Hello. Thank you all for coming again to the 18th Annual Citi BioPharma Conference. Happy to have on stage with me from BioMarin. Certainly been an exciting last few years, biggest commercial launch in history with VOXZOGO, the upcoming or ongoing launch as of just recently, launch of ROCTAVIAN for hemophilia A and, of course, a large portfolio of ultra-rare diseases. Could you start by walking us through BioMarin, its history and really these transformative recent years? Yeah, great. Thanks. Thanks, David. Thanks for having us. Thanks for participating, everyone. And yeah, you know, BioMarin has been on a steady growth journey throughout our 25-year history. We grew up around mostly ultra-orphan therapies. These are ultra-rare metabolic disorders, very small patient populations, very transformative therapies. Most of them are enzyme replacement therapies, very complex biologics replace an enzyme that's missing because of an inborn error in the metabolism, and we replace that enzyme. We grew that business, we refer to it sometimes as the base business, into a $2 billion profitable business that's also cash flow positive. We also realized a few years ago that if we want to grow into large biopharma, that it would take more than those ultra-orphan product approvals to move the needle because whether it be a large indication or a small indication, the time and effort that it takes to get a drug approved is significant, and we started to focus on still very meaningful transformative therapies, but larger market indications. And you see that with the development and approval and now launch of VOXZOGO and the development approval and launch and process for ROCTAVIAN. This is, those are achondroplasia, the most common form of dwarfism that VOXZOGO is indicated for, and severe hemophilia A, both large indications, larger than those indications that we grew up upon, but a couple more things that, you know, that base business, we refer to it as, resilient. While it is $2 billion, and you may think of biosimilar competition risk at that level, it's a very diverse set of revenue. We source that $2 billion from six different products. We sell in over 78 markets. These are very complex compounds to manufacture, so high barriers to entry, also resilient in a IRA insulated sense. These are all orphan disorders. And the base business is still growing, you know, roughly mid-single digits, potentially higher depending on the year, depending on the product. So we refer to that base business as one of the three cornerstones to the investment thesis at the time, at this time. Second is launching these potential blockbusters. So, over the last two years, with both VOXZOGO and ROCTAVIAN being these larger market indications we refer to, the approvals of those two drugs in both the U.S. and Europe as sort of these four major milestones, each of which had its own complications, challenges, which we navigated and delivered four for four on those major regulatory milestones. And we've also experienced the robust uptake of VOXZOGO. So two potential blockbusters on top of this base business, we believe, gives us a pathway to $4 billion-$5 billion in revenue by the middle of the decade, growing profitability, growing cash flows, margin expansion. That's cornerstone two. And then cornerstone three is not only is this base business profitable, growing even more with VOXZOGO and ROCTAVIAN launching, but our strategy is to reinvest a significant amount of that revenue growth back into R&D. So while we strive for margin expansion and growing profitability and cash flows, we actually plan to increase the investment in R&D in absolute dollars over the next several years. We think over the long run we can still get leverage out of R&D, but again, increasing the investment in what is a highly successful track record for organic growth. We issued a press release today announcing a bit more detail on our R&D Day next Tuesday in New York. It's gonna include more details on the several early stage candidates that we have in development, as well as some of the indication expansion opportunities for ROCTAVIAN and VOXZOGO. We've got more assets under development than any other time in the company's history. So encourage everybody to tune in or come by to visit. I'll be there. Where would you like to start? We could go Vox, VOXZOGO or ROCTAVIAN. Up to you. Oh, let's start with ROCTAVIAN. We just had a physician on stage a few moments ago who was a hemophilia doctor and was discussing his views on gene therapy and how it can play a role in hemophilia. Clearly, he was a skeptical physician. How do you launch when there's going to be opinions that are skeptical? How do you demonstrate and show the data to people to convince them of the meaningfulness of ROCTAVIAN? Yeah. Thanks, David. Great question, and you know, these type of challenges are gonna come with any new technology that, you know, is potentially disruptive to a massive market, which is made up of a number of large companies in a very unique disease space, so you touched on it. We'll start with our data. Just a reminder for those that aren't aware, we ran our phase III study for ROCTAVIAN gene therapy for severe hemophilia A in 134 patients, the largest gene therapy phase III study ever conducted, and we compared to the standard of care, prophylactic Factor VIII. Now, granted, when we were ramping up our study, the Hemlibra uptake hadn't been where it's at. I think Hemlibra may have still been in the clinic, which is also an improvement over the standard of care based on their data. But there's still this market share of patients that are on traditional prophylactic Factor VIII. And even with some of the bleed rate imputation that was done by the FDA in our final approved label, we still observed a significant reduction in actual bleed rates from the pre-ROCTAVIAN bleed rates for those patients, over a 90% reduction in the usage of the prophylactic Factor VIII. And while some of the imputation on the bleed rate impacted the mean, it actually didn't impact the median, which is still below one. I think it's 0.5 for the total number of bleeds after ROCTAVIAN. The total number of joint bleeds and spontaneous bleeds also significantly reduced less than one. I think it might be 0.2 and 0.3. And that's what matters to patients and physicians. So this is an improvement. This is bleeding control freedom from therapy. The product is approved. It's been proven to be safe and efficacious, so as we tell that story, and now that we're approved, we can deploy our marketing strategy, which includes a direct-to-consumer strategy, which is permissible in the U.S. Some of the patient stories and experiences from the phase III study are very profound, so we're in the early days. We were approved nine weeks ago, so we're still launching, but we've got a strategy in place to address all the key stakeholders. Now. Including physicians, including skeptical physicians. Towards that end, you talk about the DTC, the DTC campaign. Do you think that a lot of the demand for this will be generated from a push by physicians or by a pull from patients? And with respect to that, the timing would be different, I think, in each scenario. How do you see that impacting the cadence of the launch? Thanks. Great, great question, David. I think it's both. So there's a number of physicians that, you know, have raised their hand and are interested in ROCTAVIAN. There's the physicians that have experience with the clinical study. And after seeing how some of their patients did well with ROCTAVIAN, they can think about what other patients in their practice would be good candidates, so for sure, the physician engagement, they're one of the key stakeholders, is a key part of the launch. And that would be the push, or maybe the pull, the push coming from patients is another dynamic. The U.S. is a large, you know, complicated geography. We're seeing this, you know, with the VOXZOGO launch. We've had strong uptake, but we still have to get out there and reach, you know, the corners of the U.S. And that's where, you know, the digital aspects of a direct-to-consumer campaign should give us a lot of traction. And again, as we get more of the campaign out there, I think we're equally counting on a push and a pull from both physicians and patients. One other note on that is, you know, the Hemophilia A community is a very tight community. So beyond direct outreach to patients, another avenue is leveraging our relationships and the relationships of the patient associations with the community. As an example, we've already held and conducted since approval dozens of ROCTAVIAN branded patient group events. I'm seeing good interest. So with that in mind, do you think that the treatment experience of patients could ultimately play a great role? So while things will be slower at the beginning, as patients get dosed, that interaction between patients in the community, between physicians in the community will ultimately be a grander driver? We believe so. Yeah. So building confidence, you know, when you think about the potential for a ROCTAVIAN revenue ramp, you know, one important reminder is that different from our other therapies, which are chronic therapies in some cases, like the enzyme replacement therapies, they're lifelong therapies. In other instances, like VOXZOGO, several years, but up until the point where the growth plates close, ROCTAVIAN patients, at least for now, are a patient just once and therefore a BioMarin single sales transaction. So when you think about a ramp in revenues increasing, that actually happens more so through market penetration and, you know, gaining confidence in the drug, reaching more people, reaching more physicians. The doctor before also talked about duration. He cited three to five years. Now, he cited it as being a detriment of something that might hinder uptake. But from the economic perspective, when you're looking at payers, what does that same three to five years mean? Yeah, it's really important. And I won't be able to do the durability conversation the justice that it deserves, especially with R&D Day next week. So maybe another plug for R&D Day next week. But we do plan to talk about some longer term data. You know, we've got a phase two study, just seven patients, but have last reported last year, six years of durability. And then another concept that we're exploring about how we can maintain or restore durability in patients that have received ROCTAVIAN, but resume prophylaxis as their standard of care because they stopped expressing Factor VIII. So let's put a pin in the overall durability discussion for now. But the fact, thanks for bringing it back to the economics, it's very important. One interesting development, and for those of you that may not be aware, we filed for accelerated approval for ROCTAVIAN back in 2020, and the product received a complete response letter. At the time, the FDA had published, you know, four specific criteria for accelerated approval in gene therapies for severe hemophilia A, and a few cuts of our phase III data. Some of the phase III data we have, we thought met that. So we filed. The FDA ended up wanting to see longer term data. So that's why we refiled last year, leading up to this June's approval. Seeing this phase II data and the six-year durability, we've now shown three years of durability in the 134-patient phase III study. We'll expect to have four-year data early next year. and our warranty, which we're having success with, by the way. Back to some of the launch dynamics, we have executed several warranties. This is a four-year, essentially money-back guarantee for ROCTAVIAN to ensure that if ROCTAVIAN stops performing at some point during those four years, the payer would receive a pro rata reimbursement of the fraction of the ROCTAVIAN cost originally that they didn't realize the value of. But back to the reason why I brought up 2020 was when we were talking about the launch and the commercial potential and the cost offset value to the system, we used to talk about the cost of the standard of care at three to $500,000 a year. We recently updated that data as part of this launch preparation. It's now up to $800,000 a year. elements there are the robust uptake of Hemlibra, which is $800,000-$900,000 a year. I believe ALTUVIIIO is intended to be priced at over $1 million a year. And even the cost of traditional basic, prophylactic Factor VIII has increased significantly. So while one may recognize that the WAC price of ROCTAVIAN is a single large upfront payment, I do feel that it's underappreciated that these extremely expensive therapies over a lifetime of a hemophilia patient, or even over the few years of, you know, potential durability that we're talking about here, is underappreciated in terms of the cost offset. The gentleman you were just speaking with earlier talked about that high price tag, but for the folks in the finance offices of these practices, they're cutting annual $1 million checks for some of these expensive therapies, where ROCTAVIAN does have the potential to actually return value to the system. You talked about progress thus far with the warranty program. To what extent have you established warranty programs with payers right now? And one nuance is how do these warranty programs manage people changing insurance? Does the warranty program still exist post insurance change? How does that work? Yeah, no, it's an important question. And by the way, since you mentioned, you know, just uptake on the warranty, I should share that, you know, we're just in the first nine weeks of launch here, so happy to talk about some of the momentum and progress that we're making. We will plan to give a more detailed update on our Q3 call, which is just a few weeks away at this point, but happy to speak to some of the, again, some of the progress and momentum overall, one of which is our engagement with the payer group stakeholders, so firstly, before I come back to the warranties, we're pleased to have observed several payer coverage policies be issued in these first few weeks. And that includes some large, some of the largest U.S. payers, and we're also executing warranties. These warranties are non-negotiable. However, it's important to get a mutual understanding. So we do actually execute them as a contract with the payers. To your question, the warranty stays with the payer. So if an individual, in their compliance, of course, would be tracked in their practice, their HTC, their physician, but if an individual were to meet the criteria for triggering the warranty, then any warranty payment would go back to the original payer. What mechanism is there in play to actually, once if they're billing that, the former insurer, the new therapy, the new obvious mechanism at play, if they moved on to a different payer, what? I think the expectation is there'll be some arrangement between payers and the practice. There already will need to be on the economics for reimbursement, and so we expect that to be part of it where, you know, it'll stay with the patient, with the practice logistically, and then on our end, we won't be involved in that part of the process. On our end, we've got a third party adjudicator for warranty claims to make sure that's independently reviewed. That's certainly. I apologize for not mentioning earlier, you dosed the first patient in Germany, which probably should have been at the top end of the discussion. I guess, could you run us through the treatment journey for that patient when we might begin to see other patients come online? And then I know that obviously European, Europe's a very big difference as far as, the run into first patients, how that will differ in the United States. Yes, thanks. Thanks for the question. Great to dose our first global commercial patient last week in Germany. Because of the global data privacy regulations, GDPR in Europe, we actually get no information at the patient level, like we used to before those regulations, which in the rare disease business, you stay close to your patients. So, it's become more difficult with the privacy regulations there. So we don't have specific details on that particular patient journey. We recognize that, you know, overall pricing and reimbursement in Germany has taken longer than expected this year. We are still working on negotiating final price and reimbursement with the top-level single German national payer. In the meantime, you know, the drug is approved. Physicians are aware. Infusion sites are ready in Germany. Our last public announcement, and we haven't updated the details on this, but our last public announcement was that approximately 60 patients have undergone the testing for the AAV5 antibodies. We've also shared that approximately 40 of those have made it through as negative for the AAV5 antibodies and would be eligible for ROCTAVIAN subject to the other treatment criteria. So that activity can continue to proceed. Once we get through the pricing and reimbursement process, all those patients would be, you know, eligible as commercial patients. Differently in the U.S., very importantly, we don't have that same level of price, single price, you know, single payer price negotiation. We're able to access the market. It's important that we price ROCTAVIAN responsibly, which we believe we've done back to my comments earlier about the cost offset and the potential to truly return value to the system. In the U.S., after price, it's the payer engagement again with the total ROCTAVIAN value proposition, our robust data package, the ROCTAVIAN safety profile, and establishing the network for treatment. So not subject to the same level of gates early on. It's still a significant effort. That's why we expect, you know, the uptake to be gradual. The U.S., as I mentioned, is a large, complicated geography. There's 140 hemophilia treatment centers in the U.S. It would be inefficient to target all of those. So we're targeting a smaller number of hemophilia treatment centers that we think will be able to be ready to infuse ROCTAVIAN and contribute commercial patients early on. We're targeting physicians and patients that have put their hand up early as interested in ROCTAVIAN, but by all means, establishing the treatment network, and then letting the marketing campaign ramp up a bit. Those are key dynamics. And it's for all those reasons that we are saying that this will, you know, take time, but we do like to remind everyone that just the U.S. is roughly a $5 billion revenue market opportunity for ROCTAVIAN. And given its safety and efficacy and the strategy we have in place, we believe that we will be successful. I got one more question on ROCTAVIAN. That's regarding guidance. I sense the investment community. We have the challenge with guidance is that it's just recently approved, but of course it's $3 million per patient, $3 million per patient. And so we look at the going into year end and what type of cadence we need to see to get there. And there's a 3Q versus 4Q result. How should we think about that when putting together our models? Yeah, thanks. Thanks for the question, David. The two things I'd say there are that, you know, firstly, as you noted at roughly our estimate of net revenue per patient of approximately $1.9 million, truly means that in this first year, within the context of that guidance, every patient moves the needle. You know, getting to the bottom end of the guidance in the U.S. would be approximately 27 commercial patients. And the second important thing, as we observe these, you know, last several weeks, the first few weeks of launch and the next several weeks as we get ready for our Q3 report, and watch the ROCTAVIAN performance in Q4 is that the timing of the infusion and the commercial sale for BioMarin contributes to 2023 revenue regardless of when it happens. So while we all might like to see a bunch of patients here in September, the net revenue to the company, what we'll report for 2023, the cash inflow for shareholders, even if that infusion occurs in late November, is the same. So that's a reason, yes, you know, given where we're at today and we're still waiting to dose our first commercial U.S. patient here on September 6th, fair to say that the 2023 revenues would be weighted to Q4, but that timing element plus the first factor of every patient moving the needle, we think, are key considerations. Excellent. Thank you for that. VOXZOGO, it's been extraordinarily successful. How has the launch gone versus your initial expectations, before the launch? Important to say that our initial expectations were high. You know, back to my comments on our portfolio and R&D strategy when we started to pivot to these larger market opportunities. Some of the market opportunities for those ultra rare, metabolic disorders like MPS are literally in some cases couple, you know, one, two, 3,000 patients in the entire world. Achondroplasia is different with 18,000 patients within our global commercial footprint. So, but yeah, the underlying scientific strategy of well understood, disease pathway, targeted intervention, clearly discernible endpoints and transformative effect, those remain the same for VOXZOGO as our earlier products, hence the value proposition. Again, we had high expectations launching in this large market. So some of the factors that we've observed that have proven the strength of the launch as indicated by the, you know, several guidance raises over the last few quarters are. There's a few fold. One is. One reason to be cautious initially were the questions around how the product would perform in the marketplace. We were confident that there was this significant unmet medical need in achondroplasia, but there was a question about patient and family decisions to treat. I think we've seen with this rapid uptake that families are willing to treat. We'll be monitoring and gathering, you know, market data and generating more real -world evidence data, quality of life data. But we've had several anecdotes where parents are observing changes positively in their children. So willingness to treat was important to be cautious with on the initial guides and show that the interest to treat is high. Second is pricing and reimbursement. You know, not unlike our ROCTAVIAN conversation in Europe, you know, negotiating pricing and reimbursement for expensive therapies, outside of the U.S., especially in Europe is very difficult. And with VOXZOGO, despite its, you know, strong safety and efficacy profile, qualifies in that category of an expensive therapy. That product made it through several of the processes, faster than we had initially planned. Just like we're talking about for ROCTAVIAN, some of these European markets have very structured processes that could take 12, 15 months or more. And for VOXZOGO, it did take some time, I think, but generally the global pricing and reimbursement hurdles for VOXZOGO went faster than we might've thought initially. And the third, which was again always part of our high expectations, but we realized the value even more robustly, is leveraging our global commercial infrastructure. And this, by the way, is a key part of the strategy for the future is one of the benefits of that base business is that we grew a global commercial infrastructure, end-to-end supply chain, general administrative support, regulatory R&D support to sell our products in 78 markets. And so while it took some incremental investment for VOXZOGO and achondroplasia, because it's the first therapy available for that disorder, building that market took some investment, but operationally we were able to leverage global market access, global supply chain, and plug VOXZOGO into that engine that already existed. And so what that means is we're sourcing revenues in just the first two years of launch from over 30 markets. And all those three dynamics added together, if you start stacking these individual country launch curves on top of each other, it just really led to a stellar performance in the first two years of the product. You spoke to the benefits the patients see. And I know investors tend to make the headlines with when it comes to your data and competitor data. It's the annual growth acceleration curves and whatnot. When you bring a drug like ROCTAVIAN to patients, is the emphasis on those growth numbers or is the emphasis broader than that? And how do physicians look at the drug? VOXZOGO, right? Well, two things there. One, we're approved and that's based on this robust data set that we have with years of phase three data and over seven years of phase two data, large number of patients. Yes, annualized growth velocity was the primary endpoint. We are still working on generating additional quality of life and real-world evidence. That's why I say some of what we hear from patient families is anecdotal, so that is an absolute key priority. But you know, the belief is that while achondroplasia is you know, most often physically observed as a growth disorder, that there are a number of other comorbidities. For example, foramen magnum, the bone that protects the spinal cord compression, if that bone isn't growing properly, but the spinal cord is, it's pressure that could require surgery or other emergencies. Bowlegs, sleep apnea, these are other, you know, serious consequences of achondroplasia. It just takes time and a different pathway to generate that data. But I think there's reason to believe back to your question, we just, you know, we won't be able to market those attributes to physicians until we can generate the data in a compliant fashion with regulators. How do you view the competing data that's come out from other therapies? Early stage, small N, and in a disorder that affects growth rates where we're measuring growth rates in children, which can be very volatile from any six-month period to the next. So we'll be observing larger N, longer term data. But in the meantime, you know, we've got experience over several years. We're approved over 2,000 patients on commercial therapy. We believe that the competition, even if successful, would be years behind, by that point in time, not just rapid VOXZOGO uptake that we've seen already, but you can envision VOXZOGO being established as truly the standard of care in achondroplasia. That's the goal. If parents are seeing efficacy and experiencing the safety profile that VOXZOGO has to offer, while small molecule in some instances in other areas of pharmaceuticals might be a convenience, in this case of such a serious disorder where parents are seeing results, switching may not be as practical. Now, with every single drug launch, in the orphan area, there's always that question that comes up, bolus or no bolus, and in this, at this point, in the launch, usually when you think of bolus, it kind of ends at some point relatively early, but the growth is maintained at strength. How should we view it? Was there a bolus or is this the natural growth demand curve we're seeing? Great question. Thanks. I'll approach it a couple different ways. Firstly, fair to acknowledge that there were likely families and we know physicians watching the VOXZOGO development from the sidelines and when it was approved, you know, may have called their geneticist the next day. So in any new technology, there's likely to be some of those early adopters, but not at the bolus level in this instance. Again, we're talking about a market of thousands of patients in the U.S. and globally. So, a small number of early adopters wouldn't constitute a bolus. Excuse me. Then after that, the way to think about where we're at in the launch from a growth curve trajectory standpoint comes back to those, you know, almost 40 markets that we're currently selling in. Each one of those has their own unique attributes and is in their own place and time in the launch curve in market penetration. So, for example, on a fast penetration market, I'll use the example of Japan. In Japan, achondroplasia is not just broadly diagnosed, but they've actually established a treatment model where most of the achondroplasia patients in Japan are with a select number of physicians overseeing that patient community. And part of the reason is, human growth hormone is approved for achondroplasia in Japan. It's the only country in the world where growth hormone is approved for achondroplasia. It hasn't been approved elsewhere because, in the U.S., as an example, this is part of why the FDA wants to see longer term data. Their experience with growth hormone in achondroplasia was that you saw some initial growth in the first year, but then it pretty quickly waned. That's part of why they wanted to see longer term data from us with VOXZOGO. But anyway, growth hormone is approved in Japan. And our initial strategy, this gets back to your last question of, you know, this strong performance on the launch higher than expectations. Our expectation was that we may need it to, we've made it needed to start our Japanese experience with VOXZOGO in patients naive to any therapy and that as a second effort or a longer effort would be switching patients from growth hormone over to VOXZOGO. That didn't happen. We saw significant levels of switching and rapid uptake of VOXZOGO in a market where there is a standard of care and achondroplasia patients are seeing physicians. Dynamics in the second half of 2022 and thus far this year has you know Japan is the example of fast rapid uptake. The U.S. frankly while a large geography and you know we're also again able to market directly to consumers we have a lot of work to do and have been at it now since the product was approved in November 2021 of establishing a treatment home without any prior therapies available for achondroplasia. Because patients may have a different set of manifestations or consequences of the disease they may see a variety of physicians. If there's a patient who needs regular surgeries they may see their orthopedist regularly. If there's a patient that suffers minimal levels of the more severe comorbidities they may be with their pediatrician. So our strategy in the U.S., again, large complicated geography, is to work to establish what we call a treatment home, and we believe that is pediatric endocrinologist. So our field force is out there trying to establish these networks where achondroplasia patients that may see a variety of physicians or no physician at all can be funneled into these ped endos as a treatment home. But again, that takes time, and so long way of answering your question is a short answer when you talk about these launch curves, or the penetration or slow growth slowing down. Even with the 2,000 patients that we just announced are on commercial VOXZOGO, that's still less than. I'm sorry, that's more, it's 12% market penetration globally. So there's still a long way to go and plenty of growth, opportunity left for VOXZOGO. Now, the fast growth, of course, has on the supply side led to some constraints. Could you update us where things are there? Absolutely, and again, you know, we plan for success and you can imagine our supply chain planning involved making sure we had product supply available for a significant amount higher than our forecast, but the supply constraints that we communicated recently are an indicator of this uptake being again even more rapid and faster than even our high internal expectations, so yeah, a few things on this supply constraint, which by the way, I'll firstly note we think about and view it as a growth constraint. This isn't a current immediate issue where we're either stocking out and patients are not getting access to therapy, even with the supply constraint that we're talking about. We said that we have the ability to add several hundred new commercial patients over the course of this year. And from a supply standpoint for next year, we have the ability to supply between $550 million and $600 million. So that, which would be significant growth over this year. So again, it's a constraint on growth. A couple other important things to note. The constraint is in the fill- finish process. We do not have any quality issues with either the bulk drug substance nor the fill- finish process. We fully control the bulk drug substance manufacturing. There's a dedicated site to VOXZOGO on our Northern California manufacturing campus. We do use a contract manufacturer for the fill- finish process. And important to note is if we talk about our aspirations for VOXZOGO to be a $1 billion+ product, we already had a plan and a strategy to significantly expand the volume capacity. It's just that it wasn't for about another year. So this launch has caused us to pull forward that volume expansion capacity, which we're now doing, working closely with this contract manufacturer, which is a very reputable fill-finish contractor with a great track record. We're currently sharing the fill line with another company. Again, that was part of this launch phase, you know, part of the strategy to mitigate this supply constraint is to get a dedicated line with that same contract manufacturer. So those are the types of strategies that were out there, but we're now pulling forward. In the meantime, you know, what we can do is manage, you know, order levels, you know, maybe some of those countries or customers that were previously ordering maybe two months of product at a time because we need to manage inventory levels closely during this time. We're trying to reduce the size of some of those orders. I think that's, you know, might be what's implied in our guidance. You know, some folks have asked us, wow, $200 million first half, your full year guidance is $400 million-$440 million. That's the supply constraint that you're seeing show up in, in the revenues. One more question on VOXZOGO and then we'll wind it up with a few more questions on pipeline and elsewhere. Hypochondroplasia. Could you talk? Yeah, that was great. This was a recent announcement, just a few weeks ago. We became excited and interested in pursuing VOXZOGO beyond achondroplasia through our partnership with an investigator sponsor or an investigator who's running an investigator-sponsored study, Dr. Dauber in Washington, D.C. Dr. Dauber shared an interim view of some of his data last year with using VOXZOGO in other genetic short statures. We immediately began to pursue a development strategy there. It did take some time because we wanted to make sure that we are aligned with regulators on the development pathway and study design. For those that may have followed the VOXZOGO development and regulatory review, it was a windy road because we had a one-year study in a single age group, phase III, and coming out of the 2018 AdCom on treatment of achondroplasia. There was consensus to ask for two years, two studies in two age groups for two years. We didn't have that. Our strategy was to show the FDA the totality of our data package, which did include long-term data from the phase II study. We did have a second study in a different age group. It was just the phase II and younger children, and the product was ultimately approved. We wanted to avoid that type of misalignment with the other indications, and it took some time to engage and get alignment with the FDA, but the good news released recently was that we've done that for hypochondroplasia. The FDA has agreed to a direct-to-pivotal study and it, and as a one-year study, and the reason for that is hypochondroplasia, hypochondroplasia is different to achondroplasia. It's a mutation in the same gene. And because of the way VOXZOGO interacts with that pathway, it should be similar for hypochondroplasia as an achondroplasia. The FDA now has a lot of familiarity with achondroplasia, including its durability, including its safety. So, you can think of this as a new phase three asset for BioMarin. And, we're still doing market assessment, but it's a, you know, it is a market opportunity, not as big as achondroplasia, but, sizable. Thank you. Can you, this morning we heard from a competitor developing an achondroplasia drug that they have agreement with FDA to do a single 52- week study. Could you remind us your journey with the FDA and whether it was one year or two? I'm just trying to frame that from what we found out today. Yeah, thanks. I touched on it and I've only been able to scan a few words here and there. I'm at the conference in between meetings today, so I need to read up on it myself, but we'll be looking at that. Yeah. So I touched on it with David. Our pivotal study, our phase III study was designed as a one- year placebo controlled study. And I won't repeat it all, but it was that AdCom where there was consensus around asking for two years of data, in two age groups, two studies. During our review, a second year of phase three data became available, which was also likely helpful for the review. So we'll see again. I need to read up on that news from earlier, but you know, that is another possibility that you know, someone might file with one year, but you know, the FDA can still decide to see a second year. You know, just a reminder that this is a growth disorder in children and the amount of time that the therapy, any therapy would be taken, you know, could be 10, 15, 18 years. So that's part of why durability is a focus area for the FDA. Again, with their experience in achondroplasia, which was with growth hormone, where the efficacy waned pretty quickly. So we're pleased to have again several years of growth data, great safety track record for VOXZOGO. And again, back to some of David's initial, you know, remarks on the rapid launch, it's, we believe, becoming the standard of care for achondroplasia. So we only have a couple minutes left here. I'm gonna have slide one in on PKU. There's recent data from sepiapterin that the company believes could kind of thread the needle and get some move into some of the KUVAN side of the market, but also potentially move into some of the classical PKU. What's your thoughts on that? Yeah, you know, one way we think about it is, you know, and from a sepiapterin standpoint, KUVAN has been generic in the U.S. now for almost three years. So we've significantly pulled back on the resourcing and yes, the, you know, our share has held in there a bit better than some of the traditional, you know, big pharma patent cliffs that you'd see when a generic comes online. But given the generic competition and there's new generic competitors coming online, we're now seeing generic competition in Europe. We, you know, frankly, as KUVAN becomes a smaller part of our business, the threat, if you will, becomes that much smaller. Now, PALYNZIQ, however, we are still investing in the launch. PALYNZIQ has shown the ability to reduce Phe to normal levels with diet liberalization. We've had some challenges during the pandemic because a lot of these PKU clinics are within genetic centers, which weren't open for business during the pandemic and took a long time to reopen. PALYNZIQ has a REMS, so it's important that new patient starts happen under the care of a healthcare professional, usually in the clinic. So that was disruptive to the PALYNZIQ launch. We're getting that back on track, not only through normal mechanisms, but you know, trying to establish alternative prescribers. But PALYNZIQ is the asset that we're committed to investing in, and we feel has a different competitive, you know, profile than sapropterin. Last question. R&D Day. Could you give us a quick primer? Next Tuesday, New York, at 8:00 A.M., I encourage you to check out today's press release. We're gonna be giving updates on our early stage pipeline again, overall, including these pre-IND assets, either near IND or near the clinic or early stage clinical development, as well as assets behind those. We've got more assets in development than any time in the company's history. So more details on some of that great science. There's two new compounds that we're gonna be talking about, which is gonna be very exciting. And then, some emerging science around the indication expansion opportunities and related research for our now approved products, ROCTAVIAN, VOXZOGO. Both of those, we touched on hypochondroplasia and some of these other genetic short statures. Likewise, for ROCTAVIAN, the initial indicated label is a smaller fraction of the total severe hemophilia A population, or even some overall hemophilia A. So yeah, our, our scientists are gonna do so much more justice to this than I ever could. So I'd ask you to tune in. Excellent. Thank you. Thank you very much. Thanks, David. Appreciate it. Thanks, everybody.