Pleasure to welcome the next presenting company, Blueprint Medicines. Joining us here on stage is CEO Kate Haviland, as well as Fouad Namouni, President and President of Research and Development. Thank you both for being here. For all of you in the audience and those in the webcast, this has been one of our top picks from soup to nuts, the company that developed drugs, got it to commercialization, and now is on its way to a billion-dollar revenue stream. You do not typically see that in kind of like all of biotech. When we have such companies here, we love to spend the time kind of diving straight in. I never know exactly who is in the audience or who is listening to the webcast if they just landed on the planet yesterday and just do not know who Blueprint is. If you could maybe take two to four minutes to just tell us a little bit about Blueprint and the pipeline. Yeah, absolutely. First of all, thank you, Ren, and the entire Citizens team for having us here today. We really appreciate that. Blueprint Medicines, I mean, we are a company that is focused on making life-changing medicines for patients. Now our focus is really around diseases that are related to mast cell biology. That has been an evolution for us. Those of you who may have known us before, our heritage is more in oncology, and we still certainly have some of that. We have really moved with the science. What we have now is, I think, what's a really tremendous commercial medicine, an AYVAKIT that's treating a rare disease called systemic mastocytosis, which is caused by a mutation in mast cells. We have a pipeline of programs now coming forward across other mast cell targets, including modulating wild-type mast cells across a whole range of type 2 inflammatory diseases of allergic inflammation, which we're really excited to talk about today. I think we have a very compelling growth opportunity from a revenue perspective. We've got a pipeline to kind of seed that in those next waves of growth. We're in a very strong financial position. What we think about is self-sustainable from a financial perspective. I'm sure we'll get into all three of those pieces. To your point, we're in a strong position today. Yep. Let's start off with AYVAKIT, your lead commercial product, approved in several different indications. I guess I'd, oh, let me start off by saying congratulations again for another kind of beat and raise quarter, which we love to see, the markets love to see, and clearly shows just how much demand there is for the drug that's out there. Also a very unique company in that you follow the science, right? Like you said, you started off in oncology. You have an approval in things like advanced SM, right, and the like. Now you're more in the indolent area. You have three approvals. Can you talk a little bit about maybe the peak opportunity for each, or should we be just looking at it kind of as a whole and how you see that kind of moving forward? Just as part of that, how does all that get sequenced or taken care of by one Salesforce? Yes. OK, so it's a great question. So AYVAKIT is approved in three different indications, a very, very small indication in a subtype of GIST or GI stromal tumors, which was our first approval. Then the advanced form of systemic mastocytosis, which is very much a classic kind of blood cancer, leukemia type form where patients have much shortened lifespans. That's about 5% of the, or 5%- 10% of the overall systemic mastocytosis population has the advanced form. The 90%- 95% of the population is what we call indolent systemic mastocytosis. That is, in terms of patients, a much larger group of patients who suffer from this disease. Again, it is caused by the same mutation in mast cells. It's called the D816V mutation that causes the entire spectrum of disease. Really, the ISM opportunity is the one that is the much more scaled opportunity, given just the number of patients in the U.S., which we estimate around 60,000 patients who may have SM, of which 90%-95% of them are in the indolent form. That is where we got the approval in the middle of 2023. I have to think of my years right. That has been really the opportunity to kind of change the financial outlook for the company. When you think about AYVAKIT and the value of AYVAKIT, it is predominantly driven by the ISM opportunity and for it to continue to grow our penetration into that market. Although advanced SM and GIST still continue to contribute. GIST is pretty steady for us. We see commercial usage. We do not promote there, so we do not actually focus our sales team there. In the advanced setting, again, it is just a much smaller set of patients. We still see growth there, but it is pretty much swamped by the ISM opportunity and the growth we are seeing there. As we think about, to kind of put numbers right to this, I think earlier this year, you guys talked about kind of what your goal is for 2030, what the potential peak revenues could be in this indication. Can you just remind us kind of? Yes, where we are in that. Yeah, so where we sit kind of coming out of Q1 is our guidance for 2025 is that we believe we'll have revenue in the range of $700 million-$720 million this year. This is our second full year of launch. We think that's a tremendous accomplishment and really talks about both the really strong profile of AYVAKIT in terms of meeting the needs of patients with ISM from both a safety and efficacy perspective. What we said at the beginning of the year is that we expect AYVAKIT to hit $2 billion of revenue by 2030. That is really just understanding the size of the market, the growth we are seeing both in AYVAKIT utilization, as well as in just the growth of patients being diagnosed, which has been growing at a really nice clip over the last number of years. We believe there are about 60,000 patients in the US, and we see 25,000 diagnosed today. That is a great kind of group of patients who are currently identified and under care that we are spending a lot of time from our sales team's perspective. What we talked about is that we expect this category or SM to continue to grow well into the next decade. Even though AYVAKIT, we expect to be at $2 billion by 2030, it will grow from there. This is where our next generation program also comes into play, which is elenestinib. What we said is that we believe the whole franchise opportunity is $4 billion plus. That is why we're investing in the next generation, is that we want to be, first of all, in the driver's seat of innovation for these patients and continuing to improve outcomes for patients. At the same time, be able to have Blueprint Medicines benefit from what we expect to be this kind of many years of growth in the market. I just want to remind ourselves and investors, Blueprint is a global company. Is that $2 billion and $4 billion U.S. numbers, or is that global opportunity? It's global opportunity, of which at peak, we still expect the U.S. to be somewhere between 70% and 80% of that. Got it. Just breaking. Can I just ask one question? Just follow up on that. Can I just ask one question? Just follow up on that. At the very end. I will promise to come back to you. If we think about SM and the different pillars that are involved, right, in terms of gaining market share, you talked about the 20,000-25,000 patients that's already diagnosed. I don't think you have to get to anything more than 20% market share to reach that $2 billion number in 2030. How are you getting at those patients? What are the different pillars that you've talked about in the past that you're addressing right now to grow that? Yeah, and your math is exactly right. We expect that to get to $2 billion, you're still kind of treating a minority of patients with a disease-modifying D816V inhibitor to get there. To your point, about 6,000-ish patients in the US. That's based on today's diagnosed set of patients, where we expect that to grow. I think the pillars really are around having a really strong foundation of health care providers who have clinical experience with the medicine. When anybody launches a drug, you have kind of the world-leading key opinion leaders and investigators who've had experience through the clinical study. What we spent a lot of time and were a focus of last year was really building out a broad base of health care providers in the U.S. and internationally. Although internationally, just as a reminder, the only market that has commercial ISM approvals right now is Germany. We are going to be looking to bring more markets on this year. If you think about building that really strong base of experienced health care providers who have clinical experience with AYVAKIT, who are treating their patients, who kind of have their hands on the medicine and see what it can do for their patients, see the tolerability profile, that is a really important base. We continue to show increases in both breadth and depth. We do expect that, and we have seen this, that when a prescriber has their first experience with the medicine, they tend to then find the next set of patients in their practice or start to recommend it more heavily to the patients in their practice. We see that deepening. They continue to prescribe it for new patients. I think that's the first step. Now we're at a place where we will continue to build that base of prescriber experience. We can do more direct-to-consumer at this point. We're spending time and resources digitally with peer-to-peer programming, where we can set up a patient who may be considering AYVAKIT as a medicine with a patient who has experience with it, and they can have a conversation about that experience. What that enables us to do is really build momentum from the patient side. We've seen that actually become very successful because you want to drive a patient into an office where a prescriber is educated about the disease, educated about the medicine, and also ideally has some clinical experience. That is kind of that next step where we are in the launch, where that is more of a focus towards the end of last year and into this year. One of the pillars that I think about, and you can correct me if I'm wrong, is actually the established base of patients as well. The people that are on therapy, they're not just on therapy for a couple of months or a year. I think the latest data shows three years. Yeah, we have to model it because we're not at a median yet, to your point. Yes. That creates this great revenue, this base of revenues that's recurring. Then on top of that, you have new patients that are coming on board. Excellent point. I mean, really, the two fundamental aspects of this launch that will portend the long-term growth is how can we continue to penetrate the market and get new patients to start on therapy, and then the length of time that we can keep patients on. This is where the profile of AYVAKIT becomes really important in the sense that patients with ISM, it is a chronic disease. It is much more like a chronic disease than it is oncology. The patients need to feel better, and they also need to have a very strong tolerability profile so that they want to stay on the drug. What we have seen to date is, again, very low discontinuation rates with patients now. We model out duration of therapy to be three-plus years because, again, we have not hit that yet. We are in our second full year of launch now. We're seeing patients stay on. I think that really is a testament to the profile of the drug. When we look at other rare disease launches, and you guys discuss kind of like, hey, this is a company that we'd either like to emulate, or hey, this is a launch that didn't go well according to the plans. We'd like to stay away from that. I guess I'd love to just kind of get your quick thoughts on what are maybe some strategies that you want to stay away from, or what are some things that you might want to emulate? What is your poster child kind of rare disease launch that you kind of look at and would like to be? I mean, there's so many companies that have come before us who we look at because they've done a tremendous job. Nothing's a perfect analog, but we kind of take aspects and learnings from so many different groups, whether that's Vertex, whether that's Argenx. I mean, there's just people who have done just a tremendous job bringing innovative medicines to kind of patients who have needs. We think about all of the, we think about and are good students of what we can see from their activities. I mean, I think one of the things that we did very early on is it is a rare disease, right? It's a big rare disease, but these are not patients. Some physicians will see an ISM patient once or twice a year. How do you kind of make it so that people want to focus and invest time in this disease state? What we've done is we, very early on, invested in what I think of as a very sophisticated data operation, where we are able to provide our sales team, so data operation, which I'll talk about, but we also hired very experienced sales professionals. We are able to provide our sales professionals with information about where patients are based on what we kind of think of as real-time targeting. We can see where a patient, through claims data, may have interacted with a health care provider recently. We also can see from lab data at times if a patient has been positive on a D816V test. We can basically pull all that information together and provide it to our sales team members so that they are empowered with that, as well as their own knowledge of their own territory. That has been very impactful in terms of making sure that our sales team is prioritizing their time in the places where you are most likely to have a patient in need very recently in that office. When you go in and have a conversation with a physician, it is very relevant to them because they just saw that patient. Got it. When we think about, I think my associate had seen some AYVAKIT ads on Netflix or TikTok. I forget where exactly. I've asked this question before in the past because I actually have PTSD from a previous company that I covered who went kind of all in on DTC. It really just kind of threw off the expense line items quite a bit. This is a different kind of DTC campaign. I'd love for you to just kind of give us a sense as to, A, how you gauge this campaign and how this is moving forward, but then also just to remind us that you're also very, very focused on the expenditure line and don't plan on buying $5 million commercials at the Super Bowl or something. Yeah, yes. Unless you do. No, no, we do not. Again, in the rare disease setting, we do not believe it is a good investment to kind of have broad advertisement out there in venues, those types of venues. What we do is our team has worked with, within our team, we have very sophisticated expertise, but we also work with great partners externally to think about how do we bring forward both disease education and awareness ads, as well as AYVAKIT-specific ads. We digitally basically target them. It is actually wonderful now that a lot of people get their or watch their TVs through streaming because it is much easier to kind of digitally target folks both on social media as well as through those types of platforms. There are very sophisticated metrics and a tremendous amount of data you can get from that. Our team looks at all of that to say, OK, is this impactful? We revisit it all the time to say, are we having the intended effect that we want to have? Are we seeing at the end result, I mean, you can never kind of go one-to-one, but are we seeing more patients come into physician offices asking about the medicine? Indeed, we are. There are numerous metrics. Obviously, that is the one that is the ultimate metric that we want to be able to continue to monitor and see. Excellent. In the remaining time we have left, I want to put Fouad on the hot seat for a little bit. Then we'll come back just to some more general questions. The story isn't done with just AYVAKIT. You guys have a pipeline. You have LNS to NIB. You have BLU-808. Let's jump right into BLU-808, if you don't mind, because I think that's probably going to be one of the areas that provides the next kind of level of growth that's not factored into a lot of our models, definitely not mine. I tend to be fairly conservative. I'd love to know what's the unmet need that BLU-808 is going after? Because I think of things like allergy and the first couple of indications that you're starting off as is, I don't know, largely treatable, maybe there's enough kind of drugs out there. I guess maybe just start off with the unmet need, what 808 is designed to do. Yeah. I mean, if you think of the allergic process, or what we call type 2 inflammation, the mast cell is the key effector cell in the process. It ends with the mast cell releasing mediators and starting the allergic process. People have been trying to block the mast cell for a long period of time. It's not an easy thing, although we know what the targets are. I think we are able at Blueprint with the expertise in terms of biology of the mast cell over the last decade through SM, the way we have been targeting KIT, and the way we develop small molecules to bring 808 to a number of diseases in the type 2 inflammation space. Now, there is medical need. There are always medical needs until you solve the type 2 inflammation problems in 100% of patients. If you go and look at the totality of the medicines, whether they're used in urticaria or in asthma or in AD or improve the patient's outcome, there are still a large number of patients who do not respond to therapy. Most of these medicines are going through a variety of pathways, but none is going directly to the mast cell to block it and stop the influence of all the pathways through the actin on the mast cell. We believe there is really great opportunity in a number of diseases. Some of them, the biology has been de-risked in a very clear and established way. Some, we are working on de-risking the biology of wild-type KIT inhibition in. We are very excited. We are in a phase where we are doing a number of proof-of-concept studies to really study that. It comes next year. We'll have more information not only on diseases where the biology is de-risked, like chronic urticaria, for example, but we will have more information on allergic asthma, on allergic rhinitis and conjunctivitis, on MCAS, and so on. I know that you have started, I believe you've started some initial clinical studies or plan on this quarter. You correct me which one it is. You might see some preliminary data by the end of this year. Can you maybe give us a sense or maybe paint a picture roughly how many patients' worth of data might we see? What are you looking for, not just from an efficacy perspective, but also from a safety perspective? Because now we're hitting wild-type KIT. We've seen other companies that have shuttered their operations because of safety signals. What do you not want to see for sure? What do you want to see? To your first part of the question, we started actually, we opened a couple of studies now, allergic rhinitis and conjunctivitis and chronic urticaria, including induced and spontaneous urticaria. Later in the year, second half of the year, we will kick off the asthma study and the MCAS. I mean, these couple of studies are running, one with not open label in an open label way. I think assuming the recruitment goes as we hope, it is possible that we have some data before the end of the year. I mean, it's very difficult to really speculate today on how many patients' data we will have by that time. I think as we finish the recruitment of patients, we can have more clarity on the data. From a data perspective, I think there is something that Blueprint only has the opportunity to do, is to set a new bar for what efficacy and safety is for these patients with this type of diseases compared to all the other wild-type KIT and other targets. These patients, unlike patients in hematology and oncology, are not looking for a 100% complete response rate or remission rate and then stop the drug because they have toxicity right after four weeks of treatment. I think spending time with allergists through the SM program over the last many years, we learned that what patients are looking for is improvement of their symptoms, not at the cost of side effects, and be able to stay on the drug in a compliant way for a long period of time. Because these diseases have exacerbations if you keep windows open without the treatment. For us, having a small oral molecule is really, we see it as a great advantage in terms of the drug profile because, I mean, you may run into an AE here and there, but you can swiftly manage through with reducing or stopping for a couple of days and resuming and things like that. I think what we hope to offer with a small molecule like BLU-808 to patients with type 2 inflammation is an option that is really the perfect balance between relieving symptoms without inducing toxicities. The way we are looking at it is through dosing and scheduling. We're looking at multiple doses. We're looking at different schedules, start high, maintain low, or titrate to effect in some patients. It is a completely different approach from what we have been doing as an oncology community and in hematology. Just to remind us, I mean, this is differentiated through the fact that it's also an oral molecule, right, versus the biologics that are out there, which I think garners a lot of interest, certainly investor interest. When you kind of look at both oral and biologic, are you kind of competing against biologics? Do you kind of feel that, you know what, we'll likely be used in a different part of the pathway, right, or part of the paradigm compared to biologics? It is really going to exist quite nicely together. How should we be thinking? I think, I mean, this is type 2 inflammation. I mean, I remember, if I'm not mistaken, I heard a major company in AD talking about the drug penetrated only 14% of patients at JP Morgan. I think there are, first, these are large numbers of patients. It's not your 5% of non-small cell lung cancer or something. There is opportunity for a lot of medicines together to really help patients. I think what we will bring, I think we will really bring a new paradigm of thinking about the efficacy and the safety that you just cannot have with biologics, just by the nature of the pharmacology of biologics. I think we're excited to really introduce this notion of small molecules that you can titrate, that you can dose differently, and the patient can manage by themselves, you know, day by day, and be able to really treat for a long period of time patients to prevent exacerbation of their disease. I think that could become a major differentiation with the biologics you're alluding to. Got it. Dr. Cerulli, I'm going to be coming to you with the next question, so after this. As you think about the five-year kind of game plan, right, Blueprint always rises to the top of the list as potential M&A takeouts. Who wouldn't want to take you guys out? I mean, you have a growing revenue stream. You're going to be cash flow positive, we think, by our models, either next year or the year after. You can't necessarily build your company for M&A, right? I mean, if it comes, it comes. Five years from now, if you guys are standalone, how does Blueprint look to you? How many different does the pipeline keep getting expanded? Is it just elenestinib, 808, and AYVAKIT, or are there more things coming behind? Just a quick. Yeah. I mean, I think five years from now, AYVAKIT and LNS will continue to be growing. 808 will be on the market in certain indications, and we'll probably be exploring more because it really does have that opportunity to hit so many different indications. We have a tremendous amount going on in our discovery team. I think one of the things that from the very early days is that we continue to invest in discovery, and that team has been more productive than we can bring it forward. We have put that innovation to other people's hands at various times and focused on what we think we can do best. That has continued to add a tremendous amount of value to us even this year. I mean, we got $80 million from the IDRX transaction because we put some molecules in their hands that were no longer going to be a core priority of ours. We will continue to innovate. We'll continue to build the pipeline. I think we'll be a company that has a lot of growth in the next five years. You put molecules into IDRX. IDRX got acquired by GSK, and you had an equity stake. We gave them our molecules. We took an equity stake because we honestly did not need the money upfront, and we wanted to support their ability to establish their company. When GSK, or yes, when GSK bought them, I was thinking, our equity stake gave us $80 million. Last five seconds. My question was exactly the way you followed up what I was asking, which was the $2 billion number in 2030. I mean, it seems that that's only 6,000 patients of the 25,000 that are diagnosed. That's still not a high penetration rate, especially if you think about the other 25,000 or 30,000 that aren't even diagnosed. That's right. Do you focus on trying to help with the push on the diagnosis side to just create that bigger market and just capture instead of 10%, maybe 15% or 20%? Or is it really like, we should be 50% of the diagnosed patients already? You know what I mean? Yeah, yeah. Which is the target that you feel is lower-hanging fruit for you guys? I mean, I think we really do focus on patients who are currently diagnosed. In the context of doing that, we also are working on, with our translational medicine team and our commercial team, getting more improved diagnostics out there, blood-based diagnostics to really help facilitate diagnosis over time as well. As much as our commercial team is very much focused on the patients who are diagnosed, we have a medical affairs team. We have great science. We work with our key opinion leaders to try to actually help the SM diagnosis kind of move into the age of modern molecular medicine because it is driven by a specific mutation. We have seen about a 20% increase in the rate of diagnosis of SM over the last four or five years. We expect that to continue. There is a lot of the fact of both the work we do directly, but it is also the idea that you now have something you can do for these patients. People are more motivated to pursue a diagnosis. Over $900 million in cash, if I remember right, or? Yeah, just $900 million. Yep. Excellent. Thank you guys very much. Appreciate the time. Let's thank the presenters. Thank you.