Good day, ladies and gentlemen, and welcome to the Q2 2019 Blueprint Medicines Corp Conference Call. [Operator Instructions]. I would now like to introduce your host for today's conference, Kristin Hodous of Blueprint Medicines. Ma'am, you may begin..

Thank you, Operator. Good morning, everyone. This is Kristin Hodous of Blueprint Medicines, and welcome to Blueprint Medicines second 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 our second quarter business highlights; Christy Rossi, our Chief Commercial Officer, will provide an update on our commercial plans; and Mike Landsittel, our Chief Financial Officer, will review our second quarter financial results.

Andy Boral, our Chief Medical Officer; and Marion Dorsch, our Chief Scientific Officer, are also on the call and will be available for Q&A. Before we get started, I would like to remind everyone that statements we make on this conference call will include forward-looking statements.

Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those set forth in the Risk Factors section of our most recent quarterly report on Form 10-Q filed with the SEC and any other filings that we may make with the SEC.

In addition, any forward-looking statements made on this call 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, and good morning everyone. Welcome to our second quarter financial results call. This morning we'll focus on 3 key updates and highlight our solid foundation for long-term growth. First, I'll share an update on our recent regulatory submissions for avapritinib, as well as upcoming milestones for our broader portfolio.

Christy will then provide additional color on our commercial strategy, including our plans to evolve the GIST treatment paradigm. And finally, Mike will review our financials with focus on achievements under our strategic collaboration with CStone Pharmaceuticals in China.

Over the last 7 weeks, we submitted 2 marketing applications for avapritinib NDA to the U.S. Food and Drug Administration and the European Medicines Agency for adult patients with PDGFRalpha GIST, regardless of prior therapy, and for fourth-line GIST.

We submitted the applications less than 2 weeks apart and just 4 years after initiating clinical development. You see milestones represent defining moments in our history and highlight our commitment and urgency to deliver new precision therapies to patients as quickly as possible. The standard regulatory review timelines in the U.S.

and Europe offer a roadmap for our path forward. In the U.S., we expect the FDA to make a filing decision in August, which is favorable, we'll initiate the formal review process. Assuming the NDA as granted priority review, a potential approval decision could occur in the first quarter of 2020.

In Europe, the EMA validated our application on July 18, triggering its formal review process. Based on the standard review timeline an approval decision in the EU could occur in the second half of 2020. The submission of these first applications require tremendous effort and coordination across the company.

And we're now leveraging this experience to improve the process in advance of multiple planned regulatory submissions in 2020 for BLU-667, avapritinib and supplemental filings for avapritinib.

As we begin to engage with the FDA and EMA on the review of our applications for avapritinib, we're also working towards key milestones across our broader portfolio. This morning I'll highlight 2 milestones we expect in the second half of 2019, which have the potential to drive significant long-term value for both patients and Blueprint Medicines.

We're pleased to announce today that we plan to hold our first Research and Development Day on Tuesday, November 5. FDA then will highlight our research vision, platform capabilities and portfolio strategy. The agenda will focus on 3 areas of opportunity for our differentiated and highly productive precision therapy platform.

This include 1, indication expansion opportunities for our clinical stage therapeutic candidates; 2, opportunities to establish franchises of complementary programs that leverage our scientific and clinical expertise; and 3, new targets that highlight the strength of our science and the unique capabilities of our platform and people.

Separately, we plan to provide an important update on the avapritinib program in systemic mastocytosis in the fourth quarter. In June, we presented updated clinical data from the Phase 1 EXPLORER trial of avapritinib in patients with advanced SM at the European Hematology Association Congress.

These data, which will form the basis of our planned NDA for advanced SM in the first quarter of 2020, included a centrally confirmed overall response rate of 77%, and ongoing treatment durations up to 34 months.

The EXPLORER data reported EHA, also included encouraging clinical activity in 15 patients with indolent systemic mastocytosis, a more common form of the disease characterized by debilitating hypersensitivity reactions and severe skin and/or gastrointestinal symptoms.

Building on these results, we plan to report initial data from the dose finding portion of the registration enabling Phase 2 PIONEER trial in patients with indolent SM in the fourth quarter.

We expect these data to provide preliminary evidence of safety and clinical activity at low dose levels that could be used for chronic treatment in patients with indolent SM.

Altogether the research clinical and regulatory milestones we expect to achieve across our portfolio in the coming months represent important growth opportunities for Blueprint Medicines. In parallel, our commercial team is continuing to prepare to launch avapritinib with the goal of evolving the treatment paradigm of GIST.

I'll now turn the call over to Christy to share more detail on our commercial launch strategy..

Thanks, Jeff. It's great to be with all of you this morning. Last quarter, I highlighted our strong commercial leadership team and our plan to build a nimble and scalable field organization to support multiple plans launches over the next several years. Today with our first marketing applications for avapritinib submitted in the U.S.

and EU, I'll provide more detail on our market development plans in GIST. As you all know, our initial target indications are PDGFRalpha, Exon 18 mutant GIST and fourth-line GIST and there are currently no effective treatments for either patient population.

As a result, we'll need to work with the GIST community to evolve the treatment paradigm and expands the number of GIST patients who are able to access effective therapy. To do this, we've identified three key imperatives.

First, we need to increase tumor mutation testing, to bring precision medicine to GIST patients especially those with PDGFRalpha, Exon 18 mutations that aren't addressed by current therapies. Today, only 30% to 40% of GIST patients in the U.S. receive mutation testing as part of their treatment.

This is not surprising, as oncologists are frequently unable to offer effective treatment options to patients based on the results of testing. It's approved avapritinib will be the first therapy for a molecularly defined GIST population, offering an opportunity to evolve GIST treatment toward precision approaches.

In other therapeutic areas we've seen a similar paradigm shift, for example, as new targeted therapies were introduced in ALK positive lung cancer testing rates dramatically increased from about 10% in 2010 to about 80% by 2017.

In GIST, we'll aim to increase testing in clinical practice quickly by educating healthcare providers, patients, pathologists, and other stakeholders about the value of testing in a treatment landscape that includes avapritinib. Our second imperative is to educate healthcare providers, patients, about avapritinib and its clinical profile.

In the current GIST treatment paradigm, patients who progress on imatinib have no highly effective treatment option. In the second-line setting sunitinib offers an overall response rate of about 7%. In the third-line regorafenib offers only about 5%.

Beginning in second-line, some patients opt-out and choose best supportive care over the available multi-kinase inhibitors, largely due to limited efficacy and challenging toxicity profiles. With the introduction of avapritinib we'll aim to increase the number of patients who choose to continue treatment through multiple lines.

A similar phenomenon was observed in melanoma, where there was a 4-fold increase in the number of patients advancing into second and later line treatment, five years after the introduction of checkpoint inhibitors and targeted therapy.

Our third imperative and perhaps the most important is to enable rapid patient access so patients can start and stay on therapy.

Our approach will include a robust patient services program, as well as data, education and resources for payers and other stakeholders and the value avapritinib will bring to patients, healthcare providers, and the healthcare system.

Our goal will be to ensure that patients with PDGFRalpha, Exon 18 mutant GIST and first-line GIST can access avapritinib as soon as possible after approval.

We intend to act on these imperatives with an integrated approach that addresses the specific needs of our customers with focused sales, medical affairs, precision medicine and market access teams and initiatives.

For example, one of the ways we plan to drive growth for avapritinib, as well as our broader portfolio is through our field-based precision medicine teams in the U.S. and Europe, which we have designed to address customer needs around patient identification.

In the U.S., this focused team will collaborate with our sales team and other commercial and medical personnel to drive actionable testing and patient identification with healthcare providers, multi-disciplinary teams, including pathologists and laboratories. In addition, we're initially focused on increasing mutation testing in GIST.

The precision medicine team will also work to advance testing in RET-altered cancers, as well as address the diagnostic delay that often occurs in systemic mastocytosis.

As we continue to build out our team and enhance capabilities, we're confident that over time our approach will increase the number of PDGFRalpha and fourth-line GIST patients, who have the opportunity to benefit from avapritinib.

These efforts will also form the foundation for indication expansions in third and second line GIST and additional new product launches assuming the future success of ongoing and planned clinical trials. I'll now turn the call over to Mike to provide an update on the CStone collaboration and our financial results for the second quarter..

Thanks, Christy. Before I highlight our second quarter financial results, I just want to take a moment to acknowledge all of the progress we've achieved with CStone Pharmaceuticals, our strategic partner in China over the past year.

In June 2018, we entered into the collaboration, which grant CStone exclusive rights to our 3 lead therapeutic candidates; avapritinib, pralsetinib and BLU-554 or fisogatinib in Mainland China, Hong Kong, Macau and Taiwan. Over the course of the year we've worked with CStone to bring our ongoing trials to patients in China.

To-date, 5 clinical trial protocols have been submitted and granted approval by Chinese health authorities. CStone is now actively enrolling patients in the Phase 3 VOYAGER trial of avapritinib in third-line GIST and the Phase 1 monotherapy trial of fisogatinib in hepatocellular carcinoma.

For the other approved trials, CStone is on track to initiate patient dosing in the second half of 2019 in the Phase 1/2 ARROW trial of pralsetinib in RET-altered cancers, a bridging trial of avapritinib in PDGFRalpha D842V GIST, and a new Phase 1/2 trial of fisogatinib in combination with CStone's anti-PD-L1 therapy in HCC.

This progress has enabled us to accelerate patient enrollment across our ongoing global clinical trials, while CStone builds a foundation for potential approvals in China. We're grateful to have such a productive partnership with our CStone colleagues and look forward to building on this progress in year 2 at a collaboration.

Now let me turn to a few highlights from our financial results for the second quarter, which we reported in detail in our press release earlier this morning. First, we ended the quarter in a strong financial position with $667.3 million in cash, cash equivalents and investments.

And based on our current operating plans, we continue to expect that our existing cash balance will fund operations into the middle of 2021. We were also pleased to have achieved our first development and regulatory milestone under the CStone collaboration, resulting in a recognition of a $4 million milestone payment in the second quarter.

Second, we saw an increase in operating expenses during the second quarter due to the timing of certain manufacturing and supply activities, as we continue to build inventory to support our ongoing and planned clinical studies and support our potential upcoming commercial launches.

This timing was in part driven by the acceleration of some of our clinical development activities and filing timelines for both avapritinib and pralsetinib, that we announced earlier this year.

We expect to see future increases in quarter-over-quarter operating expenses consistent with a longer-term trend that we've seen in prior quarters, as we continue to expand our clinical activities and build out our commercial infrastructure. With that, I'll now turn the call over to the operator for questions.

Operator?.

[Operator Instructions]. And our first question is going to be from Salveen Richter from Goldman Sachs..

Firstly, just when you talk about the PIONEER dataset that's coming out in the fourth quarter, can you just discuss the side effects profile of the drug in the context of the SM indication particularly the indolent population?.

Anthony, why don't you take that call?.

Yes. As Jeff spoke to, we will be providing initial preliminary data from the PIONEER study, part 1 of the PIONEER study on the second half of the year.

And that really -- that part of the study really is focused on looking at the multiple dose levels or much lower dose levels 25 milligrams, 50 milligrams and 100 milligrams a day that we're looking at indolent systemic mastocytosis, remember we are treating 200 milligrams a day in the advanced systemic mastocytosis.

Based on the early safety data from the -- for both the GIST and the SM, systemic mastocytosis dose escalation studies, the early dose levels were very well tolerated, very few side effects.

Of course, the important aspect of the PIONEER study is to look at the uses of these lower doses for longer periods of times -- in patients with indolent disease. We actually do expect that the low dose safety profile will be very appropriate for patients with indolent systemic mastocytosis..

Thank you. And then a follow-up. With regard to the update at ASCO where for patients on the Lilly, Loxo RET program transitioned to pralsetinib.

Could you just provide us an update, if there is any?.

I don't have updated data, since ASCO, but just to remind everyone, we did report data for four patients previously treated with [indiscernible] at the ASCO presentation to add partial responses on pralsetinib BLU-667 and one has stable disease.

I think it's important to point out that we don't have access to individual patient data from patients on their prior clinical trials, such as the 292 study. So it's -- so we don't have a lot of information about what happens in them before they started our study.

So what we know -- all we can really do is talking about what happened to them once they started BLU-667..

And our next question is going to come from Michael Schmidt from Guggenheim..

Good morning, guys. This is Charles Zhu on for Michael Schmidt. Thanks for taking the questions and congrats on the progress and the strong recent data readouts. First, regarding VOYAGER, any color around expected patient demographic distribution now that you're enrolling Chinese patients.

And if there are any potential implications on regulatory timelines in that territory versus the U.S.

or the EU?.

This is Andy, I'll take that. So the VOYAGER study is open broadly international, U.S., Europe, Asia, now in China, but in multiple other countries in Asia as well. And so we think it's actually important for any broad Phase 3 study, have a broad international patients from a broad international base.

And so we actually really look forward to see CStone getting involved in the study enrolling patients. It won't have any regulatory impact per se, I think the, both the European and U.S. agencies actually like to see a broad mix of patients and we'll have plenty of patients from Europe and U.S.

We haven't said anything about regulatory plans or timing in China..

And regarding some of your programs aimed at treating some of the more chronic conditions, whether it's indolent SM or fibrodysplasia, how much longer term safety and efficacy follow up will you need to demonstrate even this initial safety and efficacy signals look highly promising?.

This is Andy, I'll take that as well. I think, of course, as with all of our programs the specifics in terms of timing of follow up size of safety database is the outcome of ongoing discussions with the FDA and the EMA. And I think the indolent systemic mastocytosis study PIONEER that we're conducting now.

We have designed with the intend of new registration study with input from regulatory authorities. So we do think that, that in the setting of safety data across other populations being treated they were breaking out remember, we have now over 300 patients, safety data from GIST and mastocytosis will suffice in the context of the PIONEER study.

In terms of fibrodysplasia ossificans progressiva, the Phase 1 healthy volunteer study is ongoing moving on along well, but really we are -- we need to have conversations with the FDA on what the specific expectations would be in that disease..

And then our shifting gears a little bit from a commercial strategy perspective how much synergy could you expect to capture between indolent and advanced SM? And to what extent do you think you could leverage your commercial teams and learnings from advanced SM, or even GIST and RET.

Christina why don't you explain into the indolent SM disease?.

Sure. So maybe I'll start with the question around indolent and advanced SM. So we know that certainly the drivers of the disease are the same across that spectrum. And I think it's interesting as we've been in the clinic and even seen in our studies.

The diagnosis and discrimination between various types of SM can be really challenging even for the top KOLs in the world and we've seen that in our own clinical studies. So we certainly anticipate that this is going to be very much more a spectrum than sort of discrete separate indications.

But as we bring avapritinib forward we would anticipate initial you'd certainly to be more non-advanced population and then as we gather additional data and we'll expand from there into [indiscernible].

But I think we'll leverage a lot of the learnings that we'll be gathering as we go forward and bring ava forward in advanced [indiscernible] indolent space. And I think you step back thinking about how SM fits into the broader commercialization approach.

Last time, I spoke a bit about our overall strategy, and I start from a perspective that we're in a really fortunate position of multiple assets and indications launching over the next 12 months to 18 months.

And that gives us an opportunity to think about commercialization in a really different way than other companies may launching 1 product and 1 indication.

And so we see nice overlap certainly between GIST and RET and non-small cell and MTC and we'll be using that overlap as we think about our initial field footprints, which will enable us to get reach out into the community, I think in a broader way.

And then as I think about SM, there's aspects of SM that are very similar and will fit nicely into the field structure that we are deploying. I think we have an approach that gives us flexibility to consider different ways of incorporating SM.

Certainly, the core concept is really bringing precision therapy approaches forward and identifying patients is a consistent theme across all of those indications.

And today I mentioned the precision medicine team that we will be fielding, that will be a focused team, but that capability is really driving patient identification and facilitating diagnosis that's a core capability that we're going to need across GIST, RET, and we'll definitely be able to leverage perhaps them as well..

And our next question is going to come from Marc Frahm from Cowen & Company..

And it sounds like you are getting some early data you're encouraged by within PIONEER.

Can you just give us an update on where you are within that dose ranging portion? Is that portion of the trial fully enrolled at this point? Do you have that -- have you selected your dose that you want to move forward into the pivotal portion yet, or when do you think you're going to be able to make that decision, if you haven't made it already?.

Part 1 study is ongoing. It is a randomized blinded dosing comparison, we look at placebo and the 3 doses that I mentioned earlier 25 milligrams to 300 milligrams a day. And so we actually have no specific deal that we can offer now. But as Jeff mentioned, we will have some preliminary information from the first part at the end of the year..

And Marc, maybe -- this is Jeff building on that. I think the view or the optimism that Andy did convene is taken from the totality of data we have for avapritinib from a safety perspective, from an efficacy perspective, across a range of populations.

And as we highlighted EHA there are in fact 15 patients in our Phase 1 study, that ultimately were determined to have indolent systemic mastocytosis that we continue to be very confident from an efficacy perspective and now we're really focused on finding that optimal dose, when we think about chronic treatment for this patient population..

And then maybe with the RET program, your competitor really put out some numbers as to that they've treated over 500 patients now and maybe to help give the confidence in the market size and the patients are truly there and are matching, what's been reported in some kind of screening databases? Can you give an update on kind of where you are in terms of how many patients you've actually seen and then -- the next time that we'll get a date update, is that going to have to wait for the NDA dataset, or do you think we can see data before that's fully immature?.

So, this is Jeff. I'll start maybe, and you can add color. So at our ASCO update, I think we -- somewhere in neighborhood of 250, 275 patients as of an April cut-off. We have expanded that trial and added additional arms, Andy alluded to 1 earlier, that the patient population focused on those that have seen another targeted RET therapy.

We've expanded the trial to focus on a higher number of treatment-naive, non-small cell lung cancer patients. So we can continue to enroll at a rapid clip and an accelerating clip. And we've also guided to at initiating our Phase 3 first-line non-small cell lung cancer trial later this year. So we think that will only increase the rate of enrollment.

And I think what you're seeing those with our ability to identify patients and Lilly's ability to identify patients is that the patient numbers that have been put out there previously are probably pretty accurate.

I think for both of us the challenge will still be to take that the early encouraging progress that we're seeing in academic centers and move that into the community.

And I think that ties in really nicely with Christy's overview of focusing on helping clinicians better identify patients and increasing testing rates and that it won't just be that specific, I think that's the broader community and the range of targeted therapies whether they will be ALK, EGFR and working with diagnostic companies to make sure that patients are being tested earlier in getting the optimal therapy.

And so we don't think this will be a light switch that just turns on upon launch. We think it will happen over time, but in cases where you have highly effective therapies, what you see over -- with the passage of time is that treatment patterns do change. And so I think the patient number guidance holds true, but there's still a lot of work to do..

And then on the data update one for the next time that we might be able to see updated data from that program?.

We've not guided to the next update just certainly coming off of our last update that there will be an opportunity when we pull all the data together that much like what we did with GIST will provided top line overview.

And then given the breadth of this Phase 1 to say at this point, we certainly think there's opportunities to provide incremental updates with either a specific category of a patient population -- of the study population, but we've not guided to specific timing of that..

And our next question comes from David Lebowitz..

Thank you, That's Dave Leibowitz. Given that the updated PIONEER, can give that the initial PIONEER data is could to be reported at the lower dose.

Is there any specific nuances that we should be mindful of when looking at the data?.

So this is, Andy, not that I can really think, if I may. As I said the data at the end of the year will be preliminary and limited on from the escalation, or excuse me, not the escalation, the dose comparison, [indiscernible] comparison.

I think the main questions will be the AE profile at the lower doses and evidence of -- is there evidence of anti-mast cell activity, well -- we want to speak to that, to the degree we can at that point in time.

And I think just going back to our prior experience during our dose escalation studies, the -- in GIST and SM, we do -- we have previously found those low doses to be well tolerated. So we will update on what those lower doses looked like over more prolonged dosing. I think, that's the main question..

Thank you for that. And then stepping back at the -- look at the treatment paradigm.

Is there any specific hurdle that you see that you hope to exceed in that the indolent program over the long haul that, that you need to be successful?.

Yes. The indolent systemic masocytosis, I think Christy spoke to this as well. It is a broad spectrum of disease across a very wide range of severity. I think importantly whether it's indolent or aggressive off masocytosis. This is driven by the D816V mutation in the KIT. So we know that mechanistically it's 1 disease entity.

And so really the question is, in a population with the indolent disease where they have a roughly normal life expectancy, but they have a -- really are severely debilitated by chronic hypersensitivity reactions and chronic diarrhea, extreme skin reactions is really to find the optimal therapeutic index.

So we can dose patients for long periods of time with avapritinib in such a way that side effects don't replicate nausea from the disease and things like that.

So I think it's really just a matter of finding the right balance between dose and activity and we think actually a very large -- a large fraction of indolent patients have disease that is not currently well controlled by available therapies anti-histamines and mast cell stabilizers.

So we give the right safety profile, we believe the avapritinib could apply to quite a large fraction of indolent systemic mastocytosis..

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

I guess I wanted to follow up on Salveen's question.

And I know you're not going to tell us a lot of the details, but obviously very interested in what happens to patients, why they left 292 and why they entered your clinical trial? I would think you would have some history to explain that as well as probably some genetic testing once they enter your trial.

So I guess how many patients do you guys have now that have been on 292 previously? And then when we will we get better color about the dynamics that led to them coming off of that trial and into your trial?.

So this is Jeff, maybe I'll start. What we disclosed it -- the 4 patients that Andy already walk through, and an important point is we did add an arm to our trial to focus in on that patient population. So I think that would be an evolving data set that obviously we and you all will be very interested in.

I think if you look at it broadly the reason patients discontinued therapies are either a lack of efficacy or alphabet and inability to tolerate any given therapy and/or resistance to an initial treatment option. And so we anticipate we'll see all of those.

And there may be varying activity for the pralsetinib after the prior RET therapy depending on which category they fall into and the timing. But I think it's quite too early to call that up for 4 patients. We continue to see those patients come over.

As I've said on calls previously, we would hope that if pralsetinib it's proved that could be an ineffective therapy that, that patients would have another opportunity with another targeted therapy. So we hope that the option would hold true as well.

And I think that it will be an evolving story and as we provide clinical updates we'll include that data in those -- at those medical conference updates..

And then maybe a question on the GIST program. At CTOS you guys highlighted the 2 mutations, 654 and 670 as biomarkers and your trial incorporates testing for those.

What would the expected safety and efficacy be if you exclude those patients?.

This is Andy, and I'll take that. So those two specific [indiscernible] mutations V654A and T670I are mutations in KIT that actually increased the sensitivity in just [indiscernible]. So they increased tumors likelihood to have responses to [indiscernible]. The NSV, as Dr.

Heiner discussed it at CTOS, they are mutations that provide relative sensitive -- excuse me, relative resistance to avapritinib.

And together those are important components of the design of our second line COMPASS study that were kicking off this year, where we will using just ctDNA, certainly tumor DNA sequencing and when the tumor biopsies required to evaluate patients prior to enrollment.

And if the patient's tumor has either of those mutations, they will not be eligible for the second line study where we compare avapritinib to sunitinib. And of course, we think that's an important aspect of the design as it will be. Really what we think is treating patients appropriately, right.

We'll be selecting patients most like the -- more like they respond to avapritinib and randomizing them and the patients who we think are purely able to better with sunitinib then they should probably go get sunitinib and not be randomized to avapritinib..

Maybe another way to look at that is that in our patient population than you would anticipate that sunitinib would have a lower degree of activity than what has been seen in there all common studies historically..

Right. So I guess I'm just trying to get a sense for how much lower would the bar be, since you have a competitor that's doing a similar trial, but not excluding those mutations..

Yes. I don't think we can -- we've really quantified that at this point. Certainly we're thinking about that as part of the design of the study and that aspect does allow us to do a small [indiscernible] allow a COMPASS study to be smaller and we think a little faster than otherwise would be..

Thanks for taking the questions and looking forward to November..

And our next question comes from Mike Ulz from Baird..

Good morning, guys. And thanks for taking the question and congrats on all the progress as well. I just had a follow up on some earlier questions regarding the PIONEER update for the fourth quarter this year. Just curious if you'll be including any data on the PRO endpoint in the initial update, it sounds like probably not.

I just wanted to get some clarity on that.

And then secondly, if I remember that PRO end point is somewhat novel, so maybe if you can just comment on your level of confidence around showing a benefit on that end point?.

This is Andy, I'll take that. At this point we're expecting PRO data not to be available by that point of time. Certainly as we pull everything together we'll see what we have and -- and I think present as complete a story as we can on with any preliminary data. But those data will take probably a bit more time to pull together.

I think the PRO, the patient reported outcome tool that we've developed for patients specifically within systemic mastocytosis is a very important [indiscernible], it's a very important piece of work that's been done here at Blueprint in collaboration with some external folks who are with expertise in this area and really make the PIONEER study, a unique study.

And one of the challenges with indolent systemic masocytosis is the patients by definition can't be evaluated for response by the IWG criteria. They do not have a C finding, or they'd have advanced disease. And they have a normal life expectancy. So it's been critical to find a tool that assesses clinical benefit in these patients.

The PRO has been developed using following all of the procedures to validate a patient reported outcome tool has laid out by both the FDA and EMEA. And we have come to an agreement that this would be an appropriate primary endpoint for registration in this study. So it's pretty critical achievement and we're excited to move it forward..

Our next question comes from David Nierengarten from Wedbush..

I just had a quick question on GIST commercialization, actually fourth-line and PDGFRalpha. You mentioned it's mainly testing from ALK or expanding ALK testing in lung cancer as an example.

Maybe I missed it, but could you point out differences plus or minus on the just testing paradigm? I mean, it seemed to me that you have probably more patients treated at special centers that might increase testing rates or the only other differences that we would look for on the adoption of testing in this patient group?.

Sure. Yes. So there certainly are some differences, right. So we see certainly in the fourth-line studying, I think we'll find more patients treated at centers. But as you broaden out into earlier lines of treatment, you certainly see a lot of GIST patients in the community.

And so we think, certainly as we think more broadly about our approach in GIST and moving towards second-line, that's going to be really critical for us to establish a precision medicine paradigm in the treatment of just overall. And that's going to be something we'll be working towards.

And certainly this precision team that we will be fielding, that will be a priority for them. In some way they think testing and just you could argue is a little bit simpler. And then certainly the approaches that can be used there, I think are somewhat simpler than what we see in lung.

But nonetheless, we know that certainly right now, the minority of patients are tested.

And again, I think for me, the biggest similarity between the spaces or sort of the analog here is, you know, what you hear and what I've heard from prescribers is, if there's not an action that you're going to take as a result of a test result, you know, there's not a lot of rationale to test.

And certainly I think academic centers right now see the value of testing. They know that even within KIT driven just, you know, 30% of the time, you may want to make a slightly different treatment decision, even thinking about doses of imatinib, based on the results of testing. And I think academic centers know that.

But when you get into the community and you're seeing, you know, just less frequently, it's not top of mind. And, you know, that's going to require some education.

And so I think we'll see differences in adoption, and certainly from thought leaders, who see just more frequently and then as we get on to the community there'll be a little bit of a slower curve..

Quick follow-up.

Do you have a good proportion or sense of the proportion updation seen in the community versus academic or specialty centers?.

If you look at GIST overall, we estimate probably 60% of patients are seen in the community. But again, when we look at fourth line, certainly that patient population tends to be referred, more frequently.

And so, as we think about our commercialization approach in fourth-line and PDGFRalpha, I would expect our initial focus to be more on centers, where fourth-line patients tend to be referred. And quite frankly where we also have -- and thought leaders and investigators who are familiar and experienced with avapritinib.

And then we'll move out from there and certainly be engaging with the community, where we will also see some synergies certainly with our activities for pralsetinib and RET..

And our next question comes from Arlinda Lee from Canaccord..

I had maybe a couple of them. Christy, you mentioned that testing, which are improving over time.

And I'm wondering, firstly going for GIST, if you assume that with some of the clinical trial datasets coming out that you're -- and if you are getting some inbounds from maybe more of the community centers trying to have patients, participate in your trial or requesting more information on what kind of testing.

And then also with respect to indolent SM, I'm wondering how these patients typically present and looking at your sites those seem to be concentrated [indiscernible]? Curious about what the mix is in a community and interest in molecular testing on that end too..

Sure. So maybe I can start and then I'll turn it over to Andy. So in terms of testing rates evolving in GIST, again, that's 30% to 40% estimate is sort of our best estimate of what current state looks like. And I do think underneath that, as you unpack it, you will see differences between the community and centers of excellence.

And an important thing to note about that, that statistic too, is that testing at some point and somebody's treatment journey, that's not necessarily a diagnosis.

And certainly, we're going to -- want to move testing earlier on, particularly to ensure that PDGFRalpha patients are identified early and are not subjected to multiple lines of therapy that are not going to be effective on the patient population. So that will be a critical point. We've had a lot of engagement with thought leaders in the U.S.

and Europe around GIST. And certainly as we've been engaging around our second-line study, there's been, I think a fair amount of interest and patients identified. And so those discussions have been really productive.

And I would expect -- as we continue to engage and as we bring it forward to patients, we'll continue to see more enthusiasm in the community as well. That's all. We'll turn it to Andy with that..

And maybe Arlinda, I'll pick up on the ISM question. And I think Christy covered the GIST situation, while I don't have any specific to add there.

But I think in systemic mastocytosis, remember it's fundamentally different in GIST, where there's no need to test from a molecular perspective essentially all patients, 90% to 95% have a [indiscernible] we are closely related activation mutation in the KIT team. So it's really the disease defines means the patient has a mutation.

In the PIONEER study, we are focused on major centers in the U.S. and Europe at this point in time. And really that's because of a couple of things. One is, these places have the infrastructure to do the study, which has its own levels of complexity.

And there are places that the indolent fallopian patient, patients who have already been identified to having on systemic mastocytosis come to -- to some degree in the U.S. and even more so in Europe, we're finding that tends to be quite centralized.

I think the real opportunity and need in indolent systemic mastocytosis is actually to find the patients and diagnose them.

Just from talking to our investigators when we ask them how the patients they see have gotten to their sites, it's typically a pretty long and complex journey and they've usually seen multiple 4, 5, 6 physicians, I think most commonly they come in through either a dermatologist or gastroenterologist or an allergist because they have some chronic hypersensitivity or other symptomatic disease that has not been responsive to the expected therapies.

And unfortunately, eventually that can be along eventually in some cases, someone thinks systemic mastocytosis and they have a bone marrow biopsy done and they may make the diagnosis. And then they end up typically referred to a major center..

I'll just add 1 other thing. So I think obviously to circle back a key aspect of what we need to do is as [indiscernible] moves forward is really to help the community docs to see these patients think of mastocytosis much earlier..

And I would now like to turn the call back over to Jeff Albers for any further remarks..

Thank you, operator, and thank you all for taking the time to join us today and for your continued support to Blueprint Medicines. And we look forward to updating you again in the near future. Good bye..

Ladies and gentlemen, thank you for participating in today's conference. This concludes today's program. You may all disconnect. And everyone have a great day..