Blueprint Medicines Corp (BPMC) 2020 Q3 法說會逐字稿

Ladies and gentlemen, thank you for standing by and welcome to the Blueprint Medicines Third Quarter 2020 Earnings Conference Call. (Operator Instructions) Please be advised that today's conference is being recorded. (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, and welcome to Blueprint Medicines Third 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 & Media section of our website at www.blueprintmedicines.com.

Today, on our call, Jeff Albers, our Chief Executive Officer, will discuss Blueprint Medicines' third quarter 2020 business highlights; Christy Rossi, our Chief Commercial Officer, will provide a commercial update; and Mike Landsittel, our Chief Financial Officer, will review our 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 statement 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. It's a pleasure to update you today on the significant progress we've made this past quarter across our entire portfolio. As we've discussed previously, our key areas of strategic focus have been threefold: one, advancing our registrational programs in systemic mastocytosis; two, building our commercial expertise as we launch multiple new products; and three, continuing to strengthen our pipeline with new investigational medicines from our research platform.

During the third quarter, and really, the last month, in particular, we made substantial progress across each of these focus areas, which highlights the strength of our portfolio as a whole and positions us well for continued growth opportunities ahead.

Let me start with our focus on systemic mastocytosis, or SM. As a reminder, SM spans both advanced and nonadvanced forms of the disease, and the medical need across the entire spectrum is significant and urgent. In September, we announced positive top line results from our EXPLORER and PATHFINDER clinical trials of AYVAKIT in patients with advanced SM. The data across both studies were consistent with previously reported results, showing profound reductions in mast cell burden, high overall response and complete remission rates, and durable clinical benefit, including prolonged median overall survival. Importantly, the data also showed an improved safety profile at the 200-milligram once-daily dose, validating our decision to capture additional data at this dose level.

Collectively, the data underscore avapritinib's transformative impact in these patients with advanced SM who are in urgent need of better treatment options. These data will comprise the foundation of our supplemental NDA filing with the FDA for avapritinib in advanced SM, which we are compiling rapidly and are on track to submit this quarter.

Nonadvanced or indolent SM remains a top priority for us based on the compelling PIONEER Part 1 data we presented earlier this year. They are again showing the high response rate and favorable safety profile at the 25-milligram, once-per-day dose. We continue to be encouraged to see acceleration of enrollment and expanding enthusiasm from existing investigators as well as from key opinion leaders more broadly.

Turning to our commercial progress. In September, we received FDA approval of GAVRETO for the treatment of adult patients with metastatic RET fusion-positive nonsmall cell lung cancer, a significant milestone for Blueprint and for the lung cancer community. This is our second precision medicine approval this year following the AYVAKIT for PDGFR-alpha-driven GIST and solidifies Blueprint Medicines as a truly integrated biopharmaceutical company.

As Christy will discuss in a moment, we're ramping up the commercial launch of GAVRETO as we also leverage the expertise of Roche, with whom we signed a transformative collaboration for pralsetinib in the third quarter. In addition, we look forward to the potential expansion of the GAVRETO label with an FDA decision anticipated by the first quarter of 2021 for RET-altered thyroid cancers.

Finally, we continue to strengthen our pipeline with new programs emerging from our robust research platform. At the virtual ESMO Congress in September, we presented important preclinical data for BLU-945, our triple mutant inhibitor for treatment-resistant EGFR-driven lung cancer. BLU-945 was specifically designed to potently inhibit the most common on-target resistance mechanisms to osimertinib and first-generation EGFR inhibitors, importantly, while retaining exquisite wild-type and kinome selectivity. This profile has the potential to provide benefit to patients with treatment-resistant disease as well as a safety profile that may enable combination strategies in earlier-treatment lines.

As we announced last month, we plan to advance BLU-945 into the clinic in the first half of 2021. In parallel, we're planning to nominate a complementary double mutant EGFR development candidate by the end of this year. Together, the triple mutant and double mutant compounds have the potential to address a broad population of patients with on-target resistance to other therapies as well as form the basis of a transformative, wholly-owned combination in early-line treatment to prevent the emergence of resistance and enable more durable patient benefit.

Beyond our EGFR programs, we continue to make progress with additional wholly-owned programs as well as through our cancer immunotherapy research collaboration with Roche, and we're excited about the strength of our platform and the opportunities for future growth being generated by our research and discovery teams.

On that front, this quarter, we welcome Dr. Fouad Namouni to Blueprint Medicines as President of Research & Development. Fouad is now leading the R&D organization, overseeing all phases of product development from discovery through global registration. This unified portfolio vision will be increasingly important as we advance the next wave of investigational medicines into the clinic.

Overall, the progress achieved last quarter significantly strengthens our portfolio across all 3 of our key areas of strategic focus. We're now entering the back end of 2020 as a fully integrated company with a range of commercial, development and research programs that leverage efficiencies, balance risk and focused on truly transformative opportunities. And with our strong financial position, we're well positioned to invest in our wholly-owned research platform as well as external innovation that can enable sustained growth and diversification over the long term.

Now let me turn the call over to Christy to discuss our commercial efforts. Christy?

Thanks, Jeff. Good morning, everyone. In many ways, our progress in Q3 highlights the incredible growth opportunity that is in front of us as we head into 2021: growth that will be driven by the ongoing launch of GAVRETO; the expansion of the Blueprint commercial footprint into new geographies; and of course, most significantly, by our efforts to bring avapritinib forward to patients suffering from systemic mastocytosis. Through this lens, our accomplishments in this quarter set the stage for the next phase of Blueprint Medicines' journey as a leading, fully integrated, global precision medicine company.

Let's start with revenue. As Jeff mentioned, with the U.S. approval of GAVRETO and the European Commission approval for AYVAKIT in September, we are now delivering a portfolio of precision therapies to patients globally. Overall, we recognized $6.3 million of product revenue driven primarily by U.S. AYVAKIT sales of $6.1 million. Following FDA approval, GAVRETO became available to patients late in the quarter, and early revenue primarily reflects initial ordering by our select network of independent specialty pharmacies. We look forward to sharing additional metrics from our first full quarter of launch at our Q4 update.

Although it is early, over the past several weeks, as we have had GAVRETO commercially available in the field, I've been pleased with the positive feedback we've received from a variety of stakeholders. Our differentiated clinical profile, which includes deep and durable responses; a predictable and manageable safety profile; and once-daily dosing, has resonated well with health care providers. We've seen early uptake in patients who are being treated with a selective RET inhibitor for the first time as well as in patients who have had safety or tolerability challenges on selpercatinib.

We have also had very positive reaction to the value GAVRETO brings to payers, pharmacists and health systems. We've seen broad payer coverage with an average turnaround time from prescription to therapy start of 4 days on our initial prescriptions and have had some early formulary wins with large community practices.

We have also been working closely with our partners at Genentech as we ramp up the launch. Their field teams, including sales, are now fully trained and actively engaging in close collaboration with our team at a local and regional level to drive biomarker testing, identify RET patients, educate prescribers about GAVRETO and support scientific exchange. The combined team is also ready for our anticipated launch of GAVRETO in RET-positive thyroid cancer, which is currently under review by the FDA under the Real-Time Oncology Review Program.

Turning to AYVAKIT. We are seeing consistent utilization driven by patients with PDGFR-alpha GIST as well as some unpromoted utilization in late-line GIST. Importantly, we are encouraged to see real-world durations continue to trend positively and exceed what we saw in clinical studies. We were also thrilled to receive European Commission approval for AYVAKIT for the treatment of adult patients with unresectable or metastatic GIST harboring the PDGFR-alpha D842V mutation.

As we've discussed previously, our focused commercial launch of avapritinib in Europe will take a rare disease approach, targeting geographical centers of excellence, enabling a foundation for future commercial efforts there, especially in systemic mastocytosis.

And finally, as Jeff also mentioned, we are truly excited about the top line data that we announced in September for avapritinib in advanced SM. As we have deepened our understanding of the opportunity, we see that approximately 1/3 of the 75,000 patients in major markets are already diagnosed, with another 1/3 identifiable but misdiagnosed. These numbers, coupled with the duration of response we just shared in our top line advanced SM data set and the chronic treatment paradigm in nonadvanced disease, make SM a significant commercial opportunity for Blueprint Medicines.

I can't overstate how great the treatment need is for these patients who suffer from debilitating symptoms that significantly impact their lives. We are working with urgency to make avapritinib available commercially to patients living with this devastating disease, first in the U.S. and then globally.

As we move through Q4 and into 2021, we will continue to focus our efforts on these growth drivers that I've outlined. We look forward to advancing the commercial launch of GAVRETO in nonsmall cell lung cancer and eagerly anticipate our approval in thyroid in collaboration with our colleagues at Genentech. We've initiated the launch of AYVAKIT in Germany and look forward to making AYVAKIT commercially available in other countries in Europe, and we'll continue our support of GIST patients in the U.S. And finally and critically, our team is ramping up our launch efforts in support of avapritinib for SM, which we hope will be available to patients in the U.S. next year. The growth ahead of us is truly exciting.

I'll now turn the call over to Mike to discuss financial updates.

Thanks, Christy. Earlier this morning, we reported detailed third quarter 2020 financial results in our press release. For today's call, I'll touch on a few financial highlights from the quarter. We recognized total revenues of $745 million in the third quarter. As Christy mentioned, we are pleased to record $6.3 million of net product revenues, primarily driven by AYVAKIT sales. We also recognized approximately $739 million in collaboration revenue, including the upfront payment, equity purchase premium and milestone payments under our collaboration with Roche for pralsetinib. Cost of sales remained low as we continue to work off commercial inventory that we expensed pre-approval.

Our total operating expenses decreased compared to the prior quarter driven by global R&D cost sharing and U.S. profit sharing under our collaboration with Roche. Looking forward, we expect to see modest quarter-over-quarter operating expense growth as we continue to advance our investments in systemic mastocytosis with avapritinib and BLU-263 as well as advance our discovery portfolio, including our EGFR programs, towards the clinic.

We also anticipate significant increases in noncash stock-based compensation expense for the foreseeable future. With approximately $1.4 billion in cash on hand, we are in the strongest financial position that we have ever been as a company. And looking over the long term, our diverse portfolio and strategic collaborations have the potential to provide multiple meaningful revenue sources, including product sales across multiple geographies and milestone and royalty payments under our 4 major partnerships with Roche, CStone and Ipsen. For example, we anticipate that total milestone and royalty payments from existing collaborations could average approximately $80 million per year over the next few years. We are in a unique position for a company of our size and age, and we look forward to sharing further updates with you as we continue to make progress across our portfolio.

With that, I would now like to turn the call over to the operator for questions. Operator?

(Operator Instructions) Our first question comes from the line of Marc Frahm from Cowen.

Maybe on indolent SM, can you just kind of give us a status update? And when do you expect to complete the enrollment there? I know historically, you've talked about end of this year being possible, but then you also talked about COVID possibly slowing things down. So just kind of where are we there?

Sure. This is Jeff. I'll take that. Yes. So we provided in the prepared statements and release that we'll provide a more detailed update on enrollment at the beginning of 2021. As we talked about previously, certainly the start-up was slowed due to COVID. And now we continue to add more sites, and there's some critical sites that are coming on now. In some cases, they're in regions where cases seem to be lower. But in other cases, some of the sites that -- I can think of one site, in particular, are about to come on, where, unfortunately, the cases seem to be spiking in that region as well. So we want to get a little more color on that. But all the markers of engagement, of patients' willingness to come in are there, so we continue to be really optimistic. But we'll have a better sense of exact timing of when it will be fully enrolled at the beginning of next year.

Our next question comes from the line of Salveen Richter from Goldman Sachs.

This is Andrea on for Salveen. Maybe just as a follow-up to that, would love to hear more about the cadence of other data readouts in the SM portfolio, particularly when we might be able to see additional follow-up for the PATHFINDER trial? And then I have a follow-up.

Sure. So this is Jeff. I'll start. So we haven't guided to the next update. Obviously, we just provided the top line data for advanced SM in September. Obviously, we're in the process of, first and foremost, getting our sNDA file pulled together, but we also certainly intend to provide updates on that data set in a more fulsome nature at a medical conference, but we haven't guided to a specific timing.

Got it. And then just with respect to the collaboration for GAVRETO with Roche, you've spoken about the potential to explore additional indications or combinations. Just wondering how you and Roche are thinking about this right now and when we might see advancement into one of those programs?

Yes. It's Andy. I'll take that. So yes, so we're working very closely with our colleagues over at Roche, and it's been a very collegial relationship. We are in the process of figuring out how to expand and accelerate the development plan. We are already pursuing the tumor-agnostic indications in RET-driven solid tumors that started out actually as an arm in the ARROW study. And really now the focus is on how to move pralsetinib earlier -- into earlier lines of therapy, both as a single agent, but also importantly in combo with other medicines, including some of which would be in the Roche portfolio. And so as we work through these details, we'll -- I think we'll update in the future.

Our next question comes from the line of Ren Benjamin from JMP Securities.

Congrats on all the progress. Can you just -- I know it's early for GAVRETO. But as we follow the trajectory of the Loxo drug, should we be thinking about this ramp kind of like neck and neck with that? Or are there differences that we need to be considering as we think about the commercialization of this product?

And then maybe just related to what's happening in the EU, you mentioned Germany. I jumped on the call a little late. And so I just wanted to get a sense as to how the other country-specific discussions are emerging and how we should view that?

Sure. This is Christy. I can take that. So as I said, we're really excited about the progress that we're seeing with the GAVRETO launch. We've had a lot of great reception to the data as well as the approach that we're taking. If I think about what we've seen from Lilly, I think the biggest thing that we can take from that, so far, is that the opportunity is attractive, right? I mean we clearly know that there's a lot of RET patients out there, and we expect that, that opportunity will continue to grow as more and more patients are identified.

I think the biggest difference is that now there's patients that are available as opposed to one. So you can't extrapolate, obviously, the ramp of an agent, when it's the only agent on the market. But we are certainly going to continue to look to new patient starts, first in lung and then anticipating a thyroid approval on the heels of that. And as we continue to ramp new patient starts, we'll see that flow through. So look forward to having kind of more of that data to share as we provide a Q4 update.

And then on Europe, to address that question as well. So we were thrilled to have that approval and have Blueprint really emerge as a global commercial company now. The German launch is underway. Germany is usually the first market out of the gate, as I know, I'm sure everyone's aware, just given the reimbursement dynamics. We would expect other countries to come online over time. Clearly, the biggest hurdle, as I think everyone is aware, is really securing pricing and reimbursement. And the time lines around that are different by market. So we will -- we are actively engaged in those discussions and look forward to having AYVAKIT commercially available for PDGFR-alpha D842V mutant patients in Europe in the coming months.

Our next question comes from the line of Andrew Berens from SVB Leerink.

Wanted to ask you guys a question regarding the ASM regulatory process which you're about to submit. I know we probably visited this in the past, but I was wondering how you think the FDA will look at your submission, which -- well, you have 2 studies. They're both noncontrolled versus midostaurin, which has a full approval based on a controlled trial.

It's Andy. I'll take that. Yes. So no, we think the data with avapritinib in advanced SM is really transformative for patients and pretty dramatically different what's been seen with midostaurin. So we are actually very confident in the data set based on both EXPLORER and PATHFINDER studies. It's consistent with the discussions we've had with FDA, and we're on track to submit that -- make that sNDA submission in the fourth quarter and are confident that we'll be well received.

I actually want to point out that while midostaurin had a randomized study in leukemia, it was a single-arm data in advanced SM. They got the approval.

Our next question comes from the line of Peter Lawson from Barclays.

Just on BLU-945, I guess the triple and the double EGFR mutant drugs. How should we think about trial designs? And when should we be thinking about initial data for both of those drugs?

Sure. Andy, why don't you take that?

Yes. So maybe I'll just remind everyone that BLU-945, which is our triple mutant EGFR inhibitor, was specifically designed to potently inhibit the most common on-target resistance mutations to both osimertinib and the first-generation EGFR inhibitors while not inhibiting the wild-type kinases -- the wild-type kinase. And really, we think this profile has the opportunity to provide very important benefit to patients, both with treatment-resistant disease but also in combination with other EGFR-directed agents. And I think, as you know, we're also developing a double mutant inhibitor, which is really focused on the resistant situation following front-line osimertinib. And really the -- what's truly exciting about this program is the opportunity to combine these 2 medicines since they'll both be wild-type sparing in the front-line setting, where we can really provide high response rates, prolong disease control, we think, by preventing the emergence of resistance really potentially of all of the known on-target EGFR resistance mechanisms. And so we are planning to advance 945 into the clinic in the first half of 2021, and we expect to nominate a double mutant inhibitor by the end of the year.

And this is Jeff. Just to underscore that, it's been interesting as we share data at the virtual meeting in ESMO, just the engagement from investigators and KOLs has really been exciting on this program. And that I think Andy has summarized that well is first establishing single agent -- the single-agent opportunity but the ability to combine these 2 therapies based on the profile that Andy just laid out and the potential from a safety perspective to move into early lines and really prevent resistance and then maximize durability is something that, internally, there's just growing enthusiasm to move those programs as efficiently and effectively at forward as possible.

Our next question comes from the line of David Lebowitz from Morgan Stanley.

When you look at the initial GAVRETO launch vis-à-vis the recent entry of the Roche partnership, would you say the commercialization effort is fully ramped up to steady state at this point given how closely the partnership was entered? Or do you expect that it will evolve more in the coming months?

Sure. Yes. So as I said, the Roche and Genentech teams have been trained. They are out engaging, and we're certainly working at a local level to collaborate on specific engagements, and of course, at a national level as well to make sure that we're fully utilizing the capabilities of both partners. So I would say the effort is ramped up. Of course, as you go through a launch, one of the critical things is to be nimble and flexible and to adapt as you learn more information. So I'm sure we will do that like we would do with any product, but we've got both teams fully engaged, and we're really excited about that.

This is Jeff. Maybe I'll just add on there that, obviously, it's going to be a continued evolution, too, because we've got the additional thyroid indication coming. And then ultimately, where we really think that the value from these 2 teams working together is going to be realized is in patient identification. So that will be more of a -- sort of a gradual realization of maximizing that opportunity.

With that in mind, understanding that since it is a RET-targeted therapy, and yes, the approval at this point is nonsmall cell, and MTC could come in first quarter. How do you expect physicians will, I guess, deal with people that come up testing positive for RET fusions and RET alterations and other indications at this point?

So our focus right now is certainly on really driving education around nonsmall cell lung and then obviously preparing for thyroid, which we're hopeful will be in the near future, that approval. And so we're ready to go there. We certainly do see RET alterations and other indications as well. That's not a commercial focus. We certainly shared some clinical data in that respect, and I think we may see utilization there. We would anticipate that, but that's not a place that we would be primarily focused from a commercial perspective.

Sure, sure. And then my last question. Certainly, the operating expenditures dropped quite a bit from second quarter in both R&D and SG&A. With the first quarter kind of being in the middle, given the recent partnership, how should we think of -- what we should think of as the right run rate as far as spend level? Going forward, would it be closer to the first quarter, second quarter or third?

Yes. Mike, do you want to take that one?

Yes. Thanks. This is Mike. Yes. So I think what you saw in the third quarter was the impact of the global R&D cost sharing as well as the U.S. cost sharing, profit sharing from the Roche collaboration. And so that caused a reset of kind of where our operating expenses are for Q3. I think going forward, we think we will see modest quarter-over-quarter increases. Maybe not unlike -- I don't want to point to a specific quarter. But the trend that we saw over the past year or so on quarter-on-quarter growth, it just will be resetting from a lower level since we have the impact of the cost and profit sharing.

Our next question comes from the line of Chris Raymond from Piper Sandler.

This is Nicole Gabreski on for Chris. So maybe just one on the pipeline, following up with some of the other questions. So I know you guys have talked about disclosing up to 3 new development candidates this year, and I know one of those is BLU-945, and the second will be the EGFR double mutant candidate. But I guess, I'm just curious, is there a certain venue where we can expect to hear more about the EGFR double mutant candidate as well as the -- potentially more detail around a potential third development candidate?

Sure. This is Jeff. I'll take that. So in terms of venue, we haven't guided to where we'll provide preclinical data. I think you could -- it's safe to assume that's going to happen for the double mutant program in 2021, and we'll sort of reset goals and guidance early in Q1 as we do every year.

In terms of a venue for the third development candidate, I think there are 2 sort of -- the team is pulling all that together. It will likely happen later in the quarter, so I think early Q1 is what -- where we would announce what that program is.

Our next question comes from the line of Dane Leone from Raymond James.

So I guess I'll just jam 2 together here. Firstly, when you're thinking about the market opportunity for avapritinib and SM, ASM and ISM and that's the 75,000 patients you listed as the market opportunity. How are you thinking about the incremental opportunity with BLU-263? Is that more in mast cell activation syndromes like hereditary alpha tryptasemia syndrome, or HATS, as is called?

And then secondly, regarding BLU-945, maybe you could put some more context in terms of osimertinib moving now to adjuvant and how you would think about running the study. And then just basically, what's the checklist to do to actually get that study started in the first half of the year from a regulatory and clinical site standpoint?

So Christy, why don't you take the first question? And then I'll probably pass it over to Andy for the second question.

Sure. So we are moving avapritinib forward obviously very rapidly in ISM, and we're very excited about the data that's emerging there in PIONEER.

BLU-263, I think about really as an opportunity to sort of solidify and expand our emerging franchise in mast cell disorders. We're thinking about that first for ISM as well. And there, I think the potential is as the profile emerges to really optimize labeling, dosing and maybe to be able to penetrate even more broadly into the indolent opportunity, and so we're excited about that.

And then we are also investigating BLU-263, as we said before, in other mast cell disorders and really feel like we can optimize the profile there for a group of diseases that really require our chronic lifelong treatment. So we'll be moving both of those forward, and I will turn it to Andy for...

So maybe I'll take your second first, so steps to getting 945 into the clinic. We're just working on the components and final nonclinical tox and other work necessary for the IND. And of course, we'll submit the IND and be on track to begin that study in the first half of next year. I think there's nothing specific or unusual that's going on there.

And osimertinib moving to adjuvant, I think is actually -- I think offers a pretty interesting opportunity, in fact, for BLU-945. Because as we talk to some of the lung cancer experts that we interact with, there's definitely a thinking that as osi goes to adjuvant in those patients when they -- as they progress for their initial metastatic progression that a lot of people will go back now to use a first-generation EGFR inhibitor. And so that gets you actually back to the triple mutant again with the drugs in the opposite order. So we think that could be an opportunity for BLU-945 and the study.

Yes. And maybe then I'll merge those 2 questions together and sort of at a 30,000-foot level. Early on when we were building Blueprint Medicines, we often talked about playing to where the puck will go rather than where it is currently, and I think that really underscores why we're so confident today in our position is that if you look at how the year has unfolded as we get into the back half of this year on the osimertinib piece of moving into earlier lines, the evolution of sort of the treatment paradigm for EGFR-driven lung cancer. The building out of 2 different programs that will be effective or provide an opportunity, regardless of when and how patients are treated in EGFR, gives us a lot of flexibility from a development perspective.

Similarly following that playbook of osimertinib moving into the adjuvant setting could impact how we think about future RET development for pralsetinib within our Roche collaboration.

And then as you think about systemic mastocytosis, we had clearly articulated that as a priority, and we took the time to really understand and characterize avapritinib. And so seeing the activity we have at 200 milligrams in the advanced form of the disease as well as 25-milligram in the nonadvanced form of the disease gives us a really strong starting point. And then we made investments in 263 to round out from a position of strength. And so there will still be patients where there's need, whether it'd be expanding, as Christy said, in indolent SM or in other mast cell diseases. But if you think about how a portfolio evolves over time, all of that is at play here. And with the strong financial position allows us to continue to invest in the opportunities that provide the greatest potential patient benefit.

Our next question comes from the line of Arlinda Lee from Canaccord.

I have a couple. One on the ASM filing for avapritinib, I'm curious what's gating for that. And then on 263, I missed when you said you were planning to initiate that trial. Also, can you briefly talk about any dimension it was not bring penetrate. But can you also talk about the other design elements that went into 263?

Sure. Andy, do you want to take those, so first the filing on advanced SM and then characteristics of 263?

Yes, yes. So in terms of what's gating for the ISM filing, it's just now getting the documents together. There's actually a fair bit of writing to do and that kind of thing, but all the -- we have all the data in hand. And so we're just doing the final parts of the process to get the filing together. And again, that will go in this year.

263. So the -- in terms of the trial, we're very happy to get that healthy volunteer study started in the first half of the year on track. Despite COVID-19, it remains on track to provide the key data by the end of this year, which is really a dose-determining data for what the appropriate dose or dose range would be for patients with ISM for the first ISM study. We haven't specifically guided to when that first ISM study will start. But obviously, that's a high priority for us.

And Arlinda, as you mentioned, we designed BLU-263 very specifically not to cross the blood-brain barrier, and that's an important distinction from avapritinib. It also has a bit more selectivity on a couple of other fronts. It's on a few other enzymes where we think are potentially -- offer potential benefit, but some of that's hypothetical.

Our next question comes from the line of Michael Schmidt from Guggenheim.

I just had one on AYVAKIT. Your sales in the third quarter suggests about 100 patients treated. Can you confirm that? And I think you mentioned some nonpromoted use. Could you maybe quantify that a little bit? How much of that is in just more broadly versus potentially in ASM patients already at this point?

Sure. I'll take that. So I'm not going to get into details on exactly how many patients we've treated. Obviously, the math there is complex. You've got patients continuing to start. We have shorter durations when we see late-line KIT-driven GIST patients on therapy. We are seeing quite long durations when you see PDGFR-alpha patients. But overall, we're pleased to continue to see revenue growth in GIST and very happy to have that option available for patients.

In terms of quantifying the exact mix, as I said before, it's challenging to do that. We can try to make estimates, but we're relying primarily on feedback we may get from prescribers and patients. The coding for these patients is the same, and so we're not in a position to be able to say with certainty. We just know that we continue to see utilization. Clearly, we have a guidelines listing in late-line GIST, and we know that the unmet need in those patients is still very high.

Understood. And then, Christy with GAVRETO now on the market. I realize it's only been a few weeks, but just wondering what the initial feedback has been from lung cancer physicians and with 2 TKIs now available. And maybe what has feedback been around some of the differentiating side effects of those 2 drugs, specifically the absence of QTc prolongation and then some of the potential differences in efficacy and dosing frequencies?

Sure. Yes. So I think the feedback has been, as I said, very, very positive. I think, first of all, the community is thrilled to have effective therapies available for these patients, right, that have not had treatments available to date. I think we're going to see utilization of both agents. I think GAVRETO is viewed to be very highly effective. I think certainly, the safety, as you mentioned, is probably where you see maybe more difference. And again, I think the idea of side effects that are sort of in the wheelhouse of prescribing oncologists, that's something that I think is comforting versus some things that may just require some different management approach. I mean QTc is one. Hypersensitivity is another, again, that I think we've continued to hear about in the real world. And it's early days, I think, with both of these agents, and so I think what we have to remember is that the clinical profile will continue to emerge over time, both from an efficacy and a safety perspective, as you start to get that real-world utilization.

The last piece, I think, that we've been very happy to get feedback around is sort of the nonclinical aspects of the profile that are also very important, right? So once daily dosing, which, again, oncologists like everybody else. In fact, we had one person say to us, "I'm an oncologist, but I still don't like to get called back around issues." And so simplicity is important. And the approach that we've taken, which is really, again, prioritized practices and dispensing pharmacies being able to retain control and treatment of their patients has been very well received.

Our next question comes from the line of David Nierengeren (sic) [David Nierengarten] from Wedbush Securities.

That's a new interpretation of the name. I'll -- just one question. You mentioned a couple of formulary wins, I believe, in the prepared remarks. I was curious as to the dynamics on formularies and payers. Are they preferring one agent over the other that -- sorry, this is regarding GAVRETO. Or is it equal or -- basically, that's it. Are they -- is there a preference for one over the other on the formularies? Or are they treated equally?

Sure. So it was interesting when you say the word formulary in the space, it can have many different connotations, right? There's different aspects of formulary choice at a payer level but also certainly at health system levels within community group practices, et cetera, that will drive selection of one therapy over another. With payers, what we've seen is broad access. I think both agents, frankly, will be covered by most payers. That's what we would expect. And certainly, we support that. We want patients to have access to both therapies.

I think at a practice level, given some of the dynamics and certainly more of a focus on quality and cost measures that are now becoming very important in oncology, the pricing strategy that we've taken, I think, has been incredibly well received, and there's clear value there that may drive preferential utilization of GAVRETO. And again, the approach around distribution and et cetera, that really, again, allows pharmacies that are integrated into community practices who want to be able to care for their patients and often are fighting broader health care system dynamics that prevent them from being able to do that have been very happy with the approach that we've taken. So that is another place where we're seeing some preference being driven.

At this time, I am showing no further questions. I would like to turn the call back over to Jeff Albers for closing remarks.

Thanks, operator, and thanks again for everyone for taking time with us and their continued support of Blueprint Medicines. Obviously, this is a really rewarding quarter to reflect on, and I'm appreciative to all the employees at Blueprint Medicines and the focus they've kept during this difficult time. And I also have been thinking about, looking forward, in a lot of ways, we feel like we're just getting started. We're in a really strong position now. We know we have to continue to execute over the remainder of the year, and then we continue to be really encouraged by the setup as we look forward and based on the investigational medicines we continue to work on preclinically, the regulatory feedback and processes that we're undertaking as well as now adding in the commercial component. So look forward to providing future updates. Thanks a lot. Have a great day.

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