It's kind of effective, for sure. Good morning. Thanks, everyone, for joining us. I'm Salveen Richter, biotechnology analyst at Goldman Sachs. We're really pleased to have the Blueprint team with us. We have Kate Haviland, CEO, and Fouad Namouni, President of R&D. Kate, maybe to start with you here. Sure. Since assuming the role of CEO, have you implemented any changes in strategy, and how are you thinking of where Blueprint goes, you know, on the forward from here? First of all, thank you, Salveen, and the whole Goldman Sachs team for having us here today. It's great to see a bunch of people in the room and those of us on the webcast. Thank you for joining. you know, Blueprint, I joined Blueprint Medicines almost seven and a half years ago, you know, we started out as a company that had, you know, very important but very discrete precision medicine opportunities, with our first approval being in PDGFR alpha-driven GIST for AYVAKIT in 2020. Where we are today is we're now a fully integrated company. We have a global footprint, both directly as we bring our medicines to patients here and in Europe, with our partners across the world. Importantly, we're in the, you know, third week of a launch of what we consider our beginning of our Precision at Scale, which is being able to bring precision therapies to a much larger set of patient populations and addressing their medical needs. That is with the launch of AYVAKIT in ISM. I wouldn't say that we've implemented any strategic changes, but I think the evolution of the company has been just tremendous over the last couple of years since our first approval in January of 2020. We're just very excited about the diversity of growth opportunities we have in front of us. Great. Let's start with AYVAKIT in indolent systemic mastocytosis. Yes. just given, some of the recent updates here. With the approval here, and I think your commentary that this is very similar to a rare disease launch, can you just remind us what the strategy is here in the context of what you learned from advanced systemic mastocytosis? Yes, absolutely. what is really exciting about the opportunity in indolent systemic mastocytosis is, first of all, we have the first and only therapy, and it is a disease-modifying therapy, so we have the opportunity to really, for the first time, bring a medicine that is designed to address the root cause of this disease to patients. That's an incredibly exciting opportunity. Importantly, it's also at a scale that is gonna let us drive revenue momentum in a much more meaningful way for the company over the next couple of years, and it's also still a specialty market. That enables us to have a very efficient commercial model as we think about bringing this medicine to patients, across the US. You know, we have a targeted therapy. We have a targeted commercial model. This is not a reach and frequency model. This is a model that we use, a very sophisticated kind of data operation that we have been putting in place and using throughout our GIST and our Advanced SM launches, where we can make sure that we are directing information to physicians at a time when it's most relevant to them, and that's gonna be when they've seen a patient recently. That's really our model, is we understand where kind of the concentrated set of patients are in a set of physicians, and then we can also see when patients engage with the healthcare system, and we can direct our field-based teams to then engage those providers. You know, again, really tremendous opportunity for us. At the same time, it's an efficient and discrete commercial model. Could you help us understand what that early launch trajectory may look like over the first year? Sure. You know, are there patients now sitting here who've been waiting for a therapy and, you know, really just get coming on board at this point to try to get access? You know, ISM is an opportunity that's 15 times the size of the advanced SM opportunity. It's still a rare disease, what we've talked a lot about is, as you think about what does a successful launch look like, there's going to be a steady growth in cadence to the launch. You know, Jakafi is a great example. We've talked about that, where they originally got approval in the more severe form, MF, and then they were able to get approval on PV, and you kind of see the ramp start to happen from there. We've said, you know, that we don't expect a bolus, you know, we are not transitioning patients out of PIONEER. We're hoping to hold patients in that trial as we develop long-term safety data on the therapy in ISM. What we will expect to see, as you do in every launch, is the patients who are most highly affected are gonna be the ones who get come on therapy first. Then we expect that we'll have that strong clinical experience with healthcare providers who haven't had a chance to have clinical experience yet with AVA, and then they'll start to widen their own view on, you know, who is a good AYVAKIT patient. I think importantly, we are really pleased with where we landed with the label, with the FDA, because that enables providers and patients who can think about whether they're well-controlled or what their medical needs are in a very broad lens, right? It does not limit patients at all, or their opportunity to treat patients to just the moderate and severe segment. I think that's a really, a really nice opportunity for us. You've talked about the first pillar of strategy being physician engagement. Yes. These 350 high-volume prescribers that you're engaging with, what has the feedback been so far? It's been tremendously enthusiastic. I'd say that we've been, you know, engaging those prescribers. We've been at some regional allergy meetings, and, you know, the physicians are very excited about the opportunity to have a treatment that is specific for this disease, that really does hit the genetic cause. Our field teams are getting great access and, you know, being able to get into offices and really talk about the clinical profile of AYVAKIT, and what we've seen in the PIONEER study, and really have a conversation with the physicians about, you know, how they're thinking about their patients and where the needs lie. Remind us, this initial group that you're targeting, what proportion of the ISM patients will be addressed, via the? In, in the three hundred and fifty? Mm-hmm. When we think about this group of 350 physicians, they have about 1,500 ISM patients who are moderate to severe. This is, it's a really great place to focus team efforts in the first few weeks. We're in week 3 here of launch. It's a great place to do. It's a ring-fence, kind of, discrete place where we can spend time, where we know that there's a substantive number of patients, and we know that we also have been engaging those physicians before launch with our medical affairs team, and we know that they have patients in need. I think that's really in the early weeks here of launch, that's where the focus is. You know, just given it's a rare disease, education is key. Yep. What is being done on the educational efforts here? Absolutely. We, you know, I think what was wonderful is you saw right after launch, we actually had our data published in the New England Journal of Medicine Evidence publication. That was a critical publication for us as we think about bringing this therapy to a broader set of providers that we've been engaging. We've been at major medical congresses, you know, starting a year ago and continue to engage. We have just numerous, you know, efforts at these regional meetings, as well as through speakers programs, which are very robust. We have numerous speakers in the different regions talking about their clinical experience with Ava, and, you know, the direct one-on-one. I mean, as I said, it's nice to be in a therapy area where these physicians have not had an opportunity to access innovation for these patients, and they're really looking for it. The, you know, we're getting a lot of engagement on a one-on-one basis, and so that's the healthcare provider, you know, angle that we're taking. In this launch, it's a little bit different than our previous launches with advanced SM. We're also very focused on going direct to patients. I think, you know, patients with ISM have had to be an advocate for themselves throughout their diagnostic and treatment journey, and they're very much involved in, kind of defining their own care and the physicians that they see. We have had an ongoing effort that was unbranded to begin with. We flipped it into a branded effort upon approval, where we can go directly to patients to actually talk about the data and to help them think about whether AYVAKIT is an option for them. I think both of those pillars are incredibly important. The third is market access. You know, market access has been a huge strength of all of our launches to date. You know, we have the 25 milligram dosage strength, which is the labeled dosage strength for ISM, already in the channel, available for physicians to prescribe and, you know, currently, you know, being covered by payers. Again, we anticipate that the market access, the third, kind of, third pillar, is also gonna just continue to be very smooth for us. The initial pool of physicians and patients. Yep. The severe, moderate to severe patients, when you speak to these doctors, what proportion of those patients do they believe they will put on drug? Is it 100%, or is it kind of a, you know, a sample of them as they take kind of a watch and see approach over time? You see a range. You know, some of the physicians who've had clinical experience or participated in our studies, I mean, they're in the place where, you know, we've had discussions where they're, you know, offering their AYVAKIT as a first option for a new patient they see. I think for physicians who have not had clinical experience yet, I mean, what we expect and what we've seen in other launches is that they will think about those one to three or four patients they have in their clinic who have just very severe disease. Their lives are incredibly limited. They're not able to go to work. They're not able to participate in family events. They can't go on vacation, and they're gonna start with those patients. What we know is that patients feel better quickly, and we saw that in PIONEER as well. You know, this is a chronic inflammatory disease, so you see improvements in symptomatology over time, but they feel better fast. I think once these new physicians start to have that clinical experience where they really see their patients dramatically impacted for the good, I think they'll then start to widen that aperture. I think you get to that critical mass moment where, you know, you start to see more acceleration. There's some occasional physicians who say, "Well, our patient's well-controlled with standard of care. Yep. You know, when you encounter a physician, who has that view, how do you respond, and how do you educate them and, you know, maybe help us understand why they have that view? Yeah, I think, you know, one of the things that we have tried to kind of help physicians think about is: what does it mean to be well-controlled? If you're on 2 or 3 symptomatic directed therapies and you are still not able to go to a family event, is that truly well-controlled, right? I think patients have learned to live with this disease for a long time, and I think as soon as we have that conversation to say, you know, "Are you talking to your patients about what in life they are not doing that they would like to do?" You kind of see the light bulb go off, and they're like, "That's a great point." You know, because that's not a conversation that these physicians have had to have because they haven't had an option, right? I mean, what they talk about is, you know, managing GI symptoms, managing skin symptoms, and you know, that's been what they've been doing for decades. I think it's as soon as you say that, I, these physicians care deeply about these patients' well-being, and I think it makes them rethink a conversation that they wanna have with their patients about how limited is their life and, like, how do they wanna think about that. The other piece is just the burden of the polypharmacy. We see, I mean, you can see in social media and other places, your patients have taken pictures of the drugs they're on. I mean, we can see their prescription medicines in claims data, but these patients are on a myriad of over-the-counter medicines. They're on these complex regimens daily to manage their symptoms. The idea that, you know, you could think about taking a once-a-day pill that is able to impact systemically all your symptoms, that's a huge change and a mind shift in patients as well. I think we try to help physicians think a little bit about You know, how do you think about well-controlled from different dimensions? ... What's the strategy for expanding beyond the 350 high volume prescribers? I mean, we're, honestly, we're already doing that. I mean, I think our sales-based team is very focused on those accounts, but our medical team has continued to, you know, engage other specialties. I mean, again, we can see in claims data there are other specialties that are involved in the, in, and, or, you know, other AIs who have, you know, don't have quite the same concentration of patients but are still involved as well. You know, as we think about launch, I mean, that's a, it's a great place to focus, the early kind of, the early months of launch. We already have engagement, and our teams engage hundreds of physicians before the approval, and we'll continue to do that after as well. On the approval call, you estimated a global peak sales opportunity of $1.5 billion in SM broadly. Just walk us through the assumptions here that, you know, fall into that estimate? Yeah, I think what we're saying. We've been talking about $1.5 billion as a ISM opportunity for some time. I honestly think now, with the breadth of the label that we got, it's really all adults with ISM, we're reevaluating. We think it's actually probably higher than that. If you think about it, if you just take the U.S. for a moment, what we know is, by an epidemiology perspective, there's 32,000. There should be 32,000 patients with SM. 5%-10% of that is going to be advanced SM, and the rest will be ISM. What we see in claims is we can see about 16,000-17,000 patients who are diagnosed. You go from the epi to the, what you see as a diagnosed population. Let's just call it 2,500 of those are advanced. You're left with about 14,000 patients who have ISM, who are diagnosed in the U.S. today. What we do is, you know, look at their prescription drug burden, their inter engagement with the healthcare system, their ER visits, and we said, "Okay, there's about, of the 14,000, let's say 7,500 are moderate to severe patients," right? They're on multiple symptomatic-directed therapies that are focused on ISM. They engage the healthcare system regularly. And when you look at that 7,500, if we're able to treat half those patients, that's $1 billion in the U.S. alone. I think, you know, I think as we sit here today with both the label and what we see from a medical need perspective, you know, the peak opportunity is incredibly compelling. Help us understand, with the advanced SM opportunity, what you can do at this point to drive growth, you know, in a, in a bigger way. There was a one subpopulation where I think, they were treating other symptoms before they were really treating the advanced SM itself. Yeah. Help us understand the plan there. Yeah, we've been pleased by the growth that we saw last year and into the first quarter. Just remember, last year, we basically doubled revenues, and we saw a 30% growth actually in the base business. The first quarter sales was on our base business of just an advanced systemic mastocytosis. What we guided to this year for just that base business, which does not include ISM, is $135 million-$145 million in revenue, which is, at the midpoint of that, is a 20% growth rate, and that's driven by advanced SM. To your point, it's predominantly by continuing to penetrate these patients who have what's two diseases, which is called SM-AHN. Right? They have the systemic mastocytosis component, and then they have another neoplasm. What we've seen, and we talked a lot about that in the last year, is that physicians are accustomed to treating the AHN because that's where they've had therapies. It's taken. You know, we focused our data at ASH last year on the impact of AYVAKIT in SM-AHN patients, where we have shown a survival benefit for monotherapy AVA treatment in those patients. We are, you know, consistently engaging healthcare providers to think about the appropriate patient to treat and prioritize the SM component. Similar to how we talked about the clinical experience in ISM, when we get a physician to take a SM-AHN patient and treat them with AYVAKIT, they have a tremendous experience, and what you start to see is that that continues to grow. They'll treat more of their patients. We, and that's the growth that we've been seeing, is really in continuing to penetrate the SM-AHN population, which we have a lot of opportunity to do. We will not be at a peak, you know, this year for advanced SM. That will continue to grow. Albeit at a smaller, you know, at a, at a more, you know, incremental rate, 20%, so. Just remind us how the GIST indication's progressing in terms of the launch there? Yeah. Secondly, with GAVRETO, given Roche is no longer leading the commercialization effort. Yeah. what your strategy is? Are you looking for a new partner globally, or how are you thinking about that? Yeah. Let me start with GIST. The GIST indication is very straightforward. I mean, it's a very steady business for us. It's about $7 million-$8 million a quarter, or... you know, it's just very steady. Any growth you see is from the advanced SM opportunity and then now ISM, as we see going forward. To be, you know, it's gonna have to be, both advanced SM and ISM are, have the same diagnosis code. Now that we're launching an ISM, you know, the opportunity to really pull apart who's an advanced SM and ISM patient is gonna get a little bit trickier, particularly depending on what, you know, part of the, you know, whether they're in our specialty pharmacy or specialty distribution. We have different visibility across that. We will certainly, you know, continue to look at that. From a GAVRETO perspective, Roche is still. You know, right now, everything has stayed the same. They kind of alerted us in February that they plan to terminate the collaboration. That's a year, that's kind of a year termination period, so nothing will change until next February. They continue to lead the commercialization efforts on GAVRETO. But what we are looking to repartner GAVRETO. You know, for us, ISM and the launch there is the most important thing that we're doing from a priority perspective, and we certainly do not want to distract the team at this point by bringing GAVRETO back in to our commercial team. There's a number of interested parties, so we've already started that process, and we have a number of really high-quality companies that GAVRETO makes a lot of sense for them in their portfolios, and so we are confident that we're gonna be able to put that in the hands of somebody who can very much drive the value of GAVRETO. What was the rationale for Roche to step away from this asset? I think, you know, people go through strategic reprioritizations. You know, they've had a lot of change in leadership there, you know, and they look at, you know, portfolios, and Fouad talks about this quite often, where you know, you may look at a portfolio and say, "Okay, if something has less than a certain peak," that you may be choosing to walk away from that. You know, we don't have all the kind of, insider knowledge on their complete decision-making on that process, but, you know, they're clearly going through some reorganization and reprioritization of their portfolio now. Maybe just a question for you. Yep. Fouad. When we look at these targeted oncology launches recently, you know, apart from a few, specific targets, it has been extremely hard to kind of see these ramps play out in the context of how big one would assume those markets should be. Why is this? You know, I think what's amazing about targeted oncology is we're having the impact on patients that we wanna have, right? When you put the right drug in the right patient at the right time, you have a tremendous benefit to those patients. I think, you know, as we think about commercializing those therapies, there's a lot of kind of just behavior change through, you know, doing the right types of testing to detect the genomic drivers, and then thinking about, you know, how to prioritize a targeted agent versus more kind of wide and broadly acting agents, and that just takes effort and time. I think that's one of the reasons why we're really thrilled that we're at a place, starting with the ISM launch, but then looking at our pipeline, where the opportunities we have are large opportunities. It's what we call, again, Precision at Scale, right? You know, the kind of first set of, you know, indications that we got approved were more discrete. Therefore, like, some of that kind of behavior change and market friction around testing becomes more of a headwind to a commercial launch. I think where we are now with the ISM opportunity, the size that it is, and then now we're moving into lung cancer, breast cancer, and others, you know, we're just in a different place from the opportunity to bring that same precision impact to a patient, but at just a much larger scale. Got it. I think one of the things the community for precision medicine might have underestimated is the uptake of testing for new gene drivers. We see that in particular in diseases, let's use lung cancer as an example, where you have immunotherapy, you have chemotherapy, you have other things. People tend to, unless it's restricted by their label, to go to the most used agents, the ones that are used to before, if they have the genetic information from the patients, get into that. The other thing. My point is that will change over time as people are more and more educated on these new gene drivers to use these medicines in smaller indication. The other thing is, we should think about is how all the treatment fits for a patient. There are treatments when you give to a patient, generate some type of toxicities like, you know, immunotherapy for lung, other things. People have difficulties using targeted agents after that. As the physicians are more educated about these, you know, gene driver, albeit small opportunities, you gave the RET as an example, I think we'll probably see an improvement in patient care. We'll see more and more use of these agents, but it's really a journey. At Blueprint Medicines, obviously, to Kate's point, we really moved the company to what we call Precision at Scale. I know we're gonna talk about EGFR and CDK2 and other things, but it's really looking to an area where the gene drivers are well understood, patients are known, and the opportunity is sizable enough, so you can have an impact on greater number of patients. Maybe jumping into EGFR and the portfolio here, you presented some safety and biomarker data we see in ASCO. Just help us understand the broad strategy here. Where are you going with all these different assets? You know, what are you trying to achieve? As the evolving kind of competitive situation, is that causing you to change strategy? When should we expect proof of concept across the portfolio? I think what we are solving for at Blueprint in this EGFR mutated non-small cell lung cancer population, is the resistance to existing therapy. Whether it is an acquired resistance after period of treatment, or a primary resistance, for reasons that the patients are not responding enough to the standard of care. At Blueprint, we developed a pipeline of agents that are based on our expertise of making them selective our wild-type EGFR. That's for toxicity reasons, with the idea is to make TKI/TKI combination happen. These are very difficult to do today with first-gen, third-gen agents in non-small cell lung cancer. We have three compounds, let me start with 945. 945 was developed with the idea to be very selective over wild-type EGFR, covering TMCS and the classic drivers of EGFR, but mostly to be a combination agent, given that window therapeutic index or window that 945 has. We're very happy to generate some proof of concept data last year that we reported at ASCO now on the monotherapy, showing that the drug clinically has the profile, a profile consistent with the preclinical data and what it was designed for. We always knew that moving forward with this agent, it was gonna be a combination with osimertinib, and maybe in the future, with 525. The combination of the osimertinib that we reported was safety from the dose escalation were really very good and quite impressive in terms of both agents are given at their full doses, and we're still seeing an acceptable safety profile with no major concerns on-target or off-target toxicity. That's not at the cost of no efficacy. In fact, we have seen some very good efficacy in second, third, fourth line plus patients who are progressing on osimertinib as the last treatment when we add 945 on top of it. We have seen in this small set of data, one patient out of two respond to the combination. The goal for us is not really to focus our strategy on late-stage patients, but to move to the first line. It's clear to us and to people who are expert in the field that patients with L858R sensitizing mutations have less benefit from standard of care than exon 19 deletion. One of the hypotheses, and based on some data generated on osimertinib, that there is no full inhibition by osimertinib of that particular driver. We generated preclinical data showing us when you put two together, BLU-945 on osimertinib, we have more action on the LR mutation. Where we are now, we are in terms of development, we are in dose escalation. We would like to go in first line. As a first step is really a small randomized phase II to really do efficacy POC, assuming that the safety continues to be as it is now with safety, and see whether we can, as in clear ctDNA, better than osimertinib single agent with the combination, have more responses better than osimertinib single agent. Towards the late 2024, have a go, no-go decision for a registrational study. To the second part of your question, Salveen, how does the landscape the studies that are changing the landscape, if the landscape changes dramatically, that question is still out there, not answered. There are two things in terms of landscape. Chemotherapy combination with osimertinib, we will see the data and have a good idea on what's the efficacy, but mostly what is the safety of this type of combination, this environment. Similar for combination of antibodies targeting MET, EGFR, and third-gen. When you talk to experts, clearly assuming the studies will be positive, that also needs to be seen. I think given the benefit risk profile, given the safety profile of these very complex combinations, probably not all patients will be eligible for these combinations. The idea behind having a safe and very effective TKI combination is really to increase the efficacy and avoid any toxicity, and then make an option available for the majority of patients. Great. Moving over to your CDK2, where we saw some data as well. I guess, how competitive is the asset in the context of the visual AE? I'm sorry. The visual AEs. Okay. Given the ocular toxicity. Solution to CDK2? Yes, CDK2. Let me just before sharing our experience with the visual AEs, just, you know, highlight the fact that CDK2 has really been 1 of the key targets in oncology, very difficult to develop. Why is it a key target? For 2 reasons. We know that our cancers are driven by CCNE1. We also know that CCNE1 is behind the primary and the secondary resistance to CDK4/6 agents in breast cancer, from the early, you know, published public safety data. Therefore, it has become something that everybody wanted to have and develop in their pipelines because it probably will solve or could solve a major problem in hormone-positive breast cancer. At this ASCO few days ago, for the first time, we see two companies, Blueprint and Pfizer, showing their phase 1 data and with experiments run separately, but convergent to the same information, and what I really think is a validation of the target as a key one for breast cancer and other tumors. We believe that from the totality of the data that we have on BLU-222 or our CDK2 inhibitor, its selectivity and just the clinical data we report on safety and efficacy, that it has a potential to become the best in class there. To the question around the visual AEs. We have seen in a handful of patients, very interesting phenomenon that without any ocular abnormalities at the ocular exam, patients had a blurred vision and some photophobia, transient, minutes to hours, and we have not seen that as really being an issue in terms of benefit risk. We were on partial clinical hold for just a few weeks, probably one of the shortest I have seen with the FDA, and we just updated the information for patients. No requirement for monitoring the ocular exams by the health authorities. The study is back on track, recruiting both monotherapy and combination, and I really think that's something that has not, in our opinion, in the investigator expert's opinion and health authorities' opinion, changed anything about the benefit risk. Lastly, where we are in terms of development on this, the development of CDK2 will be by all sponsors, combination therapy with CDK4/6 inhibitors and hormone therapy heading towards second- and first-line breast cancer very quickly. Is there anything else that you want to highlight from the pipeline? Yeah, one of the things that I'm really excited about and what we've guided to this year is we're going to have a development candidate for our wild-type KIT program. I think, you know, for us, you know, having, you know, our roots in kind of hematology oncology, but now our footprint in allergy immunology with ISM and just a tremendous amount of relationship and expertise there now, you know, this enables us to continue to build on that. Like, I think we are the world leaders in understanding KIT biology and KIT as a target. Now we have the opportunity to have both the first and best-in-class oral therapy that can, you know, that is going to be targeting wild-type KIT instead of the mutated form. you know, I think that kind of enables us to continue to build on that AI portion of our expertise and our infrastructure, in a way that is, you know, tremendously exciting opportunity for us at Blueprint, so. With that, are there any questions from the audience? We saw data both from your CDK2 program and from Pfizer's at ASCO, and wondering if you can expand on a little bit more about where you see the differentiation in your molecule relative to Pfizer's? I think, as I mentioned, I think it was a very good news to see two companies showing the validation of a very new target to breast cancer and beyond. I think on the data that we showed at with the BLU-222 and the expertise of Blueprint Medicines in making highly selective tyrosine inhibitor, we're probably given this the safety profile we are seeing with 222 in terms of hematological toxicities, in terms of being very rare, in terms of GI toxicities. That's, you know, at we went all the way to some high doses, seems to us to be a differentiating factor. Why is it differentiating? Because the future of these agents is combination therapy with agents that could bring some hematological toxicities. You better start with, you know, an active compound, as we have shown in terms of partial responses. We, partial response, we have seen in breast cancer patients with a good safety profile. We believe I mean, we'll see how, you know, we continue to generate data over the next many months on this. We believe, we have some hallmarks that we are up to a best-in-class agent. Sorry. Hi, Kate. Hi. As you think about the ISM launch and the initial patients that might come on to AYVAKIT, is there a specific phenotype that you're hearing from physicians, whether it's the baseline characteristics, the symptoms from their ISM disease, pathology, that makes them more likely to be treated in that initial tranche? It's a great question. I mean, with it, there is not one. I mean, we're seeing a range, and I think, you know, I think it's less about their baseline characteristics or their disease. It's more about what impact it's having on their life. You know, we were meeting with a physician, and one of the first patients that this person treated was a patient that actually had one symptom predominantly in their disease, so not the kind of multisystem, you know, symptomatic patients that we saw in this study. That symptom was a GI symptom, and it was very much limiting this person's. Like, the person could not. Had a difficult time, like, being out of their home. So that patient was one of the first patients that was started for that physician. That patient probably wouldn't have made it onto our PIONEER trial, honestly. It's, you know, it's interesting because I think we're all so used to an oncology hematology frame on these things, and this is really about people's lives being interrupted and them not being able to kind of do all the things that make life worth living. The patients who feel most compromised in that setting are going to be the first patients on, and they will have a broad you know, some will be multi-symptomatic across multiple domains, some will have one that is incredibly debilitating to them. Thank you so much, Kate. Thank you, Fouad. Thank you very much. We appreciate it. Thank you. Thank you.