Good morning, and welcome to the Blueprint Medicines First Quarter 2019 Financial and Operating Results Conference Call. My name is Carla, I'll be your conference operator today. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. Thank you.

And I would like to turn the call over to Kristin Hodous of Blueprint Medicines. Go ahead please..

Thank you, operator. Good morning. This is Kristin Hodous of Blueprint Medicines and welcome to Blueprint Medicines first quarter 2019 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 first quarter 2019 business highlights; Christy Rossi, our Chief Commercial Officer will provide an update on our portfolio-based commercial strategy; and Mike Landsittel, our Chief Financial Officer will review our first quarter 2019 financial results. Dr.

Andy Boral, our Chief Medical Officer; and Dr. Marion Dorsch our Chief Scientific Officer will also be available to answer your questions during the Q&A portion of the call. Before we get started, I'd 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 Annual Report on Form 10-K 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's our CEO, Jeff Albers..

first I'll highlight the recent acceleration of avapritinib, BLU-667, BLU-554 and BLU-782 programs based on clinical and regulatory progress; second our Chief Commercial Officer, Christy Rossi will review for the first time our commercial strategy, with a view towards multiple planned marketing applications for avapritinib and BLU-667 over the next 18 months..

Thanks, Jeff. It's great to be with all of you this morning to share our initial thinking on how Blueprint Medicines will approach this exciting next step in our journey towards bringing these important therapies to the patients and healthcare providers who are waiting for them.

About six months ago, I joined Blueprint Medicines to lead commercial efforts across our portfolio. Previously, I led the North American multiple sclerosis business unit at Sanofi Genzyme, where I oversaw all aspects of the franchise and successfully launched two medicines in a crowded field with multiple other therapies.

At Sanofi Genzyme, my team introduced this franchise and designed the company as a leader in MS by building our organization and operations around the specific needs of patients and healthcare providers.

A key example is the MS One to One program which we created from the ground up to provide superior reimbursement and clinical support to MS patients and the broader community, partnering with the healthcare providers who worked so tirelessly on their behalf each day.

This experience among others at Sanofi Genzyme and at Biogen taught me the importance of engaging with patients and healthcare providers deeply and directly to understand their perspective and address their unique needs. Ultimately, this customer-centric approach drives better patient outcomes..

Thanks, Christy. Earlier today, we reported detailed first quarter 2019 financial results in our press release. This morning I'll just touch on a few financial highlights from the quarter.

First, we were very pleased to have closed a follow-on public offering in April, that raised approximately $327.2 million in net proceeds to support the continued expansion and acceleration of our portfolio..

Thank you, sir. Our first question is from the line of Terence Flynn of Goldman Sachs. Your question please..

Hi. Thanks for taking the questions and congrats on all the progress. Maybe two for me. First, just on 667 and the ASCO data. Just wondering if it's reasonable for us to assume that the durability of RET inhibitors generally will match that of the EGFR and ALK inhibitors.

Or is it possible that durability is going to differ by type of RET fusion? And then one on the commercial side, you mentioned balancing kind of focus with scale. Maybe help us think about the size of the footprint that you guys are considering.

And then you'd talked a little bit about solid tumors and the overlap there, but help us think about the Avapritinib for SM. Would that require an incremental sales force build as well? Thank you..

Hi Terence, this is Jeff. I'll start with the first one and then maybe ask Andy to chime in as well and then I'll turn it over to Christy to take your second question. So the first one is around BLU-667 data at ASCO and durability.

I would just make the blink at dotcom and say, given that we're only a couple of weeks away from these ASCO -- various ASCO presentations and then EHA presentation for systemic mastocytosis, we're not going to comment or speculate on any of what data will be presented or how is that actually being worked on currently.

I would say more broadly though that where we sit today, we are very excited for a variety of reasons.

First is, the data continues to mature very nicely; secondly, the enthusiasm of our ever-expanding global investigator group only seems to be increasing with the passage of time; and three, we continue to have very nice productive regulatory engagement within the program across various paths forward.

And so we're excited to see the Breakthrough Therapy Designation today and we're really looking forward to sharing more details at ASCO in a few weeks' time.

And on the second one, Christy why don't you in terms of size of footprint and then how we think about systemic mastocytosis and how that fits with solid tumors?.

Sure. We're not going to guide at this point to a specific footprint in terms of the size of the sales force, but I'm happy to talk a little bit more about how we're thinking about it.

As I said, Blueprint is in a really fortunate position, bringing our first therapy to patients and that we're not just bringing one therapy to patients and one indication, but we have the benefit of potentially bringing two therapies in the U.S. over the next 12 to 18 months across a number of different patient populations.

And so that enables us to think about our commercial build in a different way. And that thinking really informs the plan to create an oncology focus field team taking advantage of the natural overlap that we do see between prescribers who are treating these patient populations across a variety of settings.

In terms of how we're going to focus that team, initially that team will very much be focused on centers of excellence which is where we envision initial uptake will be happening for both Avapritinib and BLU-667. But over time we will also be engaging with community oncology practices and having this type of structure will enable us to do that.

We think that's really important because we want to make sure that we're reaching those providers and patients and we know that many patients are being treated at community oncology centers and we want to make sure that they have the potential to benefit from both of these therapies as well.

In terms of SM, again we're thinking about this build in a holistic way and in a way that will allow us to be flexible and incorporate systemic mastocytosis as we proceed with our development there.

I'm incredibly excited about the opportunity in SM both advanced in the near term and in ISM down the road which as I've learned more about it has just really compelling need in that patient population and is reminiscent of some of the sort of rare more chronic therapies that I've worked in my previous lives.

Our structure will allow us to incorporate -- focus on SM. The overlap there is probably going to be not quite as significant as we see in oncology. There certainly will be some as we think about our centers. But there's aspects of SM that are going to be a little bit different.

It does feel a little bit more like a rare disease where the focus will be around patient identification and facilitating diagnosis. And so it's premature at this point to comment specifically on what the field structure will look like there, but certainly the overall organization that we are building has the flexibility to incorporate it..

Great. Thanks a lot..

Your next question is from the line of Joseph Thome of Cowen and Company. Your question please..

Hi there and thank you for taking my questions and congratulations on the progress this quarter. Maybe just first one on Avapritinib in advanced SM.

At EHA, are we going to be able to get maybe an early look at some of the PATHFINDER data? Or will that be too premature? And on that submission, tell us a little bit about the kind of the direction that you've been given with the FDA in terms of how many patients you need from PATHFINDER and degree of follow-up.

I saw on FDA they say it's essentially a 10-month follow-up period for the primary endpoint that started last year.

So is it primarily you need a larger safety database? Or do you need some active as well before this FDA meeting?.

So Andy, why don't you take that question?.

Yes. So I'll start with the anticipated presentation at EHA. So that will focus on the additional data from the Phase I EXPLORER study really with an emphasis on -- which is the study that we've reported at ASH last year with an emphasis on really deepening and responses and durability of responses.

And we will continue to update on the patients with indolent SM that have been enrolled in that study. We are -- I think -- we're pulling those data together and look forward to the presentation at EHA.

In terms of the regulatory path forward in advanced SM with the Breakthrough Therapy Designation and that gives us regular ongoing interactions with FDA and then with the -- really very nicely maturing data in the study as far as we showed at ASH last year.

We're seeing our response rate of about 80% using very rigorous IWG response criteria in patients with very advanced disease. We see that this really is a remarkable data.

So together this is -- this has given us confidence that we can submit an NDA based on complete data from the Phase I EXPLORER study, along with preliminary data from the PATHFINDER study.

Of course that is a matter of ongoing conversation with the FDA and we will map that details out over the coming months, but we are on track for our planned filing next year. Going back you did ask about PATHFINDER at EHA those data with you would not be mature any, not for EHA..

All right. Great. Thank you so much..

The next question is from Michael Schmidt of Guggenheim Securities. Your question please..

Good morning guys. This is Charles Zhu on for Michael Schmidt. Thanks for taking the question and congrats on the quarter. I have a few questions within the systemic mastocytosis. The first one being, could you just very quickly remind us how many SM patients -- advanced SM patients there were in the U.S.

and provide any color what sources of data you've used to arrive at that number?.

Sure. I'll take that. So we believe and we've communicated previously in our filings that there are approximately 2,600 advanced SM patients in major markets that includes the U.S. as well as EU5 and Japan.

As you've probably seen through your experiences while anytime you're working in new disease areas, the estimates around these patient populations are imprecise.

So we've looked at a number of data sources to arrive at that conclusion, but the actual number could be more or less and certainly in markets where there have not been effective therapies available often what we find is that when new therapies are brought to patients that facilitates increased diagnosis and treatment of patients which is a good thing for patients in the community.

And we expect we may see a similar dynamic if we bring Avapritinib forward. So we'll learn more about what this market looks like as we bring Avapritinib forward and make it available to patients..

This is Jeff. Maybe I'll just add to the two points that Christy raised around the imprecision of the data and then the fact that systemic mastocytosis broadly has all the markings of a rare disease where as effective therapy comes forward, you start to see more patients being identified. And so that only broadens that error bar.

Maybe a third component is the fact that the more we learn, the more we're convinced that systemic mastocytosis is really just a continuum of a disease rather than these distinct subtypes.

And distinguishing between an advanced SM patient or a smoldering SM patient or in many cases even an indolent systemic mastocytosis patient, who has very high symptom burden is imprecise at best.

That was well characterized by our ASH presentation, where in a study amongst the world experts in advanced systemic mastocytosis there are certainly numerous indolent systemic mastocytosis patients included in that study.

So more broadly we look at the whole group as around 20,000 patients in those major markets with that huge error bar that Christy highlighted already..

Got it. That makes sense. And then a bit more of a clinical question.

How are you guys thinking about the potential implications around patient identification diagnosis and duration of Avapritinib therapy specific for these different types of patients with systemic mastocytosis with associated non-mast cell malignancy? For example if you have a patient with an indolent SM but a severe non-mast cell malignancy or vice versa?.

So Andy why don't you take that?.

Yes. So -- I mean actually just carrying off what Jeff way saying, it is important as you were alluding to that mastocytosis is a complex disease. It covers a very broad spectrum of indolent to advanced. In the advanced setting, it can be associated with another hematologic neoplasm.

Actually by definition that would not be indolent disease and those patients certainly can have progression of their associated mast cell associated non-mast cell neoplasm? I think really importantly as we've shown today that as these evolve from the EXPLORER study, we're seeing profound activity across all of the subtypes of advanced systemic mastocytosis, the pure ASMs, aggressive systemic mastocytosis patients, the ASMs within associated heme neoplasm and they very, very aggressive mast cell leukemias.

So based on the data so far, we really don't see a distinction and there is evidence -- increasing evidence that actually the KIT mutation can be found in the other associated clonal disorder that's associated with mastocytosis.

It might be that in many cases avapritinib is active in that -- through that mechanism and there may be other mechanisms as well by which these patients are doing well..

Okay. That makes sense. Thank you. And I have one more last housekeeping question if you don't mind. It looks like you've excluded AML high-risk MDS and Philadelphia chromosome-positive malignancies from the Phase I EXPLORER trial. Are those patients eligible for Phase II PATHFINDER? And this is specific to associated to hematologic malignancies..

Yes. So those patients are excluded from EXPLORER and will be from – or for PATHFINDER as well really because they have an acute need for other therapies. So you just need to treat their AML or their high-risk MDS urgently with cytotoxic chemotherapy.

So once that's under control they would be potentially candidates for the studies but not until the aggressive malignancy is treated..

Got it. Thanks for taking the questions..

Thank you. Our next question is from the line of David Nierengarten of Wedbush Securities. Your question please..

Hey. Thanks for taking my question. I have a couple. First off with 667, if you could maybe discuss a little bit about your strategy for commercialization likely being your second to market little bit differentiated profile.

Are there any lessons from other launches like PDGFRA inhibitors that are leading to a differentiated strategy there? And then a quick one on FOP if you are planning on combination studies if or when palovarotene is approved? Thanks..

Okay. So for the first question around commercial strategy for BLU-667 I'll have Christy take that one. And then for the FOP combination strategy Andy I'll have you take that second question..

Thanks. So if you think about commercialization in a market where there's multiple options I start from the perspective that additional therapy options are a great thing for patients. So we welcome having multiple therapeutic options within this category available. I also think if you look at a number of analogs. You mentioned palovarotene.

You look at ALK as well. Having multiple options helps to really drive I think the adoption of precision strategies overall. And so we'll expect that having many therapy options here is going to be a good thing for us and for the treatment of patients.

For me personally as I commented in this space, I've worked in other specialty markets where there are multiple many, many therapeutic options available and having brought products forward eight, ninth to market.

And one thing I've learned is that often what ends up differentiating a product over time is not immediately obvious when you first bring it forward.

So real world experience real world evidence engagement with health care providers and patients in a very direct way bringing forward a sense of urgency and responsiveness to how you engage with the company all of these things can be incredibly important in terms of what happens over the long term.

So when I look at the data that is supporting BLU-667. At this point, I'm incredibly excited about the opportunity. I think we potentially have a best-in-class product here and I think we'll see how things evolve as we bring it forward and gain experience in the market..

David, it's Andy. So turning to the BLU-782 or the ALK2 inhibitors that we're developing in FOP. We are developing BLU-782 as a single agent therapy. It's once daily oral medication.

It's critical -- I think the critical distinguishing aspect of BLU-782 is it is the only thing out there that potently and selectively inhibits ALK2 which is the fundamental driver of the disease. And we think that really will make it the backbone of therapy for fibrodysplasia ossificans progressiva.

I think certainly as multiple drugs are developed for patients with FOP which is a great thing there could be in the future potential opportunities for combinations. And I think those are the things we'd have to explore. I think it depends a lot on if and when palovarotene is approved what the actual indication is.

But I can imagine situations where patients are taking BLU-782 and if someone has a flare they might -- you might want to combine it with palovarotene. Ideally, though BLU-782 will prevent the flares in the first place..

Okay. Thank you for that..

Our next question is from the line of Andrew Berens of SVB Leerink. Your question please..

Thanks. Congrats guys on the progress. Let me practice my question by saying I know you're not going to run the ASCO data. So this is more of a question about the profile of 667.

I think that the last thing that people are I guess a little concerned about is the tolerability profile at the higher doses and some of that may come from an orphan designation of 667 as a JAK1/2 agent in small cell cancer.

How should we think about the activity of 667 versus 292 in that regard?.

It's Andy. I'll take that question. So BLU-667 is a highly selective and potent RET inhibitor and clearly inhibits RET far in excess of any of the other potential targets. So we don't really see that as being a major concern or issue.

We're really -- we're very happy to see the evolving data with now response rates of about 60% in both previously treated small cell lung cancer and previously treated medullary thyroid cancer, again showing that we see similar activity in two very different molecular settings in fusions, in permutation the fusions being the drivers of the lung cancer the permutations of the thyroid cancer.

And also I want to remind you that BLU-667 is unique and that it's equipotent across all of the various fusions permutations including the various forms of the gatekeeper mutation with 804, which we think could lead to very prolonged durations of response. Of course the studies have been going on that long and that is data to be determined.

We'll certainly update the activity and safety data at ASCO, but we are confident that we have what could be a best-in-class compound..

Okay. And then just one more I guess on RET. We've seen some frontline approvals in subgroups of non-small cell lung cancer with a single-arm trial, full approval not accelerated approval.

And I was just wondering with a similar prevalence to RET, why does it seem to be -- and both I think you and LOXO have pointed to the frontline as needing a randomized trial.

Why would it be necessary in RET driven tumors versus some of the other ones like ROS1?.

Yes. So I'll take that. It's Andy. Yes certainly, we are actively looking at the most rapid and aggressive path forward to approval in frontline. Lung cancer, we will continue to discuss the possible path forward with FDA. And I think conceivably there might be an opportunity for an accelerated approval in frontline.

The ROS1 is a very specific circumstance where Crizotinib has already had an approval in lung cancer and so that was a supplementary NDA. So every situation is a little different. I think what we know is that even if we were to have a single-arm frontline approval in lung cancer in the U.S.

there's a very high likelihood that countries in Europe or other parts of the world would want a randomized study and it's also very valuable to show that you can -- that your compound is better your medicine is better than available standards of care. So for various reasons we will proceed with the Phase 3 comparative study..

Okay.

Have there been naïve patients enrolled in the 667 trial already?.

Yeah. We do have some naïve patients..

Okay. Thank you..

Our next question is from the line of Arlinda Lee of Canaccord. Go ahead please..

This is Ben for Arlinda. Thank you for taking my question.

Sorry if this has been asked before, but for the upcoming GIST dataset at ASCO, will you be breaking out survival and response data between fourth line and PDGFR?.

It's Andy. I'll like that. So the ASCO presentation for GIST will really focus on the registration data from the NAVIGATOR study. So that will -- which is our two groups the PDGFRα Exon 18 population, which is across all lines of therapy and the fourth line and beyond GIST population. And we'll update on response duration.

And really we want to focus on the data that we expect to be in a potentially -- in a potential label assuming a successful filing because we think it is an important opportunity to explain to the community more about the compound, more about avapritinib activity safety. And so that will really be the focus of the presentation.

And we look very much forward to updating at ASCO..

This is Jeff. Just as a clarification, they will be broken apart. You'll be able to see them separately as well..

Awesome. Thanks so much. Just a quick follow-up on 667.

Lung patients -- how many patients, do you think will be presented? And will you provide the durability of the go-forward dose?.

So this is Jeff. As I said in the opening comments, in terms of guiding to the specifics of any of our presentations at ASCO or EHA we're not going to go into those details.

It's only a few weeks away but we think across the board, each data set will -- there'll be a robust set of data being presented across a wide range of criteria and aspects of the clinical development plan..

All right. Thanks so much..

The next question is from the line of David Leibowitz of Morgan Stanley. Your question please..

Thank you very much for taking my question.

Could you characterize the challenge between advanced systematic mastocytosis smoldering and indolent? And when do we see data for latter tumors? And I guess, what the path forward is there?.

Thanks, David. This is Jeff. I'll start and then maybe I'll have Andy chime in as well. So, systemic mastocytosis, again, it is a -- there are various subtypes that Andy walked through a few moments ago in the advanced setting. But we continue to really view this as a continuum of disease.

I was fortunate enough to interview on a panel a patient from our compassionate use program earlier this week a woman who has indolent systemic mastocytosis. But as she describes her patient journey and the impact on her life and the life of her children, it sounded like anything, but indolent disease.

I mean, incredibly high symptom burden, clearly mass cell infiltration impacting regular organ function and variety of different organs. And we see that time and time again. And I think if there was one way I would characterize any specific patient is they're all unique. And sometimes you have an indolent patient with very high symptom burden.

Sometimes you have an advanced systemic mastocytosis patient with low symptom burden. And as Andy highlighted in his summary of data what has been strikingly compelling for us is the consistency of activity when you inhibit the D816V mutation which is common for all of those patients. And so, we've obviously gotten multiple ongoing studies.

We initiated our study focus on indolent systemic mastocytosis earlier this year and we've guided to sharing data from the first part of that study by the end of this year. But we suspect this will play out over time as we get a better handle of which patients are -- in which patient is a therapy like avapritinib appropriate within that continuum.

And we're also studying different doses, so we'll get a better sense on what dose is right for which particular groups of patients. So, Andy, anything you ....

Yeah. No. Maybe all I'd add to that is that sort of echoing Jeff's pointing that indolent is a bit of a misnomer for that disease as we've -- we're working with multiple investigators around the world really now and we see these patients. And it’s a bit of a different group than the advanced.

These are -- we're talking to allergists and dermatologists and gastroenterologists, and they all really uniformly tell us that 50% or more of their patients they think are potentially good candidates for our clinical trial with avapritinib. So, we think there's a real need that is not met with available therapies..

Thank you for that. And one additional question.

On BLU-782, when you were beginning a trial in the fourth quarter, how does I guess your design plans get affected by what happens with palovarotene considering they're probably going to have a submission in, in the third quarter?.

Yes. It's Andy. I'll like that. So, of course, we were aware of palovarotene before we even initiated our 782 program. They've been out there for a while. And their progress, I think, is in line with what we expected. It really doesn't impact our clinical trial plans..

And this is Jeff. I'll add there, because I think Christy highlighted this nicely from a commercial perspective. But one of the foundational elements of Blueprint Medicines is if you create highly selective therapies it opens up opportunities for combinations down the road. And so we see no impact on the near-term execution of our clinical trials.

We think as Andy said that 782 could potentially serve as the backbone of therapy and then we'll look to explore potential for combinations further down the road..

Thanks for that. .

Our next question is from Eun Yang of Jefferies. Your question, please..

Thank you. Questions on 667. So as you enroll more patients at the optimal 400 QD dosing, the response rate increased nicely from the dose escalation.

So as you have more patients enrolled in the 400 milligram QD, would that be reasonable to expect that the response rate would be approaching close to 70%?.

Hi, Eun. This is Jeff. I'll take that one. As we've said in earlier answers to questions, given the proximity to the ASCO presentations we're not going to guide or speculate on what or how we'll share that data. Obviously, we've now got it in hand based on data cuts.

So we'll pull that together and really look forward to seeing all of you in a few weeks in Chicago..

Okay. And then second question is, obviously, response rates are quite strong at 60% range, but as we have seen with targeted therapies tumors eventually develop secondary mutations. So perhaps it is pretty premature to ask this question but in patients who have been treated with 667.

Have you seen or identified some common secondary mutation sites that could help you guide to develop second-generation product?.

So, I'm going to have Andy take that. So the question is around 667. I think this is twofold the response rate we've seen so far and maybe just highlight the second-line patients predominantly and then also resistant and how we would speculate that that could evolve..

So, as we've already said, we're very happy with the evolution of the data over time and you'll see how – you'll see more details at ASCO. We – basic concept of Blueprint really is to create targeted therapies for targeted patient populations.

And a lot of – as you think about how we developed avapritinib that can take the path of developing a compound that addresses mutations that are resistant to other therapies. So that's an area that we're very interested in.

We are doing – circulating tumor DNA sequencing on the blood samples from all of our patients, both at baseline and over the course of therapy and it's very important to understand the mechanisms of resistance.

We think we are very well positioned to develop new compounds to address those mechanisms of resistance, but we haven't disclosed any information about what they might be yet..

Okay. The last question. What's the timing for starting Phase 3 in first-line RET-fusion non-small lung cancer? Thank you..

This is Jeff. So we've guided to that trial starting in the second half of this year..

Thank you. And now I would like to turn the call back over to Jeff Albers..

Excellent. So thank you operator and thanks everyone for taking time to join us today and for your continued support of Blueprint Medicines. And as I mentioned, we look forward to seeing you all in ASCO in just a few short weeks. Thank you. Bye-bye..

This concludes today's conference call. Thank you all for attending. You may now disconnect..