All right, I think we'll get started with the next fireside discussion here. My name is Derek Archila, one of the Wells Biotech Analysts. With us for the next fireside, we have Blueprint. We've got a nice crew here from the company. So obviously, Kate Haviland, the CEO. We have Mike Landsittel, the CFO, and then Philina Lee, the Chief Commercial Officer. So team, thanks for joining us, and look forward to the discussion. Thank you for having us, Derek, and the whole Wells Fargo team. We really appreciate the invitation to be here with you today, and great group in the room. It's so nice to see so many people, and welcome everyone who's online. Yeah. Summer's over. We're back at it. We're back at it. All right. Well, maybe, you know, to start, Kate, maybe you can just kind of give kind of the state of the business, and, you know, we can kind of dig into the specific questions afterwards. Yeah, that sounds great. So, you know, we, we've really been having a tremendous 2024, and if I think about how we set out the year with our key objectives, the first was the Ayvakit launch in ISM. I'm sure we'll be spending a lot of time on that today. We're really pleased where we are. And when I reflect on just our, you know, the debates we were having 12 or 18 months ago, and now that here we are, you know, gonna land the year, somewhere in the kind of $435 million-450 million in revenue range, you know, we're really, really pleased with where we are with the Ayvakit launch. The second has been our portfolio progress, and in particular, BLU-808, which I'm sure we'll talk more about. We're very excited about that program, and, we're right on track there with, the IND having been accepted and our healthy volunteer study underway, so looking forward to that as well. And then thirdly, you know, we're in a very healthy financial situation. So between our ramping revenues with Ayvakit, both here in the US and internationally, and our disciplined kind of approach to our capital allocation and our investment in our portfolio, we're in a very strong place from a financial perspective and, and see, you know, our path to sustainability financially. So on all three fronts, you know, we've executed extremely well this year and looking forward to kind of bringing the back half of the year home in a strong way. Sounds great. Let's start there. So in terms of, you know, your first theme there with the Ayvakit launch- Mm-hmm. You know, you updated your guidance. Obviously, you're seeing, you know, really nice growth there. I guess, you know, I guess it still seems kind of conservative to me. So I guess, what are some of the pushes and pulls here that we need to be thinking about in the second half, and what kind of gets you kind of towards the higher end of that guidance? Yeah, so I think maybe starting where, how we think about guidance generally. So, you know, as a reminder, you know, this is, Ayvakit is the first and only medicine ever to be approved for patients with indolent systemic mastocytosis. It's a disease-modifying, where we really impact the source of the disease. And so we are building a rare disease market for the first time, and because of that, you know, how we think about the patient journey, how we start to access the broad set of physicians who see these patients, that's all been something that, you know, we really are getting more experience on every quarter that passes. When we think about guidance, our philosophy is to put out our best estimate across numerous variables, which Philina can certainly talk more about, you know, relative to how that will kind of, how that entire launch process will shake out relative to those types of variables that inform revenue. We're. We've raised guidance twice this year. We did not expect to do that. We've had aspects of this business that have just been incredibly strong and have come into focus faster than we expected in the first half. You know, I think importantly, we're seeing continued growth, and the two variables that matter the most in terms of the overall opportunity for Ayvakit and SM really are: how are we seeing patients start and come on, patients coming on therapy, and then the duration of therapy. And so are we seeing that overall, kind of set number of patients on therapy continue to grow? And that has been strong and steady. So we are by no means plateauing, but we're also trying to account for the number of different variables as we move through the launch. And maybe, I don't know if, Philina, you want to talk a little bit more about, like, some of those puts and takes and things we're watching? Yeah, happy to do that, Kate. So as Kate mentioned, we continue to see strong and steady growth in the number of patients on therapy, and that's a reflection both of new patient starts as well as the duration on therapy. So we've seen very low discontinuation rates, and the early trends there signal durations of therapy that are multiyear, in line with the chronic durations of therapy we would expect in ISM. So strong and steady, consistent trends with some degree of lumpiness as well, just knowing that there are rare disease dynamics at play. I think as we unpack kind of the overall trajectory, and the variables that feed into our guidance, you know, I can't emphasize enough the importance of in first half, in addition to the strong and steady, consistent patient adds, we also saw substantial upside from the decrease in the proportion of patients who are on free goods. That was a really, I think, sizable tailwind that we saw that added to the strength that we saw in the first half of the year. I think that even surprised us, how quickly that happened, and it's really driven by two things. The first is the payer mix of indolent SM, which trends more commercial, and the second being some of the changes that we've seen with the Inflation Reduction Act that have improved patient affordability. And so I think it's important to also note, you know, I think we've gotten a lot of questions around this. The proportion of patients on free goods, you know, we talked at our second quarter call, it reached just under 20%, launch-to-date. So that number wasn't specific to second quarter, but that's a, that's a launch-to-date number. We think we've harvested now the majority of that benefit, and again, sort of that contributed to front-half growth. You know, as we think about towards the second half of the year, one thing we're keeping our eye on is price negotiations in Germany. We are accounting for that, and, you know, that would impact sort of retroactive to the midpoint of the year. But so really it's the, it's all of these fundamentals. It's the continued growth in new patient starts, patients being able to stay on therapy, as well as looking at these other dynamics around free goods, and international pricing. All of these things inherently go into and inform our guidance, which, again, is our best estimate of where we'll land for the year. I think the most important thing I would underscore, though, is all of the underlying fundamentals signal we are really well on the path to march towards that peak opportunity of Ayvakit of $2 billion or more. Again, if we look at the growth rates that we're seeing from 2023 moving into, you know, what the guidance would show for 2024, you know, that signifies just under $500 million in revenue. As we look towards other analogs of highly successful multi-billion dollar launches in this space, you know, we think we are well on that similar trajectory. Got it. So a lot to unpack there. Yes. So lots of things. Just first on the price negotiations, I know you brought that up. I mean, obviously, you know, ex-US still makes up a pretty small amount of the sales. So I guess, how should we even think about the impact of price negotiations this year? And certainly, I guess, have you been taking a reserve against, you know, kind of the pricing in Germany, I guess? Yeah, Mike, do you want to weigh in? Yeah. So maybe just for background, we, in Germany, which is the largest market that we have in Europe, we're in price negotiations. We ended our free pricing period really pretty much right at the end of second quarter. And so the impact, you know, as we don't yet know what the final negotiated price is, we should know that, hope to know that by the end of this year. You know, typically, you know, with other analogs, often you see, you know, pricing that's like a 30%-50% reduction. We don't know where we're going to end up yet. We wanna, you know, be careful as we are in active negotiations with that. You know, we are conservative in terms of how we're thinking about, like, recording revenue for the back half of the year. And so we'll... What, you know, is embedded in our guidance that Philina spoke to is kind of a step down in kind of thinking about what that impact could be Q2 to the back half of the year in terms of growth. Once you're in that new pricing mode, that should not affect our growth longer term, because underlying, you know, the price is new patient starts and patient growth, which we expect to be strong and steady in Germany, just as we're seeing in the U.S. So I think there's kind of this moment in the second half of the year that's reflected appropriately in our guidance. Got it. And then in the key pillars of growth for Ayvakit, so one of them is duration. Yep. So how is that kind of evolving? We're, we're into the launch now. Yep. Obviously, more focused on ISM here, but, like, where do you think that duration will continue to move to? Yeah ... like, longer term? And, you know, again, any kind of color that will, you know, change that? Like, is there anything, any other variables that you're thinking in terms of changing the durability of the or the duration of the treatment? Yeah, I think and duration of treatment is one of those just incredibly important variables as we think about the opportunity over the long term. And having patients who, you know, Ayvakit's clinical profile, both, the benefits that patients are seeing, as well as the really, you know, significant safety profile, where patients will be able to stay on therapy for long periods of time, really bode well to the idea that that's going to be increasingly become a big part of the driver, you know, of the overall revenue pie in the years to come. And where we are right now, ISM, obviously, it's early days to look at durations, but we can look at a modeled duration, and that looks very strong, to Philina's point. Very much, you know, in line with our view that this will be a multi-year therapy for people on chronic treatment. I think importantly, and I think we talked about this on maybe the Q4 or Q1 call, is in advanced SM, where, you know, we've had a longer duration of commercial kind of experience under our belts. We're now seeing patients at 25 months average duration of therapy, and this is. These are including patients who have mast cell leukemia, where the prognosis is 6 months to live, right? Where we're seeing actually survival impact with Ayvakit treatment. And so these are patients who are much more severely impacted and have a much worse prognosis, and we're seeing, again, you know, 25 months there. So I think that just bodes extremely well for as we continue to watch ISM, and as it matures, I think, you know, we'll have to be able to have more to say about that. Got it. In a good spot. In terms of growth, too, just for, you know, new patients, like, how much of the emphasis is on, you know, basically patient awareness versus, I guess, physician awareness and screening? Because I would just say that, like, some of our checks, we would talk to a doc, and they're like: "Yeah, I'm looking for patients. Haven't found them yet, but we're looking. Yeah. Yep. Yep. So that's interesting, but I guess, how are those two things kind of playing out? And again, what's kind of the... How are you prioritizing both of those? Yeah. I would say the two most important things we're focused on right now are both patient activation and provider kind of peer-to-peer initiatives, where providers can talk to other experienced providers who have treated patients on Ayvakit. I would say that the already diagnosed SM patient population is sizable. At JP Morgan, we talked about, you know, having seen this grown to about, I think it's around 9,500 already diagnosed SM patients who are not well controlled. So that is the primary focus of our efforts, is engaging providers who are treating and managing those patients, you know, and that already represents really substantial opportunity before we even talk about further diagnosis rates. And we're just scratching the surface on that- Yeah ... kind of prevalent pool, and then what we know is that that pool of prevalent patients is growing. Yep. Right? To your point, like we've, and we'll, you know, we'll be able to talk about this over time as well, and we'll continue to update. But that, you know, we're basically getting a growing slice of a growing pie. And so I think it really bodes well for the overall opportunity and peak. ... So, I guess, is it fair to assume those nine thousand patients that are already being treated or managed are those the more severe patients because they're seeking treatment? Or, you know, are there larger clusters of patients who were just not dealing with the symptoms or what, you know, maybe you can just- Yeah. Give us a better understanding of, like, are there more severe patients out there that, you know, now will be activated? Yeah, great question. So, I think the overall way we look at the market is that there are just over 20,000 diagnosed SM patients that we can see in claims. You know, we roughly segment this market to say, you know, about half of those are towards the more symptomatic end of the spectrum. And through our claims data, we can see these are the patients who tend to be more on polypharmacy or engaging, you know, even more frequently with the healthcare system. And so this also aligns, I think, pretty well with a lot of the surveys and research that have been done, with providers saying, you know, up to about half of their overall patient population, they would say, are inadequately managed or not well controlled today. And so I would say even beyond that boundary of who is well controlled or not, or addressable is a fluid boundary. And one of the things that I think has been really encouraging to see in the launch is that as providers have treated their first patient, right? And we've seen that initial adoption in the sort of more heavily symptomatic and range of patients. With that first positive experience, it's broadening their lens to who is an appropriate patient for Ayvakit, and they may be more open to treating patients who, for example, have one or two predominant symptoms as they repeat prescribe over time. We're starting to see that reflected in prescribing trends as well. So that boundary sort of, you know, not, not well controlled, like, that patient population certainly has room to grow, and, and sort of, you know, further the, the opportunity for, for Ayvakit over time. And all of these things, even before we talk about growing the diagnosis rate, which represents yet another lever. Right. And I think, one, maybe one other point to add to that is that, you know, we continue to bring forth the body of data that we have. So our Pioneer study is running for five years, and we just published over the summer in some key medical meetings in Europe, our longer-term safety data. And we did that earlier this year, as well as, you know, other aspects of the Ayvakit kind of clinical data set. And, you know, we were just. Our medical team actually was just talking to us about how they were doing their own market checks and market research, and that the threshold for people to prescribe Ayvakit has continued to come down. That is also a consequence of the fact that we're seeing this long-term safety and efficacy data on Ayvakit. So when you have a new medicine with a new mechanism of action, how do you help folks get more comfortable with the profile of the drug? And really, you know, the clinical data here that we continue to put out, and we will be putting it out at the end of this year at medical meetings and early into next year, is providing this body of evidence that's giving, you know, more and more treaters a lot of confidence, as well as patients, about the opportunity Ayvakit offers for them. So. Got it. Understood. One other question, just in terms of like, you know, some of the commentary you made around seasonality. Yep. So I guess, you know, how when a patient is prescribed or, you know, again, or let's take a step back. When they actually get diagnosed, like, how long is it for them to get on treatment, you know, generally? Like, how many weeks or months? But also, again, the seasonal factor that you've talked about, I mean, is that really a major concern, just given, again, this is not like an IV drug, you know, they don't have to go and, like, get the script and then go to a center and schedule and all that sort of stuff. It's, you know, oral. So I guess, what do you mean by more of the seasonal factor? And really, how much of a risk is that? Yeah, so I think when we think about ISM in particular, it is a chronic disease. And so these patients are all very different, right? In the sense that there are patients who've been living with the disease for ten years, and there's patients who have just gotten diagnosed last month, right? And I think one of the interesting things we are seeing is that patients are coming out of maybe kind of areas of differential diagnosis we didn't necessarily expect. Like, we have some patients coming out of who thought they had IBS for many years, and now upon appropriate clinical suspicion and workup, they're actually ISM patients. And so, like, we're actually really starting to see that dynamic as well, which has been pretty interesting. But so these patients are not kind of monolithic, right? There's a lot of kind of heterogeneity among them. And what I'd say is that we should really distinguish between seasonality and compliance. So to your point, with an oral compliance, has been very strong. We can talk more about that. Seasonality for a chronic disease state is something where it's when a patient chooses to start a new medicine versus... And do they wait? You know, if they're going on vacation for two weeks, do they want to wait until they get back? You know, is it and we saw a little bit of that in Q4 of last year. So we talked a little bit about that on the Q4 call, where around the holidays in the U.S., we saw some seasonality, and it wasn't kind of if the patient was going to start, it was just when, right? And so, and we saw. And so what we were saying is that the call is like, we're going to watch the summertime. This is our first point of kind of steady state in the launch, where we're going to keep watching for seasonality. We also, excuse me, we did see some seasonality in Europe last year in August. That's very typical. Yeah. In the pharmaceutical field, like. And so this is a chronic disease. We expect we will see periods of seasonality, and we'll get a lot more experience of that through the course of this year and next year. Again, I think what's important about that aspect is from the perspective and everything we're hearing in the field, it's not about an if, it's about a when. And, you know, it relates much more to managing short-term quarterly dynamics than it does to the overall significant opportunity that we see, right? In terms of seasonality. And hopefully, if you want to talk more about the compliance as well or- I mean, yeah, we can continue to see strong compliance. I think Kate, ... you know, hit the seasonality points very well. I think maybe back to your point around sort of what are some of the things that impact timing- Yes, yeah. You know, what we are really seeing is patients sort of thinking about when, you know, patients often can be acclimated to this new normal of the disease, right? If they've been diagnosed and sort of coping with ISM for a number of years. And I think that there's a carefully calibrated balance of just trigger avoidance. They may be on a lot of different types of polypharmacy and trying to manage as best they can, this to achieve as much control as they can. But I think one of the things that has been most compelling in terms of a patient's desire to start is the ability to connect with another patient who has had that experience on Ayvakit and can share sort of the thought process of what they went through. You know, the pattern we're seeing from patients who have been receiving Ayvakit is they didn't realize how you know it's been how life-changing this could be and how much of their former lives they've been able to reclaim. This is incredibly important, creating forums for patients to be able to hear from other experienced patients who have received Ayvakit, and that's one of the primary focus areas for us going forward. Got it. Maybe just, like, longer-term questions. So you guys, you know, kind of said this could be two billion- Yeah plus opportunity with Ayvakit. So, you know, top end the guidance is $450 million. Like, what's the path from $450 million to $2 billion? Yeah, I mean, we'll, you know, we'll be looking forward to talking more about that. You know, as we think about providing guidance in February of next year, as we think about what 2025. But, I mean, when we look at other really important medicines that have come into markets where it's the, you know, the first therapy to be approved, and there's some great examples or, you know, we look at Soliris, we look at Jakafi. Like, you know, no analog is perfect, but where we are in our trajectory is incredibly encouraging relative to other really important medicines that have come to market for patients. And so we are well on our way, I think, to that $2 billion plus opportunity. And, you know, I think all the fundamentals underlying that are very strong. The breadth and depth of prescribing, the desire for patients to connect with each other, the kind of strong and steady increase in patients on therapy, the long durations of therapy, you know, our continued evidence generation with Ayvakit over the long term. And we are continuously moving the bar on what the standard of care is, even with our own data set as it matures, right? And so I think all of these things just bode very well for growth, and we're looking forward to talking more about how we see that growth coming forward. You know, again, I think eighteen months ago, if we could have sat here and said, "You know, we're gonna end twenty twenty-four at almost $500 million in revenue," I, you know, I think, you know, most people would have been skeptical of that. And then here we are, and we're really pleased with how the medicine is being received by patients, physicians, payers. We haven't talked about that. It's been very smooth, and the impact it's having. In fact, we just had, you know, to Philina's point around patients connecting with patients, we had a patient who was really considering... Like, finally kind of came to the point of starting and actually has had such a life-changing experience. They just reached out to us because they want to be a patient mentor. They want to talk to others about their thought process- Mm-hmm And kind of why they hesitated for a few months before they started, and then now the impact that they've had. So, I mean, we've seen this kind of organically come as well as being very intentional about, you know, understanding how important those conversations are for people. Got it. And how do you think kind of the competitive landscape and just competition in this market? I mean, right now, again, you're kind of the sole player, so like- Mm Again, there might be other entrants. So how has that factored into that $2 billion, you know, kind of, you know, peak number? Yeah, I mean, I think, you know, the $2 billion number, $2 billion plus number, I should say- $2 billion plus ... is something that we see for Ayvakit in factoring in, you know, additional innovation. I mean, I think most importantly, we plan to innovate ourselves, and so we have our next generation program in ISM. And I think what's really exciting about that, and we'll be able to talk more about that, we're on track to start the registration-directed study by the end of this year, which is where we had kind of guided. And we are taking all the learnings from this continued kind of large data set that we have from the Pioneer program with Ayvakit and the continued treatment of these patients over time within the course of that Pioneer study. and we're thinking about how to, how to bring the next medicine forward for these patients in a kind of differentiated way, based on all the knowledge we've gained over the last few years. So we want Elenestinib to treat the disease that we understand now, which we understand very differently than we did when we started Pioneer. We have a much more advanced understanding of the biology of the multi-organ impact, how to measure that in a way that enables Elenesenib to have a very compelling and differentiated profile. I guess, and would that be, again, differentiated label or like specific patient populations? Like, how do you achieve that? Yeah. Like, you kind of mentioned, like, you know the disease better now. Like, what are the facets that you know, that you didn't know back then? There's a bunch of data coming up at ASH and Quad AI. I mean, we have some data coming up at ASH and Quad AI. I I would say like maybe a pre-advertisement about how we've looked at the Pioneer data set in different ways. And we've seen impact on kind of different parameters of disease, and we look forward to talking more about that with those. You know, I think IMS, we are looking to have a differentiated label with additional endpoints that lead to label language that can help demonstrate how a IMS as a medicine can impact multiple parameters of this disease state, you know, above and beyond what we measured in Pioneer. It doesn't mean that Ayvakit is not impacting those. It's just at the time when we designed Pioneer, we designed it with a certain base of knowledge, and we've really learned a tremendous amount with our investigators over the course of the last four years, right, where we've been developing this medicine. Gotcha. Maybe shift gears to BLU-808. Yes. So obviously very exciting. So maybe just, maybe provide a little background about that. Yes. program first, and then we can go into some of the questions. Yeah. I mean, so BLU-808 really came out of our engagement of the allergy immunology community through Ayvakit with ISM. And you know what? Basically, almost four years ago, people were saying we could really use a wild-type KIT inhibitor that's an oral option, for patients, across multiple diseases that are kind of where mast cells play a role, in type 2 inflammation. And so, you know, we started that program, relative to kind of those, that set of conversations, and we're incredibly pleased with BLU-808's profile. And we've shown some of that and then be able to publish some of that already. And, you know, we're on track now to have a data set with a healthy volunteer data set early next year. I think what's important for BLU-808 is that because we're going after kind of more core biology, where mast cells play this core role in a number of disease states, and you know, most of the other approaches have been looking at kind of you know, targeting downstream effectors of that. And so we really do think we have an opportunity to go after core biology and importantly, with an oral, to strike that kind of risk-benefit profile for patients across a wide range of disease states, and be able to very much realize the idea of a pipeline in a pill, that can be impactful across a number of diseases. And so, you know, we'll be... We have this webinar series we've been doing around mast cell biology, and we'll have a second at the second half of this year. We'll spend more time in that, talking about how we're thinking about BLU-808. But we just, you know, this is one of those programs that I think, you know, is going to be just transformative for the company. And unlike ISM, which is very much a market that we're building and it has not been well understood, what the value of that is and how much medical need there is, BLU-808 is going to address very well understood patient populations and markets, and so we expect the healthy volunteer data to be inflecting for Blueprint. I guess, should the big takeaway out of the normal, healthy volunteer study just primarily just be obviously safety, right? Yes. For a small molecule- Yes. Obviously, there was a competitor molecule that had some issues. Yep. So, I mean, how do you feel about, again, what we've seen pre-clinically with this molecule and safety and the selectivity? Yes you know, relative to some of the other molecules out there? Yeah, great question. I mean, to your point, healthy volunteer data, the predominant thing we're looking here is safety and therapeutic window. And I think, you know, one of the founding principles of Blueprint Medicines is around selectivity, and what we have is an exquisitely selective molecule on wild-type kit. And so what, you know, what we expect is that we will not be seeing kind of, you know, off-target safety issues. This is from our preclinical profile, and that what we'll be able to do is really with an oral approach, which is like dial up and down, how hard you're hitting the actual target itself, to be able to both either from a dose level or dose regimen perspective, be able to have a really safe and oral approach for patients across a range of disease states. We're very pleased with the profile of this molecule, and it's very kind of exquisite selectivity on the target itself, which enable us to do this. I guess for the phase one design, I mean, I guess it sounds like if you're going to try to find a strategy to dial in dosing, I know. I think you've talked about it, maybe even per indication. Yep. Right? So, like, you're going to have to do extensive dose work. So I guess, is there... I don't know, off the top of my head, the phase one design, is it somewhat unique to do that? Or I guess, what's your plan to achieve that type of dosing? Yeah. So the healthy volunteer will help us have just what is the therapeutic index of the compound, and we expect that to be wide, right? That gives you a lot of flexibility in terms of, you know, potentially dosing patients in different disease states just to calm the mast cells down, right? So they're not releasing mediators or they're not getting activated versus going all the way to be able to ablate a mast cell, right? Yes. What we want to be able to see is a nice therapeutic window. The idea of what dose and what dosing regimen really does have to be indication-specific. This is where what we said is that we'll be looking to do a series of kind of what I call, like, small proof-of-concept studies around a range of indications, and we'll be thinking about that relative to the biology that the mast cells play in those indications, and what is the therapeutic goal? Like, do you want to ablate? Do you want to just, you know, stop them from degranulating, and how do you want to think about that? That will have to be more indication-specific. We'll have more to say about that, too. And then just in terms of like, kind of the on-target KIT- Yeah you know, adverse events that we're familiar with, you know, from some of the- Yes -the monoclones- Yes -and others. But, you know, it should be assumed that's going to be a similar liability. And again, as you're just dialing in and out of the... From a dosing perspective, trying to mitigate that, again, that's going to have to probably be in the phase 2s, I would suspect. Yes. So I think, you know, on target, on-target adverse events is exactly what we think we're going to be able to manage extremely well with an oral. Okay. You know, I think some of the other folks who are developing drugs in this space have done a tremendous job showing the importance of targeting wild-type KIT. And I think, you know, we very much respect the work that they're doing. But with an antibody, you're just, you are limited to, you know, you're either on or off. Mm-hmm. And so I think that that just creates a certain set of limitations that we think BLU-808 will be able to have to overcome, and be able to really kind of be able to strike that balance of what you're looking to achieve in any given disease state around that safety and efficacy profile. I mean, do you think you need to have efficacy in line with the biologics to, you know, have a successful drug here? Or do you think, you know, you can be slightly below that good safety, but your earlier line, like, how do you kind of think about the overall opportunity where you guys play? Yeah. I mean, I think just philosophically, I think the overall package of a medicine is what's really important to patients. So it's the safety, it's the efficacy, it's the route of administration and convenience. I think we will, we will be able to have the same level of efficacy as, as the other kind of therapies out in that range. But the question is, like, how do you, again, what I think just thinking about Ayvakit and ISM-... Right? We're, we're treating ISM patients at 25 milligrams, and we're treating advanced SM patients at 200 milligrams. And we have a range of doses in between for any patients who kind of, like, sit along the spectrum. But we've already shown that we can differentially, from a dose level perspective, modulate mast cell behavior. These are mutated mast cells, obviously, but it's the same idea, relative, and so I think, you know, that would be the approach for 808 as well, is in certain disease states, you may just want to, again, have just a steady, lower level dose that kind of keeps mast cells calmed down. There may be other diseases where you really need to, kind of get a, you know, ablate mast cells for a certain amount of time and then, you know, and then come down and have a maintenance dose. I mean, we're really going to have to kind of figure it out disease by disease, but I think what 808 does is gives us the tool. We expect that that's what the healthy volunteer data are. We'll see what it says, but we'll have the tool need to enable that, which I think means that we can actually realize that pipeline and uphill opportunity, as opposed to having kind of like a one-trick pony. Got it. And in terms of, like, these, you know, indications, obviously, you know, we cover Celldex so that we see- Yep some of the indications that they're going after, and then other ones that, you know, kind of have been, you know, potentially pursued. Yeah. But I guess, you know, these are large indications. Yeah, they- Some of them are very large. So I guess, how do you think about, you know, balancing the Ayvakit launch? Yep ... profitability with also, you know, funding what could be very large, you know, potential trials in the future? Obviously, these are big opportunities, but how do you balance all that, and what's kind of obviously the priority right now? Yeah, I mean, I think we've been really clear in terms of our... Our capital allocation priorities are the Ayvakit, Ayvakit and the Ayvakit launch and continued. I mean, we're still running the Pioneer study and developing that long-term dataset in SM in terms of its role as a lifecycle management opportunity to extend and bring additional innovation to SM patients over time, and then BLU-808. And we're well-positioned, I'd say, over the next few years to move all of those things forward as our capital allocation priorities. We obviously are doing additional work in other places, and we, you know, talked about how we'll think about bringing that innovation forward, but those are our clear priorities, and that's where we'll be spending the bulk of our, our blueprint resources both people and financially. Got it, and then maybe a couple of questions here in the last couple of minutes, but BLU-222? Yes. Two two two. Yeah. Yes. CDK two. Yes. You know, just remind us here, so, you know, of the profile that you've seen to date- Yep We're gonna see some, you know, competitor data. Yep -at ESMO. Yep. So again, what are some of the key differentiating things that you'd be looking for in that data set? Yeah, so BLU-222 is now in the phase 1 study in combination with ribociclib and fulvestrant. I think what we showed at ASCO this year was the first time ever where you've seen a CDK2 inhibitor safely combined with a CDK4/6 in fulvestrant. So that is, like, an incredible achievement, and very much a testament to BLU-222's profile. It also, I think, helped to bring forward... I mean, people have been interested in CDK2 and understanding its role in breast cancer. And I think what we've shown with BLU-222 and the data that we had at ASCO is that it really helps validate CDK2 as an important target. So we're really thrilled with BLU-222. This is where, you know, as I just talked about our capital allocation priorities, obviously BLU-222 was not on that. Yeah. And that is more because, you know, as we think about our future and our footprint in mast cell driven diseases and our, you know, desire to continue to see operating leverage there, this is an incredibly important program, and we have a portfolio of cyclin-dependent kinase programs that we're really excited about. Yeah. So we have BLU-222, we have a next-generation inhibitor, and then we have. We've just discussed a CDK2 degrader. And we've been getting a lot of enthusiasm from external partners around all of those programs, actually. And so how those kind of shake out, we'll see over time. We're really interested to see what happens at ESMO. Obviously, there are some other companies who are looking focused on cyclin-dependent kinases. And, you know, my view at this point is that any data that continues to show that CDK2 and/or, you know, CDK4 specific molecules are impactful in breast cancer is only. It's great for all of us. Yeah As we think about bringing innovation forward into breast cancer, which is just a huge medical need, still exists, and it's a very large market, so. What's the ideal situation for the CDK two partnership or, like, a partner- Yeah -in that asset? Like, is it just to be completely hands-off and obviously not spending any more money on it, so you can focus on other things, or do you want involvement? Do you want more of a collaborative thing? You know, what, what's kind of ideal for you guys? What's the ideal scenario? Yeah, I mean, you know, I think these deals have puts and takes in them. I think what we want to make sure that we're focusing our capital to the programs we just talked about, Ava, Ella, and BLU-808. And, you know, we, of course, have, you know, a strong oncology kind of heritage. But as we think about our future, I think, you know, if someone was to with breast cancer infrastructure in place and a lot of experience in breast cancer, would be able to take this and really get it to patients in a timely manner, we'd be really pleased to see that. So- All right, cool. We'll leave it there. Kate, thanks so much, and team. Thank you. Thank you. Yeah. Thank you.