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spk10: 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 Medicine's first quarter 2022 financial results conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press start followed by number one on your telephone keypad. If you would like to withdraw your question, please press star followed by number two. Please plan to limit yourself to one question. 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.
spk06: Thank you, Juan. Good morning, everyone, and welcome to Blueprint Medicines' first quarter 2022 financial and operating results conference call. This morning, we issued a press release which outlines the topics we plan to discuss today. You can access the press release, as well as the slides that we'll be reviewing today, by going to the Investors section of our website at www.blueprintmedicines.com. Today on our call, Kate Haviland, our Chief Executive Officer, will discuss Blueprint Medicine's Pillars for Growth through 2023. Christy Rossi, our Chief Operating Officer, will provide an Advance 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 Lansdell, our chief financial officer, will review our first quarter 2022 financial results. Percy Carter, our chief scientific officer, is also joining our 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 factor 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 Haviland.
spk04: 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 12 to 18 months will be unprecedented for us as we execute on multiple milestones, driving 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 Avakit as the standard of care in advanced systemic mastocytosis, or SM, in the US, and we closed the quarter with the European Commission approval of Avakit in advanced SM. Our European launch is now underway. The global launch of Avakit and Advanced 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. Avakit 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 and 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, to the end of 2023, We expect to be launching Avakit 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 Christy to discuss the progress we have made on the Avakit launch in Advanced SM. Christy?
spk08: Thanks, Kate. Good morning, everyone. In the first quarter, we continued to build momentum in our ongoing launch of Avakit and Advanced SM, generating net product revenue of $23.8 million. The Advanced SM indication contributed the majority of this revenue, and we anticipate that it will be the primary driver of Avakit revenue growth over the course of the year. We are reaffirming our guidance of $115 to $130 million in Avakit 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 advanced SM on March 25th. Avakit is now the first approved disease-modifying precision therapy in the European Union designed to selectively target KIT-V816B, the primary driver of SM. Within one week of approval, the first patient was treated in Germany, where Avakit is now reimbursed for its expanded indication. And we are looking forward to bringing Avakit to patients in additional EU countries as we work through country-specific reimbursement processes. Now let's turn to the U.S., which contributed $21.3 million 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 Avakit has fundamentally changed the treatment paradigm in advanced SM, driving significant market growth and setting a new standard of care. Avakit is now the treatment of choice for approximately 70% of all advanced SM patients starting on or switching to a new therapy. Since the launch of Avakit, the percent of advanced SM patients who are being treated for their disease has grown by approximately 40%. 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 Avakist's impact on overall survival and advanced systems, 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 Q1, we activated approximately 65 new accounts, particularly impressive given the impact of Omicron early in the quarter. The strong base of advocate 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 advanced SM 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 Avakid. We are also seeing patients benefiting from extended treatment duration as we continue to progress the launch. Our estimated duration of therapy for Avakit and advanced SM is trending towards 18 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 and impact patients earlier in the course of their disease. when they can derive the most benefit from Avakit. 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 Avakit. 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 Dr. Felina 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.
spk09: Thanks, Christy, and hello, everyone. I've been a part of Avakit'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 Avakit. 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. 75% 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 80% of patients still report limitations in their work or daily activities, and 64% share that they avoid leaving their home due to their SM. Another study showed 83% 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 54% growth in the number of SM patients observed in U.S. claims since the launch of Avakit in January 2020. We now see more than 15,000 unique diagnosed SM patients in claims data, and most of these patients have non-advanced SM. We expect this 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-D816V. 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&D progress.
spk11: 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 that Avakit demonstrated deep reductions of clinical symptoms at all doses, a rapid reduction in mast cell burden, kit D816V allele burden, serum tryptase, and positively impacted patient quality of life. These data from Part 1 were the basis for Avakit's breakthrough therapy designation in non-advanced SM. Part 2 was designed to enable registration by demonstrating response rate superiority of Avakit versus placebo as assessed by total symptom score, or TSS. TSS is measured using the ISM Symptom Assessment Form, or ISM-SAF. 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 30% difference in the proportion of responders with Avakit versus placebo would be a clinically meaningful result that would be supportive of both regulatory filings and drive real-world utilization in non-advanced SM. 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 Avakit treatment. we remain on track to report top-line data in late summer of 2022, and pending results, we plan to submit an SMDA to the FDA by the end of 2022. 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 medicine. In addition to the pioneer top-line data in late summer of this year, we plan to report multiple clinical proof-of-concept data sets 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 blue 945 in combination with osomertinib and initial data for blue 701 in EGFR mutant lung cancer. In addition, we expect to have initial clinical data for blue 451 in the first half of 2023 in EGFR exon 20 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 blue 222 and CDK2 vulnerable cancers. With our first clinical data expected in the first half of 2023. Importantly, we plan to explore both monotherapy and combination dose escalation in part one of Vela 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 CDK4-6 inhibitors and hormonal therapy. Also, in patients with CCNA1-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&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&D day in the second half of the year. With that, I'll turn the call over to Mike to review our financial updates.
spk13: 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 $62.7 million for the quarter, including $23.8 million in net product sales of Avakit and $38.9 million in collaboration revenue. This represents approximately 164% growth in Avakit product sales from the same period last year. As Christy noted, we saw solid growth in advanced SM, which is and will continue to be our major driver of advocate 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 million development milestone payment from Clemencia related to Blue 782, our outlicensed ALK2 inhibitor in development for the rare bone disease Fibrodysplasia osficans progressiva. Turning to expenses, our total costs and operating expenses for the first quarter were $168.5 million, including $23.4 million of non-cash stock-based compensation expense. This reflects moderate planned growth in R&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 to $200 million in total revenues and $115 million to $130 million in avocate net product revenues. In addition to our diverse revenue drivers, we are in an exceptionally strong position with nearly $900 million 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 12 to 18 months. which we anticipate will lead to continued modest growth in R&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 a sustainable profile. With that, I'll now turn the call back over to the operator for any questions. Operator?
spk10: Thank you. If you would like to ask a question at this point, please press a star followed by one on your telephone keyboard. And the first question comes from the line of Mark from Cohen. Please, Mark, your line is now open.
spk03: For Mark, thank you for taking my question, and congratulations on a strong quarter. Victor, I think you discussed part one results that showed a 60% response rate on the 25 milligram arm. And I was wondering if you could remind us what the rate was in the higher dose of the 50 and 100 milligram doses. and also looking forward to the part two results beyond response rate. Are there any components of the TSS that you think are important commercially and will drive patient use? Thank you.
spk11: 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 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 and the fatigue 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.
spk03: Thank you. That's very helpful. If I can, one more question for Christy. I think you mentioned the 70% of market share for the new prescriptions. I was wondering what market share has Avakit captured for the overall advances in market or potential market?
spk08: Sure. So, you know, as I said, we're really pleased to see Avakit 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 growth, right? So this is a market where historically a lot of patients, unfortunately, have not received SM-directed therapy. So the launch of Avakit has grown the market by about 40%. And then we're looking at, of course, how many patients are actually being treated with Avakit as opposed to other therapies. And that's where we're seeing now 70% of all new initiations going on Avakit. Our overall share is trailing that, given where we are in the launch. And actually, that's That's a good thing when 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 Avakyn, and we expect that number to continue to grow as we progress to launch.
spk03: Okay. Thank you. I appreciate that, and congratulations again.
spk10: Thank you. Our next question comes from the line of Dane Leone from Raymond James. Please, Dane, your line is now open.
spk15: 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? You got some questions in around what you said around 18 months expected of treatment duration. Could you maybe contextualize that given that the drug hasn't been commercially launched for 18 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 into 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 945, 701, 451? I think investors are always trying to figure out uh 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 emerging uh signs of clinical effect at the doses reported thank you okay thanks dane um so christy do you want to take the 18 months and talk a little bit about the you've had a quarter of a quarter growth um and becker will you take the the clinical updates and what to expect sure
spk08: So thanks for the question, Dan. So duration is obviously one of the two key sort of drivers that we're watching very closely in terms of the trajectory of the overall launch. And the context here is that we know that Avacyn patients can have quite long treatment durations in advanced SM. In our clinical studies, we saw treatment durations of two plus years. And so our expectation is that over time, as we continue to find patients closer to a point of diagnosis, 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 18 months. And so at this point we are essentially looking at curves and comparing sort of 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 duration of therapy. We'll continue to take a look at that over time. One positive note there is that we're even seeing that patients who have started more recently and 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 full Q1 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 more broadly we see in pharma around Q1 in the U.S., where revenue can be impacted by factors around gross to net compliance, as well as some other factors. We were 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, etc., 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 meeting that impact. So as we go into Q2, you know, 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. Rebecca, can you take the question? Yeah.
spk11: Yeah. So, Dane, with respect to our EGFR Mutant Lung Cancer Program, just a reminder that 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. 945 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 T79M, 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 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 osomertinib, 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 osomertinib 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 701, which is our brain penetrant inhibitor, this one has really high potency on the driver mutation and then activity in the 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 945, 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 combine in 2023, both with 945 and with Austin Martin and the MNAT program. And then Blue451 is a more straightforward biology where the tumors are driven by a single driver mutation, the exon 20 mutation. We are in escalation now, and we expect to be in escalation for most of the rest of the year. But in that case, we might expect a more straightforward evidence of response as we've seen with some of the other EGFR20 inhibitors in the clinic. And so as we have a good body of data, that's what we'll be updating in that program.
spk10: Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Please, Salveen, your line is now open.
spk07: 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 etiquette sales this year and then looking forward. Thank you.
spk08: Sure. Yeah. Uh, thanks for the question. So, you know, as we've, we've shared, we're really looking at, at a very simple level, kind of two, two key drivers around the advocate launch. um new patient starts and duration of therapy and you know i i think that both of those are trending in a way that really sets us up nicely for steady growth as we go go through the year on the new patient start front as we mentioned we continue to have a lot of headroom many advanced system patients are not receiving a therapy for their disease and avakit has very quickly 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 and continue to see a lot of room to grow. And then, as I mentioned, 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, 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. So we're reiterating the overall guidance and are looking to see more steady quarter-on-quarter growth as we go through the year.
spk04: And just to add to it, one thought to that is that, you know, this, as Chrissy mentioned in her prepared remarks, I mean, 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 have been, you know, very impactful to patients. And so I think the enthusiasm we're also getting from the physicians that we're talking to about the clinical aspects, you know, their early experiences with Avacyn has been really, you know, really promising. And as Christy mentioned as well, you know, 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 Avakit relative to standard of care and other therapies, which I think is going to be incredibly compelling. And so, you know, you add kind of the early experience plus this kind of additional data as we see the benefits of Avakit turn it into really a life-extending type of therapy, I think will very much continue to catalyze physicians out of this wait-and-watch kind of attitude they've been in previously.
spk10: Thank you. The next question comes from the line of Rene Benjamin from GMP Securities. Please, Rene, your line is now open.
spk16: 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 U.S.? And then just kind of related to that, I'm pretty intrigued by the U.S. claims data that you guys are showing. How much granularity do you have with that? that data? And do you know which sites, per se, might be having a lot of the non-advanced SM patients so that once the launch takes place, you can actively target those sites? Thank you.
spk04: Thanks, Randy, for the question. Christy, if you could take the question on the EU launch dynamics, and then Felina can answer the question about the claims data.
spk08: Great. So we were really pleased 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 see, you know, a lot of interest coming from German healthcare providers and patients already out of the gate, which is really encouraging. The overall dynamics in Europe, I think, will be very similar to the U.S. Certainly the epidemiology is similar. And, you know, in fact, I would argue that some European markets, and Germany is one of them, may be a bit more organized in their treatment of SM patients through the efforts of the European Cooperative Network around Treatment of SM, or ACNM. So we're excited to see this roll out. 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 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. Generally speaking, would expect kind of the overall cadence of the launch to not look very different and, you know, expect Avakit to become the standard of care for treatment of advanced system in Europe over time as well.
spk09: And speaking to the U.S.
spk08: claims data,
spk09: Absolutely, Christy. So, Rennie, 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 allergist 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.
spk16: Thanks for taking the question.
spk10: Thank you. Our next question comes from the line of Brad Canino from Stifel. Please, Brad, your line is now open.
spk12: 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 945 plus OC combination specifically where you're focused on the LR subgroup, what doses are you going to start at? And based on your 945 PKPD analysis, will those doses already provide predicted therapeutic coverage of all the potential compound and single EGFR mutation combination clones for those LR patients in the trial? Thank you.
spk04: Thanks, Brad. This is Kate. I'll take the first and hand it over to Becker for the second part of your question. In terms of expectations and top-line data, this is going to be very similar to what we've done in the past with Gavaretto and with Avakid in the advanced setting and PGFR alpha-driven GIST. So 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 we will certainly, you know, talk about the overall results of the study and what are the critical pieces for, you know, pursuing S&DAs. So that's what you can expect there. And then, Becker, do you want to talk about that?
spk11: Yeah. So, Brad, with respect to the combination of osomertinib and Blue 945, we'll be starting Blue 945 at 200 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 we'll start with full-dose osomertinib. 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 blue 945 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.
spk10: Thank you. Our next question comes from the line of Michael Smith from Guggenheim Securities. Please, Michael, your line is now open.
spk02: Hi, good morning. This is for Michael. Thanks for taking our questions. One, on the long-term strategy for your CDK2 program, you've spoken about potential combinations with CDK4-6 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 CDK2 for six inhibitors in any way through from their initial data in San Antonio? Thank you very much.
spk11: Yeah. So with respect to CDK2 inhibitors, particularly our CDK2 inhibitors, we don't expect overlapping toxicity. Certainly, we need to look at the single agent data before we know that for sure. But based on our preclinical data, we expect these to be complementary to CDK4-6 inhibitors. We looked at a number of different combinations with chemotherapy preclinically and 4-6 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 CDK2 versus 4-6 is going to be important to both manage potential toxicity and make sure that we are in different lines of therapy addressing either the initial driver or the resistance mechanism or both at the same time. With respect to the Pfizer compounds, both their selective CDK2 inhibitor and the 2,4,6 inhibitor, we see this compound is highly competitive. It's a very selective CDK2 inhibitor, and we see it as having potential to combine with a number of different CDK4,6 inhibitors in multiple lines of therapy in hormone-resistant breast cancer.
spk10: That's helpful. Thank you. Thank you. Our next question comes from the line of Andrew Behrens from SVB Securities. Please, Andrew, your line is now open.
spk01: Hi, thanks. Can you give some additional details on the development plan for the combo of 945 plus to Grisso? Sounds like initially you're going to go after the L858R subgroup who's developed the 797S point mutation to Grisso. Do you expect that to be an accelerated pathway? And then what are the plans to penetrate the first line? Are you going to test the two-drug small molecule cocktail or the MET inhibitor, either a small molecule or a large molecule?
spk11: So let me address 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 osomertinib or blue 701 plus blue 945 would be expected to do that, but also in the resistant 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. And 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 osomertinib, 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 agents or a combination with standard of care patients. 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 945 plus osimertinib for evidence of activity in the relapsed refractory setting, but then shortly thereafter looking in the front line 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 osomertinib for a longer period of time will have higher rates of on-target or EGFR mutations driving the resistance. So we will, using 945, start to explore combinations with a number of different compounds, and that will likely include a MAP 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 15 months. OK.
spk10: Thank you. Thank you very much. Our next question. Our next question comes from the Mike Ols from Morgan Stanley. Please, Mike, your line is now open.
spk14: Good morning, and thanks for taking the question. Maybe just to follow up on an earlier question related to the claims data and the diagnosis rate, looks like you're still getting some nice traction there. Just curious, at peak, do you ultimately expect the majority of SM patients to be diagnosed, or for some reason, you know, could that 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? Thanks.
spk04: Christy, can you take that?
spk08: Sure. So we are really excited to see kind of the ongoing growth in diagnosed patients. You know, I know many of you remember a couple of years ago when we started talking about non-advanced SM and sort of more detail. And at that point in time, maybe 10,000 patients were diagnosed in the U.S. and now we're close to half. So... Our expectation is that the majority of SM patients will be diagnosed as we approach the launch and then move through the launch through our ongoing efforts and our focus. And 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, we are building that picture market by market. I can say that we were able to get a look at sort of analogous claims-like data in Germany, and it painted a very similar picture to what we see in the U.S., which was really encouraging because I think it validates the idea that these patients are definitely out there, they're being diagnosed, and we're continuing to see that growth 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 diagnosis and treatment.
spk04: And just to add one other element to that, too, for Christy, is that I think one of the things we've seen in other kind of similar launches, whether that be at Jackify or others, is that we expect a very compelling risk-benefit profile coming out of the Pioneer study in a non-advanced setting. And as physicians start treating 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.
spk10: Thank you. Our next question comes from the line of David Lebowitz from CT. Please, David, your line is now open.
spk17: Thank you very much for taking my question. First, on non-advanced SM, you had indicated that 70% of new patients starts where we're going to advocate. I guess, how can we look at the growth trajectory going forward as it seems that it's going to be shifting more from, I guess, new patients to duration over the long haul? How does that affect the run rate?
spk04: So, Christy, I think, David, I think you were saying that in the advanced setting that 70% of new patients starts. But, Christy, do you want to answer the run rate? Yeah.
spk08: Yes. Right. So, you know, as I said, there's really two kind of factors to think about when we're thinking about kind of new patients starting in advanced SM. So one is just the overall rates of treatment in this. in this indication, and despite the fact that it is such a severe disease with 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 40% growth in the number of patients being treated, which is sort of the overall market since Avakit 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 room to continue to grow the overall size of the market. And with Avakit getting about 70% of those new starts, I think we're very well positioned, as the market continues to grow, to continue to drive new patient starts on Avakit. So I continue to see both new starts as well as treatment duration to be very important drivers for our ongoing growth. And in fact, in the near term, I think new starts will be probably the more important of the two of them. And we continue to see a lot of health there, expanding prescriber base, continuing through even the last few months in Q1. And so I think we're well set up as we move through this year for the steady growth that we expect.
spk17: Sure. Thank you for that. And 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 hamper such analysis. Many of the drugs often used are antihistamines, things that actually don't require prescriptions. How do we break those numbers down?
spk04: Lino, can you kick us off? Sure. Thank you. Oh, sorry, you guys, we're coordinating remotely, but Selena, maybe if you can take a stab, and Christy, please add color. I'm happy to start.
spk09: Yeah, 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 healthcare utilization. which includes things like the treatments that they may use as well as the different physician specialties that they're 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 care interactions along that journey.
spk17: Got it. And the last question is the denominator of the questions on the left of slide six, patients on polypharmacy, is that denominator essentially equivalent to the population that's in the claims data or are there differences in the sample?
spk09: 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 SM 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 healthcare populations.
spk17: Thank you very much for taking my questions.
spk10: Thank you. Our next question comes from the line of Yun Yang from Jefferies. Please, Yun, your line is now open.
spk05: Thank you. I have a question on non-advanced SN. Previously, you mentioned about 70,000 patients in major global markets. And based on phase two entry criteria, what percent of our patients do you think could be realistically candidates for Avapritinib? And if you are targeting majority of 70,000 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 it be treated with a hematologist versus allergy specialist? Thank you.
spk04: So, Felina, again, we'll take some of the first part of that question just around the addressable patient population. And then, Christy, if you could weigh in on the pricing, that would be great.
spk09: Yeah, thanks for that question, Yoon. So, just to kick it off, as we look across multiple data points, it suggests that 60% 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 hear that up to 50% of patients are reporting potentially life-threatening anaphylaxis. And we've heard an example of a patient who peeps in EpiPen in every room of her house. As we speak to allergists and hematologists, oncologists, they also share with us that they see 60% approximately of their patients being moderate to severe and really not well-controlled on symptom-directed therapies.
spk04: Great. And Christy, do you want to weigh in on that pricing question from you?
spk08: Absolutely. So, you know, the context that Felina just shared about this disease, I think, is important when we think about pricing. So non-advanced system 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, etc., um you know as we've engaged with payers they very much understand uh that context and you know in fact through our experience with the launch of advocate so far we've had really no barriers to to access from a payer perspective a very rapid time to fill uh and we've seen some some reimbursements uh in fact in the non-advanced setting as well and so uh you know our expectation as we go forward the advocates uh you know we're on the market in price certainly in the u.s at all doses and 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 patient identification and testing, And, of course, the very positive benefit-risk profile that we're expecting to see from Avakit and the syndication, particularly at the doses for non-advanced SM based on the data that we've seen so far from Pioneer in Part 1. Thank you.
spk04: Go ahead.
spk05: I'm sorry, Yoon, what was that? Oh, I'm sorry. I missed the last part.
spk11: I apologize.
spk04: Yes.
spk08: 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 expect that, you know, our efforts will be primarily focused in allergy as well as in the hematology call points that we're already focused on for the advanced patients.
spk05: Well, can I ask you one more question to that, then? Do you have to, would you need to add the sales reps to target allergy specialists?
spk08: So, you know, our expectation is that we may, okay, go ahead, Sonia.
spk04: Go ahead, Christy. Go ahead, Christy.
spk08: 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 be significant. This is a very tractable call point for a 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.
spk05: Thank you very much.
spk11: Yuen, this is Becker. 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 chronic disease that does progress over time. The story that we've heard from patients has been that they start out and they 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.
spk10: Thank you. At this time, we have run out of time for further questions. So I will turn the call over back to Katie Haviland for any final remarks.
spk04: Thank you, operator. Our strong performance in Q1 sets the foundation for us to achieve the priorities we've laid out at the company this year. Avakit, 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 the corner. 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 Medicine.
spk10: This concludes today's conference call. Thank you so much for joining. You may now disconnect your lines.
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