Blueprint Medicines - Earnings Call - Q1 2022
May 3, 2022
Transcript
Speaker 0
Good morning. My name is Juan, and I will be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicines First Quarter twenty twenty two Financial Results Conference Call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session.
Thank you. I would now like to turn the call over to your host, Gina Cohen from Blueprint Medicines. Gina, you may begin your conference.
Speaker 1
Thank you, Juan. Good morning, everyone, and welcome to Blueprint Medicines first quarter twenty twenty two 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 we'll be reviewing today by going to the Investors section of our website at www.blueprintmedicines.com. Today on our call, Kate Havilland, our Chief Executive Officer, will discuss Blueprint Medicines pillars for growth through 2023.
Christy Rossi, our chief operating officer, will provide an advanced SM launch update. Selena Lee, our chief commercial officer, will provide a non advanced SM market opportunity update. Becker Hughes, Chief Medical Officer, will review our recent clinical progress and highlight upcoming milestones across our growing portfolio. And Mike Lansidol, our Chief Financial Officer, will review our first quarter twenty twenty two financial results. Percy Carter, our Chief Scientific Officer, is also joining our call and will be available for Q and 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 SEC filings. 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, Kate Havilland.
Speaker 2
Thank you, Jenna, and good morning, everyone. We appreciate you joining the call today. At Blueprint, we are clear in our goal to be the leading precision medicine company. Building on this quarter's success, the next twelve to eighteen months will be unprecedented for us as we execute on multiple milestones, value creation across all aspects of our business. Blueprint has an incredibly unique profile with a diversity of significant growth drivers and a strong balance sheet that will enable us to outperform the sector over time as we expand global commercial execution, progress our clinical stage portfolio and drive innovation through our leading precision medicine discovery platform.
The first quarter of this year was marked by a number of important milestones across our business. We continued to solidify AYVAKIT as the standard of care in advanced systemic mastocytosis or SM in The U. S. And we closed the quarter with the European Commission approval of AYVAKIT and advanced SM. Our European launch is now underway.
The global launch of AYVAKIT and ADVANCE SM is building a strong real world value proposition and an important foundation of relationships as we prepare for the top line data from our registration enabling PIONEER trial and non advanced SM late in the summer. AYVAKIT has the potential to be the first and only treatment approved for non advanced SM. With positive results from the PIONEER study, we will have developed a comprehensive body of clinical evidence demonstrating the remarkable efficacy and profound benefits to SM patients across the spectrum of disease while also driving significant near term growth for BLUEPRINT. Another highlight from the first quarter were the data we presented at the AACR annual meeting across our EGFR and CDK2 franchises. It is early days for these programs, but there are many reasons for us to be encouraged about the differentiation of our investigational therapies and their prospects to address major medical needs in difficult to treat and prevalent cancers.
As our strength this past quarter demonstrates, we are well on our way of delivering on the goals we have set for ourselves this year while also building a foundation to drive value well beyond 2022. If you fast forward, for instance, the end of twenty twenty three, we expect to be launching AYVAKIT in non advanced SM, engaging regulatory authorities on registration plans for our EGFR and CDK2 development programs and expanding our pipeline with new programs in areas of significant medical need. With that, let me turn the call over to Kristi to discuss the progress we have made on the AYVAKIT launch in ADVANCE SM. Kristi?
Speaker 3
Thanks, Kate. Good morning, everyone. In the first quarter, we continue to build momentum in our ongoing launch of AYVAKIT and AVANCE SM, generating net product revenue of $23,800,000 The AVANCE SM indication contributed the majority of this revenue and we anticipate that it will be the primary driver of AYVAKIT revenue growth over the course of the year. We are reaffirming our guidance of $115,000,000 to $130,000,000 in AYVAKIT revenue in 2022 based on the strength of the ongoing US launch, which I will speak about in a minute, and our recent approval in Europe where we received a marketing authorization in ADVANCE SM on March 25. AYVAKIT is now the first approved disease modifying precision therapy in the European Union designed to selectively target KITC816V, the primary driver of FM.
Within one week of approval, the first patient was treated in Germany where AYVAKIT is now reimbursed for its expanded indication. And we are looking forward to bringing AYVAKIT to patients in additional EU countries as we work through country specific reimbursement processes. Now let's turn to The U. S, which contributed $21,300,000 in revenue this quarter. We expect revenue growth to continue through the year driven by two key factors, increasing new patient starts as we reach more prescribers and support more patients and extended durations of therapy as we impact patients earlier in their disease.
Our continued launch execution is driving positive momentum across both of these important dimensions. The launch of AYVAKIT has fundamentally changed the treatment paradigm in ADVANCED FM, driving significant market growth and setting a new standard of care. AYVAKIT is now the treatment of choice for approximately seventy percent of all advanced FM patients starting on or switching to a new therapy. Since the launch of AYVAKIT, the percent of AdvanciFEM patients who are being treated for their disease has grown by approximately forty percent as healthcare providers are now choosing to intervene where historically they may have chosen to watch and wait. We know there is still significant room for growth as many patients remain untreated.
At an upcoming medical meeting, we will be sharing new real world evidence supporting AYVAKIT's impact on overall survival in advanced SM, which we believe will further catalyze urgency to treat. The momentum we are seeing in new patient starts is driven by our growing prescriber base. In q one, we activated approximately 65 new accounts, particularly impressive given the impact of Omicron early in the quarter. The strong base of AYVAKIT experience we are establishing is characterized by breadth in the community setting and depth in the academic setting. We have had strong penetration into academic centers of excellence.
And as our prescriber base continues to broaden, the majority of new accounts are coming from the community where half or more of AdvanceSysM patients are cared for. This suggests that we are effectively reaching these patients where they are presenting for care and also that providers who may historically have been less comfortable treating SM are now motivated to treat patients with AYVAKIT. We are also seeing patients benefiting from extended treatment duration duration as we continue to progress the launch. Our estimated duration of therapy for AYVAKIT and Avance SM is trending towards eighteen months. In our clinical studies, patients stayed on therapy for an average of two or more years, some for far longer than that.
And we expect duration of therapy to continue to extend as we are able to reach an impact patient earlier in the course of their disease when they can derive the most benefit from AYVAKIT. This extended treatment duration we are seeing across academic and community settings in the real world also confirms that a broad range of prescribers are comfortable managing their patients with AYVAKIT. The insights that we are gaining throughout this launch cement my belief in the growing strength of our integrated organization and the power of the leadership position we have built in SM. With that, I'll turn the call over to Doctor. Falena Lee who was recently appointed as our Chief Commercial Officer and now oversees our global commercial strategy and U.
S. Commercial organization to discuss the medical need and market opportunity we see for non advanced SM.
Speaker 1
Thanks, Christy, and hello everyone. I've been a part of AYVAKIT's development from discovery through commercialization. As I step into the role of CCO, I am honored to lead our team and deliver on the promise of this important therapy for patients living with SM. Our strong advanced SM launch trajectory, which Christy spoke to, and our growing understanding of the non advanced SM market reinforce our belief that SM is a potential blockbuster opportunity for AYVAKIT. Symptoms of non advanced SM are debilitating and arise unpredictably disrupting patients' ability to go to work and spend time with their families.
Patients can experience a range of symptoms such as uncontrolled anaphylaxis, extreme fatigue, diarrhea, skin lesions, and brain fog. Patients share that the symptom burden of non advanced SM leaves them feeling depressed, isolated, and fearful that the disease will worsen. There are no approved therapies for non advanced SM today. Current treatment options are inadequate and fail to address the underlying driver of disease. The polypharmacy burden for non advanced SM patients is significant.
Seventy five percent of patients have reported taking at least four or more classes of therapies to manage their disease. And these interventions are woefully inadequate. Greater than eighty percent of patients still report limitations in their work or daily activities. And sixty four percent share that they avoid leaving their home due to their SM. Another study showed eighty three percent of patients expressed frustration that current treatments do not address the root cause of disease.
Together with the SM community, our efforts to raise disease awareness and accelerate time to diagnosis are yielding a tangible impact. A fifty four percent growth in the number of SM patients observed in U. S. Claims since the launch of AYVAKIT in January 2020. We now see more 15,000 unique diagnosed SM patients in claims data and most of these patients have non advanced SM.
Speaker 3
We expect this
Speaker 1
population to continue to grow with our focus on disease education for healthcare providers, patients and caregivers and our emphasis on high sensitivity blood based testing for KIT VA16V. In March, we launched a new disease awareness campaign for patients with SM called It's Something. Within the first week of launch, the website had more than 6,000 unique visitors, including many undiagnosed patients seeking information and a path to diagnosis. An educated patient is a catalyst for diagnosis and treatment. As we await the PIONEER data later this summer, we're confident there are many highly engaged SM patients, both diagnosed and not yet diagnosed, who are searching for better options to manage their disease.
With that, I'll turn the call over to Becker to review our R and D progress.
Speaker 4
Thank you, Felina, and good morning, everyone. Today, I'll provide updates in two areas, expectations for PIONEER, our registrational study in non advanced SM and our anticipated clinical data milestones over the next year. Let's start with PIONEER, which has two parts. Part one was designed to select the optimal dose and demonstrate proof of concept to ensure a profound reduction of symptoms and show tolerability for long term dosing. We saw the AYVAKIT demonstrated deep reductions of clinical symptoms at all doses.
A rapid reduction in mast cell burden, KIT D816V allele burden, serum triptase and positively impacted patient quality of life. These data from Part one were the basis for AYVAKIT's breakthrough therapy designation in non advanced SM. Part two was designed to enable registration by demonstrating response rate superiority of AYVAKIT versus placebo as assessed by total symptom score or TSF. TSF is measured using the ISM symptom assessment form or ISM SAS. This is a patient reported symptom assessment tool that we developed in collaboration with the SM community and regulatory authorities over the last six years.
We believe that a roughly thirty percent difference in the proportion of responders with AYVAKIT versus placebo would be a clinically meaningful result that would be supportive of both regulatory filings and drive real world utilization in non advanced testing. We've also heard consistently from healthcare providers and patients that any reduction in symptom burden, including the most burdensome symptom, will be viewed as clinically meaningful and potentially transformative for patients. We'll also be looking at a range of additional outcome measures, including mast cell burden and other measures of quality of life. Across this constellation of outcomes, we expect to see consistent impact with AYVAKIT treatment. We remain on track to report top line data in late summer of twenty twenty two.
And pending results, we plan to submit an sNDA to the FDA by the end of twenty twenty two. Now let's shift gears to talk about the additional clinical data milestones that will drive significant growth for BLUEPRINT. Over the next year, BLUEPRINT will be defining and executing registration enabling strategies across our pipeline of investigational medicines. In addition to the PIONEER top line data in late summer of this year, we plan to report multiple clinical proof of concept datasets across our EGFR and CDK2 programs into early next year, including combination data that will enable us to expand into earlier lines of treatment and increasing numbers of patients. By the end of this year, we expect to have early clinical data for BLU-nine forty five in combination with osimertinib and initial data for BLU-seven zero one in EGFR mutant lung cancer.
In addition, we expect to have initial clinical data for BLU-four fifty one in the 2023 in EGFR Exon twenty mutant lung cancer. We will continue to initiate combination cohorts in progressively earlier lines of treatment and look forward to seeing early data from some of those cohorts in 2023. I'm equally pleased about the speed with which we're advancing towards clinical proof of concept for BLU-two cancers, with our first clinical data expected in the first half of twenty twenty three. Importantly, we plan to explore both monotherapy and combination dose escalation in Part one of VALA and accelerate development across multiple populations. This includes previously treated estrogen receptor positive breast cancer patients as well as frontline patients in combination with other agents, including CDK foursix inhibitors and hormonal therapy.
Also, in patients with CCNE1 amplified tumors including subsets of ovarian and endometrial cancer where we plan to explore biomarker driven strategies with our CDK2 inhibitor alone and in combination with standard of care. As a leading precision medicine biotechnology company, we continue to build on our successful and strong R and D engine by bringing additional transformative opportunities to patients with severe diseases, including our targeted protein degradation work currently underway. We look forward to sharing more on our vision at our planned R and D day in the second half of the year. With that, I'll turn the call over to Mike to review our financial updates.
Speaker 5
Thanks, Becker. Earlier this morning, we reported detailed financial results in our press release. For today's call, I'll touch on a few highlights from the quarter. Total revenues were $62,700,000 for the quarter, including $23,800,000 in net product sales of AYVAKIT and $38,900,000 in collaboration revenue. This represents approximately 164% growth in AYVAKIT product sales from the same period last year.
As Kristi noted, we saw solid growth in Advanced SM, which is and will continue to be our major driver of AYVAKIT product revenue, given our strong momentum with The U. S. Launch and recent approval in Europe. In addition, in the first quarter, we recognized a $30,000,000 development milestone payment from Clementia related to BLU-seven eighty two, our out licensed ALK2 inhibitor in development for the rare bone disease, fibrodysplasia ossificans progressiva. Turning to expenses.
Our total costs and operating expenses for the first quarter were $168,500,000 including $23,400,000 of noncash stock based compensation expense. This reflects moderate planned growth in R and D expenses related to the initiation of four new clinical trials across our EGFR and CDK2 programs. These new clinical programs will drive the next wave of value inflection points for BLUEPRINT and highlight our ability to sustain meaningful innovation through our best in class discovery platform. As Christy noted, we are reiterating our previous revenue guidance for 2022. This includes $180,000,000 revenues and $115,000,000 to $130,000,000 in AYVAKIT net product revenues.
In addition to our diverse revenue drivers, we are in an exceptionally strong position with nearly $900,000,000 in cash on our balance sheet. And we are now entering a period where we expect our revenue growth rate to exceed our expense growth, moderating our cash burn and setting the stage for us to become a self sustaining company. Earlier in the call, Kate and Becker outlined the significant potential we are unlocking as we invest in a breadth of exciting pipeline and discovery plans over the next twelve to eighteen months, which we anticipate will lead to continued modest growth in R and D expenses. Our strong cash position and disciplined approach to capital allocation will ensure that we are well positioned to execute on these opportunities while driving towards sustainable profile. With that, I'll now turn the call back over to the operator for any questions.
Operator?
Speaker 0
Thank you. And the first question comes from the line of Mark Suham from Cowen. Please mark your line is now open.
Speaker 6
Thank you for taking my question and congratulations on a strong quarter. Victor, I I think you discussed part one results that showed a 60% response rate on the in the twenty five milligram arm. And I was wondering if you could remind us what was the rate was in the higher dose of the fifty and a hundred milligram doses. And also looking forward to the to the the part two results beyond response rate, are are there any other any components of the TSS that you think are important commercially and will drive patient use? Thank you.
Speaker 4
Hi, Mark. So with respect to the part one data, we saw consistent response rates across all three arms. You'll remember it was 10 patients per arm, and we saw both consistent rates and depth of response across all three doses. With respect to part two, remember the TSS score is not a clinical tool. This is a clinical trials tool, so it's not something that providers will be using in the field.
However, what it does is it breaks down the patient's experience into a number of different measures of potential improvement. So patients tend to have a number of different organ systems where the disease manifests, so really, really a myriad of symptoms with often one that's most bothersome, but it's rarely just one symptom, particularly at this moderate to severe level. And so I think that people will pay attention both to the overall score, but they'll be particularly interested, depending on the types of patients that they're treating, on specific domains. You can imagine a patient who's got 20 to 30 episodes of diarrhea a day being particularly interested in those patients that have diarrhea and the improvement there. And then patients who have a more global manifestation where they're just not able to get out of bed, go to work, or they're really worried about recurrent anaphylaxis, looking at the skin score fatigue and and the ability to alter a number of different symptoms and decrease frequency of a number of different types of manifestations would speak to those providers and patients as well.
Speaker 6
Thank you. That that's very helpful. And if I can one more question for for Christie. I think you mentioned the 20 70% of market share for the new prescriptions. I was wondering what what what market share has Evoquet captured for the overall advances end market or potential market?
Speaker 3
Sure. So, you you know, as I said, we're we're really pleased to see AYVAKIT very quickly, you know, through this launch becoming the standard of care for treatment. And there's really two aspects to kind of overall treatment rates that we look at. So one is market Right? So this is a market where historically a lot of patients unfortunately have not received SM directed therapy.
So the launch of AYVAKIT has grown the market by about 40%. And then we're looking at, of course, how many patients are actually being treated with AYVAKIT as opposed to other other therapies, and that's where we're seeing now seventy percent of of all new initiations going on AYVAKIT. Our overall share is trailing that, you know, given where we are in the launch. And, actually, you know, that's that's a good thing when your new your new start share is above your total share. It's a signal that, you know, you're growing.
And so we're continuing to see ava very rapidly. I think we're kind of close to 50% of all patients now being on ava care, and we expect that that number continue to grow as we progress the launch.
Speaker 6
Okay. Thank you. Appreciate that, and congratulations again.
Speaker 0
Thank you. Our next question comes from the line of Dane Leone from Raymond James. Please, Dane, your line is now open.
Speaker 7
Hi, thank you for taking the questions and congratulations on all the progress over the course of the quarter. Two for me if I may. Firstly, could you maybe provide a little bit more commentary about some questions then around what you said around eighteen months expected of treatment duration? Could you maybe contextualize that given that the drug hasn't been commercially launched for eighteen months now? Just kind of how you're doing that math and what you're seeing play out in the clinic.
And then could you maybe comment on what you're seeing in the second quarter? I think everyone expected the launch in ASM to experience the normal issue that most drug companies have in the first quarter of the year. But any commentary on maybe how things are now progressing, you know, April to May on some of the key metrics that you talked about would be super helpful. And then finally, could you just maybe level set expectations for the clinical updates in the back half of the year for $9,457,014.51? I think investors are always trying to figure out for these early data sets, is this really an ORR data set where we're going to establish something like an RP2D?
Or are we going to be looking more for the safety signals and emergent, signs of clinical effect at doses reported? Thank you.
Speaker 2
Okay. Thanks, Dana. So Christy, do you want to take the eighteen months and talk a little bit about the you've got a quarter over quarter growth. And Becker, will you take the clinical updates and what to expect?
Speaker 3
Sure. So thanks for the question, Dane. So duration is obviously one of the two key sort of, you know, drivers that we're watching very closely in terms of, you know, the trajectory of the overall launch. And, you know, the context here is that we know that AYVAKIT patients can have quite long treatment durations and advanced with them. In our clinical studies, we saw treatment durations of two plus years.
And so our expectation is that over time, as we continue to, you know, find patients closer to a point of diagnosis, you know, we'll continue to extend those treatment durations in a real world setting. You're absolutely right. We have not been on the market for for, you know, eighteen months. And so at this point, we are, you know, essentially looking at curves and comparing sort of, you know, the curves that we see around duration of therapy in the real world, to what we saw in our clinical studies. And so we're estimating, how we're trending in terms of the median and duration of therapy.
We'll continue to take a look at that over time. One positive, you know, note there is that we're even seeing that patients who have started, more recently in the launch seem to be trending even more favorably. And I think, again, that reinforces this expectation that we have, around being able to impact patients who are not as sick as we move through the launch and see those, durations extend. Regarding the quarter over quarter dynamics, you know, we certainly this is our first, you know, SM for q one that we've gone through and, had an expectation that we would see many of the dynamics that, you know, certainly other oncology products and and more broadly we see in in, pharma around q one in The US where, you know, revenue can be impacted by factors around gross to net compliance as well as some other factors. We were, you know, pleased to see really not a lot of impact through the quarter there.
Certainly, we had some minimal impact on gross to net because of co pays, etcetera. But some of the other factors that often impact the first quarter, you know, did not impact the advocate as much as we thought they may. And I attribute, you know, some of our excellent patient support services and distribution programs to muting that impact. So as we go into q two, you know, we're we're we continue to be really happy with the trends around new patient starts and treatment duration, and we expect, really more steady growth as we go through the year, in line with the overall revenue guidance that we gave.
Speaker 2
Hey, Becca. Can you And,
Speaker 3
wanna take the question? Yeah. Yeah.
Speaker 4
So, Dane, with respect to our EGFR mutant lung cancer program, just a reminder, that what we're what we're trying to do is make sure that we bring everyone along with us on this journey to understand our compounds better and the disease better. EGFR mutant lung cancer has become a disease of combinations as is often the case as we get better and better at treating these tumors, these tumors find more mechanisms of resistance and finding the right combination partners is really important. Nine forty five is our, inhibitor that has a very high window to wild type, so we see it as a backbone for future treatment. It has activity, not only in preclinical models where there's T790M, but also in the LR mutant, population of cells. So we have presented at AACR initial data showing that this compound behaves exactly as we expected that it would with very little toxicity, really not even much of a hint of EGFR wild type toxicity and a rapid reduction in the circulating tumor DNA alleles that it's designed to inhibit.
As we move into the next phase of this study and we start combining with osimertinib, this is a, strategy to cover a more heterogeneous tumor population and drive deeper remissions. We will be in the dose finding phase of this osimertinib combination over the next portion of the study. And similar to what we did at AACR, we expect to continue to update the community on both the combination and the single agent activity. With respect to seven zero one, which is our brain penetrant, inhibitor, this one has really high potency on the driver mutation and then activity in central nervous system. It really is class defining with respect to penetration of the central nervous system.
We are in escalation right now and we, similar to the way that we presented data for September, plan to bring people along and help you understand circulating tumor DNA and the early, evidence of activity. And then our strategy and early data as we combined in 2023, both with September and with osimertinib in that program. And then BLUE four five one is a more straightforward biology where the tumors are driven by a single driver mutation, the exon twenty mutation. We are in escalation now, and we expect expect to be in escalation for for most of the rest of the year. And but in that case, we might expect a more straightforward evidence of responses we've seen with some of the other EGFR twenty inhibitors in the clinic.
And so as we have a good body of data, that's what we'll be updating in that program.
Speaker 0
Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Please, Salveen, your line is now open.
Speaker 8
Hey, good morning and thanks for taking our question. This is Elizabeth on for Salveen. Just maybe if you could provide some color on the sustainability of the growth drivers underpinning the AYVA kit sales, you know, this year and then looking forward. Thank you.
Speaker 3
Christie, you wanna take that? So this is yeah. Thanks for the question. So, you know, as we we shared, we're really looking at at a very simple level kind of two two key drivers around the AYVAKIT launch, new patient starts, and duration of therapy. And, you know, I think that both of those are trending in a way that really sets us up nicely for steady growth as we go through the year.
On the new patient start front, as you mentioned, we continue to have a lot of headroom. Many Ademtsysm patients are not receiving a therapy for their disease, and AYVAKIT has very quickly grown to become the standard of care as new patients are initiating therapy. And so we're continuing to focus on broadening our base of prescribers, going out and identifying patients closer to diagnosis, continue to see a lot of room to grow. And then as I mentioned, you know, we're pleased to see the trends and duration that we're seeing already. I think we have some room to continue to improve there as we go through the year, but in general, you know, very happy to see the patients look to be staying on for extended periods of time.
And as we move through the year, that will help us also drive ongoing revenue growth. Reiterating the overall guidance and are looking to see more steady quarter on quarter growth as we go through the year.
Speaker 2
And just to add to it, one thought to that is that, as Chrissy mentioned in her prepared remarks, SM has been a condition where physicians have been really in a wait and watch for quite a bit of time. Right? They just haven't had directed therapies that that have been, you know, very impactful to patients. And so I think the enthusiasm we're also getting from from our the physicians that we're talking to about the clinical aspects, Their early experiences with AYVAKIT has been really promising. And as Christy mentioned as well, we at a near kind of upcoming medical conference, we plan to also present data based on some real world evidence on showing improved survival in patients who are receiving AYVAKIT relative to standard of care and other therapies, which I think is gonna be incredibly compelling.
And and so, you know, you add kind of the early experience plus this kind of additional data as we see the benefits of AYVAKIT, you know, turning to really a life extending type of therapy, I think we'll very much continue to catalyze, physicians out of this wait and watch, the kind of the, you know, attitude they've been in previously.
Speaker 0
Thank you. The next question comes from the line of Rene Benjamin from GMP Securities. Please, Rene, your line is now open.
Speaker 9
Thanks for taking the questions and congrats on the quarter. Can we get a little bit more color on the European launch? I guess in particular, you know, how that's going to build out over time? And should we be thinking about, you know, maybe a year from now, the revenues or the uptake, you know, kind of mirroring what's happening here in The US? And then just kind of related to that, the I'm pretty intrigued by The US claims data that you guys are are showing.
How much granularity do you have with that that data? And and can you do you know which sites per se might be, you know, having a lot of the non advanced SM patients so that once the launch takes place, can actively target those sites? Thank you.
Speaker 2
Thanks, Randy, for the question. And Christy, if you could take the question on the EU launch dynamics and then Selena can answer the question about the claims data.
Speaker 3
Great. So we were really pleased to to see the European approval come through several weeks ago. And, you know, as I mentioned on the call, have already launched in Germany and and see, you know, a lot of interest coming from German health care providers and patients already out of the gate, which is which is really encouraging. The overall dynamics in Europe, think, will be very similar to The US. Certainly, the epidemiology is similar.
And, you know, in fact, I would argue that some European markets, and Germany is is one of them, may be a bit more organized in their treatment of of SM patients, through the efforts of, the European, Cooperative Network around treatment of SM or ECNM. So we're excited to see this roll out. You know, we expect in terms of the cadence of the launch, Germany is obviously often the first market, out of the gate in Europe given the reimbursement dynamics and because we already have a reimbursed price there. We expect Europe or Germany to really be kind of the primary driver in the immediate term. We will have additional European markets coming online as we move through the year and then certainly into next year as we look through those reimbursement processes.
But generally speaking, would expect kind of the overall cadence of the launch to not look very different and, you know, expect AYVAKIT to become the standard of care for treatment of advanced system in Europe over time as well. Speaking Absolutely, to The U. S. Claims
Speaker 1
Christy. So Reni, regarding The U. S. Claims data, we have visibility into a number of factors in our patients and provider claims. We can see that the majority, in fact, of these patients have non advanced SM.
And in fact, these patients we think are on the more moderate to severe spectrum of disease in terms of how they're engaging with the healthcare system. We have visibility into the fact that it's mostly medical oncologists and allergists immunologists who are the most involved in the diagnosis and overall management of these patients, with other specialties such as dermatology and GI more focused on the symptom management of these patients. And to your question, we do have some visibility into who is treating and managing these patients and are very focused on efforts to raise disease awareness among these providers.
Speaker 9
Perfect. Thanks for taking the question.
Speaker 0
Thank you. Our next question comes from the line of Brad Canino from Stifel. Please, Brad, your line is now open.
Speaker 10
Good morning and congrats on the quarter. Now that we're closer to the ISM readout, can you outline the degree of data disclosure you expect to put in the top line press release versus what data points you might save for a medical conference? And then I want to ask on the nine forty five plus OC combination, specifically where you're focused on the LR subgroup, what doses are you going to start at? Based on your nine forty five PKPD analysis, will those doses already provide predictive therapeutic coverage of all the potential compound and single EGFR mutation combination clones for those LR patients in the trial? Thank you.
Speaker 2
Thanks, Brad. This is Kate. I'll take the first and hand on over to Becker for the second part of your question. In terms of expectations on top line data, this is going be very similar to what we've done in the with GAVRETO and with AYVAKID in the advanced setting and and PGFR alpha driven GIST. So we will we will plan to put out, you know, particularly the results on the primary endpoint, a safety overview, as the primary kind of anchors to that communication.
We will save the majority of that data for, you know, presentation at a medical meeting. So so we will certainly, you know, talk about the overall results of the study and what is what are the critical pieces for, you know, pursuing, sNDA. So that's what you can expect there. And then, Becker, do you want to talk about that?
Speaker 4
Yeah. So, Brad, with respect to the combination of osimertinib and, BLU-nine forty five, we'll be starting BLU-nine forty five at two hundred milligrams. This is a dose that begins to approach the LR coverage in the blood, but it's important to remember that we're really trying to get deeply into tumors in patients with very bulky disease in some cases. We have a number of different and and we'll start with full dose osimertinib. We have a number of different combination doses to test during this escalation period to get the right balance between the two.
We don't expect there to be additional toxicity by adding BLU-nine forty five because it doesn't hit the wild type EGFR until very high doses. But nonetheless, we'll still need to look at a number of different combinations to get the optimal one for these patients.
Speaker 0
Thank you. Our next question comes from the line of Michael Smith from Guggenheim Securities. Please, Michael, your line is now open.
Speaker 11
Hi. Good morning. This is Ige on for Michael. Thanks for taking our questions. One, on the long term strategy for your CDK two program.
You've spoken about potential combinations with CDK four inhibitors. How should we think about that combination from a safety perspective and in terms of sequencing therapy? And how would be positioned relative to Pfizer's CDK2foursix inhibitor in any read through from their initial data Thank you very much.
Speaker 4
Yeah. So with respect to CDK2, inhibitors or particularly our CDK2 inhibitors, we don't expect overlapping toxicity. Certainly, need to look at single agent data before we know that for sure. But based on our preclinical data, we expect these to be complementary to CDK4six inhibitors. We looked at a number of different combinations with chemotherapy preclinically and four six inhibitors.
And so we look at Pfizer's data and we're pleased by the fact that they're seeing, activity. However, I think that it's been mentioned both by us and them multiple times that being able to control CDK two versus four six gonna be important to both manage potential toxicity and make sure that we are in different lines of therapy addressing the either the initial driver or the resistance mechanism or both at the same time. With respect to the the Pfizer compounds, both their selective CDK two inhibitor and the two four six inhibitor, we see this compound as highly competitive. It's a very selective CDK two inhibitor, and we see it as having potential to combine with a number of different CDK four six inhibitors in multiple lines of therapy in hormone resistant breast cancer.
Speaker 0
That's helpful. Thank you. Yes. Thank you. Our next question comes from the line of Andrew Berens from SVB Securities.
Please, Andrew, your line is now open.
Speaker 10
Hi. Thanks. Can you give some additional details on the development plan for the combo of nine forty five plus Tagrisso? Sounds like initially, you're gonna go after the l eight five eight r subgroup. Just developed the seven nine seven s point mutation of Tagrisso.
You expect that to be an accelerated pathway? And then, what are the plans to penetrate the first line? Are are you gonna test the two drugs, molecule cocktail or the MET inhibitor, either a small molecule or a large molecule?
Speaker 4
So, let me address those those individually. So with respect to the combination, again, as I mentioned, the reason for the combination is twofold. One is to hit the driver mutation as hard as possible. So the combination of either osimertinib or BLU-seven zero one plus BLU-nine forty five would be expected to do that, but also to in the resistance setting, to address heterogeneous tumors and in the frontline setting to prevent the emergence of resistance. Our goal in the frontline setting is to really shut down the EGFR signaling pathway.
It's been shown multiple times in hematologic tumors that when you can do this, you get longer durations of response and eventually longer overall survival. With respect to pathways to approval in the relapsed refractory setting, even in the second line following first line osimertinib, there's really not much besides chemotherapy that's showing activity at this point. And so we do think that there are potential rapid pathways to approval either for the single agent or a combination with standard of care that that would then be followed up with randomized trials to, confirm that clinical benefit of that combination. So we will look early in our, study of nine forty five plus osimertinib for evidence of activity in the relapsed refractory setting. But then shortly thereafter, looking in the frontline to show that we can achieve rapid deep responses with that combination.
With respect to MET inhibitors, MET is an important but certainly not overly dominant mechanism of resistance. I think that it is important to remember that some of these other non EGFR mediated mechanisms of resistance are really the drivers of early resistance where patients that have been on osimertinib for a longer period of time will have higher rates of on target or EGFR mutations driving the resistance. So we will, using nine forty five, start to explore combinations with a number of different compounds, and that will likely include a MEK inhibitor. And the utility of that in different, lines of therapy or maybe in early relapse patients will be something that we'll be determining over the next, year to fifteen months.
Speaker 0
You Our very next question comes from the Mike Ulz from Morgan Stanley. Please, Mike, your line is now open.
Speaker 12
Good morning and thanks for taking the question. Maybe just a follow-up on an earlier question related to claims data and the diagnosis rate. Looks like you're still getting some nice traction there. Just curious, at peak, you ultimately expect the majority of SM patients to be diagnosed? Or for some reason, could that number be lower and maybe it's because you're not capturing mild patients, for example?
And then secondly, just can you remind us what the current diagnosis rate is in Europe? Christi,
Speaker 2
can you take that?
Speaker 3
Sure. So we are really excited to see the ongoing growth in diagnosed patients. I know many of you remember a couple years ago when we started talking about non advanced SM and more detail. And at that point in time, maybe ten thousand patients were diagnosed in The U. S, and now we're close to half.
So you know, our expectation is that the majority of SM patients will be diagnosed as we approach the launch and then move through through the launch through our ongoing efforts and our focus. And, you know, we're kind of close to that point now. We also think that moderate to severe patients, because of their symptomatology, are on the margin more likely to find their way to a diagnosis versus patients who may be milder. So we will continue to really be putting effort against that. In Europe, you know, we are building that picture market by market.
I can say that, you know, we were able to get a look at sort of analogous claims like data in in Germany, and it it came in a very similar picture to what we see in The US, which was really encouraging because I think it validates, you know, the idea that these patients are definitely out there. They're being diagnosed, and we're continuing to see that that growth, you know, both through our efforts as well as I think just the efforts of the overall SM community and these patients who are just so motivated to really seek seek diagnosis and treatment.
Speaker 2
Just to add one one other element to that too for Chrissy is that I think one of the things we've seen in other kind of similar launches, whether that be a Jakafi or others, is that, you know, we we expect a very compelling risk benefit profile coming out of the PIONEER study in the non advanced setting. And as as physicians, you know, start treating and and get comfort, we certainly see that less symptomatic patients start to be more included in those treatment paradigms. So I think upon the PIONEER study and our launch in the non advanced setting, we would expect that patients with less symptomatology would start to be included, again, as physicians gain that experience and comfort.
Speaker 0
Thank you. Our next question comes from the line of David Lebowitz from Citi. Please, David, your line is now open.
Speaker 13
Thank you very much for taking my questions. First, on non advanced SM, you had indicated that seventy percent of new patient starts were going to AYVAKIT. I guess, how can we look at the growth trajectory going forward as it seems that it's going to be shifting less more from, I guess, new patients to duration over the long haul? How does that affect the run rate?
Speaker 2
So, Christy, I I know. I think, David, think you're saying that in the advanced setting that seventy percent of new new patients start. But, Christy, do you wanna do you
Speaker 3
answer the run rate? Yeah. Yes. Right. So so, you know, as as I said, there's times really two two kind of factors to think about when when we're gonna give out kind of new patients starting in advance of that.
So one is just the overall rates of treatment indication. And despite the fact that it is such a severe disease with, you know, a very limited life expectancy, we know that many patients have not been treated. Providers have taken more of a watch and wait approach, I think largely because the available therapies simply haven't been, you know, very effective at treating the disease. And so, you know, the fact that we've seen forty percent growth in the number of patients being treated, which is sort of the overall market since AYVAKIT has launched, I think, really speaks to that. But the majority of patients are still not being treated.
And so there is a lot of of room to continue to grow the overall size of the market. And with AYVAKIT getting about 70% of those new starts, I think we're very well positioned if the market continues to grow to continue to drive new patient starts on AYVAKIT. So I continue to see both new starts as well treatment duration to be, you know, very important drivers for our ongoing growth. And in fact, in the near term, you know, I think new starts will be probably the more important of the two of them, and we continue to see a lot of help there, expanding prescriber base, continuing through even the last few months in in q one. And so I think we're we're well set up as we move through this year, for the steady growth that we expect.
Speaker 13
Sure. Thank you for that. And we're looking at the claims data regarding systemic mastocytosis as a whole. How are those numbers actually determined? What factors goes into determining differentiating one patient versus another, given that polypharmacy is a substantial issue, which could be hamper such analysis?
Many of the drugs often use are antihistamines, things that actually don't require prescriptions. How do we break those numbers down?
Speaker 1
Can you take that? Sure. So Yeah.
Speaker 3
They know Oh,
Speaker 2
sorry. You guys were were remotely. But Selena, maybe if you can take a stab and Christie, please add color.
Speaker 1
I'm happy to start. Yes, so thanks for that question. So first off, I would say we're fairly confident that these are indeed unique patients that we're looking at as we're able to follow their journey through initial diagnosis and their health care utilization, which includes things like the treatments that they may use as well as the different physician specialties interacting with, both for chronic care as well as sort of acute or episodic care. And so some of the features that we're able to see are both the initial diagnosis of SM as well as the SM diagnosis code associated with all of these interactions along that journey.
Speaker 13
Got it. And the last question is the denominator of those the questions on the left of slide six, six patients on polypharmacy, is the Yeah. Is that denominator essentially equivalent to this the population that's in the claims data, or are there differences in the sample?
Speaker 1
Yeah, that's a great question. There are actually a number of different publications on this topic. And so some of these facts that we're showing on slide six come from a touchstone survey that has been done with both patients living with non advanced FM as well as the allergist immunologist and hematology oncologists that are managing these patients. We also see, though, that these numbers correlate very well across a number of other published literature that surveys patient and provider health care populations.
Speaker 9
Thank you very much for taking my questions.
Speaker 0
Thank you. Our next question comes from the line of Eun Yang from Jefferies. Please Eun, your line is now open.
Speaker 14
Thank you. I have a questions on non advanced test then. Previously, you mentioned about 70,000 patients in major global markets. And based on phase two entry criteria, what percent of patients do you think would be realistically candidates for Avapritinib? And if you are targeting majority of the seventy thousand patients, what do you think would be a reasonable pricing for rapid adoption?
And the second question is, what percent of a target patient population in ISN would be treated with a hematologist versus allergy specialist? Thank you.
Speaker 2
Phoebe, again, we'll take some of the first part of that question just around the addressable patient population. Then, Kristi, if you could weigh in on the pricing, that would be great.
Speaker 1
Yeah. Thanks for that question, Yoon. So just to kick it off, as we look across multiple data points, suggests that sixty percent or more patients may ultimately be candidates for disease modifying therapy. So we've talked about the vast majority of these patients receiving polypharmacy and despite this, still reporting significant impacts on their quality of life. For example, we fifty percent of patients are reporting potentially life threatening anaphylaxis.
And we've heard an example of a patient who keeps an EpiPen in every room of her house. As we speak to allergists and hematologists, oncologists, they also share with us that they see sixty percent approximately of their patients being moderate to severe and really not well controlled on symptom directed therapies.
Speaker 2
K. And, Christy, do wanna do you wanna weigh in on the on the pricing question from you?
Speaker 3
Absolutely. So, you know, the the context that Polina just shared about this disease, I think, is important when we think So non advanced is clearly a much bigger indication versus advanced. However, it is still very much a rare disease. And it's a rare disease where patients are suffering from very severe morbidity, impact on ability to work, quality of life along the lines of cancer patients, etcetera.
You know, as we've engaged with payers, they very much understand that context. And, you know, in fact, through our experience with the launch of AYVAKIT so far, we've had really no barriers to to access from a payer perspective, a very rapid time to fill. And we've seen some some reimbursement, in fact, in the non advanced setting as well. And so, you know, our expectation as we go forward, the advocates, you know, we're we're on the market and price certainly in The US at all doses. And, you know, would expect to be able to continue to ensure patient access as we go forward into the non advanced launch.
And so I don't really see price as being kind of a major driver of that launch. I think it's going to be much more about our continued engagement with healthcare providers and patients, education around, you know, patient identification and testing, and of course, the very positive benefit risk profile that we're expecting to see from AYVAKIT in this indication, particularly at the doses for nonadaptism based on the data that we've seen so far from PIONEER in part one.
Speaker 14
And, Becky, I'm one person. On the population. Thank you.
Speaker 0
Go ahead. Go ahead.
Speaker 2
I'm sorry. You? What was that?
Speaker 3
Oh, I'm sorry. Just on the line. I apologize. Yes. Hematologist versus allergist.
Yes. So what we see is that non advanced patients generally are, you know, managed by allergy primarily. Hematology is often involved in co managing these patients. And so we we expect that, you know, our efforts will be primarily focused in in allergy as well as as in the hematology call points that we're we're already focused on for for the advanced patients.
Speaker 14
Well, can I ask you one more question to that then? Do you have to would you needed to add the sales reps to target allergy specialist?
Speaker 3
So Yes. So know your expectation is that we may okay. Go ahead, Sonia.
Speaker 2
Oh, go ahead, Christy. Go ahead, Christy.
Speaker 3
Our expectation is that we may modify our commercial footprint as we go forward towards that non advanced approval to make sure that we are really adequately directing resources into the allergy space, but we don't expect those changes to to be significant. This is a very tractable call point for a, you know, specialty commercial organization and kind of the context of a biotech company. And we are already quite adept and skillful at utilizing some of the claims data that we've already been talking about to make sure that we're directing our efforts in a really efficient way.
Speaker 14
Thank you very much.
Speaker 0
Hey, Yoon. This is Becker.
Speaker 4
I I just wanted to make a point about the first part of your question. I think we need to think of these patients as having a a chronic disease that does progress over time. The the story that we've heard from patients has been that start out, may start out with mild symptoms, but that they tend to get worse and worse over time and become more and more debilitating. To date, we haven't had an option for these patients. So I think that what we're going to see is providers looking to understand the depth of the disease, sometimes by trying the treatment that we know wipes out the clone that causes the disease.
And also starting to work with the community to understand the value of preventing the progression of this disease even in the non advanced setting. So I wouldn't think of patients as showing up at a certain level of severity and simply staying there for good.
Speaker 0
Thank you. At this time, we have run out of time for further questions. So I will turn the call over back to Katie Havilland for any final remarks.
Speaker 2
Thank you, operator. Our strong performance in Q1 sets the foundation for us to achieve the priorities we've laid out as a company this year. AYVAKIT, as we just talked about, is off to a very strong start in its first full year of launch with the opportunity to expand to the non advanced SM right around We are also maintaining our growth momentum with the execution of our pipeline through key data milestones this year and next. We look forward to talking with all of you on this continued progress very soon. So thank you for taking the time to join us today, and thank you for your continued support of Blueprint Medicines.
Speaker 0
This concludes today's conference call. Thank you so much for joining. You may now disconnect your lines.