Citizens JMP Life Sciences Conference. It's my pleasure to introduce Blueprint Medicines. Presenting for the company is Kate Haviland, CEO, and Becker Hewes, CMO. Welcome, both of you. Thank you for being here. So it's always a distinct pleasure for me to welcome Blueprint. It's one of our favorite names. We've been talking about it for a while. Not too many biotech companies become commercial stage, and those investors who follow biotech for as long as we have know that b ut Blueprint is one of the exceptions. So thank you guys very much for coming here. I never know who exactly is in the audience and who's watching us from the webcast. So I always like to start these sessions with maybe just a 2- 5 minute overview of what Blueprint's about. Yeah. So first, just thank you, Ren, for having us a nd thanks to the entire JMP team. Appreciate the people who are here and everyone who's joining us online. So very excited to talk about where we are at Blueprint Medicines. So from the perspective of an overview, I think we have just tremendous momentum at Blueprint Medicines. For those of you who don't know us, we are a fully integrated biopharmaceutical company. A s Ren just mentioned, we are now bringing the medicines that we discovered in our labs and developed through the company over the last years to patients commercially globally. S o it's a very exciting time at the company to be in that phase in terms of having really a fully integrated infrastructure and expertise and being able to see the impact our medicines are having very broadly on patients around the globe. So this year, our three kind of key imperatives, which we have great momentum around, the first is to execute on AYVAKIT's launch in indolent systemic mastocytosis, or ISM. I'm sure we'll talk a lot about that today. The second is to advance our pipeline of very innovative and exciting programs, particularly in the area of allergic inflammation, with our next generation or our first, excuse me, wild-type KIT inhibitor, BLU-808. R eally, with this investigational medicine and some of the other things we have going on our pipeline, we aspire to fundamentally change how diseases of allergic inflammation are treated a nd that is by going after the primary effective cell in many of these disease states called the mast cell. T hen third is to be able to both drive our top-line revenue growth as well as invest wisely in great growth drivers for the future while maintaining financial discipline and a self-sustainable, durable financial profile, which we're well on our way to doing as well. So I think those are the three key areas we're focused on this year a nd as I said, we have great momentum around each. So let's dive right into it. AYVAKIT, your flagship drug. Got approved originally in PDGF-alpha GIST, then SM, Advanced SM, then ISM. Maybe you can just take us through these different indications and how they're leveraged, right? One existing sales force. I guess ideally, how should we be thinking about the kind of peak market potential of each? Yes. So as you said, we've now had the AYVAKIT approved in three different indications. I think our PDGF-alpha-driven GIST indication was really the first where we showed proof of concept and the ability to very much change the outcomes for patients with this mutation, which is actually homologous to the D816V. The D816V mutation is the mutation that is causal in the spectrum of systemic mastocytosis, which goes from advanced systemic mastocytosis, and these are patients who have a life expectancy impact from their disease. It can be six months to three years, depending on whether you have mast cell leukemia or aggressive SM, to indolent systemic mastocytosis, which we got approved last year. What's important about indolent is that it is 95%-90% of the overall systemic mastocytosis population. So with that approval, it really enables us to now launch AYVAKIT into a very broad population of systemic mastocytosis and to drive kind of significant top-line revenue for the company. I f you think about SM, where kind of epidemiology sits in the U.S., we'd estimate there's probably 30,000-35,000 patients who have systemic mastocytosis. We updated at the beginning of the year in January that we see about 22,000 of these patients in U.S. claims data today. So we can see diagnosed patients a nd that rate has grown significantly over the last three or four years since we've been developing AYVAKIT and then also got it approved in the advanced setting. S o at this point in time, we're really penetrating into what is a substantial rare disease population, particularly with that ISM approval. So I love the rare disease kind of story a nd one of the other companies we cover is Incyte. M yelofibrosis is kind of that quintessential poster child, if you will, right? It started off, people thought it was a $500 million market. Suddenly, later on, it became a billion-dollar market potential a nd now we're closer to $3 billion market potential. S o I feel like ISM is kind of on the same path for that. Maybe you can talk a little bit about the different pillars that are part of your strategy to gain market share and grow the market. Yeah, absolutely. I think first, to your point, Ren, I mean, we look at the SM opportunity as being a greater than $2 billion market. We are great students of amazing drugs and launches like Incyte with Jakafi or Soliris and PNH a nd we see a lot of parallels and similarities to how we see SM, which is there was no approved treatment before AYVAKIT. So we're building a new market where patients have predominantly been receiving symptomatic-directed therapies, nothing that's been specifically designed to address the underlying cause of their disease a nd what we're seeing and what we know is just by looking at claims data, if we just focus on the U.S. for the moment, we can see about 9,500 patients who are what we call not well-controlled. We assess that by looking that there are multiple prescription therapies that are directed towards their SM, which means that they're being treated for SM, and they're being treated to try to address multiple symptoms they may have and continue to engage heavily with the health care community. If we were to penetrate about 1/3 of those patients, let's just call it 3,500 patients at a point in time, that would be $1 billion in the U.S. alone a nd so when we say we can see a $2 billion + opportunity, that's really based on just the prevalent population of currently diagnosed SM patients. But to your point, we've also been growing that market. I think we've seen this in other rare disease settings where once you have an effective therapy, physicians are much more motivated to go and find these patients and to work up patients where they may have a clinical suspicion that they could have SM. But previously, there wasn't really much that you could do with a definitive diagnosis. S o we have seen the diagnosis rate actually increase substantially since 2019, where we could see about 11,000 patients in U.S. claims data to now 22,000 patients who are diagnosed and being treated for their SM in the U.S. So those are U.S. numbers only, so you can think about that as international as being scaled up from there. So I think we have the opportunity to continue to grow and make diagnosis more efficient, which we've been doing, and that's been effective. We also got a label last year upon the approval that we studied moderate to severe SM patients in our registration-directed study. The label we got from the FDA was for any adult patient with indolent systemic mastocytosis. What that allows is physicians and patients to really have much more latitude in thinking about who is an appropriate patient for therapy. We do see patients who are coming on who wouldn't have been qualified to enter into our PIONEER study. So these are patients who may have one specific symptom that greatly impacts their quality of life, their ability to leave the house and go to work, their ability to socialize. So already we know that that aperture can open for advanced patients and are able to easily get access to therapy even if they aren't what we had considered moderate to severe. That was the entry criteria for the PIONEER study. Got it. I always like to early on in launch, there's so many different factors that you're trying to tackle. I guess what kind of keeps you up at night in terms of things that either worry you or you know that you know what, you're going to have to handle? I guess how much does competition weigh into these sleepless nights? Those are great questions. I think, first of all, the launch is off to an incredible start. So in our third full quarter of launch, we had $92.5 million of revenue exceeded our expectations internally and we can talk about some of those tailwinds a nd it shows that we are reaching patients, and we are able to kind of convert patients onto therapy. Importantly, patients are staying on therapy. T hat's what we expected with the profile of AYVAKIT being so strong, both on its efficacy as well as its safety profile. S o I think as we see that growing number of patients on therapy, that is a consequence of multiple things, to your point. It's new patient starts, it's compliance, it's durations of therapy. We're also launching in the EU. So there's a lot of variables, all of which have kind of error bars. We're not even a full year into this launch at this point. But when I think about the areas we're focused on, really awareness and education is a key in rare disease launches. I think what we've seen is great awareness among the health care provider community a nd we've really made inroads in terms of growing the breadth of prescribers who now have some experience with AYVAKIT. W hat we see is when a prescriber gets a patient on therapy, they tend to then go look and put additional patients. So then we see depth growing as well a nd that's been a tremendous foundation we've set over the last three quarters in ISM. It's seen that breadth and depth. W here we're focused now this year is more on the awareness and direct to patient. So we're doing quite a few activities now going direct to consumer with both educational information about what does it mean to be well-controlled. Many patients who've been living with ISM, and Becker Hewes can speak to this too, have adjusted their lives in ways that they don't even remember what they've done. They've isolated themselves. They've limited what they can do in their life to try to avoid triggers. They don't work outside the home. They don't go to events. They don't go to family gatherings a nd that may be that they've found a way to control their disease. But is that really how you want to live, particularly if you have a therapy that can address an underlying cause? I think we've seen a lot of stories and anecdotes of patients who've kind of regained their life on AYVAKIT. Yeah, the term that I hear most often is a new normal a nd people have lived with this disease for 10, 20 years. They've learned how to deal with it. A s Kate said, often they're not going to work. J ust the opportunity to try something that's going to potentially give them back control of their symptoms, that concept of control is really important b ecause when you have a chronic disease, either that disease controls you or you control the disease, and this is the first opportunity that people have to control their disease. T hen what we've heard repeatedly is they feel better than they ever have. A lot of times, people who have had a disease for 10, 20 years start to attribute some of the symptoms to just getting older or being worried about things. As they experience AYVAKIT, they really start to feel like a new person again. SM is interesting. It's kind of a mimic disease. It looks like inflammatory bowel disease. It looks like just random flushing. It looks like menopause. S o one of the reasons that the patient population is expanding is people start to share their experience of what symptoms they're losing, a nd then people that they talk to, even family members, are saying, I feel like I have something like that a nd so the number of patients that are being tested is much larger. We have our sponsored testing program that looks just with peripheral blood testing at D816V prevalence a nd that's really given practitioners an opportunity to screen patients where they have a suspicion. S o that's really led to a lot of the expansion. You can tell we have quite a well-rested, not too many sleepless nights imagine team up here. Yes. Competition. You want to talk? Yeah. So I think what we know is when you have a greater than $2 billion market where you're the only approved therapy, that competition will absolutely be coming. Right now, we just don't see anything that we think is commercially relevant. I think AYVAKIT sets an incredibly high bar in terms of what can come multiple years later and in the bar that something needs to exceed in order to win market share in this space. I n fact, as we have a next generation wild-type KIT inhibitor called elenestinib a nd it's a challenge for us to think about how are we going to bring that forward. I think we've learned a tremendous amount about the biology of this disease. S o we think we have a way to bring that forward and have a differentiated clinical profile, not because it's different from a molecular perspective. It is slightly different b ut more about how we develop it with a deeper understanding of the disease state. S o I think, honestly, Ren, we're going to out-innovate ourselves before anyone out-innovates us. Yeah, I think that so elenestinib is our non-brain penetrant D816V inhibitor. So in addition to not being commercially relevant, I don't think we've seen anything that's biologically relevant either. Every D816V inhibitor out there has similar potency a nd what's really important, particularly in the indolent disease, is really being able to dose to effect. Allergists are used to dosing patients with the lowest effective dose and then working their way to the right dose for the patients a nd that's the approach that we've taken with avapritinib. A s Kate said, we're looking at a much broader patient population with symptoms that are similar to what we've looked at in the PIONEER study, but really looking at patient populations beyond that. You mentioned some really nice revenue numbers. I have it written in our notes as a blowout quarter. That's how I felt. When we saw it, it beat our estimates. You raised guidance, which is always a great thing to see. Not a lot of companies do that, especially early on in launch, because you're still pretty unsure. I guess I'd love to understand a little bit more of the factors that go into your evaluation before you actually raise guidance, so the factors that help you with that confidence. Yeah, absolutely. So guidance for us, I mean, so first of all, it was tricky for us to provide guidance this year in January when, again, we only had a couple of quarters of ISM launch. W e are still understanding the seasonality. Every quarter has its own personality in terms of what can be going on Q4 with holidays, Q1 with benefits re-verifications. You often see compliance and gross-to-net hits for people. So we really do want to see all four quarters before we feel like we can have a better handle on the ISM market. But I think what we also want to do is help get us all into the same playing field. What we try to do with guidance is say, this is our best estimate for how we think we're going to end the year with a multitude of variables, all of which have a range of possible outcomes around them. So the Q1 results were a surprising upside for us as well. I mean, again, we expect the continued strong and steady growing of patients on therapy, which we continue to see. That is an expectation. That's a consequence of both new patient adds as well as duration of therapy. One of the things we talked about on the Q1 call is that duration of therapy in the advanced SM setting, so this is a place where we've had patients now on for or we've had that launch since June of 2021, is now trending to 25 months. So these are patients with a clonal malignancy that's more like leukemia a nd they are staying on AYVAKIT for 25 months, which I think bodes well we're early days in the ISM launch, and we're seeing great compliance and good durations. Too early to really kind of tell what that duration is going to look like. But we expect between the duration of therapy and new patient adds, that growing base of patients on therapy continues to be a really important driver of revenue. S o we saw that in Q1. I think we also saw favorability in free goods that we knew we'd be seeing over time, b ut I'd say it came in faster than we expected a nd so it took us for a pleasant surprise as well. T hose are two factors. One is just the payer mix in general. So ISM patients tend to be younger. S o it is more favorable from a payer mix perspective in that they have a bigger percentage of commercial payers compared to Advanced SM and GIST. So Advanced SM and GIST, we expect about 30%-35% of patients have Medicare. and in ISM, we think it's 20%-25%. So as ISM becomes a larger portion of the overall treated patients, we did expect that payer mix to skew more favorable. Well, that's happened faster. So we've grown the ISM proportion of our total treated patients. S o we're seeing that favorability in the payer mix. T hen the second dynamic we saw in Q1 was a consequence of IRA. So because now with IRA, we had the first step in the Medicare Part D revisions where they've capped the out-of-pocket expense for patients, what we see is that patients who are able to kind of make it through that first out-of-pocket, which with a drug like AYVAKIT tends to be in the first fill, they can now be on commercial paid therapy for the rest of the year. S o we had a little bit of a tailwind different for different reasons in Q1 of last year, b ut what's different about this year is that we expect these patients now to stay on commercial paid therapy because they've made it through that kind of more limited out-of-pocket exposure than they've had in previous years. Excellent. So a lot of nice headwinds that are coming along with the launch. I think your guidance, correct me if I'm wrong, went from $360 million - $390 million - $390 million - $410 million. That's correct. So we tightened the range and raised it. R aised it, right. So looking forward to that, obviously. You also had, and we get this question a lot, a webcast that was done looking at kind of mast cells as a whole and kind of where to go. So I guess I'd love to just touch on kind of what's your strategic outgrowth over the next kind of several years on this mast cell franchise. Yeah, I mean, if you think about SM, it's been an opportunity to really learn how mast cells work a nd that includes the fact that KIT really can control not only the survival of mast cells but also a lot of their functions, like the degranulation. Kate, you used the term allergic inflammation, a nd people often say allergy and inflammation. But we're starting to see it much more as one entity. To imagine a mast cell that's so powerful with so many mediators coming from it, leukotrienes, histamines, and a number of others, including things that cause vasodilatation, and not wreaking havoc in the local environment would be naive. S o that's what we've seen in SM, a nd that's what we are noticing in the biology of a lot of these other diseases. So there are diseases where the mast cell is the main culprit, like chronic urticaria, where the release of histamines and the swelling, the local swelling, is what causes most of the symptoms. T hen there are diseases like asthma, where mast cells play a huge part of the disease. But there are a lot of other cells involved as well. S o the way I've thought about this is that the BLU-808, which is our wild-type KIT inhibitor that's exquisitely selective and highly potent, is the central anchor for what could be a large suite of different combinations and single-agent development pathways. So just like Dupixent is a drug that you use in a number of different inflammatory diseases, anything that involves a mast cell and if you think about all the symptoms that are in systemic mastocytosis, it can give you a hint. You have diarrhea. You have skin symptoms. You have fatigue. S o there are a lot of diseases that involve mast cells a nd most of the therapeutics up until this point have worked around the mast cell rather than hitting the mast cell directly a nd hitting KIT, just like we have in SM with a wild-type KIT inhibitor, is our strategy for really expanding into a much larger patient population. Excellent. Yeah, so one of the things that I always like to talk to investors about is you guys have taken it from concept to commercialization, not once but twice. We're not going to touch base on GAVRETO. But But done it twice. So it kind of just increases the confidence that you can continue to do it. I want to switch gears real quick i n the last couple of minutes. We have the ASCO conference coming up. You have an asset there, BLU-222. Kind of just want to get your high-level thoughts on what investors should be expecting there, looking out for. T hen if you can just expand to it seems like it's really more about the mast cell franchise and maybe less about oncology going forward. Kind of want to get your thoughts on BD and how you're thinking about BD and BLU-222. Do you want to start with ASCO? Then I can jump in. Yeah, so BLU-222 is our highly selective CDK2 inhibitor. It's being developed primarily in breast cancer. There is a possibility that there's activity outside of that. But really, our focus has been on breast cancer. If you're going to go into breast cancer, you need to combine with a CDK4/6 inhibitor. As you know, that completely changed the way that frontline hormone receptor-positive breast cancer patients are treated. We started about a year and a half behind Pfizer. Now we believe we have surpassed Pfizer. So there are a couple of different things to think about. One is the ability to combine with a 4/6 inhibitor. That relies both on the CDK2 cleanliness and the 4/6 inhibitor cleanliness, meaning not hitting other CDK members and not hitting other off-targets. So we are in combination escalation. We've started to, w e are a few cohorts into the combination with ribociclib, which is the most selective CDK4/6 inhibitor on the market. We've started to see really good safety and early evidence of clinical activity. So what we'll share at ASCO will be the details of that. We'll be looking at a number of other things that are developing. We have such a lead in the CDK2 area. To- date, we haven't seen anything that's this selective coming into the clinic. So as we think about business development, too, your second part of your question, Ren, is as we think about where we are at Blueprint, I mean, we now have expertise and a full set of infrastructure that we want to look to continue to leverage. We have that all the way through commercial now in both hematology, oncology, and now allergy inflammation or allergy immunology, as we call on that call point for SM. So as we think about BLU-808, it fits perfectly into the infrastructure that we currently have and is an operating leverage opportunity for us as we go to and advance really exciting science to very large patient populations. I think obviously, a lot of our roots are on oncology. We continue to do really great research. We will also do development on oncology, like with BLU-222. There, as we think about oncology, we really want to think about something where we can be first in class and best in class. I think that's incredibly important as you look at what that commercial return can be when you bring forth a new oncolytic agent. As we sit here with this opportunity with breast cancer, which we know is going to be a $10-$15 billion market, we believe that we'll be best situated to realize the value of 222 by partnering that with a big partner who has infrastructure in breast cancer already. So that's where, in terms of the value of that molecule, the opportunity for it now to be first in class and best in class is incredibly exciting. We really would like to see a big partner come and help fuel that development quickly into first-line breast cancer. This is something that I believe you said on the call. Correct me if I'm wrong. You're hoping to strike a partnership in the second half of this year. That's right. You guys have done partnerships before. We've seen some really nice ones, the last one, I think, being Roche for a significant amount. But I guess the way to think about it is you don't want this, well, you tell me how you want it. But I was thinking it's not a 50/50 kind of a split. It's really take this asset and run with it and take it off our kind of balance sheet sort of a strategy o r is it different? No, you're right in the sense. I mean, when we think about doing a 50/50 split, we would do that in a case where we would like to build infrastructure in a certain therapy area for our future portfolio or pipeline a nd where we sit today at this moment, that is just not where we are for breast cancer. S o I think what makes the most sense is for a partner to be able to take the asset and move it forward. Excellent. So in the last, let's say, one minute, what are the key drivers everyone should be focused on for kind of the rest of 2024 a nd just remind us what your cash position is and how long you think that'll take, how long that'll take you out. Absolutely. So quarterly performance as it relates to AYVAKIT's launch, clearly a big area of focus for everybody. I think second of all is BLU-808. So we are on track to submit our IND and start our healthy volunteer study a nd we said we'd submit the IND in second quarter and start thereafter. We really do believe that the Healthy Volunteer data is going to be a big inflection point for us because the diseases that sit behind that are well characterized, where KIT is clearly a driver of disease. So we think when we show the pharmaceutical properties of 808 and the fact that it has a large therapeutic window, which is what we hope to show, that will be a significant value driver. BLU-222, a partnership, second half this year. F rom a cash perspective, we have about $735 million in cash on the balance sheet. So what we're saying is between that top-line revenue growth that we continue to anticipate and how we're thinking about investing in the business, which would be about flat. I mean, I think where costs and expenses are from a consensus perspective around $715 million this year is, we think, about right. We're in a great spot to be self-sustaining. Excellent. Thank you very much, guys. Appreciate it. Appreciate it.