Ladies and gentlemen, thank you for standing by. And welcome to the fourth quarter 2019 Blueprint Medicines Conference Call. At this time, all participants are in a listen-only mode. After the speakers’ presentation, there will be a question-and-answer session. And I would now like to hand the conference over to your speaker today, Kristin Hodous.

Thank you, and please go ahead, ma'am..

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 trials; 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 represents 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..

Thanks Kristin. This morning in addition to financial results for 2019, we will highlight key value drivers for Blueprint Medicines in 2020, discuss topline pralsetinib 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 three 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 PDGFRalpha Exon 18 mutant GIST. AYVAKIT is the first precision medicine for GIST and the only highly effective treatment for patients with PDGFRalpha mutation.

With this launch, we're building the foundation and momentum for additional plan launches of AYVAKIT and pralsetinib across multiple indications and geographies..

Thanks, Jeff, and good morning, everyone. In early January, we announced topline data from our Phase 1/2 ARROW trial of pralsetinib in patients with RET fusion-positive non-small cell 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 topline data..

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 PDGFRalpha Exon 18 mutant GIST. Of course, our approval occurred after the close of Q4 that 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 highlighted the urgency of our team, as well as the strong initial reception from healthcare providers and payers to the approval. On January 9th, we were thrilled to receive our first FDA approval AYVAKIT five weeks ahead of the February 14th 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 communities.

As we've previously shared, over the course of last year, we designed a number of go-to-market strategy, balancing a focus on the specific needs of patients with PDGFRalpha Exon 18 mutant GIST and an ability to scale over time with additional approvals.

With this approach, we built an integrated sales team, including about 40 area business managers, as well as focus groups of precision medicine and market access experts. These teams are fully trained and actively engaging with healthcare providers and key accounts around the country.

Within hours of the approval, our products website and initial marketing materials were available, and the Blueprint Patient Support program was open to receive patient and healthcare provider inquiries. Within one week of the approval, our specialty pharmacies have product on hands and had processed the first payable prescriptions.

We’ve been very pleased with the initial receptivity of healthcare providers to the approval and we are encouraged to see prescribing interests 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 will 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 updated data lines now include AYVAKIT as a frontline treatment for patients with PDGFRalpha Exon 18 mutant GIST, as well as a treatment for patients with fourth line GIST..

Thanks Christy. So earlier this morning we reported detailed fourth quarter and full year 2019 financial results and 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 the 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 timeframe 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 3 AcceleRET of pralsetinib and front-line lung cancer.

We expect to see continued moderate increases in quarter-over-quarter expenses, consistent with a 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?.

Thank you. And our first question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open..

Good morning. Thanks for taking my question.

So as we think about the upcoming AAAAI meeting, you have to understand what data will be and what is meaningful to move forward to Part 2 of the pioneers study? And then secondly can you just see to the ongoing AYVAKIT launch and initial learnings feedback from prescribing physicians? And then also with inclusion of AYVAKIT and NTCN guidelines fourth line GIST.

How should we think about pricing for the drugs in that indication? Thank you..

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 NTCN question. So first off, given the AAAAI’s upcoming we're not going to address specific data questions.

But as a reminder, the purpose of Part 1 is to guide the registration enabling Part 2. So what we'll be looking for to inform dose -- 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 indolent SM patients treated with avapritinib from the EXPLORER trial. And I think Andy then highlighted some of the components of that repeating..

Yeah. Maybe just to say that then, of course, we'll be looking at objective measures of mass reduction mass cell burden. We've showed a little bit at ASH, but those are things that we should think, that we shown before like tryptase, bone marrow mass cells, D816 via little burden.

And of course, we'll be tying that together with the results from the patient report outcome to all that are part of the interim study..

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 a 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 and prescribing AYVAKIT and the breadth of prescribing that we're already starting to see. So that's been really gratifying.

In terms of thinking about fourth line, as I said, when we when we set the initial price raise, we were thinking about the transformational benefit in a targeted patient population and GIST.

I anticipate that that strategy will continue to hold as we think about an approval on 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..

Okay. Thank you..

Thank you. And our next question comes from the line of Dane Leone with Raymond James. Your line is now open..

Hi. Thank you for taking the question and 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?.

Yeah. So, again, we have -- we'll be starting that study this year as we've described, and again, importantly that's as I 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 as we get started we’ll update..

Yeah. This is Jeff. I just add, as we 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 a fortified 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 will 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..

Great. And maybe one follow up on the RET. I think everyone's been really pleased without a lung data is matured with the RET data.

Where -- can you give us kind of a sense of the scale and scope of thyroid data that we expect to see around the filing and that's probably the second quarter is here?.

So – yeah, we're incredibly thrilled with the evolution the data from the ARROW study, the lung data that we recently presented. So 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 know, we will at medical meeting present those data..

Okay. Great. Thank you..

Thank you. And our next question comes from the line of Joe Thome with Cowen and Company. Your line is now open..

Hi there and thank you for taking my question.

Maybe just on the pralsetinib non-small cell lung cancer filing, what is remaining in order to complete the rolling submission there? And then one on avapritinib been on third line stand with now, have you had the last event of the third line study and you're just waiting for data cleaning or patients, are you still waiting on additional follow up from patient? Thank you..

Andy, do you want to start with RET..

Yeah..

Okay..

So – yeah, 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 filed the materials as they become completed and become available. But there's no, we’re completely on track to complete the full submission..

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 second quarter and have time to turn it around quickly to provide topline data to FDA to take action by the May 14th PUDFA date..

Great. Thank you..

Thank you. And our next question comes from the line of Michael Schmidt with Guggenheim Security. Your line is now open..

Good morning, guys. This is Charles Zhu on from Michael Schmidt. Thanks for taking the questions and congrats again on the quarter.

One quick follow up on the AAAAI data on indolent SM, just one quick clarification, would there be potential differences between the information released and the abstract text on the weak of the 24th versus the actual presentation of the conference?.

Yeah. Certainly. So we always strive to present the most current update at the time of the conference and we will certainly be providing more information on the abstract – then is in the abstract. And perhaps even more so in this case, given that the unblinding of the data occurred after the abstract..

Very good point..

Got it. Makes sense. Thanks for that clarification.

And another follow up on RET, 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 over time new responses occurring or particular differences between independent versus sensible review on these patients?.

Yeah. So – this is 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. It's 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 it was 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..

Understood. Thanks for the color and congrats again. Thanks for taking the questions..

Thank you. And our next question comes from the line of Eun Yang with Jefferies. Your line is now open. If you line is on mute please unmute it..

No. Thank you. I have a couple of questions on of course avapritinib. So, first, the Phase 3 first line non-small cell lung cancer trial that just as started. Can you comment on how the study that power for the primary end point of PSX compared to second doublet with or without prembro.

And also previously, you mentioned the phases to combo study with non-small cell lung cancer. Can you give us an update on that trial? Thank you..

Yeah. This is Andy again. So the Phase 3 front-line lung cancer study what we call the accelerate study. So there we are comparing pralsetinib to platinum double 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 based the design on -- there's plenty of available data with in frontline lung cancer with doublet but triplet with checkpoint inhibitors based on those data and this data that we've seen from our of study we have a well powered and well controlled study to -- I think show benefit in frontline.

In terms of the osimertinib pralsetinib combination, here we have not kicked off a specific study with that combination yet.

We do have some cases that we've actually recorded in the literature and are still working on deciding the best time and mechanism to do a study like that and to part of its really understanding how to find the patients where there who have EGFR mutant disease that actually relapses due to RET fusion so we continue to work on that project..

Thank you..

Thank you. And our next question comes from a line of David Lebowitz with Morgan Stanley. Your line is now open. If your line is on mute, please unmute it. And our next question comes from the line of Andrew Berens with SVB Leerink. Your line is now open..

Thanks a lot guys. Appreciate you taking the questions. I also have a couple for Andy from the pipe.

Just wanted to get your thoughts on the initial data that Lilly and Larkson recently published for resistance what they are seeing for pralsetinib? And then, I guess, primarily what do you think the primary liability for that drug and how do you think pralsetinib profile could differ and then I also have one on the EGFR program?.

Okay. So, yeah, so the Lilly recently published I guess, a couple of case reports showing a solvent front mutations as mechanisms of resistance to 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 to look carefully at mechanisms of resistance with pralsetinib, we are measuring certainly in tumor DNA at baseline over the course of treatment. So far we've been pleased with what we've seen, we've seen really 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, don't have a sense that it's a major mechanism of resistance and I think that's still to be to be understood.

What the second half?.

.

Oh! Talk about EGFR, yeah..

Yeah. 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 mutations if I can 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 gross out failures could be potentially drastically either of these drugs?.

So, yes, in terms of the rationale, so we think this combination of two new programs is actually a very rich next step in developing our lung cancer portfolio. We know that that around the world the use of is really kind of very. It started as a second line EGFR inhibitor in the U.S.

and globally and in many – well, it’s moving into front line 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 two programs which is looking at 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 mutation is what we expect to see in the setting of asthma as a second line agent.

So you get the T790M from something like avapritinib and then you get C797S as mechanism refers to osimertinib. We think that will continue to be a very important group of -- sorts of resistance for many patients globally.

We now of course with the shift of osimertinib to earlier – to front line 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 complimentary opportunity as osimertinib start to move frontline the U.S., but again, I think, that's going to take a much longer elsewhere..

Jeff, maybe I would just add to that at a higher level, much as we see BLU-263 is really complimentary to what we're doing with avapritinib and systemic mastocytosis in terms of building out a franchise here with this blend of EGFR programs.

We find that they're incredibly complimentary to the work that we're doing with pralsetinib and more broadly if you think about it, that if treatment paradigms remain where osimertinib is still globally use often second line. Dark 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 first line are double mutant would be the most likely on target resistance mutations that would emerge.

So we think it's complementary to what we have with pralsetinib and it will serve what is going to be an evolving need within patients that with EGFR driven disease..

Okay.

Is there any epidemiology to predict the percentage of the rest of those to get the 797 mutation?.

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

Okay. Thanks a lot..

Thank you. And our next question comes from the line of Reni Benjamin with JMP Securities. Your line is now open..

Hi. Good morning. Thanks for taking the questions and congratulations on the quarter. Maybe just starting off with Christy.

Can you talk a little bit about – 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 they primarily being used in work-line, just any sort of trends you can provide for us of course?.

Sure and sort of just the way I'm answering the question in the right way.

When you say sequencing campaign, are you talking about driving mutational testing and sort of what line of therapy we're seeing AYVAKIT being used for PDGFRalpha mutant patients?.

Correct, correct. .

Okay. Right. Yes. So, we've 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 will get the most leverage is really by trying to influence behavior at a national account level.

So there is a lot that we can do in terms of making sure that for example, PDGFRalpha mutations are reflex 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, they're 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 and having those discussions with prescribers because now they have a therapeutic intervention that is being meaningful to them.

And so, we expect this will take some time to evolve. Certainly, we'll see PDGFRalpha 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 a AYVAKIT being used more and more in early lines of therapy..

Got it.

And then just maybe one Andy regarding the VOYAGER study are you sequencing the patient's tumors now and trying to get a sense as to, outline I guess our patients being stratified based on mutations in the PDGFRalpha, Exon 18?.

So, we do baseline ctDNA and archival tumor, assessment of mutations and on study we – follow evolution mutations actually by circulating 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 if they have PDGFRalpha or KIT based mutation for the randomization..

And we think more broadly, that's going to be very important because it 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 sets to think about where which patients are most likely to see optimal benefit from avapritinib..

Got it and then just regarding the fourth line indication and FDA review and what exactly they might be looking for.

Is it the crossover arm that have now moved on pralsetinib that are now getting AYVAKIT and a technical fourth line patients? Is it that data set that goes on to the FDA for review prior to May 14 PDUFA?.

No. I think it's way simpler than that. They're just looking for the topline I think primarily efficacy data meaning the primary PFS assessment from the primary study the Phase III competitor of ava versus regorafenib and as part of the topline data.

Of course, they also see that the summary safety data, I think they really just want to know that the study is going to be positive?.

Great. Thank you very much. Good luck..

Thank you. And our next question comes from the line of Arlinda Lee with Canaccord. Your line is now open. If you’re phone is on mute, please un-mute it..

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 particularly on gatekeeper mutations or patients increase their terms.

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 a SM, SSM expansion cohort this year? Thanks..

So maybe I'll start with those Andy you can add color so our RET data set in lung cancer will be presented at a medical meeting. And that will obviously be a robust update. So that will be the central reviewed full data set that we're submitting to FDA.

And so, there'll be a variety of efficacy safety, and certainly will break down subsets 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 that too will be a meaningful update that it will pull together the unblinded data at the various doses. And the whole purpose of part 1 is to inform part 2 and so that very much still is on track.

That will be looking to select the dose and to move forward with based on feedback from – with investigators based on a blend of the efficacy and safety..

Thank you..

Thank you. And our next question comes from the line of George Farmer with BMO Capital Markets. Your line is now open..

Good morning guys. .

Yes. So I think there is three questions. The first one, I think so I’m certainly sorry so you were breaking up a little bit. I think it's the first question is on VOYAGER..

Carving a fourth line I guess?.

Yes. so the top line results for VOYAGER again this is a, the FDA is looking for the global topline results of the study not which include everyone who is involved, 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'll be the it'll be the topline data will include the mix of primarily third but also including some fourth line patients they are randomization stratified for those two groups.

So, the total PFS assessment and of course, high level safety assessment and importantly, I think your question about third line approval is actually a really important one. So no, the May 14 PUDFA 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 studies positive would be based on complete submission of the full NDA later in the year and a subsequent complete review. I wasn’t quite sure if I – you broke up a little bit on the part 2 PIONEER I think you're asking for stratifying by symptom score.

And yes, the study is designed such that patients to be eligible have to achieve a minimum symptom score on a PRO and by doing that – we, I think address the question of is there heterogeneity of symptoms.

So – we don't see that as an issue but at the same we will look very carefully at the part 1 data and we will use those data to help them optimize design of part 2..

Thank you. And our last question comes from the line of Chris Raymond with Piper Sandler. Your line is now open..

Hey thanks, 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. But we just noticed on clin trials that last week, I think it was posted. This was actually a dose ranging study.

Again I think it looks like it's starting at a lower dose than that – those approved in the U.S. Just curious if you have any color there, was this a requirement from Chinese regulators or why what's the need I guess, to run a break way a dose ranging study with given the full approval in U.S.

given approval?.

Yes. This is Andy. 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 small group not as 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..

Okay. And then just I know a lot of questions have been asked on the broader fourth line fine.

But I could say one question we've gotten a lot from some investors is have you guys consider what happens if avapritinib is granted accelerated approval before FDA sort of makes a call on avapritinib in 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?.

Yes. So that that's not corrected there is multiple examples where there are multiple accelerated approval so it should have zero effect..

Great, thank you..

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

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..

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