Blueprint Medicines Corporation

During this time, simply press star, followed by the number one on your telephone keypad. If you would like to withdraw a question, press the star followed by the number two. Please plan to limit yourself to one question. Thank you. Jenna Cohen, you may begin your conference.

Thanks, Faith, and good morning, everyone. Welcome to Blueprint Medicine's first quarter, 2024, 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 .blueprintmedicines.com. Joining me today are Kate Haviland, Chief Executive Officer, Helena Lee, Chief Commercial Officer, Salad Na Mouni, President, Research and Development, and Mike Lansdell, Chief Financial Officer. Kristi Rossi, Chief Operating Officer, and Becker Hughes, Chief Medical Officer, are also on the line and available during Q&A. Before we begin, I'd like to remind you that some of the statements made during the call today are forward-looking statements as outlined on slide three and are subject to a number of risks and uncertainties. These may cause our actual results to differ materially, including those described in our reports filed with the SEC. You're cautioned not to place any undue reliance on these forward-looking statements, and Blueprint disclaims any obligation to update such statements. I'll now hand the call over to Kate.

Thank you, Jenna, and good morning, everyone. We delivered another very strong quarter in our launch of AvaKit and Endolent System Systemic Mesocytosis, and we are entering 2024 in a position of strength. We have great momentum across all aspects of our business as we execute on our three priorities that we laid out in January. Our first priority is the launch of AvaKit and Endolent Systemic Mesocytosis. We have driven impressive revenue growth, and importantly, we are building the foundation for top-line revenue growth well into the next decade. We are also making significant progress in advancing our pipeline of innovative programs that are focused in our most compelling opportunities where we believe we have the greatest prospect of improving patient outcomes. And third, we are maintaining a strong and durable financial position in a self-sustainable financial profile. I'll briefly touch on each of these. Starting with the exceptionally strong commercial performance we delivered in Q1, we achieved $92.5 million in AvaKit net product revenue for the quarter. This result surpassed external consensus, as well as our own internal expectations. Felina will discuss in more detail the components of our continued commercial success, but I wanna take a moment to say how incredibly proud I am of our hardworking and dedicated commercial and medical team members. Their commitment to delivering for patients with SM globally is resulting in this type of performance. These results also reflect the profound impact that AvaKit is having on patients, as well as our strong and growing prescriber base. Today, we are also increasing our AvaKit guidance for the year to 390 million to 410 million. Later on the call, Mike will share more of our thinking around today's AvaKit guidance increase, which is setting a squarely on a revenue trajectory to peak sales of greater than 2 billion globally. This revenue trajectory makes AvaKit one of the most exciting rare disease launches happening right now, and puts us on a similar path to other notable rare disease product launches of -in-class medicines that built new multi-billion dollar markets. We are also strengthening our presence in allergy and inflammation with Blue808, our wild-tip kit inhibitor. The Blue808 program builds on the significant insights we have gained in mast cell biology and in targeting kit, the master control switch on mast cells, which we believe has the greatest prospect of improving outcomes for a large number of patients across allergic and inflammatory diseases. Our recent webinar titled The Powerful Mast Cell highlighted the scientific rationale for our aspiration to fundamentally shift the way many allergic and inflammatory diseases are treated by targeting this primary effector cell, the mast cell, with both mono and combination therapeutic approaches. We are on track to file the IND for Blue808 this quarter to enable initiation of a phase one study in healthy volunteers. We've established a successful track record with AvaKit, and you can continue to expect Blueprint to discover and develop potent and highly selective molecules as we expand our mast cell franchise beyond systemic mastocytosis. Turning now to the oncology side of our portfolio, next month at ASCO, we will be presenting data demonstrating that Blue222 is the first CDK2 inhibitor to be well tolerated in combination with an approved CDK46 inhibitor. With this data, we now have the clinical evidence that Blue222 is a differentiated, -in-class CDK2 inhibitor. Blue222's ability to combine with approved CDK46 inhibitors also position it to move quickly, with the potential to also become the -in-class CDK2 inhibitor approved for patients with hormone receptor-positive, HER2-negative breast cancer. I remain confident that we will execute a strategic partnership in the second half of this year to rapidly move Blue222 forward into registration-directed trials. Importantly, we are executing across the business while maintaining financial discipline. Our total costs and operating expense continue to decline, and with $735.6 million in cash on our balance sheet, we are in a strong and durable financial position. I am proud of the tremendous progress Blueprint has made in the first quarter of this year and continue to be impressed by the heads-down executional focus I see across all of our teams to make sure we're achieving our goals quarter after quarter. Now, let me turn it over to Felina to discuss this quarter's commercial performance. Felina?

Thanks, Kate, and good morning, everyone. We had an exceptional first quarter, generating Avakit net product revenue of $92.5 million, including $83.1 million in the U.S., and $9.4 million XUS. Avakit revenue has grown more than 135% year over year. We saw positive trends across all key business fundamentals, continued strong and steady growth in patients on Avakit, reflecting a strong pace of new patient starts and low discontinuation rates. Our mix of commercial versus free goods also skewed more favorable than we anticipated. Compliance remains high. Our international ISM launch is off to a robust start with Germany off to the races. Let's look at our key fundamentals in more detail. Starting with growth in patients on Avakit, we drove a really strong pace of new patient starts coming out of the holidays throughout the first quarter of the year. We continue to see low discontinuation rates driving positive trends in duration of therapy. For advanced SM patients, duration of therapy is trending even longer than our last update, now at an average of 25 months. And while it's still early days, duration of therapy in ISM patients is trending significantly longer. This is exactly what we expected based on Avakit's benefit risk profile. Q1 tends to be a tough quarter in our industry with patients benefits reverifications, lower growth to net and impacts on compliance. Our market access team did a great job managing through all of this. Our free goods share once again has been a surprise to the upside and is now averaging about 20% since ISM launch. The favorability in commercial versus free goods is really driven by two things. First, the pair mix of ISM patients skews more commercial and we estimate that ISM patients now comprise the majority of patients on therapy. Second, Medicare patients were able to access paid therapy as we saw last year. Importantly, unlike last year, we expect these patients will be able to stay on paid therapy for the rest of the year due to changes to the -of-pocket cap as part of Medicare Part D benefits redesign in the Inflation Reduction Act. In this third full quarter of launch, we are seeing strong and steady performance against our key revenue drivers just as we expected. The favorability in commercial mix exceeded our expectations and provides a tailwind for the remainder of the year. This, along with confidence in our strong continued execution is a key driver for our guidance update today. We'll continue to watch the fundamentals that drive revenue over the course of the year, such as the ongoing pace of new patient starts, duration of therapy, compliance and free goods, as well as our ongoing European launch performance. Taken together, our ISM first three launch quarters are showing a clear inflection point for AvaKit revenue growth. Now let's talk about why we expect to sustain this growth for years to come. Our team is executing well against our commercial strategy and we continue to make headway across multiple paths to drive sustained growth. We continue to grow breadth and depth in the AvaKit prescriber base across all specialties and settings. Prescriber breadth is one of the most important lead indicators for revenue growth. The number of new AvaKit prescribers continued to grow this quarter, including a growing number of allergists who have been activated to treat SM patients. Overall prescribing is still split evenly across the academic and community setting. The chart on the left shows AvaKit adoption into the top 400 providers by SM patient volume. And as you can see, we're starting to see even more depth from repeat prescribing as positive first experiences lead providers to start their second, third or more patients on AvaKit. Because the chronic burden of ISM is often underappreciated, a key part of our ongoing execution is redefining what disease control means for providers and patients. And we continue to expand our direct to patient and provider educational initiatives to foster greater awareness of the burden of disease with the goal of activating patients to ask about AvaKit. Living with ISM can be very isolating. Establishing patient to patient connections is a critical part of the journey to treatment. In Q1, we launched a monthly educational series where patients can learn from the experiences of other patients who are taking AvaKit. As part of our ongoing community building efforts, we held a first of its kind summit, bringing together patient advocates, patients and multidisciplinary thought leaders. Just this month, we launched an unbranded direct to patient campaign to drive further awareness of the toll of living with ISM and the availability of a new treatment option. All of these efforts are yielding impressive results. Unaided awareness among patients has grown nearly eightfold since approval. And we expect our expanding peer to peer and patient initiatives will continue to activate more patients and providers to try AvaKit. In closing, the momentum we've shown in our first three quarters of launch make us incredibly confident about the path we are on to achieve a more than $2 billion peak opportunity with AvaKit. We are building and shaping this market. We are growing the prescriber base. We are activating more patients to seek treatment. We're growing the number of diagnosed patients and there is plenty of headroom to continue to grow. We knocked it out of the park this quarter and we remain laser focused on our mission to help more patients in need. With that, I'll hand it to Fuad who will share how we're expanding our efforts in mast cell disorders to help more patients with allergic and inflammatory conditions beyond SM.

Thanks, Felina. Last week, Dr. Mariana Castells, the renowned researcher and clinical expert in mast cell diseases joined us for a webinar titled The Powerful Mast Cell, a promising and yet underappreciated target for treating allergic and inflammatory diseases. The webinar was the first in a new series we have planned to keep you updated on how we are thinking about the evolving science behind our portfolio and R&D strategy. If you haven't yet had a chance to listen to the discussion, I encourage you to check out the replay which is live on our website. The mast cell is a key driver cell responsible for the pathogenesis of a wide range of allergic and inflammatory conditions. Research into mast cell biology and its involvement in inflammatory diseases has recently increased with the goal to identify novel therapeutic targets in allergy and inflammation. This webcast focused on the biology of mast cells, including their essential roles as driver of and contributors to inflammatory responses, their core involvement in biological pathways relevant to an array of allergic and inflammatory diseases and Blueprint's approach to modulating mast cells and building a pipeline in allergic and inflammatory diseases. Blueprint has a long and proven track record of leadership in this space as evidenced by the success of Avacad and the ongoing development of LN-SPNib. And we have built what we believe is one of the most advanced mast cell drug discovery capabilities in the industry. BRU808 is poised to help us beyond systemic mastocytosis. Tackling the challenge of developing a potent and highly selective tunable oral wild type kit inhibitor is a logical evolution of our capabilities in this space. And the opportunity we have ahead of us is significantly larger than any we've pursued in the past. Our vision for scientific leadership in mast cell diseases is built on four key pillars. First, lovers deep understanding of the mast cell biology and to moderate its activity. Second, select the best targets, modalities for monotherapy and combination strategies to achieve first and best in class positions. Third, establish a strong preclinical and early clinical POC or proof of concept to de-risk development. And lastly, pursue pipeline opportunities in major mast cell associated disorders where there is a medical need. We will continue to provide updates on our mast cell franchise throughout the course of the year, including BRU808 IND submission on track for this quarter, which will enable us to initiate the healthy volunteer study. We will also initiate part two of the Harbor trial for LNS in indolent systemic mastocytosis in the second half of this year. As we expand our mast cell focus, we continue to drive innovation in systemic mastocytosis as our understanding of the spectrum of patients and the underlying biology of the disease evolves. Moving from allergy and inflammation to our oncology part of the portfolio, we are happy to report for the first time at the 2024 ASCO meeting, the safety and the signal of early clinical activity of BLU222 in combination with ribocyclic and full vestrant in hormone positive hertune negative breast cancer patients. We believe these data clearly demonstrate the first and best in class potential of BLU222 to become the combination partner of choice with CDK46 inhibitor in hormone positive hertune negative breast cancer. With this, I will turn it over to Mike to discuss our financial results. Thanks,

Gaurav. Earlier this morning, we reported detailed financial results in our press release. For today's call, I'll touch on a few highlights. In the first quarter, total revenues were $96.1 million, including $92.5 million in net product revenues from sales of Avakit and $3.6 million in collaboration and license revenues. As Felina discussed, Avakit revenue was driven by continued strong and steady growth in patient starts, positive trends underlying extended duration of therapy and favorability in the mix of commercial patients. Given the strength in Q1, we are raising our Avakit product revenue guidance and now expect to achieve $390 to $410 million in net product revenue in 2024. We've had a stronger than expected start to the year and we are still learning about the seasonal trends and impacts in ISM as we make our way through the first year of launch. Our guidance philosophy is to provide our best understanding of where we may end the year, given the various puts and takes on revenue, both in the US and EU each quarter. This update relatively early in the year reflects that commitment. The increase in today's guidance reinforces that we are on our path to capturing Avakit's peak opportunity of greater than $2 billion. This revenue growth, coupled with expense discipline and focused investment, is what continues to give us confidence in achieving a financially self-sustaining profile. Our total costs and operating expenses continue to decline and we're $174.9 million for the first quarter. We anticipate that our research and development expenses will remain relatively flat for the remainder of the year with some quarter to quarter variability. We also expect our SG&A expenses to remain relatively stable as we continue to gain operating leverage from our commercial infrastructure. We believe that the current full year sell side consensus for total costs and expenses of approximately $715 million, which includes non-cash stock based compensation expense, reflects an appropriate estimate for 2024. We remain in an exceptionally strong and durable financial position with $735.6 million in cash on hand. Avakit's revenue performance and today's guidance increase, coupled with our continued focus on managing operating expenses, will result in our goal of further reducing our cash burn in 2024. Our solid financial profile drives our ability to generate long-term value as we invest in the commercial success of Avakit and advance an innovative portfolio of medicines. With that, I'll now turn the call back over to the operator for questions. Operator.

Thank you. At this time, I would like to remind everyone in order to ask a question, press star, then the number one on a telephone keypad. We'll pause for just a moment to compile the Q&A roster. Your first question comes from the line of Brad Canino from Stiefel. Brad, the line is open. Please ask your question.

Thank you. Great quarter. Kate, I remember back at the Quad AI meeting in February, you referenced a strong sense of ISM awareness and the desire to treat patients. And the company also had a strong presence at the meeting. So in your view, how much of that awareness momentum is baked into the trajectory exiting the quarter? And what does the team still see as headroom? Thank you.

Thanks for that question, Brad. And to your point, I think one of the things that was very notable about Quad AI this year was just in comparison to the year previous where we were kind of introducing Blueprint for the first time and showing the Avakit pivotal data for the first time. And then here we were kind of sitting with a large group of now people who had clinical experience with the drug and were treating patients, which was such a kind of notable step change to your point. So basically, we want to talk a little bit about how our awareness, the impact of awareness in healthcare providers, the growing prescriber base and how that's really fueling our future growth this year and beyond. Yeah, thanks for the

question, Brad. And to your point, Quad AI, certainly we could, the excitement was palpable from treaters across the academic and community setting. That said, I would still say we're still just getting started with significant headroom to grow. The team has the ongoing pace of interactions of regional meetings, the cadence of Congresses throughout the year. And I think as we really look at our lead indicators on the provider side, with our breadth and depth of prescribing, this is a really strong foundation for continued growth and certainly leaves significant headroom for continued penetration, not just into the top 400, but well beyond that into the broader treating community. In addition, touching on some of the direct to consumer initiatives, we're really excited to really be rolling out the next wave of engagement for patient activation. And that also leaves significant headroom to grow in sort of patients awareness and likelihood to ask their providers of Avacit. All of those, we think bodes exceptionally well that we are well on that path towards that over $2 billion peak opportunity for Avacit.

Thank you. Your next question comes from the line of Mark Fran from TD Cowan. Mark, your line is open.

Hi, thanks for taking my questions and congrats on the quarter as well. Maybe following up on Brad's question, how are you seeing maybe trends leading indicators to get into that bigger population that hasn't been well diagnosed historically, things like testing rates and stuff like that to really access maybe the next 10,000 patients that you've talked about being out there that haven't been cared for historically. And then related to some of that, just with the top line really taking off here maybe Kate and Mike talk about kind of the goal of getting the profitability. How important is that for the company, particularly as you start thinking about things like 808 coming in that could have a very broad development program ultimately?

Yeah, thanks for the questions, Mark. Maybe we'll start with talking about how we see, I mean, we're building a brand new market here with Avacit and SM and how we think about the different kind of avenues of growth to building that market. That's some of the things you mentioned already, which is the increasing rate of diagnosis, which is a critical part, but also the fact that we know that there is a number of patients who are diagnosed and that we are just kind of starting to penetrate. We have a lot of room there as well. So, Felina, how do you think about both penetrating the currently diagnosed group versus the opportunities to continue to grow the overall size of the market?

Yeah, I would say thanks for the question, Mark. First and foremost, if we just look at the patients who are already diagnosed, which continues to steadily increase, penetration into that patient population already represents an over $1 million opportunity and that's where sort of like here and now primary focus is dedicated. And you spoke to sort of the, there are multiple prongs for continued growth and you spoke specifically to continued growth and diagnosis. There we are really focused on continuing to drive initiatives like the high sensitivity kit testing, the disease awareness, the sponsored testing from Blueprint. And we're really encouraged to see significant increases in the volumes of high sensitivity kit testing, especially even in the allergy segment where that's really important. And even beyond that, we know there are further levers for growth for AvaKit and that's adoption into a broader range of patients, sort of widening that line of who is seen as not well controlled, as well as expansion into further geographies. And we're seeing, as I said, really strong initial performance in our international launches. All of this bodes really well towards that peak opportunity.

Yeah, and one thing maybe to add there is, this feels very similar to other rare disease launches we've seen where the epidemiology and these disease states tend to be kind of dated and very small studies that inform that. And what we're seeing is even in our sponsored testing, patients coming out of other pools of patients, be that MCAS or others, that I think have been very much underrepresented in the current epidemiology. So we'll be providing more views on that as it comes, but our view is this market has a long way to go in terms of continuing to grow the number of patients on therapy, as well as the number of patients who are diagnosed with this disease. Maybe now turning to your question about the importance of profitability and how we think about that. Do you wanna start? Yeah,

I'll start. I think, Mark, I think the key is, we're trying to build a sustainable business for the longterm. And so part of that is making sure that we stay laser focused on our top priority investment areas, such as Blue 808, which is upcoming, and that requires financial discipline and focus, but longterm, we're looking to find these key value drivers where we can add longterm value to the company, and that's the longterm goal.

Yeah, and just adding, I completely agree. And I think one of the things we've been known for at Blueprint Medicines is our research and development capabilities, and we have a just tremendous opportunity to continue to drive innovation and to make really meaningful impacts on patients. I think Blue 808 is certainly in everyone's radar, but we have some of our favorite programs we haven't had a chance to talk to anybody about yet. And so we're looking forward to talking about our continued innovation in this space.

Great, thank you.

Thank you. Your next question comes from the line of Michael Schmidt. Michael, your line is open.

Hey, good morning, this is Paul on for Michael. Thanks for taking our question and congrats on the quarter. Mine's on advocates for the ex-US opportunity. I know you mentioned Germany is sort of driving European sales this year. Do you still see a roughly 10% contribution to this year's full year sales? And how are you currently thinking about the longer term trajectory in Europe, perhaps beyond this year? And then maybe just squeezing one on CDK2, any updates on sort of the color or the tenor of the progress of your partnership discussions for that? And are these exclusively on Blue 222 or perhaps more broadly for the CDK franchise? Thank you.

Yeah, Michael, thank you for those questions. I think one thing is that the European team has just done a tremendous job out of the gates with ISM approval at the end of December, with Germany really coming on strong in terms of getting patients onto therapy. And so they've done a tremendous job there. So Christy, how do you think about the overall contribution for Europe and its growth trajectory? And maybe also, could you take the BD covered question as well?

Sure, thanks, Paul. Yeah, we're really pleased with the performance of the international team. As Kate said, they're very much off to the races. And I think it's been particularly encouraging to see that some of the underlying dynamics in the German launch early on have looked very similar to the United States, including where we're seeing prescribing, et cetera, lots of patient demand. So really encouraging to see. Of course, there's other dynamics in Europe that are different from the United States, and most notably, that would be price negotiations. So some of those cards will start flipping this year and then into next year as well. So when I think about the overall opportunity in Europe, it's certainly significant. It's gonna be a contributor to our overall top line. But for this year, as I said, that 10 to 15% of revenue, as a rough estimate, is probably not a bad place to be. This frankly is one of the levers that we think about when we're trying to set guidance ranges. This is a variable that informs how we may perform over the year. But I think 10 to 15% is probably a good estimate. And then at peak in markets like this, we'll see how things evolve in the coming years as we continue to grow the opportunity. But you often would see the US still representing certainly the majority of the dollar value of the SM opportunity. And as Felina said, it's very easy math to get to a multi-billion dollar opportunity just in the US based on what we are seeing. In terms of CDK2, as we said in the prepared remarks, very, very excited about the data set that we're gonna be sharing at ASCO. We really see this as the first data that we'll be showing that you can safely combine a CDK2 inhibitor with a 4.6. Our partnership discussions are progressing well. We've always been very clear that second half of this year is when it makes sense to have a partner on board strategically based on where the program will be heading as we exit this year and into next. And certainly, as we think about the tenor of those conversations, our focus is on CDK2. That's where having a Bluetooth 2.2, having a partner on board to advance the program makes the most sense. Of course, there's a lot of innovation in our pipeline that partners may be interested and excited by. We always have those conversations and we'll continue to do that.

Thank you. Our next question comes from the line of Laura Brendergast from Raymond James. Laura, your line is open.

Hey, guys, congrats on the great print today. Another one on CDK2. You know, thinking about how the cost of CDK2 impacts your OPEX flux throughout the year, I'm assuming you guys are looking to outlicense and not cost share. If you could just provide any input here about how you're thinking about how you're gonna CDK2 moving forward.

Yeah, thank you, Laura. Maybe, well, Christy, we start with just strategically how we're thinking about BD and then, Mike, maybe you can weigh in on just how you, any kind of impact on financially. Yeah,

sure. So from a strategy perspective, we've always been very intentional using business development to advance programs and really complement what our own capabilities and our own sort of internal priorities may look like. And certainly at this stage, as we said, we are very focused on continuing to really develop a broad portfolio in mass cells-driven disorders, certainly executing the ongoing on-chababic kit. We have LNS-Nib and Blue808 coming behind that. CDK2 is a very, very significant commercial opportunity and one that, because it's primarily in breast cancer, is obviously in a somewhat different space. And so that's really the driver behind us having these conversations. We'll be open as we go through, in terms of what the exact structure will look like, but we have a partner on board because we think, we think the capabilities that our partner brings are relevant to how we advance it. I always think about having co-development, co-commercialization makes sense in places where you're trying to build and leverage scale. In the short term, breast is not a place where we're trying to build and leverage scale. So again, we'll continue to advance those conversations as they make sense, but we have a very clear idea strategically of what we're trying to accomplish.

You know, I think with respect to the financials, you know, we obviously don't comment specifically on partnership structures or financials at this point. It's too early, but for 2024, you know, we're continuing to execute on our phase one study. That's baked into all of the financial guidance that we've given. We feel very confident about that. And then longer term, you know, as Christy mentioned, strategically, it makes a lot of sense to bring a big partner on, you know, and part of that is driven by the fact that these studies to move forward in breast cancer are gonna be very expensive and we want partner to, you know, both strategically as well as financially help support us there.

Thank

you.

Thank you. Our next question comes from the line of Salvin Richter from Goldman Sachs. Salvin, your line is open.

Hi, thanks. This is Matt on for Salvin. On Blue 808, could you talk about your strategy for determining which indications to expand into after proof of concept has been established in chronic uticari? Thanks

so much. Well, do you wanna start and talk about 808?

Thank you. Yeah, I mean, for Blue 808, and I actually would encourage you and others to really go back and listen to the live replay of our powerful mass cell from last week where we treated this topic in depth. The way we are thinking about it is, as we said, chronic uticari is our leading indication. On the other hand, given the profile of the molecule, we believe is really a very good profile and we are finding the IND and taking it to the clinic this year, it's really look at a number of other indications because the involvement of mass cell in the biology of numerous diseases is clearly and well established now. We'll be doing a lot of preclinical work in other indications, but also we're doing proof of concept clinically for a number of indications and we see where we really think the full scope is and how to line up the additional indication beyond chronic uticari. So we believe this molecule, if the clinical profile is consistent with the preclinical data that we are seeing, has the opportunity to really tackle a number of diseases and therefore we'll have to look at the POC for many of them.

Thanks Matt, I may just add that we also believe that the profile of the compound and the fact that we have an oral therapy here is gonna enable us to be able to kind of tune the therapy to address different patient populations across all these different disease states. We think we're really well positioned in terms of the target product profile of the compound to evaluate this and bring forward what truly will be a pipeline and a pill opportunity.

Got

it, thank

you. Thank you, your next question comes from a line of Ren Benjamin from Citizens JMT. Your line is open.

Hey, good morning guys, thanks for taking the questions and congrats on an amazing quarter and really good guidance. That's the question for me, of the top 400 or so in prescribing physicians, how many are prescribing and what's the split between allergists and hematologists? And as we think about reasons that eligible patients might not be being prescribed the advocate, are there any reasons, is that a potential group of patients that is incorporated into that kind of headroom calculation of how the area could grow and how do you plan on addressing that, thank you.

Yeah, thanks Ren, I mean, for me maybe to address both how we see kind of demand coming from the physicians who have the most patients as well as out of physicians from the tail and how you see that kind of dynamic in terms of demand and penetration, as well as talking a little bit about kind of the cadence of new patient starts and how that is informing our growth into the future.

Yeah, thanks for the question Ren. I would start with the initial breadth and depth of prescribing that we've established in these first three full quarters of launch in ISM, sets a really strong foundation for us, both in terms of the breadth of the penetration, what you wanna see in rare disease is not that it's concentrated in just a handful of centers, like what really fosters, plants the seeds for sustainable growth and continued growth is that breadth of prescribing and the fact that we're seeing adoption across both hematology, oncology, as well as allergy immunology and split across academic and community settings is extremely important and is a great lead indicator for continued growth. When we look at the top 400, that's really something that we laser into to illustrate what we see as more the kinetics of prescribing, it doesn't speak to the full penetration, because that's really just a snapshot of the highest volume providers. But so what's really important I think to see from that is that first prescribing is really leading to positive experiences that lead to subsequent repeat prescribing for two, three or even more patients. Even within that mix, we see a really great mix of allergists, immunologists, hematologists, but I think headroom just across all segments and defiles of providers to continue to grow there. In terms of your question around eligible patients and prescribing there, the most important thing that we're focused on is identifying when a patient is not well controlled and that is really, that's sort of like a crux across both our provider engagements as well as patient engagements. From a patient perspective, patients can also become acclimated to living with a new normal, they may be avoiding triggers and so it's really important to make them aware of a new treatment option and that reclaiming some of the freedoms of their prior life is actually possible. And so really our direct to consumer efforts are really focused on driving that and again, there are a lot of headroom to grow.

Thank you. Our next question comes from the line of Derek Archela from Wells Fargo. Your line is open.

Hey, good morning and congrats on the quarter. Was hoping maybe you could discuss some of the assumptions behind the updated guidance. It seems to suggest a slowdown in that patient ads relative to the prior quarters and I guess, trying to reconcile that with the very bullish commentary and the prepared remarks, thanks.

Yeah, thanks Derek. I think just to start there, when we think about, Mike has talked about philosophy on guidance and we are in the early days of building a brand new market and so as we think about the low and high end of our updated range, it's driven by ranges around a multitude of different inputs across numerous variables. I don't know, Flynn, if you wanna talk a little bit about how you think about all those variables, but we certainly expect continued growth and the overall opportunity.

Yeah, Derek, I think the first answer to your question is no, we do not expect a slowdown in net patient ads. We see strong and steady growth in the net patient ads and we expect that to continue. This past quarter, we saw that really driven by a strong cadence as new patients starts, very low discontinuation rates, which really penned well, I think, for chronic durations of therapy. And that's also, there are a number of additional key revenue drivers that contribute to our guidance in addition to that continued strong and steady growth of net patient ads that we expect. So it's things like our compliance, the proportion of free goods, which exceeded for this quarter and is something we'll be looking to see how that evolves over the course of the year, as well as things like our ongoing European launch. And so it's the inherent variability in these key revenue drivers moving forward that factor into our guidance range. All of that said, if we look at sort of the midpoint of that range, that represents nearly a doubling of the revenue that we achieved last year. And we believe it firmly does put us on that trajectory towards the peak.

Got it, thank you.

Your next question comes from the line of Peter Lawson from Barclays, the line is open.

Thanks so much, thanks for taking the questions. Just as we think about the ISM patients, you mentioned there was kind of a low discontinuation rate. Anything else you can kind of comment around those patients, whether there's any shifting compliance after essentially 10 months of use and any sense of drug holidays, for instance? Thank you.

Yeah, thanks Peter for the question. I think one of the things I think the team has just done a tremendous job in Q1 is, and we know that Q1 can often be very challenging kind of across, as Polina mentioned, her prepared marks across pharmaceutical industry and biotech. And they just did a tremendous job on executing the re-verification process and making sure that compliance stayed very high. But I don't think since launch, have you thought about seeing anything that you would say that's thematic from a patient discontinuation perspective?

Yeah, thanks Peter. So what we've seen in terms of discontinuation rates so far has been very much in line with what we've expected when we see AVICIT's really favorable benefit risk profile from Pioneer. So discontinuation rates have been low. The very early trends towards duration of therapy have been very, very positive. And we've even seen a lengthening on the advanced SM side. To your question around sort of compliance and holidays, in fact, that has also trended extremely positively in terms of patients staying on therapy. When we think about this patient population, they're very sticky, right? Like they have a regimen that they are adapting to and they're really not taking those holidays. And so this is a really important point because as we progress in the launch and we increase the total number of patients on therapy, it's not just new patient starts anymore, but also the cumulative effect of these patients remaining on therapy that will contribute to overall revenue growth. Yeah, I think that

last point is really important in the sense that as that pool of patients on therapy gets so much larger, point changes in compliance and or free goods make a big difference from a revenue perspective. So I think that we're certainly seeing that.

Your next question comes from a line of Matt Bigler from Oppenheimer. Your line is open.

Hey there, congrats from us as well on the quarter. I'm curious if you're seeing any signs of growth in advanced SM maybe because of the increased prescriber awareness from the Inglund launch or I guess should we just still think of advanced as pretty flat going forward? Thanks.

Yeah, I'll just start quickly to say, I mean, we are so pleased to see that the duration of therapy in advanced SM being at 25 months. I mean, I think these are pretty good results for patients with very, very aggressive disease. And I think that bodes well for both the advanced SM opportunity as well as the read through to the ISM opportunity. But you wanna talk about the growth and number of new patients in advanced SM?

Yeah, Matt, so I would say we do continue to see growth on the advanced SM portion of our business. That's obviously relatively moderated compared to ISM, which is our primary growth driver and now represents the majority of patients on therapy with AvaKit. But we do see, I think a potential kind of halo effect that with the now the awareness of AvaKit for ISM as our breadth of prescribing increases, what's happening, not just in allergy, but also with a number of new hematology oncology prescribers as well who are activated and interested to get involved through ISM.

That's great, thanks.

Your next question comes from the line of Amy Fadia from Needham. Amy, your line is open.

Thanks, congrats on the quarter. My question is on Blue808. What data do you need to generate to understand your go forward clinical development plan for indications beyond chronic agitaria? And how soon can you start to initiate clinical trials on those indications? And separately, if you could provide any additional color on how you're planning to develop LNSNIB, any update from Priesis, thank you.

Amy, thank you for those questions. Rebecca, do you wanna talk about the data you wanna see at 808 and how we're thinking about getting those broad group of concepts as well as the plan for harbor study with LNSNIB, which as we've said before, Amy, LNSNIB is really positioned to maximize the long-term performance of our SM franchise. And so we certainly are gonna be spending more time talking about that in second half this year.

Yeah, Amy, so Blue808 being our exquisitely targeted wild-tie kit inhibitor is one that we're taking into healthy volunteers first. And that's obviously to get the initial PK and tolerability, but it also gives us an opportunity to see the ability of the drug to reduce trip days, even in normal healthy volunteers. And we believe that that'll give us a good steer of what the therapeutic range may be in patients. And as Kate mentioned earlier, this is a very tunable drug where we expect to be able to use it across a wide range of therapeutic doses. And that may be as a single agent, as we illustrated in our mass cell webcast last week, where the mass cell is really the driver like chronic urticaria. And then we've shown in our Bluetooth 2 program, in our AGFR program that we make highly combinable and that's gonna be the essence of that next wave of investigations where we're looking in more complex diseases where the standard of care is well established, such as asthma, where the combination is gonna be necessary to really forward the field in those indications. And so as we enter into patients next year, that'll give us a sense of what our dose range is for patients who have mass cells that are causing disease. And then we'll be able to look at, as Flood said, in a number of different more complex indications and understand where that therapeutic range is and get a quick brief of concept in those indications. And then with respect to Alanastinib, as we've said, we are getting more and more data as we study the patients on Pioneer and we learn more from commercial patients about the really complex nature of systemic master cytosis and the broad breadth of patients that can benefit in many different ways. And so we look forward to sharing more before the end of the year about our design of Harbor and really our holistic approach to the development of Alanastinib and ESM.

Your next question comes from the line of Colleen Cousy from Baird. Colleen, your line is open.

Great, thanks, good morning. Thanks for taking our questions and congrats on the quarter. Any commentary on how you're measuring the early success of your DTC campaign and what your plans are to invest further in the second half of this year?

Yeah, so I think, headed to Felina, I think our -to-consumer campaign really is evidence of our conviction that we have a tremendous opportunity to help just a vast array of patients with ISM. Felina, how do you wanna think about those efforts and how we make sure that we understand their bearing fruit?

Yeah, Colleen, one of the most direct things that we look at is the patient's awareness of Avakit and we've been really encouraged that the efforts to date have already increased the unaided awareness of Avakit eightfold while continuing to have a lot of headroom to grow. So this is really an area that we will continue to lean into in a highly targeted way. We know where these patients are looking for information on the disease and we're really targeting both our media campaigns and another thing we've talked about is the monthly opportunities we have for patients to come together with other patients to share their experience on Avakit. That element of patient storytelling is so important in a rare disease where in many cases an SM patient hasn't yet met another patient, so the opportunity to connect, hear about their experiences and what the journey to Avakit has been like for them, we believe will be really compelling. So we do expect to continue growing on these initiatives through the second half of the year in a highly targeted way.

That's helpful, thank you. And as a follow up, just in your early market research, what's resonating most of the patients to keep them on treatment and what gives you confidence in maintaining this low discontinuation rate in the future?

Yeah, Kelly, I think that really is a testament to Avakit's clinical profile. I mean, patients, it's a highly tolerable drug, easy to take, I mean, we saw in the Pioneer study that the side effect profile of Avakit was superior to standard of care and the kind of cocktail of symptomatic treatments that patients are on. And then it's testament to the activity and the fact that we see clinical impact across a wide range of symptoms in patients. I think it would not be a good idea in such a heterogeneic disease, that is absolutely critical. And that a patient, regardless of what their most bothersome symptom is, is seeing great impact in Avakit. I think that is just a profound kind of equation for people that we see as resonating and patients are staying on. Dr. Deeb, do you have something to add?

Yeah, I think this is, a couple of questions have piqued my interest. The one about drug holidays and then this one about convincing patients to stay on the drug. You know, as Kate said, when they feel better, they don't need to take holidays. They don't need to be convinced to stay on the drug. And so that really speaks to also the way that allergists think about treating this disease and having a very tolerable therapy and treating patients, see how they do. And it just speaks to why there's consistent treatment duration. And I also wanted to comment on the advanced SM duration. You know, we're into two years in a leukemia like disease. And that really bodes well for the endolent situation as well.

Yeah, Elena, do you wanna add? Yeah, maybe I would add on Colleen. These are patients who are really highly motivated to regain quality of life and just to share, I think even just some sound bites from engaging customers across the country who've shared some of their patients experiences is what we hear is patients getting their energy back, being able to go back to work at the jobs that they had to pull back on previously due to the symptoms of SM, the ability of patients to participate in activities with their kids or friends or loved ones, going to camp for the first time and really reclaiming and starting to remember what normal looks and feels like. So it's really kind of a profound thing. And I think we really are even just at the beginning of this journey.

Great, thanks for taking our questions.

Thank you. Our next question comes from the line of David Lubowitz from Citi. David, your line is open.

Hi, this is Devangina on behalf of David. On the free patient proportion, I wanted to ask that the levels went from 25% to 20%. How should we think about patient growth versus actual sales growth? And what proportion of patients will be on free does by the end of the year? And I have one more follow-up.

So unfortunately, we have to limit to one question just because we're coming on close to time here. But so I believe the question is around, how are we thinking about just the overall dynamic relative to free goods, again, being very early in the launch of a new therapy and building a new market? Selena, how are you kind of thinking about that as you kind of gave this view of around 20% since launch? And how do we think about that as a driver of top line versus some of the other variables, including compliance, new patient starts, our European launch, all the other things that are adding into top line?

Yeah,

so

to your question, I think there's really a couple of things that factor into our free goods mix, as we saw that decreased to 20% this quarter. So it's both the payer mix of patients with ISM, which trends more towards commercial. The second piece is that more patients were able to access paid therapy. In terms of what to expect through the rest of the year, free goods mix is really something we'll need to continue to watch, because as you said, more patients will continue to add on and be treated with Avakit. So we're in the early days of the IRA, and so we'll need to watch how that plays out. Our expectation continues to be continued strong and steady growth in the number of patients on therapy, favorable, low discontinuation rates, high compliance. We'll watch the free goods mix and continue to watch our international launches.

Thank you. There are no further questions at this time. I will now turn the call back to Kate.

Thank you, operator. We feel great about the progress we've made in Q1, and we recognize that there's a lot of work ahead of us this year. And as we move forward into the middle of the year, we do so from position of strength. We are well positioned to build on the momentum we've achieved here coming out of Q1, and we look forward to updating you on our progress. So thank you all for taking the time to join us today and for your continued support to Blueprint Medicines.

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