST as well as a treatment for patients with fourth-line GIST. For both indications, AYVAKIT is recommended as a category 2A treatment, which indicates uniform consensus that an intervention is appropriate among a committee of expert physicians from leading U.S. cancer centers. This is a very positive step forward and provides additional support for the adoption of AYVAKIT in clinical practice as well as payer coverage.

Over the course of 2020, we look forward to sharing additional color on the launch as we gain more experience and insight.

I'll now turn call over to Mike to review our financial results for the quarter.

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Michael Landsittel, Blueprint Medicines Corporation - CFO [6]

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Thanks, Christy.

So earlier this morning, we reported detailed fourth quarter and full year 2019 financial results in our press release. For today's call, I'm just going to touch on a few financial highlights from the quarter as well as the year.

First, we're entering 2020 in a very strong financial position, which enables us to focus on the execution of our strategy ahead of critical milestones across our portfolio, including multiple planned commercial launches. We ended 2019 with $548 million in cash and in January 2020, we closed a public offering, resulting in net proceeds of approximately $308 million. Based on our current plans, we believe we have sufficient capital to fund our operations into the second half of 2022. Importantly, as Jeff mentioned earlier, this runway extends into a time frame in which we expect to achieve meaningful commercial revenues.

Second, collaboration revenues increased in the fourth quarter to $66.5 million, primarily due to revenue recognized under our license agreement with Clementia Pharmaceuticals, a subsidiary of Ipsen, for the development and commercialization of BLU-782 for fibrodysplasia ossificans progressiva. The revenue recognized includes a $25 million upfront payment as well as an additional $20 million payment that is due in the third quarter of 2020.

Third, there was an increase in total operating expenses in the fourth quarter of 2019 compared to the prior quarter due to investments in our global commercial infrastructure as we prepared for the potential launches of AYVAKIT and pralsetinib as well as the acceleration of clinical development activities, including preparation for the Phase III AcceleRET trial of pralsetinib in frontline lung cancer. We expect to see continued moderate increases in quarter-over-quarter expenses, consistent with the long-term growth rate that we've seen over the past several quarters.

With that, I'll 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) And our first question comes from the line of Salveen Richter with Goldman Sachs.

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Salveen Jaswal Richter, Goldman Sachs Group Inc., Research Division - VP [2]

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So as we think about the upcoming AAAAI meetings, can you help to understand what data we'll see and what is meaningful to move forward to Part II of the PIONEER study? And then secondly, can you just speak to the ongoing AYVAKIT launch and initial learnings feedback from prescribing physicians? And also with inclusion of AYVAKIT in the NCCN guidelines for fourth-line GIST, how should we think about pricing for the drug in that indication?

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

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Thanks, Salveen. So this is Jeff, I'll take the first part of the question, maybe I'll have Andy add some color if necessary and then, Christy, why don't you take the launch and NCCN questions.

So first off, given that AAAAI is upcoming, we're not going to address specific data question. But as a reminder, the purpose of Part I is to guide the registration-enabling Part II. So what we'll be looking for to inform the study will be things like dose selection, sample size and duration for the second part of the trial. And we'll -- then we'll watch for results that are consistent with those that we've seen previously in indolent SM patients treated with avapritinib from the EXPLORER trial. And I think Andy then highlighted some of the components of that (inaudible)?

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

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Yes, maybe I'll just say that, of course, we'll be looking at objective measures of mast -- reduction in mast cell burden, we've showed a little bit of that at ASH. But those are things that we've shown before like tryptase, bone marrow mast cells, D816V allele burden. And of course, we'll be tying that together with the results from the patient report outcome tool that are part of the indolent study.

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Christina Rossi, Blueprint Medicines Corporation - Chief Commercial Officer [5]

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And I can comment on the launch and how we're thinking about fourth line. So I'm very pleased with how things have been going over the last several weeks. We had built a very strong relationship with the GIST community over many years. And I think this launch, certainly amongst the community that's been helping to support the development of AYVAKIT, there was just real sense of pride and excitement about having a highly effective, innovative agent available for the first time in many years to treat these patients. I think for investigators that are experienced, they were certainly very excited. But for me, I think the thing that I've been most excited to see personally is the interest outside of our investigators in prescribing AYVAKIT and the breadth of prescribing that we're already starting to see. So that's really been gratifying.

In terms of thinking about fourth line, as I said, when we set the initial price for AYVAKIT, we were thinking about the transformational benefit in a targeted patient population in GIST. I anticipate that, that strategy will continue to hold as we think about an approval in fourth line, where again, there are no currently approved effective therapies and the unmet need is very significant. So we're looking forward to FDA action in the second quarter.

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Operator [6]

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And our next question comes from the line of Dane Leone with Raymond James.

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Dane Vincent Leone, Raymond James & Associates, Inc., Research Division - Research Analyst [7]

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Congrats on the update. So maybe on the 263 highlight that you will be in a healthy volunteer study in the first half of this year. Do you have any further thoughts in terms of the cadence of that program? Or where you hope to get it to by the end of the year?

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

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Yes. So again, we will be starting that -- we'll be starting that study this year, as we've described. And again, importantly, that's a -- as you said, a healthy volunteer study, it -- really to identify the appropriate starting dose in systemic mastocytosis patients, indolent systemic mastocytosis patients in particular. And we haven't speculated on the subsequent timing of that study, I think we'll -- as we get started, we'll update.

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [9]

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Dane, this is Jeff. I'll just add in, as we've talked about frequently is we see systemic mastocytosis as the cornerstone opportunity of our commercial build over time. And when we think about that, we want to fortify our leadership position within this disease area. So we think the complementary nature of avapritinib, focused on advanced systemic mastocytosis patients, and those with moderate to severe indolent systemic mastocytosis align then with BLU-263, where we'll be initially starting patients with maybe more mild to moderate indolent systemic mastocytosis will put us in a really strong position over the long term.

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Dane Vincent Leone, Raymond James & Associates, Inc., Research Division - Research Analyst [10]

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Great. And maybe one follow-up on RET. I think everyone's been really pleased with how the lung data has matured with the RET data. Where -- can you give us kind of a sense of the scale and scope of the thyroid data that we expect to see around the filing in probably the second quarter of this year?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [11]

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So yes, we're incredibly thrilled with the evolution of the data from the ARROW study, the lung data that we recently presented. So the thyroid data is coming together. We will -- we're on track to file the registration data from that study in the second quarter. It is a -- it will be a robust and sufficient data set to support an application for an accelerated approval. And certainly, as we will, at a medical meeting, present those data.

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Operator [12]

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And our next question comes from the line of Joe Thome with Cowen and Company.

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Joseph John-Charles Thome, Cowen and Company, LLC, Research Division - VP of Healthcare [13]

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Maybe just on the pralsetinib non-small cell lung cancer filings, what is remaining in order to complete the rolling submission there? And then one on avapritinib in the third-line (inaudible). Have you have had the last events of the combined study and you're just waiting for data cleaning or patients? Are you still waiting on additional follow-up from patients?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [14]

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Sure. So Andy, do you want to start with the RET?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [15]

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Yes. Okay. So yes, so that -- as we announced, we initiated the rolling submission for pralsetinib in RET-driven non-small cell lung cancer. We are on track to complete that this quarter. And it's -- we were -- we filed the materials as they become completed and become available. But there's no -- we are completely on track to complete the full submission.

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

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And then on VOYAGER, we're still waiting on events and still on track that we'll be able to see that data early in the second quarter and have time to turn it around quickly to provide top line data to FDA to take action by the May 14 PDUFA date.

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Operator [17]

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And our next question comes from the line of Michael Schmidt with Guggenheim.

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Yue-Wen Zhu, Guggenheim Securities, LLC, Research Division - Associate [18]

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This is Charles Zhu on for Michael Schmidt. Congrats again on the quarter.

One quick follow-up on the AAAAI data on indolent SM. Just one quick clarification now, would there be potential differences between the information released in the abstract text on the week of the 24th versus the actual presentation at the conference?

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

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So yes, there will be. So we always strive to present the most current update at the time of the conference and we will certainly be providing more information than the abstract -- than is in the abstract.

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [20]

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And perhaps even more so in this case, given that the unblinding of the data occurred after the abstract submission.

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [21]

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(inaudible).

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Yue-Wen Zhu, Guggenheim Securities, LLC, Research Division - Associate [22]

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Got it. Makes sense. And another follow-up on RET. I'm wondering if you could provide any color around the drivers of the higher complete response rates over time. Is it, I guess, a true response beeping over time? New response rates occurring? Or potential differences between independent versus a central review on these patients?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [23]

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Yes. So -- it's Andy. We've been really thrilled to see the evolution of the lung cancer data with pralsetinib. And in particular, these very deep, robust responses that we think really are unique for lung cancer, you've just not seen in patients with lung cancer. So this is evolution of the responses over time. We certainly see deepening, as we've shown and I think it's always hard to know what drives that. But we -- but I think, usually, that's due to good access of the tumor tissue by the medicine. And I think pralsetinib just shown to -- it's probably achieving very highly effective concentrations in the tumor tissue itself, something we don't typically have a way of measuring in patients.

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Operator [24]

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And our next question comes from the line of Eun Yang with Jefferies.

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Eun Kyung Yang, Jefferies LLC, Research Division - MD & Senior Equity Research Analyst [25]

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I have a couple of questions in pralsetinib. So first, so Phase III first-line non-small cell lung cancer trial that just started, can you comment on how the study, the power for the primary endpoint of a PFS compared to platinum-doublet with or without pembro? And also, previously, you mentioned that Phase II combo study with the Tagrisso is similar with resistant EGFR-mutant non-small cell lung cancer. Can you give us an update on that trial?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [26]

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Okay. This is Andy again. So the Phase III frontline lung cancer study, the -- what we call the AcceleRET study, so there, we are comparing pralsetinib to platinum-doublet therapy with or without a checkpoint inhibitor that's up to the treating physician. The study is well powered to achieve the primary endpoint of progression-free survival. We make the design on -- there's plenty of available data with -- in lung cancer, frontline lung cancer with platinum doublets, with the triplet with checkpoint inhibitors. Based on those data and the data that we've seen from the ARROW study, we have a well-powered and well-controlled study to, I think, show a benefit in frontline.

In terms of the osimertinib-pralsetinib combination, so we have not kicked off a specific study in that combination yet. We do have some cases that we've actually reported in the literature and are still working on finding the best time and mechanism to do a study like that. And to -- part of it is really understanding how to find patients where there -- who have EGFR-mutant disease that actually relapses due to a RET fusion. And so we continue to work on that project.

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Operator [27]

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And our next question comes from the line of David Lebowitz with Morgan Stanley.

(Operator Instructions) And our next question comes from the line of Andrew Berens with SVB Leerink.

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Andrew Scott Berens, SVB Leerink LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst [28]

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I also have a couple for Andy on the pipe. Just wanted to get your thoughts on the initial data that Lilly and Loxo recently published for resistance that they're seeing for selpercatinib. And then, I guess, primarily, what do you think is the primary liability for that drug? And how do you think pralsetinib's profile could differ? And then I also have one on the EGFR program.

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [29]

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Okay. So yes, the -- Lilly recently published, I guess, a couple -- a paper in complication for showing solvent front mutations as mechanisms of resistance to selpercatinib. I think that would be -- that wasn't surprising to us based on what we know about the compound and potential mechanisms of resistance for the RET kinase. We continue to look carefully at mechanisms of resistance with pralsetinib. We are measuring circulating tumor DNA at baseline and over the course of treatment. So far, we've been pleased with what we've seen. We've seen really on-target RET -- we see RET -- on-target RET resistance mechanisms has been relatively rare. We haven't yet seen a gatekeeper mediated resistance mechanism. We have actually also seen this solvent front mutation, which we would have expected. But at this point, we don't have a sense that it's a major mechanism of resistance. And I think that's still to be understood.

I'm sorry, what was the second half?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [30]

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He didn't ask it yet.

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [31]

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Oh, he didn't ask. [Something EGFR.]

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Andrew Scott Berens, SVB Leerink LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst [32]

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Yes, about the EGFR program. I guess, I just -- there seems to be a little bit of confusion behind the rationale for having a triple mutation drug and a double mutation. So can you just walk us through the rationale there? And then also, if you have any idea, I know it's probably early days, but what percentage of Tagrisso failures could you potentially address with either of these drugs?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [33]

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So yes, so in terms of the rationale, so we think this combination of 2 new programs is actually a very rich next step in developing our lung cancer portfolio. We know that around the world, the use of osimertinib and Tagrisso is really kind of varied. It started out as a second-line EGFR inhibitor in the U.S. and globally. And in many -- while it's moving into frontline in the U.S., but it remains a second-line standard, second-line therapy in many parts of the world. And the first, the lead program of our 2 programs, which is looking at what we call the triple mutation, which inhibits the EGFR kinase in the setting of the driver mutation plus the T790M mutation plus the C797S resistance to osimertinib mutation is what we expect to see in the setting of osimertinib as a second-line agent. So you get the T790M from something like erlotinib and then you get C797S as a mechanism of resistance to osimertinib. We think that will continue to be a very important group of -- source of resistance for many patients globally.

We -- now, of course, with their shift to osimertinib to earlier -- to frontline therapy, then that raises the possibility of seeing the C797S mutation in the absence of the T790M. And that's the whole rationale for the second program that we're working on and see that as a very complementary opportunity as osimertinib starts to move frontline in the U.S. But again, I think that's going to take much longer elsewhere.

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [34]

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And so -- this is Jeff. Maybe I'll just add that the -- at a higher level, much as we see BLU-263 as really complementary to what we're doing with avapritinib in systemic mastocytosis in terms of building out a franchise, here, with this blend of EGFR programs, we find that they're incredibly complementary to the work that we're doing with pralsetinib. And more broadly, as you think about it that if treatment paradigms remain where osimertinib is still globally used off as second line, our triple mutation molecule is the most frequent on-target mutation that should occur. And as that paradigm shifts, particularly in the U.S. and in many countries in Europe, where osimertinib is first line, our double mutant would be the most likely on-target resistance mutation that would emerge. So we think it's complementary to what we have with pralsetinib and it will serve a -- what is going to be an evolving need within patients with EGFR-driven disease.

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Andrew Scott Berens, SVB Leerink LLC, Research Division - MD of Targeted Oncology & Senior Research Analyst [35]

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Okay. Is there any epidemiology to predict the percentage of [progress or] barriers to get the 797 mutation?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [36]

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Yes, we think it should be the most common on-target mutation. I think the actual epidemiology data are evolving.

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Operator [37]

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And our next question comes from the line of Ren Benjamin with JMP Securities.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Senior Research Analyst [38]

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Congratulations on the quarter. Maybe just starting off with Christy. Can you talk a little bit about your -- the sequencing campaign? And I know it's only been a month, but do you have any sort of a sense as to whether that's working well? Are the scripts coming in from the frontline? Or are they primarily being used [fourth line]? Just any sort of trends you can provide more for us.

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Christina Rossi, Blueprint Medicines Corporation - Chief Commercial Officer [39]

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Sure. And so just so I'm answering the question in the right way, are you -- when you say sequencing campaign, are you talking about driving mutational testing and sort of where -- what line of therapy we're seeing AYVAKIT being used for PDGFRA mutant patients?

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Senior Research Analyst [40]

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Correct, correct. That's correct.

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Christina Rossi, Blueprint Medicines Corporation - Chief Commercial Officer [41]

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Okay. Great. Yes. So we do have a team of precision medicine focused, really diagnostic experts who have come from a variety of backgrounds and have been focused in this area. Where we think we'll get the most leverage is really by trying to influence behavior at a national account level. So there's a lot that we can do in terms of making sure that, for example, PDGFRA mutations are reflexed every time KIT is negative, making sure that as results are reported, AYVAKIT is flagged as the appropriate therapeutic intervention in those cases. And we started to see early wins there already. We know that mutational testing in the community, certainly -- well, less than 50% of patients are receiving it, and there's been good reason for that. But we've had a lot of success even in early days in having those discussions with prescribers because now they have a therapeutic intervention that is very meaningful to them. And so we expect this will take some time to evolve. Certainly, we'll see PDGFRA patients who have been on numerous other therapies because they just -- they haven't had other options until now. But I think over time, we'll start to see AYVAKIT being used more and more in early lines of therapy.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Senior Research Analyst [42]

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Got it. And then just maybe one for Andy regarding the VOYAGER study, are you sequencing the patient's tumors now and trying to get a sense as to, I guess, are patients being stratified based on mutations in the case of PDGFRA (inaudible)?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [43]

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So we do, do baseline ctDNA and archival tumor assessment of mutations. And on study, we do -- we follow the evolution mutations actually by -- strictly in tumor DNA sequencing. Especially in a large study, it's pretty hard to get more tumor tissue. But the study does stratify patients based on their status of PDGFRA or KIT-based mutation for the randomization.

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

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And we think more broadly, that's going to be very important because this will be an incredibly rich data source. And it is our view that over time that patients are going to be treated with the right therapy for the right patient based on that mutational status. And this will give us a really rich data set to think about where -- which patients are most likely to see optimal benefit from avapritinib.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Senior Research Analyst [45]

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Got it. And then just regarding the fourth-line indication and FDA review on what exactly they might be looking for. Is it the crossover arm that have now moved on past regorafenib that are now getting AVA and technically, fourth-line patients? Is it that data set that goes on to the FDA for review prior to the May 14 PDUFA date?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [46]

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No, I think it's way simpler than that. They're just looking for the top line -- I think, primarily, efficacy data, meaning the primary PFS assessment from the primary study, the Phase III comparator of ava versus regorafenib. And as part of the top line data, of course, they also see the summary safety data. I think they really just want to know that the study is going to be positive.

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Operator [47]

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And our next question comes from the line of Arlinda Lee with Canaccord. (Operator Instructions)

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Arlinda Anna Lee, Canaccord Genuity Corp., Research Division - Analyst [48]

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Sorry about that. I was curious about the lung cancer RET data set. Can you provide additional detail on what the scope of the clinical data we should expect to see with the -- particularly on gatekeeper mutations or patients with resistance?

And then on the SM data at AAAAI, what would you consider clinically meaningful? And are you still planning to start the Phase II avapritinib as an SM expansion cohort this year?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [49]

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Sure. So maybe I'll start with those. Andy, you can add color. So on our RET data set in lung cancer will be presented at a medical meeting and that will obviously be a robust update. That will be the centrally reviewed full data set that we're submitting to FDA and so there will be a variety of efficacy, safety, and certainly, we'll break down some sets of information that we think are impactful. For AAAAI, again, given the proximity of the conference, we're not going to get into the details beyond what Andy's already highlighted. But this -- that, too, will be a meaningful update. It will pull together the unblinded data at the various doses. And the whole purpose of Part I is to inform Part II, and so that very much still is on track, that we'll be looking to select the dose and to move forward with -- based on feedback from our -- with investigators based on the blend of the efficacy and safety.

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Operator [50]

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And our next question comes from the line of George Farmer with BMO Capital Markets.

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George Farmer, BMO Capital Markets Equity Research - Analyst [51]

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Maybe two from us. Regarding VOYAGER trial, topline results (inaudible) [talk about first-line patient and approval]? And assuming the trial is positive, would that be (inaudible)? And then -- sorry. Second question regarding the PIONEER trial Part II. You mentioned 2 (inaudible). I guess, do you plan to let [those stratify these Part II patients by] (inaudible)?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [52]

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Okay. So yes. So I think -- so there's 3 questions there. And the first one, I think, is about -- so I'm sorry. So you said -- you were breaking up a little bit. But I think the first question is on VOYAGER...

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [53]

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(inaudible) first-line. I can, I guess, get that. So on the first -- so the top line results for VOYAGER, again, this is a -- the FDA is looking for the global top line results of the study, not -- which includes everyone who's enrolled, which is a mix of third- and fourth-line patients. It is primarily a third-line study, actually, and it's pretty typical for confirmatory studies in oncology to be performed in earlier indications. So it will be -- the top line data will include the mix of primarily third but also including some fourth-line patients. They are randomization stratified for those 2 groups, so the total PFS assessment and, of course, high level safety assessments.

And importantly, I think your question about third-line approval, that's a really important one. So no, we -- the May 14 PDUFA date is in order for FDA to make an assessment of the fourth-line NDA submission that we've already submitted. The third-line review and approval, assuming the study is positive, would be based on complete submission of the full NDA later in the year and a subsequent complete review.

Yes, the -- I'm not quite sure if I -- you broke up a little bit on the Part II PIONEER. I think you were asking for stratifying by symptoms or -- and the study is designed such that patients, to be eligible, have to achieve a minimum symptom score on the PRO. And by doing that, we, I think, addressed the question of is there heterogeneity symptoms. So that's -- I don't -- we don't see that as an issue. But the -- at the same time, we will look very carefully at the Part I data and we will use those data to help optimize design of Part II.

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Operator [54]

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And our last question comes from the line of Chris Raymond with Piper Sandler.

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Christopher Joseph Raymond, Piper Sandler & Co., Research Division - MD & Senior Research Analyst [55]

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Just a couple ones. So I noticed -- I know that you guys have talked about CStone doing bridging work in China with avapritinib and GIST. We just noticed on clin trials that -- last week, I think, it was posted. This is actually a dose-ranging study. And I think it looks like it's starting at a lower dose than that -- those approved in the U.S. Just curious if you could give any color there. Was this a requirement from Chinese regulators? Or why -- what's the need, I guess, to run a dose-ranging study with -- given the full approval in the U.S. or given approval?

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Anthony L. Boral, Blueprint Medicines Corporation - Chief Medical Officer [56]

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Yes, it's Andy. I think, yes, this is a standard requirement from the Chinese CDE that they require that the PK and safety and activity be reestablished in the Chinese population in a small group, not at a statistically significant level. And you need to start at a lower dose, just in case exposure in Chinese patients is higher than in western patients.

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Christopher Joseph Raymond, Piper Sandler & Co., Research Division - MD & Senior Research Analyst [57]

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Okay. And then just -- I know a lot of questions have been asked on the broader fourth-line file. But I guess like one question we've gotten a lot from some investors is, have you guys considered what happens if ripretinib is granted accelerated approval before FDA sort of makes a call on avapritinib in getting the broader fourth-line setting? That is, I think, from my understanding, your ability to get accelerated approval when another drug has an approval that there might be some question there. Can you maybe talk about that scenario?

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [58]

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Yes, so that's not correct. There's multiple examples where there are multiple accelerated approvals. So it should have zero effect.

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Operator [59]

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Thank you. And this concludes today's question-and-answer session. I would now like to turn the call back to Jeff Albers for closing remarks.

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Jeffrey W. Albers, Blueprint Medicines Corporation - CEO, President & Director [60]

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Thanks, operator. And again, thanks, everyone, for taking time to join us -- tomorrow, I know it's a busy time of the year -- and for your continued support of Blueprint Medicines. And importantly, we look forward to seeing all of you in a few weeks at AAAAI as we provide an update on the indolent SM data set. Thanks a lot. Bye-bye.

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Operator [61]

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Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.