Great. Good morning, everyone. Thank you so much for joining us. Really pleased to have the Blueprint Medicines team here with us. We have Kate Haviland, CEO, Christy Rossi, COO, and Fouad Namouni, President and Head of R&D. With that, maybe Kate, to start here, could you just walk through the key strategic priorities for Blueprint and how we should be thinking about the Blueprint of today and tomorrow? Yes, thank you, and thank you, Salveen, and the entire Goldman Sachs team for having us here today. We really appreciate that. Yeah, we're in a great place at Blueprint, and as we think about our areas of focus for today, and as you said, into the future, first and foremost is to continue to drive revenue growth and treat additional patients with AYVAKIT in systemic mastocytosis. And then also to really solidify the durability and value of that franchise as we think about bringing innovation forward with our kind of next- gen KIT wild or mutated KIT inhibitor, elenestinib. And so that, for us, SM is very much the foundation as we think about our growth this year and beyond. I think a second priority for us is to establish our next pillar of value, which is really very much focused on BLU-808, which is our wild-type KIT inhibitor, that we think has an opportunity to be very impactful across a number of different disease states in the allergy and inflammation area. And so we're very excited about that program, which I'm sure we can talk more about. And then really our third area of focus for this year and beyond is maintaining our financial discipline, our path to financial sustainability. And given kind of the opportunity that sits with AYVAKIT, which we see as a multibillion-dollar opportunity, it gives us a significant amount of capacity to continue to invest in innovation while maintaining a very durable financial profile, and again, that path to... And a sustainable financial profile. I'd say those are really our three key areas of focus. And with AYVAKIT in SM, it's, you know, based on the recent indication add, you've had a really nice launch trajectory to date. Help us understand the confidence in achieving that $2 billion in peak sales guidance that you've given. Sure. So, the AYVAKIT launch, as you said, has been off to a really strong start, and we have a lot of conviction in the size of the overall opportunity, and in fact, I would say that our level of conviction grows with every passing quarter, and that's in part due to the performance we're seeing with AYVAKIT. It's also in part due to what we're seeing in the underlying disease. So you know, this is, I think, a dynamic that you classically will see with rare diseases, where our understanding of the true epidemiology and the prevalence of the disease grows as effective therapies are developed and launched, and we're seeing that here. So, you know, historically, we had thought about the prevalence of this disease as being maybe one in 10,000 patients, so about 32,000 patients in the U.S. There's actually a study that came out about a month ago that suggests that the true prevalence may be twice that, so you know, more like 62,000-63,000 patients. We're seeing diagnosed patients grow in the United States at a really good clip, so, you know, 20% year-on-year growth. We talked about 21,000 visible diagnosed patients as of January, and we continue to see that grow in real time underneath us. So to get to, you know, north of $1 billion in the U.S., you just need 15% of those patients, frankly, to be on, on therapy. What we're seeing is that, you know, the incredible clinical impact that AYVAKIT has, really favorable benefit-risk profile that sets the therapy up well for kind of chronic dosing and a very broad label that enables, you know, really any SM patient to be treated, give us a lot of conviction around the ramp that we're gonna see for many years to come. You had a very strong first quarter. Maybe talk about the drivers behind the first quarter performance and how you're thinking about maintaining that momentum into year-end. Are there any quarterly dynamics we should be thinking about here? Yeah. So we've talked a lot about some of the key drivers that underlie commercial performance. So certainly continuing to see new patients initiating therapy, and we've seen strength there, very strong and steady cadence of new patient starts, which we, you know, expect to see continue. We also see really good trends in terms of patient persistence. So this is a chronic therapy, one where we think we are well set up to see patients stay on therapy for hopefully several, you know, to many years on average, in the setting of a chronic disease. And in our advanced SM launch, we're now up to 25 months of median duration of therapy. So I think that's a really good indicator of what we may see in ISM, where we expect persistence to extend beyond that. And then there's factors that we're seeing around compliance, free drug, et cetera, that impact quarter-on-quarter performance, as well as our European launch, where we had the approval before the end of last year and are seeing ISM now really off to a very similar strong start in Germany as what we saw in the U.S. And so as we think about performance on the year, we've really tried to factor in what we may see along all of those variables. We did have a really strong Q1, and we saw strength across all of those factors, really. But again, we're in the first year of this launch, so this is a new market, you know, new launch in a new market, and so trying to set, for example, guidance in a way that really accounts for the variability that we may see on all of those variables, as well as, to your point, some of the seasonal dynamics, which we're learning. We are. You know, we just passed our one-year anniversary of the AYVAKIT approval several weeks ago, which is a great milestone, but we are, you know, still early in this launch, and so learning about how quarter on quarter may impact and sort of see some of those seasonal dynamics play out. ...With regard to ISM here, based on the physician and patient feedback you've received to date, what are the key aspects of the therapeutic profile that is driving interest, and uptake? And how do you think about differentiation versus competitors? Sure. Maybe I'll start with sort of what are we hearing? I would say there's you know amongst many aspects of the profile a couple things that you know really stand out. So one is from an efficacy perspective you know the data that we have and the compelling profile where regardless of the complexion of a given patient's symptoms they are likely to have benefit with AYVAKIT. And so we've seen really consistent benefit across different symptom domains. And this is in the context of a disease that can be you know pretty heterogeneous in how it presents from patient to patient. So I think that's been very compelling for prescribers knowing if I treat a patient it's likely to work regardless of kind of what their individual clinical situation looks like. The other aspect that has been, you know, really compelling is safety and tolerability, and particularly in an indication that we see allergy really wrapping its arms around and adopting that safety profile has been very compelling, and the fact that we've seen consistent safety as we've continued to follow patients out over PIONEER. We just recently shared an update at EAACI, looking at safety over two years and continue to see a very strong and consistent profile that's been also quite compelling. And then, of course, having a range of doses available for the disease state of, you know, ISM all the way to advanced, I think, really helps prescribers customize therapy for the individual needs of their patients. In terms of competitive dynamic, I don't know if you want to talk at all about how we see our presence with- I think from a competitive standpoint, given the lead position that we are in with AYVAKIT, avapritinib, I think it's very difficult to really come with a compound and really compete with where AYVAKIT is. All that we are seeing from a competitive landscape are maybe some me-too agents, I mean, not that differentiated. We think this is really a unique opportunity for us at Blueprint Medicines to continue to push on AYVAKIT. I think to that point, I mean, AYVAKIT sets a very high bar. And in fact, even for ourselves, as we think about... You know, I talked about the fact that, you know, we plan to continue to innovate in this space and have a very durable and to maximize the franchise potential we have in SM, because we have our next generation product in elenestinib, which we will be talking more about in the second half of this year, is how we plan to bring that forward into registration studies. And AYVAKIT sets a very high bar, and so we're thinking about elenestinib in terms of we're learning a lot from the PIONEER experience. As Christy just said, we're now kind of publishing data where patients have been on for multiple years, but we've learned a lot about the biology of the disease. We've, you know, we have a tremendous amount of experience to think about, you know, what can we do with elenestinib that, honestly, we could probably do with avapritinib, but will enable us to drive innovation and really kind of out-innovate ourselves before anyone else does. How are reimbursement and access progressing here, and the free and commercial drug mix, how do you think that will evolve going forward? Yeah. So access has been a strength of this launch. You know, I think it's been a strength, actually, of the AYVAKIT commercial experience since we were initially approved in 2020. We see very strong coverage to label, which means that, you know, really, any SM patient should be able to obtain access to AYVAKIT. We're continuing to see really rapid times to fill and would expect, you know, that to continue as we progress through the launch. The free goods dynamic is one where we've also seen some favorability with the ISM approval for a couple of reasons. One is that, our Medicare patient population is beginning to become a smaller proportion of our business as ISM becomes a bigger proportion of our business, because these patients do skew a little bit younger, so we have less Medicare exposure. And then in the short term, some of the impacts of the IRA in terms of limiting a patient out-of-pocket copay have actually driven some favorability to enable those patients to be treated with paid therapy. Beyond Germany, as we think about the ex U.S. opportunity, what are the other markets that could really be key to the growth opportunity? Yeah, so we're really excited by what we're seeing in our international launch. Again, the fact that the initial German experience is so similar to what we're seeing in the U.S., I think is really validating to a lot of those core market dynamics that we do think are gonna be similar in Europe versus the United States. Obviously, a difference in Europe versus the U.S. is pricing and reimbursement, and so you know, we'll be navigating that. Germany, we're still in kind of that first window of launch, and then we'll be working through pricing negotiations through the remainder of this year. We'll have other markets come online. Now, we're still launching an advanced SM, actually, in some of the European markets where you know, we've been negotiating price there. We're very focused on, you know, driving our European business in the larger markets, where we think there's a lot of opportunity and where that return on our effort is gonna be highest. But overall, I would continue to expect Europe to grow and to be a nice contributor to our top line. Probably on a percentage basis this year, we've said that we would expect it to be relatively in line with what we saw last year, which is sort of in that 10%-15% of overall revenue range. So in sum, when you look at your territories, what do you think the overall total addressable population is? Yeah. and maybe how you think about early versus late adopters? It's a great question. I mean, we, we've talked about the value of the opportunity being north of $2 billion, and you know, it would not surprise me if our view on that continues to evolve in a favorable way as we, as we get into this and really see, you know, the market growing as it has been underneath us. You know, historically, we had said 70,000 patients between the U.S. and, and Europe, roughly, based on that 1 in 10,000 estimate of prevalence. But again, you know, as newer data is coming out to suggest that the opportunity could be much larger than that, I think, you know, that that will grow. So you know, we'll, we'll see, we'll see as we get into it. But again, you know, we see a lot of headroom here and upside as we continue to progress through the launch. ... So turning to the pipeline, you recently hosted an event centered on your allergy and inflammation pipeline. How are you thinking about leveraging everything you've built in mast cell biology to drive mid and long-term growth? I mean, at Blueprint Medicines, we spend more than the 10 years or since, probably since inception, 13 years now, working on mast cell biology, understanding c-KIT, and how to modulate that specific target. Having been working with the allergy community in ISM, with AYVAKIT for the last many years, I think we have been urged as experts in this field to really go and study the wild-type KIT and make deliberately a highly selective, wild-type KIT inhibitor to target some allergy and type 2 inflammation diseases. And that's what we have been doing over the last, three or few years, I would say, to really design something that is uniquely differentiated, that can go to patients with allergy and inflammation diseases, and bring a highly selective profile that could clinically be becoming impactful for these patients. Could you speak to the wild-type KIT inhibitor, BLU-808, which you highlighted at the event, and remind us of the development timelines and strategy for this asset? Wild- type KIT inhibitor, BLU-808, is really a highly selective molecule that, as I mentioned earlier, we spent a few years really designing in a very deliberate way to serve this population of patients in type 2 inflammation allergy. We are on track for our IND submission and starting the healthy volunteer study this second half of the year. The molecule will, after that, go into specific development. So first, I think showing the healthy volunteer data next year, and we'll guide to the timing of that when we are more advanced in that work, will be a major inflection point for Blueprint Medicines. Because inhibiting wild-type KIT through different strategies in chronic urticaria has already demonstrated a strong proof of concept, or POC. We believe with small molecule, with good pharmacology, a wide therapeutic index, a good safety profile, and good pharmacodynamic markers, we can really inflect that in terms of the value of what that program can bring to patients and to Blueprint Medicines. We will also be looking at a number of POCs beyond chronic urticaria, because we believe we really need to see at the, you know, at Phase 1c or maybe 2 level, what are the other diseases where we can shown in chronic urticaria. 2025 will be really a major year for our Phase 1 data with BLU-808. You talked about how this asset was designed for flexible dosing, which could widen the addressable indications, as you talked about. But could you just walk us through the preclinical data here and how you plan to gain insight about the opportunities beyond? Absolutely. We reported some key data in terms of preclinical profile. So first is, as a kinase inhibitor, this molecule—I mean, and the reason it took us this, you know, good amount of time to make it, is to make it very selective. So it, it is selective over most of what you would be concerned for a patient who is not suffering from cancer. It is an oral molecule with, you know, hours of half-life, not months of half-life, like, you know, a monoclonal antibody, so gives us flexibility in terms of dosing. We also studied, you know, the level of inhibition that you need to do for a mast cell to not activate and degranulate versus, you know, going, you know, with higher doses deeper to run into on-target toxicities by blocking c-KIT at the very, at the strongest level, I would say. So all these elements in our preclinical data are really showing us that we can go to these diseases clinically and show really a very optimal profile, assuming we reproduce what we are seeing in the clinic, in the preclinical data. As a reminder, we have not started the healthy volunteer study yet. The other thing we learned is that you can inhibit, and we reported this at VantAI, and you can inhibit the mast cell without from degranulating and activating, without completely depleting it. So we'll track this with biomarkers and pharmacodynamic markers and understand how that plays out in the clinic. Lastly, we published 2 preclinical models, 1 in chronic urticaria and 1 in type 2 asthma, that is really making a preclinical case for us to go to a number of diseases. We'll continue to work with, you know, well-established preclinical models in other diseases to better understand the impact as we are preparing for the clinical work. I think importantly, you know, as Fouad just described, as we think about that range of being able to kind of, you know, stop a mast cell from degranulating or not activate versus kind of depleting the mast cells, you know, this is, this is something that obviously we need to get in the clinic to really show what that utility looks like. But we've done this with SM, right? So if you think, you know, in SM, our labeled dose in the advanced setting where patients have a very aggressive malignancy is 200 mg, and then in the indolent setting, it's 25 mg. So we have a very good sense of how to think about this kind of differential impact on mast cells and how you can kind of strike the right risk-benefit profile for a given patient population. ... Could you provide an update on where the next generation KIT inhibitor BLU-263 stands? Yeah, definitely. Leading the field in the mast cell, in the mutated, KIT-mutated mast cell disorder, ISM, I think it is important for us to continue to innovate. It's important for us to continue to move the science and the medicine by developing elenestinib in a way, and in the life cycle of avapritinib and the SM franchise, to answer questions that we did not answer with avapritinib. To benefit from what we have learned from Pioneer over the time, we have learned from SM, from the treating physicians, from people we spend most of our time with, what we are learning from translational medicine work and the biology of the disease, and take elenestinib to that next level. As we mentioned, we'll be sharing, this second half of the year, our strategy on how we are moving forward, elenestinib. I think of it as really something that will really take our franchise, SM franchise, to the next level. Pivoting to the oncology portfolio, and I think we recognize that you're taking oncology off your balance sheet and, you know, focused on autoimmune and inflammatory disease here. But you had talked earlier in the year about the CDK2 asset and the ability to kind of partner it, which seemed like it was coming sooner rather than later, and that's been pushed out to the second half. Can you just walk us through what's happening with regard to that partnering dynamic? Yeah. So, so we've guided to a deal for CDK2 in the second half of this year. So we've been pretty consistent about that over the last year or so, because what I think we showed at ASCO, and, and Fouad can talk more about this, is that, you know, the key to a CDK2 inhibitor is to be able to combine in a powerful way at active doses with a CDK4/6. And that is the data we just presented at ASCO, and we knew that that was gonna be a critical kind of piece of evidence to continue to progress the deal process, the collaboration process, which is why we always thought second half of this year is when we'd be looking for that collaboration to really come into focus. But, Fouad, you wanna talk more about the CDK2 data? Yeah, I think, I mean, at Blueprint Medicines, you always believe that for hormone positive, the HER2-negative breast cancer, a complete inhibition of the cell cycle is critical, and so CDK4/6 do a part of it, but CDK2 are important. In fact, some molecules that were CDK2/4/6 developed, had some decent activity, but the problem is that people ran into toxicities because they cannot titrate both CDK2 on one side and CDK4/6. So for the first time, this 2024 ASCO, we showed the first CDK2 inhibitor of BLU-222, combining with a CDK4/6 inhibitor, ribociclib, in this case, in a safe and also a way that started showing some early signals of activity. From a biomarker perspective, but also from clinical perspective, we have seen, you know, responders. We have seen stable diseases and people benefiting, patients benefiting from the drug. We have seen improvement in a number of symptoms for patients, and we are not at the RP2D. We have not determined the RP yet. So even in early times, we are seeing some very good activity. And the reception by the expert community of our phase 1 combination data at ASCO was really very good. Do you wanna talk? I don't know if you wanna talk a little bit about the deal process and just kind of where we are in that, what we're looking for? Yeah, I mean, we're continuing to, you know, be in active negotiations. And just to your earlier point, I mean, I think a driver of this deal has been that, you know, at this moment in our sort of development as a company, our priority is very much continuing to execute on the SM opportunity, bring elenestinib forward, and then of course, BLU-808, where we see just enormous potential across the breadth of potential indications. And so, from a capital allocation and focus perspective, in the near term, that's absolutely the priority, which means that, you know, building into breast cancer at this moment doesn't make a lot of sense for Blueprint. We do think that the CDK2 opportunity is a, you know, multi-billion dollar opportunity that will also take, you know, fast and sort of parallel development execution that really starts to ramp, you know, next year. And so part of the driver of timing around the second half of this year is to have a partner on board that can really help to drive that and provide sort of input into some of the key strategic decisions. So, you know, those conversations are continuing to progress, and we'll share more when we can. Could you put the response rates seen and the safety profile in the context of how we should think about the drug versus the competitive landscape? Yeah. I mean, CDK2 combination with CDK4/6 has not been very easy for majority of people, and mostly because of the hematological and GI toxicities. Why we are able to achieve what others could not in now showing clinical data and now becoming the first CDK2 inhibitor with clinical data in terms of combination, is because this is what Blueprint expertise is, making highly selective molecule, really knowing where the off-target toxicities and on-target toxicities will come from, and then make molecules that are combinable with others, and it has been our strategy. And now actually it's showing up clinically, our preclinical hypothesis and design of BLU-222 showing up clinically and confirming what we thought about combination with the CDK4/6. If you look at our data, and you can put it side by side, even with some new monotherapies, CDK4/6 or CDK4s, the level of hematological toxicity is lower in our combination. The level of GI toxicity is. We don't see a lot of high-grade toxicities, quite frankly. And then that matched with, you know, very early on in the dose escalation, we are seeing some real responders, patients without lesion that we can measure. We call them non-target lesion. We are seeing stable diseases. So it has to do with the way we always think about our molecules in terms of selectivity and in terms of combinability with other drugs. With regard to the company overall, could you touch on business development and your approach there, and also the updated thinking on the path to profitability? Yeah, absolutely. So I think, maybe starting with the path to profitability, I mean, what we've been, we've been saying is that given the really nice growth we're seeing in the AYVAKIT launch and our prioritized investment in the pipeline, where we see the most compelling opportunities for growth in very large populations, but also particularly with BLU-808, you know, this is, this is, these are specialty markets that, that, are very much, have full operating leverage off of our current, you know, infrastructure and footprint. And so that, from a financial efficiency perspective, enables us to really think about driving significant growth over the medium to long term, in a very efficient financial way. So I think we have what we said is we can see our path to sustainability, and that we intend to maintain that, and but we also have an incredible amount of innovation that we believe is gonna be very important for patients to drive kind of the next waves of growth at Blueprint beyond AYVAKIT. So we're, we're looking to do that. From a BD perspective, and I think one of the things we've done at Blueprint over the life of the company is done business development from a very strategic perspective. And Christy just was talking about how, you know, we think CDK2 is an incredible target. We think it's gonna have the opportunity to help thousands of women with hormone positive breast cancer. But at this point in our evolution as a company, it doesn't make sense for us to build a breast cancer franchise, right? Or to build that breast cancer expertise. We are gonna allocate our capital in a way that makes more sense for what we should do. And I think we've made these decisions over our lifecycle. You know, we, we chose to hang on to AYVAKIT because we saw something in the systemic mastocytosis market that we thought was really important and, and an opportunity for Blueprint to grow with a specialty kind of market in a very compelling way. And we, you know, we, at that time, chose to out-license our second program that became a commercial program for RET-driven solid tumors. And so we've continued to kind of make these decisions along the way. You know, we also, I think, are now in a place where, you know, we are a growth story, and we have a tremendous amount of expertise. We have a tremendous amount of infrastructure now here in the US as well as in Europe, and we think we have the opportunity to potentially bring to think about external innovation as well. And what's important about that is that's not an imperative, because we have a lot of our own organic growth coming through the company, but it's more a way of thinking about how to optimize the business over the medium to long term. And so that just kind of gives us that flexibility to think very broadly around that. So business development has... I mean, we've brought in over $1 billion in capital from BD over the last 10 years, and that's all been around supporting our corporate strategy. So we will continue to do both, both sell side and buy side BD, as we build the company, you know, to be a $10 billion-$15 billion market cap company. And you, you've acquired two drug discovery or AI-enabled drug discovery companies, and you're partnered with a few others. What have the early benefits been from integrating these technologies or the partnerships? I think it is very important, and at the Blueprint, let's talk about discovery. Machine learning apply to our library of compound has been applied for many years ago and help us in our generation of highly selective molecule. Partnering with other companies, I mean, the VantAI partnership we talked about, is really allowing us to get to a new level of using generative AI to look at the protein-protein interaction in silico, leverage the in silico part more than what we used to do. And I think in all that we are doing, whether from small molecule perspective or from protein degrader and heterobifunctional perspective, applying to the oncology, but more and more now to outside of oncology, it's gonna be very, very helpful to us. I think our Chief Scientific Officer, Percy Carter, kind of came to Blueprint, and he's had the opportunity to build targeted protein degradation platforms at other companies, including large pharmaceutical companies. He says, you know, it's gone faster and more seamlessly at Blueprint. I think that has a large part to do with the ability to leverage the tyrosine kinase inhibitor library we have, but also in terms of some of these more innovative ways to think about, you know, continue to advance that field. Actually, our TPD platform is gonna start pushing out the next development candidates very quickly from the time that we've established it. It's a really tremendous achievement. Great. Well, with that, thank you so much, Kate- Thank you. and Christy and Fouad. I really appreciate your time today. Thank you. Thank you, Salveen. Appreciate it. Thank you.