Blueprint Medicines Corporation

Good morning, my name is Angela Lang and I'll be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicine's FASTQ 2025 earnings release and 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 section. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, Press the star followed by the number T. Please plan to limit yourself to one question. Thank you. Jenna Cohen, you may begin your conference.

Thank you, Angela. Good morning, everyone, and welcome to Blueprint Medicine's first quarter 2025 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 investor section of our website at www.blueprintmedicines.com. Joining me today are Kate Haviland, Chief Executive Officer, Felina Lee, Chief Commercial Officer, Becker Hughes, Chief Medical Officer, and Mike Lansdell, Chief Financial Officer. Fuad Namuni, President of Research and Development, and Christy Rossi, Chief Operating Officer, are also on the line and available for 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. Your caution 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 at Blueprint Medicine strive to be a standout top-tier biotech company with a core focus on innovation, commercial excellence, and maintaining a durable financial profile that enables disciplined global investment across our portfolio. Following strong performance in 2024, we've continued our executionable momentum in 2025. This quarter, we achieved 61% year-over-year advocate revenue growth. as we continue to capture the substantial and growing multibillion-dollar commercial opportunity and systemic mastocytosis, which we expect will drive our global revenue growth well into the next decade. With every additional quarter of performance, Avakit progresses on the path to our goal of $2 billion in revenue by 2030. The underlying fundamental demand, driven by growth in patients on therapy, is the critical determinant of long-term revenue potential. And we are pleased that our results in Q1 reflect continued strength in this metric, as we expected. This strong fundamental growth, coupled with significant favorability in our free versus paid good mix, is leading us to raise our revenue guidance for the year. Felina will go into this more specifically in a moment. We also advanced our industry-leading pipeline of mass cell-directed investigational medicines. Our two prioritized pipeline programs, LNS to them, and Blue808 have the potential to drive significant upside value for Blueprint as they progress in the clinic this year and beyond. With Blue808, our wild type kit inhibitor, our goal is to raise the bar on what a treatment for a wide range of allergic and inflammatory diseases can offer by considering the full patient experience, efficacy, tolerability, and the burden associated with administration. Blue 808's early clinical profile supports our differentiated approach to development, allowing us to explore a range of doses as well as dose regimens. As we announced this morning, Blue 808 has achieved key milestones with the initiation of two proof-of-concept studies, one in allergic rhinoconjunctivitis and one in chronic urticaria. We hope to be able to share some early data this year from these studies, which Becker will talk more about later on the call. L-anestinib, our next generation kit D816V inhibitor, has the potential best in disease profile that builds on our years of experience in SM. Given the strong receptivity of Avakit by both physicians and patients, we know it is not enough to incrementally innovate with a follow-on medicine that will enter the market years after Avakit. With the pivotal Harbor study up and running, We have a plan to deliver substantially differentiated and meaningful innovation with LNS NIP that goes beyond symptomatic control to measures of organ healing and disease modification. Blueprint's durable commercial growth profile, strong cash position, and disciplined capital allocation strategy afford us the ability to focus on executing our business to plan, despite the broader market volatility. With our intellectual property being domiciled in the US and our low cost of goods, we are insulated from potential biopharmaceutical tariffs and do not anticipate any material impact on our business. In terms of the staffing changes at the FDA, we do not have any major regulatory filings planned over the next 12 months, and we have not experienced an impact in our routine engagements with the agency to date. We will, of course, continue to monitor the rapidly evolving external environment and work to mitigate any changes that do impact our business. Our results today are possible thanks to the impressive team of people we have at Blueprint Medicine. And I thank them for their thoughtful and urgent commitment to the people whose lives we set out to improve every day. With that, I will turn it to Felina to discuss the quarter's commercial performance in more depth.

Thanks, Kate. In the first quarter, we achieved $149.4 million in Avakit global net product revenues, with $129.4 million in the U.S. and $20 million ex-U.S. Our strong commercial execution drove revenue growth in what we expected to be a challenging quarter due to the typical Q1 financial headwinds inherent in our industry. Let's walk through the headwinds and tailwinds. The short-term financial headwinds we've discussed previously played out as we expected, including typical first quarter insurance dynamics impacting gross to net and the impact of fewer ordering days. With our growing base of business, these factors can have a meaningful impact on a quarter. As Kate mentioned, fundamental demand growth driven by a growing number of patients on therapy is a critical determinant of long-term revenue potential. This is a function of more patients starting and staying on therapy. We're pleased that Q1 met our expectations as we saw growth in new patient starts, both in the US and in our international business. This continuation rates remained low and we continue to see encouraging trends towards multi-year duration of therapy in both advanced SM and ISM. A key variable we were watching this quarter was our mix of free versus commercial goods as we managed through the Q1 reauthorization process and monitored the impact of the Part D redesign and foundation funding availability. This played out more favorably than we expected, with our free goods rate now well below 10%. As a result of these favorable dynamics, today we are raising our guidance range to $700 to $720 million for the year. We are exactly where we want to be at this point in the year. and we are well-positioned to drive growth through the rest of 2025 and beyond. We have a clear view of the SM opportunity in front of us as we move further down the path towards $2 billion in advocate revenue by 2030 and a $4 billion peak SM franchise opportunity. SM diagnoses are increasing globally, and with approximately 25,000 diagnosed SM patients in the U.S., we know we're in the early innings of market penetration. Roughly 20% penetration of currently diagnosed patients in the US alone gets you to $2 billion in annual revenue. We expect to grow new patient starts through the end of the year and beyond. Of course, it all starts with the right medicine, Avakit, an effective therapy with a broad label that addresses the root cause of disease and is also very well tolerated, enabling patients to start and stay on therapy over the long term. Becker will discuss the growing body of evidence supporting Avakit's long-term benefit in SM. In addition to Avakit's compelling clinical profile, we know that what drives prescribing in this market is the powerful combination of an aware and ever-expanding educated prescriber base and an activated patient base. both recognizing the benefit and urgency to treat the root cause of disease with Avakit now. Let's start with prescribers. Since launch, we've been focused on increasing the breadth of our prescriber base through education and awareness. Driving awareness among allergy has been a key focus and is critical to long-term growth, as the providers managing the highest volume of SM patients are predominantly allergists. A first experience with Avakit predictably leads to broader use in more patients, so a growing foundation of experienced providers, prescribers, directly drives growth in the number of patients starting Avakit over time, increasing market penetration. Since ISM approval, our prescriber base in the U.S. has tripled, with adoption split across academic and community sites of care. Against the backdrop of a growing number of diagnosed patients, this creates an engine to drive growth in the number of patients prescribed Avakit. What really catalyzes deepening of use over time are positive perceptions and experiences with Avakit. Since ISM launched, we have conducted market research with over 700 providers. Initial favorable perceptions of Avakit from the Pioneer study results have grown even more positive with firsthand clinical experience and now with longer-term data. Across all specialties, even dermatology and gastroenterology, where we haven't yet started to deploy promotional effort, the vast majority of providers view Avakit's profile as favorable. Since launch, we've been targeting hemox and allergists. Hemox treat less than a third of all ISM patients. We've talked about the importance of allergy for the long-term opportunity, and by expanding our call point to include DERMs and GIs, we will meaningfully increase the addressable patient pool. Across these specialties, roughly 70% of the providers managing the highest volume of SM patients are allergists, DERMs, and GIs. This is why we're investing in expanding our field team to increase our reach and frequency where it matters most. Our field force expansion is designed to capitalize on where the majority of SM patients are treated. We have just hired new team members who are onboarding and training. They bring a diverse set of experiences with an emphasis on allergy, dermatology, and rare disease. They'll be in the field by second half of this year, and I look forward to the growth that they'll catalyze in 2026 and beyond. Avakit's positive reception among providers is matched by growing enthusiasm in the patient community. SM patients are highly engaged and active in their care decisions, and we're starting to see the clear impact of marketing efforts launched last year, including new direct-to-consumer and peer-to-peer programs. Providers report that significantly more of their ISM patients are asking about Avakit compared to last year. And once patients are on treatment, they have a very positive experience with over 95% of patients saying they're highly satisfied with Avakit as a treatment for their SM. The SM market is highly promotionally sensitive with the top two drivers being the efforts of our experienced sales team who are outperforming industry comps in promotional effectiveness scores and our direct to patient marketing efforts. Our growing base of experienced prescribers An increasingly engaged and activated patient base and the compelling profile of Avakit put us in a great place to drive growth in 2025. But we're not just focused on this year. We are on the path to driving continued growth towards $2 billion in revenue by 2030 and are committed to continue to grow this market well into the next decade. We plan to drive that growth by taking this same powerful combination of aware and educated prescribers with activated patients and amplifying it with a strategic investment in our field. We are confident in our multifaceted approach to develop and capture this market. I'll now hand the call over to Becker to share clinical updates across our portfolio.

Thanks, Paulina. First, I want to talk about Avakit's long-term data in systemic mastocytosis that we presented at Quad AI and that Felina just referenced. What was remarkable in Pioneer is that the safety profile of Avakit was superior to best supportive care at six months, a rare occurrence for an efficacious treatment. Now, after three full years of treatment, we see the same safety profile. This is extraordinary in my experience. Generally, the safety profile becomes more complex over time. But for Avakit, the frequency and severity of treatment-related adverse events have been consistent and remain low throughout three years. And importantly, only 3% of patients discontinued due to treatment-related adverse events over this extended timeframe. The 25-milligram dose of Avakit provides an exceptional benefit-risk profile for the vast majority of patients. In our real-world post-marketing experience, more than 90% of patients who start at 25 milligrams stay at that dose. Patients are highly compliant, satisfied, and our discontinuation rates are very low. However, we know that there is a spectrum of disease severity in systemic mastocytosis, and a one-dose-fits-all approach is not appropriate in this disease. The Pioneer study included patients with very high disease load. We've enabled more severe patients to dose escalate to 50 milligrams in part three of the study. We recently presented data showing that these patients have had a safety profile consistent with that we've seen at 25 milligrams. Efficacy continues to improve for pioneer patients, as indicated by durable responses measured by TSS and quality of life measurements through three years. Among the patient subsets in Pioneer who titrated their dose to 50 milligrams, 93% of patients saw improved or stable TSS benefit at 50 milligrams without any tradeoff in safety. We're expanding our commercial and medical reach to an even larger target physician audience of allergists, dermatologists, and gastroenterologists with multiple years of consistent data demonstrating that AvaKit is a safe and effective treatment in hand. This helps drive comfort in trying a new therapy and prescribing a new kit. Finally, we continue to advance the science of systemic mastocytosis in the HARBOR study of elanastinib. Our study design explores disease-modifying measures of clinical benefit, notably the impact on bone health and recurrent anaphylaxis. These have been enthusiastically received by investigators and may report also from patients interested in the study. Turning now to our wild-type kit inhibitor, Blue808. At Quad AI this year, we presented data from the Healthy Volunteer Study. And with this promising data in hand, we're moving into four proof-of-concept studies this year. We know that a strong safety profile is critical in the field of allergic disease. And with Blue808, we have a wide therapeutic index to work within. We're building in a range of flexible dose strategies across these studies. including consistent dosing, induce and maintain, and titrate to effect, which we know is in line with how allergies treat. We've initiated our first two proof-of-concept studies, one in allergic rhinoconjunctivitis and one in chronic urticaria. We will be initially testing doses between one and six milligrams. This covers the IC90 well and will allow us to examine a spectrum of biologic impact that ranges from calming or stopping mast cells from degranulating to killing them entirely. This will allow us to determine the impact on symptoms so that we can achieve the right balance of safety and efficacy for chronic treatment. I'll start with chronic urticaria, where the role of mast cells as the key driver of disease is already well established. In our proof of concept study, we're using this indication to explore various dosing regimens for BLU808. Our initial 12-week Phase IIa study will include two key parts, an open-label study of patients with chronic inducible urticaria, or CINDU, and a randomized double-blind placebo-controlled study of patients with chronic spontaneous urticaria. Both parts will include multiple doses and dosing regimens. Our goal is for Blue808 to become an attractive oral option that achieves that balance of tolerability and efficacy and differentiates us from the rest of the field. Now, let me turn to the Phase IIa study in allergic rhinoconjunctivitis. We see this as a way to demonstrate the activity of Blu808 in the respiratory tract. This is a 28-day placebo-controlled challenge study where patients are exposed to allergens, then treated with Blu808 or placebo, and then re-exposed to compare their before and after treatment reactions. Similar to chronic urticaria, in this study, we will assess multiple doses for safety, PK, and clinical efficacy. We expect to have some early data by the end of this year in the CINDU cohort. In the second half of the year, we plan to initiate studies in allergic asthma and in MCAS. We discussed the role of the mast cells in allergic asthma at our webinar last year, and similarly plan to share Blueprint's approach to MCAS at our webinar on June 4th with Dr. Matt Giannetti, the leading expert in mast cell diseases at the Brigham and Women's Hospital here in Boston. Results from these proof of concept studies will help guide Blue 808 development plans as we work towards improving the lives of patients with mast cell-driven diseases. Now, I'll turn the call over to Mike.

Thanks, Becker. Earlier this morning, we reported detailed financial results in our press release, and for today's call, I'll touch on a few highlights. In the first quarter, we achieved total revenues of $149.4 million from net product sales of Avakit. Based on the positive fundamentals that Felina discussed, as well as the additional insight we gained around free goods and Q1, we are raising our Avakit net product revenue guidance to $700 to $720 million for the year. Consistently strong fundamentals and continued growth in new patient starts in all markets will continue to drive performance through the remainder of the year. For our international business, the timing and outcome of ongoing pricing and reimbursement negotiations are another consideration. Turning to operating expenses, we observed an incremental quarter-over-quarter increase in R&D expenses related to LNSNIB and Blue 808 clinical studies. SG&A expenses were flat in the first quarter relative to the prior quarter, and we anticipate that we will see continued modest increases in both R&D and SG&A expenses as we invest in our priority pipeline programs, as well as increase investment in our sales and marketing efforts for Avakit, as Felina spoke to in detail earlier on the call. We continue to expect that our operating cash burn will decline significantly on an annual basis. To reinforce what Kate said earlier in the call, we are in an incredible position of strength today, particularly when you consider the macroeconomic environment. We have strong and consistent top-line revenue growth driven by global sales of Avakit, the ability to continue to invest in innovation to drive future growth, and a strong and durable cash position of $900 million. Our commercial and financial profile stands out among biotech as a positive differentiator. And now more than ever before, we are in a position of incredible strength to drive sustained growth for the long term. With that, I'll turn the call back over to the operator for questions.

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

Thanks for taking my questions. First, on the commercial side, can you frame the type of rebound in growth or acceleration of growth you might see in Q2, given the fact that the free goods is already so low, which maybe limits some of the typical Q1 to Q2 rebounds that we see across the industry? And then on the R&D side, for the 808, just talk to the strategy on the dose selections that you put into those products. you know, are the two doses supposed to really kind of test that intermediate range with the titration? Or are you trying to, you know, maybe with the top dose really show the full power of 808 and ability to get close to it without matching the antibodies?

Thanks, Mark, for that question. Maybe, Christy, do you want to talk a little bit about how we've considered kind of the fundamental growth and drivers of demand as we think through the year? And then maybe, please add color. Becker, you can add into the question on the mic, please. Yeah, sure.

Hey, Mark. So, you know, if we think about the year, we obviously updated guidance. And so if I think about the remaining three quarters, Um, I would certainly think about the guide and that guide does imply, you know, growth, which is really what we expected when we, when we set guidance at the beginning of the year as well. We always knew that Q1 was going to be, um, challenging for all of the reasons that Felina said, but you know, what we expected to see was, you know, strong underlying growth in terms of those drivers of the longer term potential for Avakit, which includes patient starting, um, persistence, duration, et cetera. And so, and that's exactly what we've seen that's played out in line with our expectations. And so if you kind of play that forward through the year, we would expect to see growth in the remaining quarters. You know, the one wrinkle we saw in Q1 around sort of a shorter quarter from an ordering perspective, I believe, if I'm not mistaken, is made up actually in Q3, interestingly enough. But, you know, we definitely expect to see, you know, nice steady growth as we go through the remainder of the year.

Let's say in our results this year, really our big card flip in Q1 was around how we're going to see free goods play through. And I know, Selena, do you want to talk a little bit more about that?

Yeah, as we entered the year, I think one of the biggest variables that we had that informed our guidance range was that we had a large book of business, i.e. a really large number of patients, and we didn't know to what extent these patients would be able to transition and access paid versus free goods. Over the course of Q1, this is a big variable that has been tremendously de-risked, and that has been one of the the key drivers for our guidance update together with the expected growth in the underlying fundamentals, i.e. growth in patients on therapy, as Christy just said. So I think at this point, thinking about the free goods trends, looking for the rest of the year, certainly, you know, the range has narrowed. We have a better sense of the range to expect. You know, we're below 10%. We don't expect, you know, this to be able to really be able to go appreciably down further. And really, over the rest of the year, we'll need to be watching as new Medicare patients come on therapy, their ability to access commercial versus free drug. But I would just take it back to the trajectory that we're seeing in Q1, we firmly believe puts us on pace for our guidance, as well as marching towards that $2 billion by 2030. Do you want to talk about the motorcycle question?

Sure. Let me talk about the dose range of blue 808 and how we selected this and what our strategy is here. Just a reminder that we do have all three regimens, one which is consistent dosing, the other which is an induce and maintain, which will look at speed to symptom resolution and then our ability with a lower dose to maintain that symptom resolution, and then one where we will allow titration to the effect. And I think it's important to remember that in many diseases, including chronic urticaria, there are a multitude of symptoms. And really driving the relief of the patient at the right dose is what we're exploring. And we're doing it in a way that the antibodies really can't do. So we're going to better understand the biology of the disease and the response with respect to the symptomatology as we use these different dosing strategies. And the intent of the study is to really set things up for the next phase of studies in chronic urticaria and in other indications where we get the optimized dosing for each of these indications. As we said earlier, the 1 to 6 milligrams gives us a range that covers the IC90 well. And all mast cells don't die at once. And so we'll look at different levels of killing in different patients. to better understand killing dose and a dose that's designed to calm down the mast cells. With respect to comparisons, again, these studies are designed to help us understand how to use the drug, and then to understand the full efficacy in the next wave of studies, we will bring that optimized dosing into a more definitive study.

Thank you. The next question comes from Laura Prendergast with Raymond James. Your line is open. Hey guys, congrats on the progress this quarter.

Just maybe to reiterate that question, you know, what exactly have you guys baked into the guidance? You know, any expected seasonality, EU contribution, any specific tailwinds or headwinds on new starts that you expect? And then just if you guys could comment on part two harbor data, you know, when should we expect that? Any L&S data priced into the $2 billion by 2030? Sorry, the $2 billion by 2030, is that pricing in L&S being on the market? Thank you.

Thanks, Laura. Just a reminder, everybody, let's try to keep it to one question, just given the number of people we have in the queue. But we'll try to handle some other things offline if we can. Maybe, Kristen, or Christy, excuse me, will you take the guidance question? And then, Becker, we can talk about Part 2 Harbor. I can just clarify right away. There's nothing from an LNS NIP perspective in the $2 billion by 2030 that's completely driven by Avocat. And we expect Avocat to grow beyond that, to be honest. So just so I can take that one. Christy, do you want to talk about guidance?

Sure. So, you know, the factors that we think about with guidance are very much consistent with how we framed it at the beginning of the year, actually how we talked about it last year, right? So, you know, the two biggest determinants in my mind of Avakit getting to $2 billion by 2030 and the $4 billion opportunity we see across the SM franchise over time is is really treating more patients, right? So having patients start on therapy and having them continue to stay on therapy. So those are the two, you know, big drivers. And, you know, we expect to see, you know, growth in new patient starts as we go through the year based on our expanding breadth and depth of prescribing that we're seeing in the US and increasingly activated patient base, et cetera. This is obviously, you know, still in the context of our disease market, you're going to see fluctuations there, but the overall trend line is, you know, clear and positive. We expect to see strength and duration of therapy as patients are staying on therapy for, you know, we think three plus years, potentially multiple years here. And so, you know, those are two of the most important variables as we go over time. Then there's a number of other things that, you know, actually may have more impact in the short term. And so, you know, we think about gross to net, free goods rates, you know, et cetera. And then, of course, our international business is coming along. So those continue to be the most important variables. You know, as Felina said, we had a major, I would say, car flip in the first quarter by understanding – how a very large base of patients who are now on therapy, as they went through the re-verification process, understanding how that free commercial mix was going to play out, we knew was going to be important. We knew that was going to be a big swing as we thought about top line revenue. And so We're really pleased to see how that played out in the first quarter and also pleased to see continued strength along the other variables that we mentioned that really, again, portend that longer-term potential. So those are still going to be the things that we'll continue to watch. There's ranges of outcomes on all of those variables, but pleased to see that we were able to raise the guidance off of Q1 performance. In terms of quarter-to-quarter performance, We know our business. You talked about things like seasonality, et cetera. We've, you know, we're now far enough into this launch where I think we have a good sense of, you know, how these factors will play out in terms of impacting quarter to quarter revenue. We've baked that into the guide. And in fact, it baked it in, you know, when we started the year and expected Q1 to kind of play out as it did.

Decker, do you want to talk a little bit about Harbor? Obviously, we're just getting this up and running now.

Yeah, so we're just starting the study. We have a highly motivated group of investigators, and I'm hearing patients as well who are very interested in the study. As we see the evolution of systemic mastocytosis in the world and we see how this study unfolds, we'll be able to keep you all more well-informed about when we might see top-line data, but I think it's premature to speculate at this point.

Thank you. Your next question comes from the line of Michael Schmidt with Guggenheim. Your line is open.

Hey, this is Paul from Mycola. Thanks for taking our question. Just on AdaKit, so for the XUS, it looks like it was sort of flat quarter on quarter. Can you just comment on what your overall expectations are for the international market drivers this year, including when ISM reimbursement beyond Germany could start to kick in? And then maybe a quick follow-up, you know, on those escalations that you mentioned in ISM patients, you know, your quad AI data suggested around a quarter escalated to 50 milligrams. What's your current visibility into what percentage of commercial patients have moved to 50 for ISM? Thank you.

Yeah, thanks for the question. And we'll start, Chrissy, we'll take international. And then I know you talk a little bit about what we're seeing in dosing. One thing I should say is the international team has just done a tremendous job. And their year-over-year performance more than doubled from Q1 last year. So we're really excited about where we are. But do you want to talk about the Q4 to Q1 dynamic, Chrissy? Yeah, absolutely.

So, right, as Kate said, you know, the international team has been doing very well. We've talked about the fact that, you know, if we think about just contributions to the top line, last year we expected it to be sort of in that 10% to 15%. range this year on a much bigger base. We expect it to also be within the 10 to 15% range, right? So, you know, the international team continues to perform and we're seeing nice growth there. It's important to remember that Germany is the only ex-U.S. market with ISM reimbursement at this point. We do expect some others to come online through the year, but, you know, we'll really start to see ISM growth across a number of markets as we head even into next year and beyond. You know, the business in Germany is doing quite well. We're continuing to see trends that look very similar to the U.S., which has been really encouraging to see. So nice growth in patients being treated, very similar trends in terms of uptake. You know, fluctuations can happen quarter to quarter. There were some, you know, things between Q4 and Q1, for example, like timing of distributor orders, which can be lumpy. A little bit of FX at the beginning of the year. We're still talking about a relatively small revenue base relative to the U.S., right? So these little factors can obviously, you know, have a role when we look at Q on Q. And we've seen that before if you go back and look at international performance over the last year or so. But, you know, the bigger picture is that business is doing well. German launch is doing really well. And we're, you know, looking ahead and looking forward to having some other ISM launches come online.

And to the question on dosing, the 25-meg benefit-risk profile, continues to serve the vast majority of patients very well. It's under 10% of patients that we're seeing who may dose escalate to 50 mg over time, and this is occurring against the backdrop of the profile of the 25 mg holding strong and improving with continued long-term efficacy and safety outcomes. We also see this reflected in just the really positive sentiment for Avakit reflected in both our provider and patient satisfactions.

And just one thing to add to that is that even, you know, what Becker showed you from both the safety and efficacy of the 50 mg is that what we see is that, you know, with Avakit at 25 mg or 50 mg, patients don't have to weigh a tradeoff between efficacy and safety. And they can experience a very low treatment burden that really allows them to just get back to their lives and kind of, you know, with a medicine that really empowers them to live and do the things they want to do. So both the 25 and 50 have really come through in a very nice way for these patients.

And the other thing to remember is that the pioneer population was a highly advanced patient population, you know, enrolled in the middle of a pandemic, first study out there with a really effective therapy. And so it's probably not indicative of what will be seen in the real world.

Thank you. Your next question comes from the line of Michael E. with Jefferies. Your line is open.

Thanks. Good morning. Congrats on the continued growth. I'm thinking about growth for the rest of the year. I know you've gotten a bunch of questions about headwinds and tailwinds and different dynamics. Can you help give some color as to perhaps the trajectory or shape of the curve in Q2, Q3, Q4? Is it sort of consistent year over year growth each quarter? Are there different things that impact those quarters? And as part of that, perhaps even OUS, given that it appeared to be more flattish and just wondering if that's a factor as well into any of these quarters for the rest of the year. Thank you.

Thanks Michael so I think what you're asking is as how to think about kind of the remainder of the year, you know, obviously we're really focused here and how we're exiting the year, because that is what. really drives us to that laser focus on that $2 billion by 2030, but understand that you guys want to kind of get a sense of how we're thinking about the quarters. I don't know, Mike, if you want to provide a little bit of color on how you think about that.

Yeah, I'll start. I mean, I think, you know, what's most important is to put this in the frame of what our updated overall annual guidance is and using that, like that's the benchmark that we're guiding to. And as we've talked about before, like each quarter can have unique variables in the U.S. and international. I think the one thing that Christy mentioned that we you know, did want to point to, if you think about like the growth, especially over like Q2, Q3, it's like we've talked about, we've missed an order day in Q1, right? That actually gets made up in Q3 in the calendar. And just for context, our biggest customers tend to order on the same day each week. We had one less of those in Q1. It gets made up in Q3. So right there, you're going to see a differential dynamic between Q2 and Q3, where you'd say there's probably a little bit more shifted into the Q3 period. But fundamentally, I just point to consistent underlying patient growth. And that's been as expected.

and we continue to to you know drive towards that as we as we go for our updated guidance range thank you your next question comes from the line of calling kusi with bad your line is open great good morning thanks for taking our questions and congrats on all the progress uh one quick one from us for the growth this year can you talk to how much of that is driven by the newer specialties that you're going after in DERMs and GIs versus the allergists and hemolytics that are your first target prescribers?

Yeah, thanks, Colleen. Do you want to talk about how you're thinking about the prescriber mix this year versus, you know, next year, I guess? Yeah.

Yeah, thanks for the question. So, I think as Christy started alluding to, we expect growth, we expect to drive increased treatment rates and growth in the number of patients on therapy. We have a strong engine in place to do this already with what we've established across our target specialties and an increasingly activated patient base. So I would say a primary driver for growth over the course of this year is really that activated prescriber base and our ability to both grow and expand that as well as deepen it over time. Our chart shows we understand very well the dynamics of how a first patient starts and then a positive experience leads to growth and deepening over time. Secondly, we see more and more patients coming in and asking about Avakit, showing that our direct-to-patient efforts are really working, and we expect this to also catalyze growth over the course of this year. As we shift into the newer specialties, we think this will enable us to further amplify these efforts. There's really an untapped opportunity of additional SM patients. who are being seen by derms and gastros. I think what we've learned from this market is, you know, hemox alone are only about a third of the opportunity, so we know it's important to expand. Our objectives with derms and gastros are really the ability to move these patients towards treatment, whether or not they're literally the prescribers at the outset, but they can also refer to our very strong and growing prescriber base. And we expect this to further catalyze growth, you know, really in 2026 and beyond.

So just for clarity, Felina, we really do expect our primary prescriber base to be that growing base of allergists, our stable base kind of of the hemong group, which sees the minority or the smaller group of patients, and then the growth into GIs and derms will really be 2026.

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

Hey, good morning, and thanks for taking the questions. I just want to understand how durable a sub-10% free drug rate is, and I wonder if you could characterize how the patient ads have trended in April relative to 1Q. Thanks.

So, Doug, we don't really talk about kind of the ongoing quarter, but we can certainly talk about our view of the durability of the free patient goods rate. And just to note, it's actually well below 10% at this point. So, Selena, do you want to talk a little bit about how you're thinking about that for the rest of the year, the free goods rate?

Yeah, I think what we're really emphasizing is we've majorly de-risked the variable of free goods by just moving this big base of patients. This large number of patients have been able to access commercial therapy and and that's been due to the availability of foundation funding, the ability of patients to navigate the new smoothing process. And so we also feel like, you know, with this type of floor, you know, there's probably not room for this to further improve, but we expect that rate to remain relatively durable over the course of the year. Now, of course, what we'll be watching is as new Medicare patients come on, how able will they be to access commercial therapy? And that depends on factors like, you know, how long will foundation funding continue to be available as well. But I would say, you know, it's the de-risking of the patients who have already moved, which have led to a favorable, more favorable than expected upside. That's one of the key factors in our updated guidance range. But really, it's the underlying fundamentals that we expect continued growth in patient starts and patients on therapy that we expect to grow throughout the course of the year.

Thank you. Your next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open.

Hey, good morning. This is Mark on for Salveen. Thanks so much for taking our question. You guys mentioned you may show 808 data from the PSV studies in Sindhu this year. In your view, what is the bar for 808 in Sindhu and also in allergic rhinoconjunctivitis, and how do you think this will compare to the antibodies here?

Yeah. In terms of the cadence of the data, we're going to need to see how the enrollment goes. Sindhu is a relatively rare case. form of the disease, and we'll update you all as we know more about how the enrollment's going. And as I stated earlier, in terms of the bar, I think they're going to have to stay tuned over time to really understand the full efficacy of 808 in these diseases, because what we're really trying to do is learn the optimization of the regimen and which symptoms matter most to the patients and how quickly we can resolve these with various testing regimens of 808.

I think for the allergic ARC study, again, we're watching enrollment there. The study is up and running. And again, we hope to have some data by the end of the year, and we'll kind of keep you guys posted on both of those as we continue to execute those programs.

Thank you. Your next question comes from the line of Brian Chen with JPMorgan. Your line is open.

Hey, guys. Thanks for taking our question. Can you elaborate a little bit more on the drivers behind the flat growth XUS this quarter? Is the flat growth there driven partly by the negotiated price? Thank you.

Thanks, Brian. I think as Christy was mentioning, the underlying fundamental growth in terms of growing patient starts and keeping patients on therapy was exactly where we expected it internationally. As Christy had mentioned, we do get some lumpiness in terms of our distributor markets in particular, and there was some pull forward ordering in those markets in Q4 that really just kind of influenced the dynamics between Q4 and Q1. I think what's most important is that the international growth year over year nearly doubled. And as Christy mentioned, we're just in Germany right now in ISM, and we're going to have more of the larger markets coming in line this year. And so it's flat from a revenue perspective. It's certainly not flat growth from an underlying fundamental demand perspective.

Thank you. The next question comes from the line of Fran Benjamin with Citizens. Your line is open.

Hey, thanks guys for taking the questions and congratulations on the quarter and the raise of guidance. I'd love to just learn a little bit more about the metrics you guys use to gauge the success and failure of the DTC advertising strategy. Those tend to be quite costly and I'm curious as to how you evaluate that. And I think, Felina, you mentioned that there'll be promotional efforts that you're going to employ to dermatologists and gastroenterologists. Wanted to see how big that physician pool was and whether this would increase the total pool of diagnosed patients or that 25,000 that you mentioned already is, you know, taking into account the dermatologists and gastroenterologists.

Yeah, thanks, Ren. I mean, all DTC is not the same. And we certainly have a more targeted approach here. But, Selena, do you want to talk a little bit about what we do from a DTC perspective? And then also just kind of the universe of additional specialties we're looking to target.

Yeah, absolutely. I would say that our direct-to-patient efforts are really focused on two things. The first is increasing the awareness of Avakit as a new treatment option. And the second is really creating opportunities for patients to hear from the very positive experiences of other patients who have benefited from Avakit. And so we use a lot of metrics. I think it really comes down to the growth in awareness in Avakit non-users. Obviously, we've seen the number of users increase, but continue to drive the awareness of Avakit using our direct-to-consumer ads. We are, I think, importantly executing on these initiatives in a highly, highly targeted way for this rare disease market. And some of the, I think, most resounding metrics we've seen is more patients going into offices asking about Avakit as well as the growth that we're seeing in the patients who are starting. To your question about dermatology and gastroenterology, I would say it's a bit of both things that you mentioned. The first is there's already an untapped opportunity of already diagnosed SM patients being treated by these additional specialties. And secondly, you know, we would actually expect us to grow the treatment rates over time, which can lead to some of that longer-term sustained growth.

Thank you. Your next question comes from the line of Ami Fadia with Nihao. Your line is open.

Hi, good morning. Thanks for taking my question. If you think about the sort of different buckets of physicians, the derm and gastros, the allergists and the hemoncs, can you give us a sense of, you know, what's the mix of the patients that are being treated by each specialty? And maybe give us a sense of your penetration in terms of reach and frequency where you are today and then how you see that evolve with this expansion into the DERMS and GASTROS data this year. Thank you.

Catalina, do you want to talk a little bit more about our specialties?

Yeah. So I'd say there are a number of SM patients being treated across all of these specialties today. It's our conviction in the market opportunity that's really triggering us, I think, to invest in expanding the field force, which enables us to increase reach and frequency across the allergists and hemox where we've targeted primarily to date, as well as expand into the derms and GIs. I would say there's incredible headroom across all of these specialties to continue the growth. Most of the prescribing to date has, of course, been in allergists and hemox. One of the things we've been really pleased to see is that the growth of breadth of prescribing has actually been faster into allergy. And we know this is really important to capture that long-term opportunity. And again, for derms and GIs, we are just getting started. And, you know, we know that they are both treating an already diagnosed number of SM patients, but there are also patients coming in who can increase that diagnosis rate. They're presenting with, you know, cutaneous mastocytosis in the dermatology offices or things like IBS with some other signal of systemic involvement in the GI office.

Maybe one thing I'll just add is that, you know, as we think about, you know, Avacyn it really is the opportunity, the long-term safety data that really lowers the bar as people think about the patients who could really benefit from the treatment. And so we all use these kind of measures of TFS score, and we try to classify patients as moderate, mild, severe, all these things. That's really a regulatory tool. And what we see out in clinical care is it's about a patient and whether or not they are well-controlled and whether or not they can do the things they want to do, go to work, participate in family events. And what we know is that there's a lot of patients who cannot do across all of these specialties. And that's really the clinical context in a commercial setting that is very different than a context that we need for a regulatory approval. And so I think the fact that Avacyn is so well tolerated, we have three years now plus data, really makes us believe this is the right moment to be continuing to expand an allergy and moving into GI and derms who we know will be very positively received that clinical long-term profile.

Thank you. Your next question comes from the line of Peter Lawson with Barclays. Your line is open.

Hey, good morning. It's Alex on for Peter. Thanks for taking the question. Just a quick one on the new field force you've hired. Could you quantify that relative to the most recent or, I guess, existing sales force? Thank you.

So you want to talk about the size increase? Yeah, so this is an incremental field force expansion that will enable us to both increase our reach and frequency on the current prescriber base, as well as to expand to these other specialties. But importantly, we're able to do this in an incredibly targeted way, leveraging the strength of our analytics to know where patients are engaging most frequently across these specialties. You know, I think the key piece sort of underlying all of this is like most of this market we can see resides outside of hematology. And so this is an important lever for us to continue to drive growth in allergy as well as moving into other specialties.

Thank you. Your next question comes from the line of David Dive of CVS. Your line is open.

Great. Thanks for taking my questions. I just wanted to drill down on the advocate prescriber base. Last you mentioned that, you know, as you're expanding to the dermatology and the GI prescribers, how should we think about the compliance rate of these patients, given that these patients could be living with moderate symptoms?

Yeah, David, that was a little bit to what I was mentioning, is that it's The idea of milder symptoms is not really the pull through here. In a clinical care setting, it's patients who do not have enough control over whatever their symptoms may be to be able to do the things that they want to do in life. Really, in the commercial context, that is the context. It's around, is a patient well controlled or not? The rubric of patients being kind of more severe versus less severe across specialties is really not relevant for the commercial setting like it is for a clinical development setting.

The only thing I would add to that is that our commercial compliance across the board has been exceptionally high, which I think just speaks to the profile of Advocate. Once a patient makes a decision to start on therapy, we see patients doing really well. They're staying on therapy. They're highly compliant, and they're stickies.

Thank you. Your next question comes from the line of Judah from with Morgan Stanley. Your line is open.

Hi, thanks for taking the question. Just to follow up on the urticaria indication for 808, I'd be curious how you're viewing unmet need in in Sindhu and CSU, whether the DUPICS and approval in CSU affects that and whether risk-benefit profile could be viewed differently by derms versus allergists? Thanks.

Hi. Yeah. So, just first of all, I think that in most of these diseases, having a small molecule daily oral solution is really what patients are looking for. And so, we were pleased to see that Dupixent had the activity that it did, really helping everyone understand that this is a chronic inflammatory disease. But we still believe that addressing the mast cell directly, which is the driver of the disease, is the right way to approach it, and that a small molecule will be the preferred solution.

Thank you. Your next question comes from the line with Sudan, Logan Nelson with Stevens. Your line is open.

Hi, good morning. Thank you for taking my questions, and congrats again on the sales results for Avocates. So my question is, you know, regards on the progress with L-inestinib, Blue 808, and goals to nominate your first protein degrader programs, you know, how's your OPEX spend breakdown between the commercial and development programs prioritized? Is the profitability and free cash flow in the cards potentially this year? Or could we expect any of those earnings from Avacate to be reinvested into the pipelines?

Yeah, Mike, do you want to take that?

Yeah, sorry. Yeah, this is Mike. Yeah, so I mean, as we've talked previously, like capital allocation and prioritization has been one of our key priorities really over the last couple of years to make sure that we are investing in what we see are the greatest opportunities to drive, you know, top-line growth, both now with Avokit and in the future with Pipeline. And so we've been really disciplined on You know, both being able to make sure that we're investing appropriately and advocate, but also targeting within our pipeline, where we think we have. You know, the greatest potential to drive growth. So it's not so much like we're, we're expecting to see, you know, modest increases, as I mentioned in both SG and a spend and R and D spend, because we'll be investing in both areas to drive, to drive again, both near-term and long-term growth. And I think in a specifically, we don't typically break down like within the pipeline where that program spend is going, but clearly LNS and 808 are going to be the top priorities, uh, in the year term to drive that.

And one thing I would just add is that I think we, we have a really good track record here at Blueprint at, as, um, in terms of business development strategy. And, you know, I think we are very committed to maintaining a durable financial profile, making sure we're sustainable. and able to kind of invest in the highest, you know, prioritized drivers of growth. And if there are programs that, you know, either we believe we would benefit from a partnership in terms of execution and or maybe not our highest strategic priority, we have a track record of having outlicense those. And, you know, for instance, just recently we put a program in the hands of IDRX and, you know, we just received $80 million at the beginning of this year due to that transaction. And that was a program that we chose not to move forward ourselves, but certainly needs, you know, was beneficial to move forward in someone else's hands. So we will continue to look at using business development to enable us to first and foremost, meet our corporate strategic interests. And then secondly, to make sure we're maintaining that really sustainable financial profile.

Thank you. That's all the questions we have time for today. Kate Huffington, I will turn the call back over to you.

So thank you, everybody. We are off to a very strong start here in 2025 with Avakit firmly on the path to realizing its multibillion-dollar peak opportunity. We're advancing our pipeline. We have the assets in place, we have the strategy in place to really achieve our goal of fundamentally shifting the way allergic inflammatory diseases are treated by targeting the mast cell. So we thank you all for your continued support of Blueprint Medicine, and we invite you to continue to follow our progress throughout this year.

Thank you. This concludes today's conference call. You may now disconnect.