Blueprint Medicines Corp (BPMC) 2020 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by. And welcome to the 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. (Operator Instructions) I would now like to hand the conference over to your speaker today, Kristin Hodous of Blueprint Medicines. Thank you. Please go ahead, ma'am.

Thank you, operator. Good morning, everyone. This is Kristin Hodous of Blueprint Medicines, and welcome to Blueprint Medicines' first quarter 2020 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 2020 business highlights; Christy Rossi, our Chief Commercial Officer, will provide an update on the initial launch of AYVAKIT for the treatment of PDGFR Alpha Exon 18 mutant GIST; and Mike Landsittel, our Chief Financial Officer, will review our first quarter 2020 financial results. Dr. Andy Boral, our Chief Medical Officer, is also joining 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 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 statement.

Now, here's our CEO, Jeff Albers.

Thanks, Kristin. And good morning, everyone. I want to start by acknowledging the challenges we're all facing as a result of the evolving COVID-19 pandemic. At Blueprint Medicines, we're doing everything we can to protect the health and well-being of employees, patients, and providers, while we also seek to maintain continuity across our business. At our core, Blueprint Medicines is driven by a culture of urgency, and our team has always been agile and resilient when faced with challenges. As we've dealt with the situation, I've been proud of our employees, who have stayed focused on the needs of patients, embraced new ways of working with purpose in good humor, and continued to deliver on goals. This is evident by the sustained productivity across our portfolio in the first 4 months of the year.

Nevertheless, the pandemic is having a range of global impacts that create uncertainties for our business. For example, some sites participating in our clinical trials have experienced temporary disruptions, and social distancing restrictions certainly make externally facing activities more difficult. So far, we've worked effectively to address these issues with tailored solutions. We provided individualized support and accommodations for impacted trial sites, and we've expanded our use of technology to engage healthcare providers and other stakeholders. While we continue to expect to achieve the company goals laid out earlier this year, we know the uncertainty of the current environment brings the potential for future impact. In the face of this uncertainty, we will continue to be vigilant in assessing risk as we bring transformative medicines to patients.

Now, I'd like to turn to our first quarter highlights. As reported in our press release this morning, we made significant progress in advancing our RET and systemic mastocytosis programs, which continue to be key value drivers for the company. Similarly, our commercial launch of AYVAKIT in PDGFR alpha driven GIST is off to a strong start, although last week, we were disappointed to announce that our third line GIST study did not meet its primary endpoint.

Before turning the call over to Christy, who will discuss the commercial launch, I'll focus on recent accomplishments, as well as upcoming milestones for pralsetinib in RET-driven cancers and then avapritinib in systemic mastocytosis. So let's start with pralsetinib. As you all know, in recent months, we announced top line data from our ARROW trial in patients with RET altered lung and thyroid cancers. The centrally reviewed data in both populations were compelling with high response rates and prolonged durability. Based on these data, we submitted an NDA for RET fusion positive lung cancer in the first quarter, and this morning, we announced we've also completed the submission of an MAA in Europe. Later this quarter, we plan to submit a second NDA for previously treated RET mutant medullary thyroid cancer under the FDA's Real-Time Oncology Review Pilot Program, which aims to accelerate the review process for promising oncology medicines.

In addition, the FDA has invited us to participate in the Project Orbis initiative, which enables the concurrent review of marketing applications for oncology medicines by multiple countries. Through this program, we plan to submit additional global marketing applications for RET fusion positive lung cancer, and we're working with the FDA on next steps. Finally, we are pleased that multiple pralsetinib abstracts were accepted for presentation at the upcoming ASCO meeting, which will be held virtually this year. We look forward to sharing these presentations, as well as continued regulatory progress across the pralsetinib program.

Similarly, we meaningfully advance our systemic mastocytosis program in the first quarter. We presented transformative data from Part 1 of the PIONEER trial of avapritinib in patients with indolent systemic mastocytosis in March of this year. These data revealed a compelling clinical profile for avapritinib, with patients showing improvements in disease symptoms, patient reported quality of life, and measures of mass cell burden. We're now working to initiate patient screening in this trial's registration, enabling Part 2 for later this quarter. These activities are largely on track, despite the pandemic, although we continue to work to address trial site needs on an individualized basis.

We're also excited to have opportunities to share new data from our SM program in the second quarter. At the European Allergy, Asthma and Clinical Immunology Congress, we plan to present updated data from Part 1 of the PIONEER trial in patients with indolent systemic mastocytosis. In addition, we plan to share updated data from our EXPLORER trial in patients with advanced SM at the European Hematology Association Congress. We remain on track to submit an NDA for avapritinib for advanced SM, based on data from the EXPLORER and PATHFINDER trials in the second half of this year. Today, we also announced that we received clearance from the FDA to proceed with clinical development of BLU-263, our next generation KIT inhibitor. We're working with our clinical partners to initiate a Phase 1 trial in the second quarter, with the assumption that the trial site will be active as the U.S. begins to reopen.

And finally, we continue to advance multiple research programs, including our program for treatment resistant EGFR driven lung cancer. For this program, we plan to present preclinical data, as well as share more detail on our future clinical plans in the second half of this year.

Now, I'll turn the call over to Christy to provide an update on the AYVAKIT launch. Christy?

Thanks, Jeff. Good morning, everyone. Today, I'm pleased to provide an update on the commercial launch of AYVAKIT, as we report product revenues for the first time. In the first partial quarter of launch, we achieved net sales of $3.5 million. More importantly, we've made progress against our goal of establishing Blueprint Medicines as the leader in precision medicine with oncology and hematology centers of excellence. With an experienced and nimble team in place and executing well, we are building a solid foundation for the multiple launches we anticipate in the coming years.

Since our approval in January, we focused on educating prescribers to ensure positive first experiences with AYVAKIT, and I have been incredibly encouraged by the early breadth in prescribing that we've seen. So far, we've had more than 100 unique prescribers of AYVAKIT, and approximately 40% of them practice in the community setting. We're pleased with this initial uptake, which highlights increasing awareness of AYVAKIT among healthcare providers, even as our ability to engage in person has recently been impacted by social distancing restrictions.

A key element of our strategy is to provide best-in-class patient support to optimize access and adherence, and ensure patients are treated quickly after receiving a prescription. We worked hard to provide robust service offerings immediately upon approval through YourBlueprint, and we're pleased with the positive feedback we've received from patients, healthcare providers, and advocacy organizations to date. In fact, so far, approximately 80% of AYVAKIT prescriptions are coming through YourBlueprint, which is higher than typically seen in oncology, and a testament to the important role that our support program is playing for patients.

We're also happy to share that we've been able to rapidly achieve broad coverage of AYVAKIT. Today, more than 90% of commercial and Medicare lives have confirmed coverage at or better than our label. We continue to engage payers on the AYVAKIT approval, with the goal of maximizing access for patients. We're also leveraging these opportunities to educate payers on our broader portfolio.

Finally, a key focus of our current efforts is planning for future launches. Our precision medicine team has been actively engaged with national and regional labs to facilitate testing algorithms and patient identification. Their priorities have mirrored our corporate priorities, with a primary focus on patient identification and testing for RET and systemic mastocytosis, in addition to PDGFR Alpha exon 18 mutant GIST. With the pralsetinib NDA filing in the first quarter, our sales team has also been increasing their focus on disease education and planning for our upcoming launch. In fact, just last week, we held a week-long virtual training meeting, focused exclusively on pralsetinib.

As we look towards planned launches in lung and thyroid cancers and systemic mastocytosis, we believe we have the right strategy and the right people to be effective over the long term. More than 2/3 thirds of our team has worked in lung cancer, and more than 80% have worked in hematology, with a mix of large pharma and biotech launch experience. Overall, the AYVAKIT launch is off to a very strong start, and I'm excited about the best-in-class capability we are building to effectively deliver multiple precision therapies to patients.

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

Thanks, Christy. Earlier this morning, we reported detailed first quarter 2020 financial results in our press release. For today's call, I'll touch on a few financial highlights from the quarter. We ended the first quarter with $750 million in cash, as compared to $548 million as of December 31, 2019. This increase reflects net proceeds of approximately $308 million received from our public stock offering in January of 2020, partially offset by cash used in operations. Based on our current plans and anticipated product revenues, we continue to believe that we will have sufficient capital to fund our operations into the second half of 2022.

As Christy noted, we were pleased to record $3.5 million of AYVAKIT net product revenue in the first quarter. Our total operating expenses during the quarter were flat compared to the prior quarter, reflecting sustained investment in both our global commercial infrastructure and our research and development activities across our portfolio. As in the past, we expect to see future increases in quarter-over-quarter expenses. However, we anticipate that this growth will moderate compared to the growth we saw in 2019 when we were building our core commercial infrastructure, which is now fully in place.

So with that, I will now turn the call back over to the operator for questions. Operator?

(Operator Instructions) Your first question comes from Salveen Richter from Goldman Sachs.

This is Andrea on for Salveen. Maybe a question for Christy. What has been the key drivers for the rapid uptake that you've seen for AYVAKIT here? And how should we think about the launch trajectory on the forward? And maybe if you could comment on whether there has been a bolus of patients or any inventory stocking in the first quarter.

Sure. So as I think about the uptick over the first quarter, we were clearly pleased to see that rapid uptake. I think it speaks to the unmet need in GIST, to be frank. These patients have not had good, effective therapy really beyond the first line, and certainly PDGFR alpha patients, as we know, have not had any effective therapy. And the community I think has been very aware of that need. And so, the availability of a new therapy to address those patient needs, I think, has been incredibly well received. I think it also speaks to the experience of the team that we brought on board, many of whom have relationships, particularly with the community oncologists, and with key centers, and we're able to rapidly get access to those centers to help drive education.

As I think about going forward, the unmet need in GIST is high. And so, I don't expect that to change. It's difficult to speculate how the trajectory may evolve from here. We're dealing with a partial quarter of launch. Obviously, there's other macro factors around COVID, et cetera, that could impact how things move forward from here. But I think it really speaks to, again, the unmet need in GIST, which remains.

Great. And then maybe just a follow-up on that about the bolus of patients or how these -- maybe where these patients were coming from, if they're all new patients that were just recently identified.

Yes, sure. So we had a small number of patients who were on compassionate use prior to launch that were able to transition over, but it was small relative to the number of patients who were prescribed through the first quarter. And in fact, one of the things that I was very pleased to see starting really out of the gate is that we saw prescribing breadth that went beyond centers that were either participants in our clinical studies or where somebody had prior experience through compassionate use. So we're seeing a significant amount of demand coming from new prescribers who have not had prior experience and who are identifying patients through the work of our team that's been engaging and educating.

And I know you also asked a question about inventory, which I didn't address. Apologies. That really was not a significant factor. This is still a small patient population, and we're managing primarily through a network of specialty pharmacies. And so, inventory is not going to be a huge factor as we think about the quarter.

Your next question comes from Dane Leone from Raymond James.

I wanted to touch on one thing that you mentioned around building up a network for testing and patient identification for all of your programs that -- you also highlighted systemic mastocytosis as well. A number of labs do the testing. I'm not sure how standardized is it. But can you just expand on that? Is the idea here as you go through and develop it into a commercial launch and ISM into a latter part of the clinical study that you want to have standardized testing for the D816V mutation specifically, and that in your view would be something that would be specific to the label of the drug ultimately? And then I have one follow-up.

Sure. So the overall goal with systemic mastocytosis is to facilitate patient identification and shorten the time to diagnosis, which we know right now can take years for many patients. And as you said, KIT D816V testing is really key to that. That is the driver for these patients. And so, what we're doing I would say is two-fold; one is just trying to work to build up capacity around highly sensitive KIT D816V testing. That is something that we want to make sure is available and accessible to healthcare providers. Labs vary right now in terms of sensitivity of the test that they offer, particularly if you think about blood-based KIT D816V, which I think could be something that could really help facilitate patient identification. You really need a sensitive assay and so we're working on helping to stand up that capacity and capability.

The other piece around this is thinking about algorithm second help patient identification. To give an example elevated trip case is something that often can be used to flag these patients. It would be great to have that then trigger further testing and so working with labs to help put in place some of those algorithms so that we can help the community walk down the path to identify those patients. We are not at this point anticipating that our labeling would require KIT D816V testing.

Okay and then just one follow-up on the upcoming dataset for RET at ASCO, is it fair to say that we'll be getting what would be considered the primary analysis set with centrally reviewed response rates at ASCO? Basically what would probably reflect what we would see on the FDA label for both lung and thyroid?

Sure. Dane, this is Jeff. I'll take that and Andy could add color if necessary. I think you said that up correctly that we, as you know disclosed the top-line data for pralsetinib non-small cell lung cancer filing earlier this year. This presentation would be a more detailed look at that data. If you think back to what we did last year with PDGFR alpha-driven just, it's very similar. We announced the top-line data when we pull that together for the regulatory filing and then at a subsequent medical conference, we dug into the data and talked more about the response rate, durability of response, safety profile with greater detail. So it will be a similar path to what you saw at that time.

Your next question comes from Joseph Thome from Cowen & Company.

The first one on the initial AYVAKIT launch. I think in the prepared remarks, it was mentioned that the confirmed coverage is at or better than the approved label. Can you just talk a little bit more into what the or better could mean for some of the coverage decisions and has everyone that's been treated so far had a confirmed PDGFR mutation if you're able to get that information? Then on the second point, given we know that there is COVID related dynamics, but do you still anticipate that Part 2 of PIONEER will complete enrollment by the end of the year this year or sometime around that? Thank you.

This is Jeff. Obviously we're in different locations so we're coordinating here. I'll take that question in reverse order. I will do the first part and then I'll hand it over to Christy to answer the first part of your question. So the second part, when do you timelines going forward and you alluded to the COVID-19 pandemic. Where we sit now is as a reminder, the indolent systemic mastocytosis was a two-part study. Part one we shared data on in March and then based on that data informed the design, size, dose et cetera for Part 2 so it's the same study. So this isn't something that we have to initiate a new trial per se. In some ways, we're fortunate in that the second quarter was a time where we are collecting all that data, working with our investigators to set up Part 2 so really plan to have that be a study that would be accelerating enrollment in the second half of this year.

Where we sit today is we're still on track for that plan to begin screening and we're working with investigators now on Part 2. Precisely when the first patient will be screened or dosed is obviously more difficult given the COVID-19 pandemic and a lot of it depends on where that first patient would be from a global perspective and a site-specific perspective. But I think we are increasingly optimistic. We're seeing some signs of things opening back up. As I talked about in the opening remarks, there is no doubt uncertainty about exactly how it will roll out when you add a pandemic on top of general clinical trial execution but we have no reason to change the guidance at this point. We're continuing to plan to begin screening this quarter and really start enrolling in earnest in the second half of the year.

And then Christy, the first part?

Sure. So to the question around coverage and what we're seeing in terms of our patient mix over the first quarter, as I think about what it means to cover at or better than label clearly what we want to see is that payers are covering patients with no more restrictive criteria certainly than are currently label which is PDGFRalpha Exon 18 mutant GIST. That is what we're seeing. We're certainly not seeing anything around step at it or additional prior authorization criteria that would be more onerous than that. As I mentioned, I think on earlier calls, GIST is a small indication with very high unmet need. We also see NCCN guidelines that specified on only AYVAKIT but other therapies that are used in GIST it may not be indicated. So certainly some payers are going to take a broader approach in terms of how they cover not only EBO but other therapies and we're certainly seeing that in reality. I think your question, getting to what do we see around mix of patients.

We're certainly seeing strong utilization among PDGFRalpha patients but I think an important point for everybody to remember is that it is just not possible with precision to be able to clearly pull apart patients and just we are promoting this drug clearly for PDGFRalpha patients. That's the indication, but ICD-10 codes don't allow you necessarily to figure out what the mutational status is of every patient. We have some insight certainly through our field and through other means in terms of what some of these patients look like and certainly see a healthy utilization among PDGFRalpha but also indication that we're seeing utilization outside of there as well that's not being driven by us, but that is organic, coming from the community due to the high unmet need and KIT driven GIST.

Your next question comes from Konstantinos Aprilakis from Deutsche Bank.

I've just got a few on pralsetinib perhaps for Andy. For the upcoming update at ASCO, how much additional follow-up can we expect from the last time we saw data in lung cancer back in January and in thyroid in April? Should we expect mature response durability data in lung cancer, either in the abstract once it's released or the actual presentation?

Konstantinos, this is Andy. So, of course, at this point, just the titles have come out for ASCO. We're going to be giving I think as Jeff already started to speak to an update across the study as you can see from the Titles 1. it focuses on the lung cancer fusion-- RET Fusion lung cancer data. The other is a broader across other RET fusion tumors and we certainly have more follow-up since we've presented the top line data back in January and will give an update with additional follow-up compared to what we presented before. I think at this point we should just wait for the abstracts to come out.

Your next question comes from Ren Benjamin from JMP Securities.

Congratulations on the initial launch. Maybe just a question regarding pralsetinib and revenue in MTC; said you're on track to submit the NDA for the FDA. I'm curious as to your thoughts regarding the European filing, should we be assuming calculating European filing as well? I don't remember if you've talked about this in the past, but what are your plans regarding sales force and a go-to loan strategy in Europe versus potential partnering.

Sure. This is Jeff. I'll take that. And again I'll open up to Andy or Christy if they want to add any color. For European filing plan is very similar to what we've done in other instances where first we filed in the U.S. and then shift our focus to a European filing for pralsetinib. In terms of go-alone strategy, we have already initiated a build in Europe. We've got a team on the ground. And as we looked at the diversity of our portfolio and the strength of our research pipeline, felt like that was the right move. We've got a file already in for PDGFR Alpha-driven GIST and, as we disclosed today, we have now filed for non-small cell lung cancer. So we think we'll have a similarly robust offering, as you look at those 2 potential indications and then similarly at systemic mastocytosis. So both in the US and in Europe, we plan to bring these medicines directly to patients.

Got it. And then I guess just as a follow-up regarding the rightsizing of sales force, just kind of given your thoughts regarding GIST, has there been any changes or what are your latest thoughts in terms of the size of the sales force and the commercialization strategy?

Sure. So I'll start this, but I'll turn it over to Christy quickly. Really, we talked about this a bit last week that there is in fact no change to our plans and Christy hit on some of this in the opening remarks as well. Our priorities, as we've articulated, really beginning at the R&D Day last year have been around pralsetinib for multiple indications and avapritinib beginning with systemic mastocytosis. And as we build out the commercial team, really focused those 2 areas with [GFP&A],a more modest focus. And so I don't think that changes, but I'll hand it over to Christy who can talk about that in a bit more detail.

Yes, thanks. So agreed, we-- as I thought about the build here, I feel like we were very fortunate to have AYVAKIT and then pralsetinib launching in very close proximity. And so really thought about the commercial structure with a portfolio view and in fact, if we have been launching AYVAKIT GIST, I wouldn't have built the team in this way. And so it was very much focused on having pralsetinib come behind it, we hired for that experience. We've been clear with our team from day one when they walked in that we were really looking towards pralsetinib and that ultimately, that would be the priority because, as we think about our corporate priorities, SM and PRO have really been where we're focused longer term.

And so, our team has been actively engaged there. We saw some natural overlap between lung and GIST targets and we've been able to take advantage of that already. But our team has started the pivot towards lung, which had been planned all along and so, while I'm certainly disappointed about the VOYAGER outcome, it really doesn't impact how I think about how we move forward from here.

Your next question comes from Michael Schmidt from Guggenheim Securities.

Hey guys, this is Charles Zhu on for Michael Schmidt, thanks for taking the questions and congrats on all the progress. First one, as a follow-up on some of the previous questions that been asked, kind of wondering, given you guys have highlighted some of your patients assistance programs, how should we think of that percent free drug supply, gross net pricing adjustments and also similar another question along the launch trajectory. How should we think about patient stocking as opposed to inventory channel and stocking, given potential of COVID social distancing measures? Thanks.

Sure. So I will try to address those, although patient stocking is a new one, so I may have to ask you to clarify that one. But in terms of gross to net and free drug, our gross to net, as we said, has come in line with sort of where we expected, which was around 85% mid-teens. That of course can fluctuate over the course of a launch as everyone understands, as you grow revenue, some of the things that impact gross to net are percent sales, others are absolute fixed cost and so we will keep an eye on that as we go forward.

I spoke a bit about free drug at our launch call back in January. And at that point, said that we expected our Pap utilization to be significant, we made a strategic choice to provide support to patients. That's our focus and priority and that includes Medicare patients and, as I know, this group is all very well aware that's a challenging patient population in terms of options to really manage out-of-pocket costs. And so, our experience has sort of been in line with that, we've seen significant pap utilization, but it's fluctuated through the quarter and so I think it's a little premature to speculate on where exactly it's going to land. I think we'll be able to give more color on that as we go forward. When you're dealing with a small base and you're dealing with kind of payers coming online, et cetera, it can move up and down quite a bit and I've seen that over the first quarter. So, we'll keep an eye on it going forward, and also be looking at things like for example COVID and how the economic impact of that may impact on pap utilization as well.

Your last question around patient stocking, I think, were you asking around bolus or maybe if you want to just clarify what your question is there, and I can try to address it.

Yes, sure. I guess you know with-- especially with respect to some of these early self-administered medications, is there a potential ability, for example, for patients to obtain more than I guess the usual amount of drugs at one time, so there is limited [performance].

Yes. Now, thank you. Thank you for the question. So certainly I think at a macro level, if you look at trends across multiple therapeutic categories, I know that there have been some push towards, for example, 90-day sales; that is not something we've seen in a significant way in GIST. I think these patients are sick enough where certainly there is a desire to keep in contact with them, they tend to be managed pretty closely and so we have not seen big changes in terms of how patients are being dispensed the therapy.

Make sense. And then just switching gears a little bit over to advanced SM, and maybe this is one for Andy Boral. How should we think about potential differences in the AYVAKIT treatment duration in advanced SM patients between those with purely mass cell driven diseases versus those with an associated hematologic malignancy, and, as a related follow-up, would it be a fair characterization that the AHN portion likely contributes more towards patient mortality given AYVAKIT's potency against purely mass cell driven diseases and the apparent survival in mass cell leukemia with the caveat, of course, that patient number-- reported patient numbers have been small, so far.

Yes, this is Andy. I mean, I think the potential differences in activity of avapritinib across different subtypes of advanced systemic mastocytosis is certainly something we've looked at, we've brought up, we've pointed to early data in some of our presentations. I think what we've been really thrilled to see with them, if avapritinib is just the broad consistency-- consistent activity across advanced systemic mastocytosis, in terms both response rate and durability, really irrespective of subtype, pure ASM, ASM within neoplasm and mass cell leukemia.

Now, of course, we continue to follow patients from EXPLORER and Pathfinder studies for progression-free survival and overall survival and those data will mature over time. But, currently, we are seeing very durable activity across the board. In theory, you might expect on the AHN patients to have progression of their AHM. But I think in many of these patients actually the dominant problem is still mastocytosis.

Yes. And maybe I'll just add to that because I think it's a really important question and it ties in closely to the consistency with which we put forward that systemic mastocytosis and pralsetinib in both lung and medullary thyroid cancer, as well as PDGFR Alpha during GIST have been priorities because in each of those cases, you will have a monogenic driver and what that is translated into in the data that we've presented to date are really durable responses. And I think that's an important point when you have a clear driver. And as you think about how long could these patients stay on, we've got patients in our systemic mastocytosis trials out 3, 3.5 years at this point, and that is really a transformative-- provides a potential transformative impact for those patients.

And that's probably even more clear when you think about the potential and in indolent systemic mastocytosis, obviously weren't earlier days there, but that is why we were so pleased with the early data in the ISM patient population that we shared in the first quarter of this year, at a low dose of 25 milligrams once per day seen a true impact across all the parameters of clinical efficacy that you often think about for chronic treatment and that's why tie that back to Christy's comments of our patient identification becoming so important, that if you have these clear drivers, you want to identify the patients and then, the focus is on maintaining that durability of activity to really change the lives for the patients.

Your next question comes from Eun Yang from Jefferies.

I have a question on pralsetinib. So, in terms of patient identification to drive commercial success, can you discuss what percent of the eligible non-small cell lung cancer patients are currently seen in the academic versus community settings and how long do you think you would take to fully implement the diagnostic testing in the community setting from the launch? And I have a follow-up question.

Thanks. Sure, this is Christy. So, what we see with lung cancer, certainly, the majority of patient volume would be in the community. And that's true. Generally, I think as you look at some of the larger oncology indications, testing ramp, I think, is going to be very much driven by the availability of effective therapies. So we've seen us -- if we look at other analogous -- you know -- sort of precision medicine trajectories around ALK or [Ralph1], you see a very quick ramp with the availability of a treatment that will drive testing. We have been out actively promoting RET-testing and really helping to educate around that through a precision medicine team as well as through our disease education efforts and of course, we won't be the only ones driving that which I think is actually very healthy and good thing. So, I would anticipate that with the availability of effective treatment, we would see that ramp relatively quickly and probably faster than what we've seen for other precision therapy launches, for example ALK.

And then, follow -- quick follow-up question. I understand that PFS is not required for approval for pralsetinib in non-small cell lung cancer, but your competitor has reported PFS data. So at ASCO, are you also presenting PFS data in addition to response and duration of response data?

Hi, it's Andy. I'll take that. So yes, so in -- first of all, just back up. We just have been thrilled with the evolution of the pralsetinib data in lung cancer and across-the-board thyroid cancer as well, and we'll be showing for the first time the other RET-fusion tumors in a kind of comprehensive way in the other presentation. So certainly, from a regulatory perspective for us or any other compound, single-arm study -- approval based on single-arm studies are driven by response rate and duration of response, not progression-free survival. Certainly though, we will be pulling together much more data than that for the presentation. But again, as I said earlier, I'd really rather as we're getting very close to ask, I'd really rather not comment on what we will have in the abstract presentation and even that still being finalized now.

Your next question comes from Chris Raymond from Piper Sandler.

This is Nicole Gabreski on for Chris. I guess first just on inclusion in the RTO program for pralsetinib and [RET MTC]. For the 2 new molecular entities approved using this pathway, we've seen a pretty quick review and approval process. So I guess, just in light of this, how are you thinking about the competitive setup with Lilly's selpercatinib given the PDUFA date? Is that drug expected in Q3? And then I guess maybe second, just for the advanced SM update in the third quarter. Can you be more descriptive about what we'll see for the topline data from exploring Pathfinder trial? Thanks.

Hi, it's Andy. I'll start out on this. So, in terms of the [RTO] that we've talked about is regarding the medullar thyroid cancer submission. So, we've already submitted the lung and I can say that certainly as with any submission, we have regular interactions with the FDA following the submission. We think that's moving along well but of course timing is something that we'll understand better as the review moves along. In terms of RET-MTC, now we see that as a great opportunity. Of course, the whole concept is that we -- that under RTO sponsors -- can submit datasets ahead of the first written documents and so that allows the FDA to start looking at the materials sooner than they otherwise could and certainly there, the FDA's goal with that program is to expedite the review of programs for products that they think bring particularly -- potentially the highest benefit for patients.

But so, we would hope that that will move things along quickly, but of course, we can't really speak to specific timing yet. And that initiation is on track for this quarter as Jeff mentioned. The advanced SM update -- that will be a broad -- the update that we're planning we'll probably update across the Explore and Pathfinder data in terms of what will be the topline data for the registration for the submission this year. Beyond that, I can't really comment too much on what will be in there. But of course, we'll be talking about response rate the [IWG] activity, will update on durability. I think it'll be the broad general information that we would include safety.

This is Christy maybe, I can -- maybe I'll just chime in just to add a bit on the competitive aspect of your question regarding pralsetinib. If I just kind of take a very big step back, I think the picture here has really evolved very significantly over the course of the last five to six months even. I think we're now in a place where if I start with just the datasets that have come out, I think the clinical differentiation that we're starting to see in terms of our rate of complete responses, which we're hearing from KLOs, is something that they find incredibly compelling; it could be differentiating as well as the thyroid dataset, I think, is really starting to evolve the picture of how people are thinking about the landscape here with these 2 assets. And I think [RTO] and some of the other initiatives and what were -- the speed, I guess and urgency that we're hearing from the FDA, I think speaks to the desire to make this therapy available to patients quickly.

So, while there may still be some time lag between the approval of selpercatinib and pralsetinib, I don't anticipate that it would be significant. And I think particularly in a therapy area like this, with [RET] where you're dealing with a relatively rare mutation, I don't think that difference in terms of approval timing is going to end up being all that material as we think forward on the trajectory of these 2 products.

Your next question comes from Peter Lawson from Barclays.

Just maybe on the initial launch. If you could provide any more color around the line of therapy whether to extend use in non-PDGFRalpha patients? Any details you can provide around the kind of patients taking the drug would be much appreciated.

Sure. So as I alluded to earlier, we've been very pleased just to see the breadth of prescribing and the uptake broadly in GIST. I think it speaks to the unmet need and PDGFRalpha for GIST but also in GIST more broadly. Our focus -- our educational focus has really been on obviously PDGFRalpha for GIST; that's the indication and that's certainly what our team has been focused on identifying patients and driving testing. And as I said earlier, we're certainly seeing healthy utilization there, but we don't have visibility at a level of precision in terms of the exact breakdown of whether somebody has a PDGFRalph limitation or they do not. The ICD-10 code, as I said, is the same; that information is often kind of buried in the clinical history of a patient. It's not straightforward to sort of pull that out from available data.

So, we very much rely on the intelligence that we're hearing from our field in our discussions with KOLs and based on that, I would say that while we're seeing healthy utilization in PDGFR alpha patients, we're also seeing utilization, as I said, outside of that. Line of therapy is even more complicated to tease out, so we know that, again when you get beyond first line, GIST, the use of imatinib, it starts to become challenging and patients tend to move through those treatments relatively quickly. So when we're outside of PDGFR alpha, I think you're probably seeing a mix of later line KIT-driven GIST patients, but again we just do not have perfect insight into that.

And then maybe if you could talk about potential pricing and how we should think about it in systemic mastocytosis given that the release is encouraging long durations you're seeing?

Sure. So I can start and Jeff if you want to add you absolutely can. We are -- I'm not going to speculate on our pricing strategy at this point, it's a little -- it's a little premature, but I start again from thinking about value, just as we did with the PDGFR-alpha-driven GIST with avapritinib. We have a therapy that is really the only therapy to show really profound activity on KIT D816V. We have a therapy -- therapeutic area in systemic mastocytosis where there are significant morbidity and mortality in that patient population, whether it's advanced SM with a shortened life expectancy across the board or even in indolent forms where we're seeing patients hospitalized multiple times a year, threat of anaphylaxis, etcetera.

So what we'll be thinking about those factors and we also have obviously a benchmark approved therapy in advanced systemic mastocytosis in Rydapt, and our launch price of avapritinib was nearly 15% below actually -- that price and I would argue that the value that we could be delivering to patients and the healthcare system with avapritinib will be significantly higher than Rydapt and so we'll be thinking about all of those things and as we go forward, and of course the most important thing from Blueprint perspective is to really prioritize patient access and make sure that our pricing strategy enables our patients to gain access to the drug and to stay on it.

You have a follow-up question from Dane Leone from James -- Raymond James.

Just had 2 quick questions that came in from some other people. Jeff, can you just give us the qualification of where you're thinking about potential partnering on the RET program? I know I ask you this all the time, but I think there were some comments earlier in the Q&A that might have confused some people. So can you just clarify what you're currently thinking about? Whether you would partner program in the US or ex-US or not partner at all?

Sure. So I'm not sure about which piece was confusing, but I think it's a direct enough question, and I'll just take it from a high level perspective. So, partnering strategy for us has never really varied that -- our goal is to bring these medicines directly to patients that we think that's the way to drive long-term value. But that said, we're also constantly evaluating partnering opportunities and our bar is high there that it's, if we believe a partner can either accelerate or expand our reach, whether it be a geographic reach, or whether it be, we have to -- identifying more patients conducting a wider array of clinical trials, et cetera. We'll evaluate that, but we are certainly planning to bring these therapies forward on our own. And the deals that could be interesting might may range from something that's geographically based or something that's earlier research based, something akin to what we did with Roche previously in the field of cancer immunotherapy or just something that's incredibly compelling for all those reasons.

Okay, great. And then the one follow-up is, I was just asking on any timeline update for BLU-945 or the double-mutant research program. I think people then just kind of asking if you have any incremental thoughts on when those could -- at the clinic or get through an IND?

This is Jeff. I'll take that one as well. As we started laying out at R&D day last year, we continue to be very enthusiastic about a range of preclinical programs that we have ongoing. And as I think about the legs of the stool that will drive long-term value at systemic mastocytosis with avapritinib, with pralsetinib across lung, MTC, and other solid tumors. And then it's the additional programs moving forward whether it be BLU-263, our next-gen KIT inhibitor, or either of our EGFR programs or frankly the Roche collaboration. So, we've guided to the potential for 2 additional development candidates over the course of this year, and I think those are still on track based on work being conducted internally.

In terms of timelines, I talked about this a bit in the opening remarks that we'll look to share more data on the preclinical programs in the second half of this year, both at scientific conferences, but also spent some time elucidating our clinical plans including that for BLU-945. So our goal is that file an IND late this year or early next year, and map for that remains on track, but I think there is more to the research story than any one program.

I would now like to turn the conference back over to Mr. Jeff Albers.

Thank you, operator. And again, thank you all for taking time to join us today and for your continued support of Blueprint Medicines and we look forward to updating you again soon. Stay well and good bye.

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