Good morning. Welcome to BioMarin's Investor Day. I'm Traci McCarty, Head of Investor Relations. Before we get started, we have a couple housekeeping items. We do intend to go straight through our presentations, so if you'd like to take a break or grab a refreshment, please do so when you choose. We will be emailing all of you the presentations at the end of our prepared remarks, and they will also be posted to our website at BioMarin Investor Relations. We will be making forward-looking statements today, so please refer to our SEC filings for further details. In addition, we will use non-GAAP financial measures as defined in Regulation G during the presentation today, and you can find those reconciliations in the back of the presentation. Finally, we'll be including market, industry, and third-party data in this presentation as well. I would now like to invite our President and Chief Executive Officer, Alexander Hardy, to the stage to begin our presentations. Thank you, Traci. Good morning, everybody. It's incredibly exciting to be here, specifically because for the last nine months we've been saying, "Wait until Investor Day. We'll tell you at Investor Day," in response to many, many questions. And today we're gonna have a chance to tell you the answers to the questions that have been on your mind. So the last nine months, we've taken on a transformation of BioMarin's strategy, our operations, our ways of working, all with the goal of accelerating and increasing the substantial increase in value to all of the stakeholders that depend on us: patients, most importantly, employees, but of course, investors. And today, we're really excited to share our new vision and our strategy with a particular focus on the shareholder perspective. Next slide, please. Thank you. So the work that we're gonna be sharing today has been done by over 180 employees at BioMarin, with 15 work streams to produce all the detail and thinking that we're gonna share with you today. It was done in conjunction with the Board of Directors, and the strategy work, and all this work was overseen and led by the BioMarin leadership team, and I'm really pleased that they're all here joining with me today in delivering an Investor Day. I'm gonna be joined up at the podium by Brian Mueller, the CFO, by Hank Fuchs, who'll be joining remotely. I'll explain that in a minute. Head of R&D, and Cristin, who is our Chief Commercial Officer. In the room, we've also been joined by Eric Davis, our Chief Legal Counsel, Marnie Cottle, Head of Public Affairs, Amy Wyman, Head of HR, and Greg Guyer, our Head of Manufacturing. It's really fantastic to have them here, and on this slide, you can see the full team, and you can also see two new additions. We've got Greg Friberg joining us as the Head of R&D when Hank Fuchs retires after 15 years of tremendous service to BioMarin, and then James Sabry, who's joining us as the Chief Business Officer. Both Greg and James will be joining us in the next four to five weeks. We've got a really strong team that is ready to take on, and take BioMarin forward into the future. So with regard to the agenda today, I'm gonna kick off and give you an overview of the strategy. I'm gonna provide key quantitative outcomes that you can expect from us at a high level, and also how we will achieve them. Then I'm gonna hand over to Brian. He will provide the long-term financial guidance. He will break down specifically how we're gonna achieve these numbers, and he'll also, of course, cover the capital allocation strategy. Now, Hank will then come up and provide the innovation strategy, and he'll specifically cover the life cycle plans, which are a very, very important part of BioMarin's growth story, and also a perspective on the pipeline NMEs. Now, as I mentioned, Hank cannot be with us today. Unfortunately, he tested positive for COVID two days ago. I will hasten to add that. He traveled to New York on his own, so he's had no contact with the leadership team. So you can interact with us freely in the confidence that we're not also infectious. But unfortunately, he has to join us remotely from his hotel room here in New York. And of course, he'll be joining us for Q&A as well. And then our last presenter is Cristin. She's gonna provide the commercial strategy that supports our very strong growth outlook. She's gonna provide a specific focus on the enzyme therapies and on the skeletal conditions. And then, of course, we'll move to Q&A. So, before we get started with the forward-looking strategy, I just want to take a moment to look back at the priorities that I set out for the company at the JP Morgan conference at the start of this year, and just briefly cover what our progress is against these. I mean, I'm really proud of BioMarin and the progress we've made against the priorities that we set out. With regard to Voxzogo and accelerating and maximizing the opportunity there with this tremendous drug, we've got regulatory feedback on five new indications. We are moving forward at pace with that development program. We also resolved the Voxzogo supply constraint ahead of when we said we were going to. We said we're gonna do it by the middle of the year, we did it slightly before that. With regard to Roctavian, at the second quarter earnings, we provided our decision on the future of Roctavian with a clear strategy. With regard to R&D, we prioritized our entire pipeline from research through to development. We're very excited about the NMEs we have in our pipeline now. They reach a very high scientific and commercial bar. And then lastly, when it comes to accelerating EPS and profitability, we've shown already a strong increase in profitability so far this year, and we've also taken decisive steps to optimize our organizational model and our structure. This is both to support the strategy that we have going forward, but also to realize savings and increase profitability. So I think by any benchmark, the last nine months have been incredibly productive for BioMarin. We haven't just been planning and producing nice PowerPoint slides for the presentations today. We've taken on the big topics, we've been decisive, and we've executed really well on these, starting to pull through these decisions, and if I could just say so, we've done this all while maintaining very strong business performance for the first and second quarter of this year. Now, before joining BioMarin, I knew BioMarin extremely well, and to me, it was a preeminent rare disease drug developer, an unparalleled manufacturing powerhouse, ability to produce multiple different types of drug, and a very strong commercial platform across approximately eighty markets. Now, this snapshot here provides a really good way to describe BioMarin's 25-year history of drug discovery, development, regulatory approvals, and commercialization of eight drugs. These capabilities that it took to achieve these metrics are all contributing to the really strong foundation that we have to take us forward into the future. BioMarin is really, I think, positioned to be one of the most exciting growth stories in biotech. This potential, together with the mission of BioMarin, I don't know if you saw all the patient videos and the pictures around the room. These are the reasons why I joined BioMarin, and I have to say that having been here nine months, the potential that I see at BioMarin is even greater than I observed from the outside and when I started. Let's get going into the future outlook for BioMarin, and let's start, of course, with our purpose. It's so very important to us. This is the new purpose for BioMarin. What is not changing is the focus on patients. We have a scientific expertise when it comes to genetics, understanding how genetics is changing our understanding of diseases, understanding how genetics can change the way that those diseases are treated. And we then take that, and we can translate that into different modalities, and we have the ability to deal with multiple modalities, whether that is a small molecule, whether that's a protein, a peptide, or a nucleic-based treatment. We see the effect of our science in relevant cellular and animal models, and this lights up the pathway for us into patients. The effect of our medicines is very apparent at the patient level, and this really is what makes BioMarin really spectacular. Every patient, their parents, their healthcare professional, can see the difference that our medicines make for the patients that depend upon them. And you know what? Regulatory agencies and payers also see that difference. That translates to access, to guidelines, to earlier diagnosis, all which leads to more and more patients being diagnosed and benefiting from our drugs. We know as a company, when we deliver for patients, we will deliver for all stakeholders, including investors. Now, at the bottom of this chart, you're gonna hear a lot of different metrics today around our future plans. But for all of us at BioMarin, the most important one is the statistic on the bottom of this page, that by 2034, we expect to be able to treat four times as many patients who will benefit from BioMarin's drugs as there are today. That's really compelling and exciting. With regard to our strategy, our strategy has three pillars: innovation, growth, and value commitment. Now, these are all interdependent, hence the diagram on the slide. Innovation, let's start with it. That's not by accident, that it's, it's the first one, because innovation is at the heart and the engine of everything we do at BioMarin. As I've already talked about, we build upon our history of developing innovative medicines that target the genetic causes of diseases, and we're going to leverage that unique set of capabilities to accelerate a pipeline of really highly valuable medicines into the future. Secondly, growth. We can fuel organic growth through that innovation. We've got a pathway to significant and sustained high levels of growth and a very credible line of sight as to how we're going to do this. That's really, really important to see that our growth is driven largely by approved products and life cycle expansions of our existing medicines. That's very, very exciting to see that. And then, because we've got this very clear innovation and growth story, and we're confident of our execution, as you already can see in the first nine months of this year, we're able today to make a very strong value commitment to you all around revenue, increased profitability, and substantial cash generation. That gives us then the option, and it's an option, to reinvest in driving more growth through business development or external innovation, but it's an option. This is not central and critical to us delivering what is already a very compelling plan. So let's get into the numbers and get specific and share some of the numbers that this plan delivers over various time frames, and we're going to focus on revenue here and operating margin. We're going to, of course, provide more numbers as we go through the presentations. Now, BioMarin aspires to be both a story of strong, sustainable revenue, top-line growth, and significantly expanding margins. For revenue, we have been expanding and growing strongly in our past and currently. In the future, we aim to achieve $4 billion in revenue by 2027 and mid-teen CAGR growth through 2034. This puts us in the top quartile of the biopharma industry. For operating margin, we achieved profitability on a GAAP basis in 2022. Margins have already expanded significantly this year. We have already begun to implement, as I mentioned, significant cost transformation and efficiencies totaling $500 million in operating expense reductions. This allows us to target 40% operating margin by 2026 and a sustainable range of 40%+ going forward beyond that. Now, it's really important to have a structure and an operating model and a culture that supports your strategy, and today we're announcing a new structure built around the three business units. These are going to drive accountability. They're going to drive and strengthen performance and efficiency. Now, why business units, and why three of them? It's because we have three very different types of business within BioMarin's operations. And by having dedicated senior leadership, by having accountability and clarity on performance, we think we'll be able to drive increased levels of performance, efficiency, and a real sense of urgency in doing more for patients and delivering more for all of our stakeholders. Now, in our second quarter results, of course, we already discussed and outlined the smallest of the business units, Roctavian, designed to implement that very focused strategy around that product. Cristin's going to elaborate in her section on our plans for the enzyme therapies and for the skeletal conditions. How are we going to grow to $4 billion in revenue and sustain mid-teen CAGR over the next ten years? The most important growth driver that we have at BioMarin is the skeletal conditions business unit. This is going to build on our success with Voxzogo in achondroplasia, and we're really confident of the path into five subsequent indications. In total, we estimate a TAP, or a Total Addressable Patient population, of 420,000 in the geographies that BioMarin serves. Now, TAP is defined as the diagnosed and eligible population, and it does not consider access or competition. But when we apply reasonable assumptions of penetration by indication and net pricing by indication as geography, as we expand out to larger populations with different comparators and different value propositions, we're confident in a peak sales potential of greater than $5 billion for the skeletal conditions business at BioMarin. Now, Hank's going to share the scientific rationale behind each of the five indications, the highlights of the proof of concept data that we've generated, and the development plans that are going to bring these indications to market. Cristin's gonna summarize the commercial plans for each of the indications to achieve global leadership in skeletal conditions. So she'll specifically outline the market opportunity, and the go-to-market strategy that we'll follow in each of the indications. Now, I just wanted to mention here on the left-hand part of your slide, that the launch in achondroplasia has in and of itself been a huge success. We have thousands of patients on treatment in over 40 countries. But even in achondroplasia, this is only the beginning for Voxzogo in this indication. We still have more than 80% of achondroplasia still to penetrate, and Cristin will also cover how we're going to do that. But bottom line from this slide and from today's presentations, I think you'll get a clear picture that Voxzogo is clearly the most exciting multi-indication product in our portfolio and one of the most exciting in the entire industry. Now, moving on to enzyme therapies. Now, this has been obviously the primary driver of growth in BioMarin's history, and the perception that everybody has externally is that this is very durable, with low competitive threats and relatively low level of impacts from policies such as the Inflation Reduction Act. Now, that's true, and those features are very, very important. But what is not appreciated is that this portfolio has been growing historically at a growth rate of 8% CAGR, so 8% per year over the last three years. We believe that this growth rate can be sustained and even accelerated going forward. So with our capabilities and our global reach, together with new tactics, which Cristin will outline, we believe we can reach more patients. You can see here, I hope, that the new structure with the business units will allow us to have that focus to be able to realize more growth from enzyme therapies going forward. Again, Cristin's gonna share more about the sources of growth and the tremendous opportunities with enzyme therapies in the future in her section. Now, the strength of our enzyme therapies and skeletal conditions is further augmented by our robust pipeline. We're targeting 11 launches by 2034, and two by 2027. Now, this year, we obviously did a refresh of our pipeline, and that's really led to a very attractive set of high-quality assets that meet a new higher bar in terms of commercial value and delivery for shareholders. I want to take this opportunity to reiterate again that our strong performance that we're sharing today is really primarily based on our current products and our indications that we're seeking, so our lifecycle plans, and very little on molecules where we have not yet received the proof of concept data. I think this is a really unique risk profile in the industry, that we're able to commit to high levels of growth with very low levels of scientific risk in that growth outlook. Also to reiterate, business development is not needed to deliver this plan. It's not assumed in this plan, but it does offer the potential for us to augment what is already a really compelling growth outlook to 2027 and on to 2034. Now, what is the rationale for business development? It's really threefold. One, it's a very target-rich environment. There's lots of great science that focuses on genetics out there right now, and it's a great fit with our scientific capabilities. But unfortunately, biotechs are highly capital constrained. This creates a very target-rich environment for us. IPOs over the last two to three years are depressed versus levels over the prior five years. Over 50 companies are at a negative enterprise value, and more than 100 are trading at less than their 52-week highs. So there's a tremendous opportunity for us. Secondly, we have a great right to win. I've already covered our scientific capabilities. We will use the same criteria as we use to assess internal assets to assess external opportunities. This is the BioMarin Five. Now, many of you will know the BioMarin Four extremely well, but earlier this year, when we undertook the assessment of our pipeline, we added a fifth criteria that focused on commercial potential and competitiveness of molecules. So this is the BioMarin Five, and Hank, in his section, will explain the BioMarin Five further. Now, added to our scientific prowess is obviously our capabilities in manufacturing and regulatory, which are world-leading. But we also have a global commercial footprint in approximately 80 countries, and we have a track record of the ability to find novel paths to access and successfully commercialize in those markets. I think very simply, I would say that we believe that there are assets out there that are worth more in our hands than where they're sitting right now. So what sorts of deals are we going to focus on? We're going to focus on deals less than $1.5 billion in transaction size. We are going to be able to do that because we're going to be generating significant levels of cash going forward, over $1 billion-plus of deployable cash, and we're going to be generating, on an annual basis, significant cash generation, and Brian will cover a little bit more of that in the future. Investors can be really confident we're going to be very focused with our approach here, and I hope that comes across from this slide. We're growing our capabilities to be able to identify, transact, and integrate deals at BioMarin, and I think the appointment of James Sabry, who's one of the most well-known deal makers with a track record of over 1,500 deals done. I think that should give investors confidence that we're going to do good deals really well. So in closing, in the first section, BioMarin offers a really compelling growth story, driven by a renewed focus on innovation, growth, and value commitment. We aim to deliver top-quartile revenue growth. We aim to double non-GAAP operating margin, and we're already well underway towards doing that. We're going to prioritize our innovation on the highest value assets from a scientific and potential standpoint. Finally, we're going to generate significant levels of cash flow that gives us enormous optionality to include and possibly augment what is really already very compelling levels of growth. We're really looking forward as a team to executing on this plan. We've got a lot of momentum right now, and we're very confident in our ability to execute and deliver for shareholders. Brian, Hank, and Cristin will now cover elements in more detail, and I'm going to, at this point, ask Brian to come up and cover the financial strategy that's going to deliver this high growth and value creation. Thank you. Thank you, Alexander. Good morning, everyone. I'm excited to take you through this value commitment section of today's presentation. As Alexander described, the focus and agility over just the first nine months of his tenure at BioMarin delivered substantial growth in revenue and profitability, and yet we are still at the early stages of our future growth journey. Today, we reaffirm our full year 2024 financial guidance, and we will be providing long-term outlook on total revenue, non-GAAP operating margin, and operating cash flow over the next several years. This is the first time that BioMarin is providing specific long-term financial guidance. In terms of structure, we are giving guidance for 2027. We believe that the next three years represent both strong growth years for BioMarin, but will also provide the momentum necessary to execute on our long-term strategy over the next decade. With respect to total revenue, we plan to reach $4 billion in 2027 and maintain a mid-teen revenue compound annual growth rate through 2034. On non-GAAP operating margin, we have already achieved significant improvement in 2024, mostly through natural leverage in the business and cost constraint. However, we believe, with several levers identified during our strategic and operating review, that we have the opportunity to significantly expand operating margins further into the future, into the low- to mid-40% over time, starting with 40% in 2026. Importantly, this increased level of profitability will result in significant operating cash flow generation. We estimate that by 2027, we'll be generating more than $1.25 billion of operating cash flow on an annual basis and growing from there. This will also provide a significant level of optionality with respect to capital deployment, and we've got a thoughtful capital allocation strategy that I'll come back to in a few minutes. We believe that we'll achieve $4 billion of revenue in 2027, and importantly, we feel that this guidance carries a high degree of probability because the Voxzogo component can be achieved within the achondroplasia indication alone. The enzyme replacement therapies have a proven track record of growth, and this revenue guidance, to be clear, is not dependent upon business development nor Roctavian. Specifically driving this goal are high single-digit revenue growth rates for the enzyme therapies and Voxzogo growth rates greater than 25%. Beyond 2027, we are targeting sustained growth in the enzyme therapies and expect significant growth in Voxzogo through the new indications, which we believe are heavily de-risked. Over the next decade, we do expect some revenue contributions from the launch of some of our current pipeline assets. However noteworthy, those are a smaller contributor to the long-term targets. Again, importantly, as Alexander's noted, neither the $4 billion nor the mid-teen CAGR through 2034 assumes revenue contributions from business development. Altogether, BioMarin is scaling to close to $3 billion of total revenue in 2024, and when we look at the 13% compound annual growth rate, that would get us to $4 billion in 2027. We observe that we are in the top quartile of biopharma companies that have between $2 billion and $10 billion in revenue today. Over the last nine months, the Board and we completed a comprehensive strategic and operating review that drove both this growth strategy, as well as a comprehensive examination of our cost structure in an effort to find opportunities to be more efficient. As a result, we identified a comprehensive cost transformation program totaling $500 million to be completed through the rest of this year and next year for full realization in 2026 to support our achievement of this 40% non-GAAP operating margin goal. Importantly, this cost transformation program is not outright cost-cutting. We strategically evaluated our operating model and opportunities to achieve new cost efficiencies, and we believe that we can both work more effectively and operate within a lower cost structure. The left side of this page captures two investment prioritization decisions already made in 2024. It is critical that we invest only in the most value-creating opportunities, which involved the discontinuation of several of our early-stage research programs earlier this year, as well as rightsizing our Roctavian operating expenses. In the middle of the page are three operational cost reduction levers. We redesigned BioMarin, looking at all opportunities to be more efficient, with a focus on making sure all of our employees are focused on the right work at the right level within the organization. We've also identified a material level of cost of goods sold efficiencies, and we've designed an enhanced strategic sourcing and procurement model aimed at optimizing our external spend. Lastly, on the right side of the page, through the enablement of new technologies and global process standardization, we have a plan to consolidate BioMarin's global support functions into a single, lower-cost location, where we believe we can provide a high level of business services to BioMarin, but operate within a smaller cost envelope. Next, it is important that we share not just our operating margin targets and a list of initiatives. We thought it would be helpful to quantify some of these levers for investors to convey the clarity and confidence that we can achieve these operating margin goals. We expect to continue to realize operating leverage in the business as revenue is growing substantially and expense growth rates, excuse me, expense growth rates will be constrained, driving more profitability. With respect to the cost transformation program, some of these elements are already implemented, and others will take time to implement over the rest of this year and next year, again, for full realization in 2026. We also thought it'd be helpful to provide more details behind the 40% operating margin. The table on the right summarizes our last reported fiscal year, 2023, and provides estimated ranges for each of our primary non-GAAP expense line items that drive the 40% in 2027. Starting with gross margin, where we expect to earn a gross margin of between 82.5%-85%. That's driven through some of those cost of goods sold efficiencies that I mentioned, as well as Voxzogo, our highest gross margin product, becoming a larger contributor to the P&L. We estimate R&D expense going forward to be in a range of 21%-24%. We believe it is essential to maintain a healthy level of continued investment in research and development. It is the fuel of our innovation engine, and we believe that R&D expense at 21%-24% of revenue provides us with the ability to fund an innovative pipeline that will drive BioMarin's sustainable long-term growth. On SG&A, where we estimate we'll be in a range of 19.5%-22.5%, this represents a substantial improvement over historical levels. We expect that G&A expense increases going forward will be limited to inflationary costs, the investment in key efficiency levers, and other essential corporate support. On sales and marketing expense, because of our high-touch, rare disease sales and marketing model, there are limits to how far down we can push sales and marketing expense. However, the implementation of this new business unit structure is gonna help provide the visibility and confidence in every dollar that we spend.... In summary, when we look at our 40% operating margin, we observe that we are in the top quartile of biopharma companies that have more than $10 billion in revenue today, and we're excited to execute on this strategy going forward. We believe that this operating margin target in the low to mid 40% strikes the right balance between generating significant levels of cash flow while also investing in our future growth. Lastly, our substantial improvements in profitability drove a comprehensive review of our capital allocation strategy. We expect that the substantial increases in cash flow over time will provide us optionality to deploy capital judiciously to create shareholder value. We are also pleased to announce today a new $600 million revolving credit facility. This non-dilutive financing instrument will allow BioMarin to access liquidity and flex our balance sheet as appropriate when we deploy capital. This page outlines our top three capital allocation priorities. Starting with organic growth investments, the combination of our historical R&D track record and our enhanced portfolio evaluation criteria tell us that continuing to invest in our internal innovation engine is our top priority. Next, we will prioritize the careful deployment of capital to external innovation. As Alexander mentioned, our revenue targets are not dependent upon business development. However, the right deals over time can be additive to what is already a substantial level of growth. Also, the right deals over time can have a multiplying effect, diversifying and augmenting our portfolio. Lastly, as we accumulate cash over time, return of capital to shareholders becomes an increasingly available tool. We fully recognize our responsibility to appropriately deploy BioMarin's cash, and we and our Board regularly discuss all options for return of capital to shareholder. That includes items such as managing through our 2027 convertible debt maturity in a non-dilutive manner, as well as opportunistic share repurchases. In prioritizing external innovation ahead of return of capital to shareholders, we fully recognize, again, our responsibility to be careful and appropriately deploy BioMarin's capital, and we will regularly explore all options. However, for the near term, we believe that investing in long-term sustainable revenue growth has the potential to deliver more value to shareholders than the outright return of capital. I will now conclude and hand it over virtually to Hank, who will describe our innovation engine that's designed to deliver a sustainable pipeline of high value, creating new medicines well into the future. Hank, are you there? Hope so. Thanks, Brian. So it is a pleasure to be speaking to you all today, albeit remotely. I'm sorry very much that I can't be with you in person. But our strategy to deliver significant value creation is rooted in our approach to innovation, and having spent the last 15 years developing a quite differentiated engine, we've now prioritized our R&D pipeline so that we work on medicines that meet high standards for future success. And we believe, moreover, that the sustainability of our approach to innovation is gonna be driven long term by the ongoing genomics revolution. On the next slide, we quickly recapitulate 25 years of translating genetic discoveries into transformative medicines that have high impacts on patients. We've worked in a variety of therapeutic areas, and importantly, we've also worked on a variety of modalities of therapies, from small molecules to fairly complex biological molecules, such as not just enzymes, but particularly glycosylated enzymes. Nucleic acid therapies in their most complex form in gene therapy, but can be also worked on in less complex formats like antisense oligonucleotides. We've had tremendous success over the past 20 years at BioMarin, and that's really been driven by a very high bar for advancing compounds through the various stages of development. On the next slide, I wanted to capture why our innovation strategy is both sustainable, but also replicable and scalable. The genomics revolution has been really powerful in identifying more therapeutic opportunities to address even larger patient populations, and when filtered through, what I'm gonna talk about momentarily, our BioMarin Five, we can create a very large pipeline with tremendous potential through regulatory and commercialization to deliver transformative medicines, so to speak to the Five and its enablement of transformational impact for patients, I wanted to start by recognizing the importance of genetics in providing a clear etiology of the condition to the affected population. We develop therapeutics that are targeted to the most proximal and fundamental cause of the defect in the patients, and work in therapeutic contexts in which there are readily accessible endpoints that track the effect of our interventions at a very early stage, and finally, will lead to transformational impacts on patients. These are impacts that are quite perceptible at the level of how patients feel or function, or even survive. Now, as was mentioned, we've also added the lens of wanting our assets to be commercially competitive. Especially now, with so many people entering into the genetics medicine space, it's been important for us to have compelling end-to-end profiles for our products, commercially and competitively. And one in particular, this considers to a greater degree than in years gone by, is the characterization of the unmet medical need, the creation of the target product profile, what are we aiming to produce for patients, and particularly also the value that this will represent to patients, to regulators, and to payers, and finally, will be consistent with our emerging growth strategy. I wanna start illuminating how genomics and genetics powers the future by talking about C-type natriuretic peptide as a case study, if you will, in the power of genomics medicine. This began some years ago in the study of the condition of achondroplasia. Shown and I'll talk about the right-hand panel shortly, but I wanted to start with the left, which is a picture of mice and a graph of growth rates in mice. And the mice can be engineered to have the mutation, in the middle mouse, of FGFR3, that is the achondroplasia mutation, and those animals are short relative to unaffected control animals. Not shown on this slide is a picture of a mouse who bears a mutation in a gene called NPPC, which renders the animal tall. The interesting aspect of these mutations is that when the NPPC tall mouse is cross-matched with the FGFR short match mouse, on the bottom you get an animal whose length is similar to non-transgenic or wild-type animals. This is captured in the dots on the left, where you can see restoration of length in this cross-matched animals. Now, the interesting part about the especially interesting part about this is that encoding for NPPC, we recognize that it, that this is the gene that cause that is produces the protein CNP. We recognized a therapeutic opportunity to leverage CNP as a driver of growth. For those of you who are unfamiliar with achondroplasia, this is where we started. It's the most common form of dwarfism. This is a slide that was provided to us by our very important colleague, Julie Hoover-Fong, from Johns Hopkins University, in her summarization of the experience of children with achondroplasia. Shown on the horizontal are the child's age in years, and the rows convey the challenges that patients who have achondroplasia experience. In the first several years of life, there is a substantial risk of mortality, somewhere between 50 and 250-fold higher than the standardized mortality rate is 50 to 250x higher than in unaffected children. This can arise from cervicomedullary compression, or obstructive sleep apnea, or central sleep apnea, which all derive from defective ossification of endochondral bone, which is the hallmark of achondroplasia. Past infancy and toddlerhood, problems like otitis media and hearing loss ensue. These are particularly problematic for children because they cause a lot of time missed from school, or challenges in learning, and so they result in developmental delays, as well. Continuing the life journey of a child into later ages consists of problems of thoracolumbar kyphosis or spinal stenosis, lower extremity malalignment. Many of these conditions require surgical intervention for these children, and obesity is a lifelong complication of achondroplasia. So the unmet need in untreated achondroplasia was, is quite substantial. Now, we've had the opportunity to evaluate the effect of Voxzogo for a large number of years and in a large number of patients, but I wanted to talk about the accumulation of the effect of treatment with Voxzogo over a longer period of time. On this graph illustrates two separate studies in two separate non-overlapping age groups. And on the left, you see the ongoing results of our phase II study in children with achondroplasia, and here we measure the endpoint of height. And you can see that year- on- year, as time goes by, there is a progressive accumulation of height gain over and beyond what would have happened had a child not been treated with Voxzogo. And by year four, this adds up to over seven centimeters of incremental height gained. On the right-hand side, we truncated it, so we start the counting at year four, and through year seven, one can see an incremental gain in height over untreated children of 11 cm. And because these are non-overlapping populations, it's reasonable to amalgamate the data, which indicates that the expected final adult height gain should be greater than 17 cm or 6.7 in. I want you to remember the 17 cm, because we're gonna come back and talk about this as we contemplate other statural disorders. Now, on the next slide, height, of course, is only, if you will, an intermediate measure of the health benefits of treatment with Voxzogo. Strong bones leads to healthy bodies, and I'm gonna now walk through a number of parameters that have also been documented to be advantages of Voxzogo treatment. On the left is the upper to lower body segment ratio, reflecting proportionality. This is simply a measure of the standing height versus the sitting height of a child, which should be. It's a ratio of one to one. But in achondroplasia, the disproportionality leads to a ratio of over two. Over a three-year period of treatment with Voxzogo, these are data presented by Dr. Ravi Savarirayan, who is a key driving force in our program, and we've achieved statistically significant improvements in proportionality. Moving to another dimension of health beyond height, on the right are measures of quality of life improvements using a tool called the QoLISSy score, which has improved overall, but also contains subdomains measuring improvements in physical function, social function, and emotional function, all consistent with improved state of well-being for children with achondroplasia. On the next slide are documented improvements in anatomical function on the left, anatomical anthropometric measures on the left. This consists of... Technical difficulty here. Excuse me. This consists of improvements in the volume of face, the area of the foramen magnum, and the volume of the sinuses, and on the right, improvements in bone strength. I mentioned healthy bones leads to healthy children. What we don't want to observe is improvement in length with weakening bones. And in fact, Dr. Raggio presented this year data on cortical thickness of the bones, which is a reflection of the strength of bones improving year over year in children whose bones have been measured on treatment with Voxzogo. Now, the early understanding of the effect of the CNP pathway on overcoming the fundamental defect of FGFR overexpression gives us an opportunity to look back and consider the roads that we didn't take. I wanted to contrast where we are with Voxzogo to where the followers in the FGFR inhibitors have progressed. We've been on the market globally since 2021, and the FGFR inhibitors are entering into the phase III clinical trials, with still some years to go before these are globally available for patients. We've accumulated over 6,000 patient years of experience. This is very, very important for families because oftentimes infrequently occurring side effects are not documented until there's been several hundred or even thousands of patient years of experience. So we can say with quite a degree of confidence that very rare but very potentially important side effects with Voxzogo won't be anticipated, in contrast to FGFR inhibitors, which are still early in their journey with about 18 patient years of experience. I've showed you seven years of ongoing durability. It's really longer than that when you amalgamate the early study and the later study, but the effects of Voxzogo continue to accumulate, and this will be very important when we talk about other statural disorders. The FGFR journey, of course, is still just beginning with approximately 18 months of data. We've demonstrated health improvements beyond height in terms of proportionality, quality of life, bone structure, and function, and published quite extensively on these findings, I should add. Whereas, so far what we've seen has been, in the FGFR inhibitors, has been limited in regard to proportionality. We have approval globally for children who are under three years of age. As I mentioned, this is so vital because this is when the condition is at its most serious, and we've been able to make the product available on a global basis for children under three years since 2023, and the FGFRs are uninvestigated. I mentioned how important it is to have healthy bones because that's leads to the overall health of the child. And one of the key aspects of healthy bones is maintenance of normal status of the components of mineralization of the bone. We look very carefully at phosphate balance in our children, and there are no abnormalities or perturbations in phosphate balances that we've observed to date. And there have been alterations in phosphate balance observed with FGFR inhibitors. Excuse me. Of course, important in that is not just whether the phosphate level is in an abnormal range, because even within the normal range, a high phosphate level compared to a low phosphate level conveys significant cardiovascular and bone health risk. A route of administration is sub-Q. Patients and families have had a high degree of satisfaction with this. Of course, the FGFR inhibitors have the potential advantage of being oral, all things being equal. And then lastly, I wanted to just comment on the multiple indication potential for the CNP pathway as opposed to the FGFR pathway. We believe that the CNP pathway represents a therapeutic target, and I'm gonna talk about that in a little bit more detail shortly. Whereas in the case of the FGFR inhibitors, those are thought to have benefits only in the case of FGFR overexpression. Interestingly, in a condition like hypochondroplasia, where mutations occur in different spots of the FGFR gene, this could potentially convey limitations in efficacy of FGFR inhibitors, beyond achondroplasia, and certainly not into other statural disorders not caused by mutations in the FGFR3 pathway. It's simply put, it's not feasible to grow a child and to restore health by tweaking the FGFR axis because that will be accompanied by important health sequelae. Now, I wanted to pivot and talk about how our interest in CNP has really illuminated the path to multiple indications embodied by the BioMarin Five. This is a very important chart on the right, depicting a merging of functional data, genomics data, and a probe of large genomic databases. What we've done is characterize the functional effect of a mutation in the lab by basically making different mutations that occur in humans who are walking around, who, in genomic databases, have annotations of their final adult height achieved. Mutations were characterized as either losing function, which is on the left, gaining function, which is on the right. The dots represent individual types of mutations in the NPPC gene. Remember, this is the gene that encodes CNP. You can see that loss-of-function mutations, as expected, convey shorter stature, and in contrast, gain-of-function mutations in CNP convey taller stature. This is what relates us to conclude that CNP is a master regulator of bone growth over and beyond whatever else is going on genetically in those children. This is very important because it's led us to have an increase in confidence in the development of Voxzogo for a related condition called hypochondroplasia. The features of hypochondroplasia can overlap with both achondroplasia and idiopathic short stature, and because of that, diagnosis is often delayed. Outside of Japan, there are no approved therapies for hypochondroplasia worldwide, but there is a similar pathophysiology and burden of condition in hypochondroplasia as there is in achondroplasia. And we'll be targeting the subset of hypochondroplasia patients who are under two standard deviations different from average stature children. Through work by our colleague, Dr. Andrew Dauber, at Washington, D.C. Children's National Hospital, he has conducted a study in children with hypochondroplasia, and he's presented data at the American College of Medical Genetics in 2024 in demonstrating a mean increase in the annualized growth velocity of children of 1.8 cm per year in 24 children, which is similar to that observed in achondroplasia children. This has enabled conversations with global health authorities and alignment around a direct-to-phase III program, and that will consist of a placebo-controlled study with annualized growth velocity at 52 weeks as the endpoint for registration if the study is successful. What about beyond achondroplasia and hypochondroplasia and statural disorders? And I wanna first talk about what the available therapy is for many of these conditions, namely the use of human growth hormone. Shown on the left is a graph of a study, a placebo-controlled study, in which human growth hormone was applied to children who have idiopathic short stature, who were then followed annually for approximately five years. You can see that there's a separation of the two groups in the early years, one and two, after treatment, but by years three, four, and five, the effect of growth hormone has waned, so on the right, we've summarized the untreated final adult height for four different conditions: idiopathic short stature, Noonan syndrome, Turner syndrome, and SHOX deficiency, and we've also then summarized the height gain in children who have been treated with human growth hormone. What you can see is that children who have idiopathic short stature, their tallest height for girls, 4 ft 11 inches, and for males, 5 ft 3 in, can be augmented by less than 3 in or 7.5 cm. This is consistent for Noonan syndrome, Turner syndrome, and SHOX deficiency. Now, some of these conditions have variable statural degrees of stature impairment, and I'll talk about that next. On the basis of the compelling evidence of Voxzogo CNP as a master regulator of bone growth, we've actually made a phenomenal amount of progress in conversations with authorities around the world, gaining alignment for four additional Voxzogo indications, and that would be the result of placebo-controlled studies in which the annualized growth velocity at 52 weeks would support registration if the studies are positive. Now, as I mentioned, the burden of condition can simply be summarized as related to the ineffectiveness of human growth hormone over time because of its waning effect. And then the children who have the more severe forms of these statural impairments have very similar types of life journeys as children with achondroplasia, especially related to quality of life, et cetera. Dr. Dauber has studied five children who have idiopathic short stature, presented data at the Pediatric Endocrine Society, demonstrated high-velocity gains of over five centimeters, and he's also studied children with Noonan syndrome on the right, with high-velocity gains of 4.3 cm. These are over untreated, the growth velocity prior to treatment. As I mentioned, we'll be targeting the most severely affected children for inclusion in the clinical trial, specifically children who have heights less than two and a half standard deviations different from average stature children. Our clinical studies are well underway. I omitted to mention on hypochondroplasia, we're well underway in our phase III program there, actually tracking to completion of enrollment in hypochondroplasia, slightly early, as compared to previous communications. Our phase II programs for idiopathic short stature and the four and the other three additional indications will be first in a phase II study, to find the optimal dose for these patient populations, followed by our phase III efforts. Interestingly, the FDA has allowed us to, if you will, bucket Noonan syndrome, Turner syndrome, and SHOX deficiency into one master protocol, for, improving, efficiency of the conduct of the clinical trials. Last, I just wanted to comment on our efforts to develop a longer-acting CNP that builds on our Voxzogo, franchise. We've developed a compound, BMN 333, that has similar chemistry from other approved drugs for prolonging the half-life and leading to a potentially weekly dosing. This, would offer the potential for even better efficacy, better convenience, or both from sustained exposure, and would leverage further the safety experience of Voxzogo, because it's, rooted on the same active compound, C-type natriuretic peptide. This would extend the value of CNP therapies for patients, and importantly, we have a patent portfolio that covers multiple long-acting CNP variants, both in the United States and in Europe. The fact that we have confidence in the sustained half-life is documented in the upper right-hand panel, demonstrating the concentrations of CNP are maintained in the therapeutic range, even on a weekly dosing schedule, and in the bottom right, that we can enable higher levels of growth following exposure to CNP, to yield potentially even greater growth in humans when those studies are conducted, so our skeletal conditions portfolio timelines are indicated in the amalgam here with the target patient profile, product profiles. And next, I want to pivot to the remainder of the pipeline, but I also wanted to mention that we have an additional thirteen exploratory assets not named on this slide, each of which fulfills the BioMarin Five criteria and will support sustained growth of BioMarin over the coming years. First, I wanted to talk about Palynziq for adolescents with phenylketonuria, because this addresses a fairly high unmet need. Now, PKU requires strict adherence to an intolerable level of protein restriction, and untreated PKU can lead to serious cognitive and psychiatric impairments. And earlier therapy that reduces dietary restriction would facilitate transition to adult living, independent adult living. And of course, the earlier the intervention occurs in genetic diseases, the better off patients are. However, this requires today strict adherence to a diet. What we'd like to show is the safety and benefit in a high-need population, namely adolescents in the United States and Europe, because the data are expected to be consistent with adult data and would lead to an expansion in the Palynziq label. We've concluded an enrollment, and we'll be analyzing a study in adolescents with PKU, excuse me, with phenylketonuria. That study is well underway, as I mentioned, and its expansion would unlock access further. Now, this is illustrated more at a patient level by this child who speaks about the level of protein restriction in late adolescence. And the important considerations there is that a dietary restriction is not simply, it's not simple. It, it really involves eating a terrible, bleached food diet, and, patients are rather eager to be able to eat, a normal, healthy diet. And by starting this before the patient is transitioned from their parents' care into, from adolescence into young adulthood, patients are able to make that journey into adult life in a much more streamlined fashion without dietary restriction. Improving further on Palynziq, on the next slide, we've developed a compound called BMN 390, which may even further strengthen, enzyme therapy for phenylketonuria, with a tremendous opportunity to greatly expand the number of patients by lowering hypersensitivity, which is really the treatment-limiting side effect of Palynziq and would enable expansions into younger ages if safe. We've developed a novel, enzyme, with reduced immunogenicity deriving from novel pegylation. Importantly, this would leverage blood phenylalanine as a proven approvable endpoint, and would have the opportunity to replace diet from an even earlier time in children with phenylketonuria. That we can demonstrate that we believe that we will be able to demonstrate in humans lower immunogenicity, as shown on the right. The principal driver of serious immune reactions to Palynziq is pre-existing antibodies to the polyethylene glycol that's used in the PEG. This is referred to in this chart as linear PEG. Our novel PEG has lower immunogenicity, as demonstrated on the right-hand side of the figure, as having a much lower number of patients. Each bar is an individual patient and their pre-existing immunity to the novel form of the PEG that is used in BMN 390. And so as we transition this into patients with phenylketonuria, we'll be looking for early signs of reduced immunogenicity, which would be quite an advancement for patients with PKU. I next wanted to touch on BMN 351, which is a novel approach to the treatment of Duchenne muscular dystrophy. Genetics insights revealed a novel site for exon skipping in comparison to where all of the first-generation molecules that have been studied so far for addressing exon skipping. The chemistry of BMN 351 leverages the first-generation molecule that went all the way through phase III clinical trials before its termination as a program. And we have shown in animal studies that we can achieve a near full length dystrophin expression, up to 40%, which is multiple folds higher than approved therapy. Why would this be transformational? This is a beautiful study from an integration of electronic health records and genomic databases. In pink are patients who have the mutations that would be amenable to 351 therapy, demonstrating time to wheelchair loss in their early teens, and most patients are wheelchair-bound by their mid-20s. Similarly, in the genomic databases are children and adults who have mutations in their dystrophin gene that are like what would happen when 351 is applied to them, and you can see dramatic delay in need for ambulatory assistance. That we can achieve dystrophin levels that would be similar to that which is shown in blue derives from an integrated analysis of data that was generated in our earlier first-generation drug program, and an evaluation of those achieved concentrations in relevant animal models. On the horizontal axis is the tissue concentration of that first-generation drug at various time points, 12 weeks, 24 weeks, in its steady state. On the vertical axis shows the amount of dystrophin that's produced when those tissue concentrations are achieved, essentially demonstrating the point that our similar chemistry with better biology will achieve massive increases in dystrophin expression. Next is a compound called BMN 349, a potential best-in-disease treatment for Alpha-1 antitrypsin deficiency. Alpha-1 antitrypsin deficiency is a complex results in a complex disease state. There's two effects of one mutation. The first effect is a mutation that causes a loss of function in the Alpha-1 antitrypsin protein and results in hereditary emphysema, a lung disease. Second effect of the mutation is that the defective protein gets trapped in the liver. The protein aggregates and polymerizes, and those polymers cause progressive liver disease. We've developed a molecule which has a unique mechanism of action and stabilizes the mutant protein to address the fundamental pathophysiology of in the liver disease by increasing protein secretion, which would reflect reduced polymer burden and the potential to transform liver health. Now, this would be fully complementary with the replacement therapy that's already available on the market. The unmet need here is the opportunity to transform liver health. Now, the potential competitive advantages of this approach are its unique applicability to a broader heterozygous patient population and its oral titratability to readily achieve a corrective effect. The need for therapy for prevention of liver disease in patients who have the heterozygous mutation can be numerically illustrated by the fact that there are two million adults in the United States alone who have high risk, what was formerly called NASH, who have progression potential who have liver fibrosis stage greater than three and the potential to progress. Of these two million patients, 5%-10% of them have that heterozygous phenotype, where they only have one copy of the gene. The risk of liver events in these patients is increased 50%-100% in comparison to patients who don't have the mutation, and that progression to liver disease in patients who have compensated cirrhosis over a two-year period alone can be a 30%-50% event rate of liver decompensation, the need for transplantation, or liver-related death. That BMN 349 is well-tolerated and has a sustained pharmacodynamic effect, as demonstrated on the right, where we measure the pharmacokinetics of BMN 349 after dosing in healthy volunteers, and the product is well-behaved over the range of doses that have been studied, so we're very excited about 349. Next, BMN 370 for the treatment of von Willebrand disease. Von Willebrand disease is a fairly common mutation in an important blood carrier protein known as von Willebrand factor, which in severe cases can cause exaggerated bleeding and can only be, in especially severe cases, controlled by administration of replacement, recombinant replacement therapy on a three times weekly basis. This is particularly problematic for women during menstrual cycles or childbirth. We've developed a targeted bispecific nanobody for subcutaneous administration, which would replace the thrice weekly IV therapy, and has the attribute of facile measurement in early clinical studies because von Willebrand factor's levels are readily accessible. And has transformational potential to normalize von Willebrand factor levels through monthly and at-home, self-administration, and with a substantial reduction in bleeding, which is demonstrated on the right in, animal models of von Willebrand disease, where we can normalize, clotting time in animals who are treated with our nanobody. In summary, we have quite a robust pipeline across our business units and our innovation and enterprise, with eleven launches expected by 2034, two of which will be, launching by 2027. And as I mentioned, also, a fairly rich exploratory pipeline behind that for ongoing renewal of the pipeline. So with that, I'd like to turn it over to Cristin to invite her to the stage to share our strategic plans for ensuring reach to patients. Cristin, over to you. Thank you so much, Hank, and I certainly hope that you feel better quickly. Now, I'm delighted to be here to share more about how we intend to continue to deliver for patients, but while also building on the momentum that we have in the business. Now, having only been here now for three and a half months, I have to say I am genuinely impressed by the depth of expertise and the drive that underlies all of our successes. I'm really excited to build on this foundation to achieve the future growth that we are truly committed to deliver. Now, we do have an opportunity, as you've heard throughout this presentation, to grow both our enzyme therapies and our skeletal conditions businesses. Over the last 20 years, one thing that we have been assuredly good at, it's our ability to create, to develop, and to sustain markets. We have done this with our enzyme therapies, and we intend to introduce new initiatives that are gonna revitalize the growth of that portfolio, and I'll share those momentarily. Similarly, we intend to build on the business in with Voxzogo and achondroplasia, and then expand into the potential of new indications to serve more children with this safe and effective treatment. Let's talk about our plan and our ambition. Now, what you can see here is that we anticipate top-line growth that will be generated from the potential combination of our on-market products on new indications from existing products and the new products that are under development. Now, our midterm aim is to reach $4 billion in total revenues by 2027, with a longer-term mid-teen CAGR through 2034, which squarely puts us in the top quartile of peers that are currently in the $2 billion-$10 billion revenue range. Now, what you can see here is that if we look over to our enzyme therapies, we have had incredible underlying growth. It's been a foundational growth over time, and this really has been about our ability to understand the disease, understand the patient journey, and then importantly, ensure that we can get pathways to access for the patients that need it. We've had sustained market leadership with this portfolio, and as Alexander mentioned, we've also had very limited competition and are insulated from policies such as the Inflation Reduction Act. Now, moving over to the skeletal conditions business, this is a business that we expect to expand at a higher rate, and this is in large part due to our ability to meet significant unmet need, which we'll get into, as well as the potential to treat greater population sizes. Now, with Voxzogo, we're gonna have continued expansion in the achondroplasia space, which I'll speak to, and then we have those five potential new indications on the horizon, with hypochondroplasia, ISS, Noonan syndrome, Turner syndrome, and SHOX deficiency. But then importantly, we also have BMN 333, the longer-acting CNP, which I'll get into momentarily. What you can see here is that we expect substantial growth from both of our businesses, with skeletal conditions eventually outpacing that of enzyme therapies, and in large part, this is again due to those multiple indications that we have on the horizon. But let's talk first about our enzyme therapies business, because it really does remain a key contributor to our growth plans. Now, since our first commercial launch in 2005 with Naglazyme, we've been building on our experiences there with Kuvan, Vimizim, Brineura, and Palynziq. And we have established substantial capabilities to find patients with these rare genetic conditions and then to ensure that they gain access to our therapies. Now, our commercial presence, as you've heard today, it's in approximately 80 countries, and really, our goal is to reach and treat patients sooner in their journey to ensure that we're maximizing outcomes. Especially when we think about MPS and PKU, this really has been incredible, how we've been able to find those treatment access pathways, but also importantly, have patient support programs that really ensure maximal adherence to our therapies. Our track record really does demonstrate that we can maintain leadership positions as standard of care in these otherwise untreated conditions, and as such, we delivered 8% CAGR in the 2020 to 2023 timeframe. Now, building on this success, we believe we can continue to drive growth and deeper market penetration with our enzyme therapies portfolio. We have a number of levers that I'll get into that will enable this expansion, and these are really based on smart investments and based on our learnings- to- date. So these are some of the new initiatives that we have to drive growth, and across our portfolio, we'll be introducing various initiatives. And what I think is really important to note here as well is exactly what Alexander spoke to in the beginning. And that is that this business unit approach, this organizational model that we'll be moving into, will really enable us to drill into making sure that we're making the right investments in the right countries in our commercial model, as well as into a lifecycle management for this specific portfolio. Now, moving over to MPS and CLN2 specifically, so talking about Vimizim, Naglazyme, and Brineura, we are driving tactics that are intended to accelerate and increase accurate diagnosis and to facilitate regular treatment. So what I mean by that in terms of increasing diagnosis: so we are targeting diagnostics or diagnostic efforts in areas where we know that there's a higher prevalence, and we're expanding initiatives that will help us to efficiently identify those new patients across these markets. So what this might look like is shifting resources, where we know screening is well-resourced in some countries into those where there's more limited funding for this space. We're also investing in testing within a known patient's family tree, and we've actually found in a recent pilot in a specific region, that by doing this, by testing family members from a known patient, that we have identified, patients that would have otherwise gone undiagnosed. Now, over to enhancing patient adherence. This is something where we want to make strategic and very targeted investments in initiatives. So in initiatives such as home infusion or patient support programs that will help us to increase adherence. And these programs are particularly relevant in areas where there might be high travel and burden for patients to get to their regular treatment. We're also targeting countries where we know that there's a baseline adherence that's required for the country to reimburse the product. And then lastly, moving over to investment in emerging markets. We, having operated in 80 countries, we know what works in countries, and frankly, we know what doesn't work. And so what we're doing here is we're really taking many of these learnings, and we're applying them with discipline and limited investment to unlock some opportunities that we know remain. So specifically, we're looking at countries in both Latin America and in the Middle East, where we believe there's more opportunity to expand access. And now let's talk a little bit about Palynziq and PKU, and that is a. It's a different disease area, and I want to be able to specifically drill into this. Now, with Palynziq, we have a much more targeted commercial footprint, and this is in large part because we have focused where we know that we can get access and bring that patient impact. And in this, the U.S. plays a leading role in our growth in Palynziq, and this is fueled by a lot of what Hank spoke to, and that is those substantially lowered Phe levels, as well as that freedom from a restrictive diet. And this, quite frankly, is what I believe differentiates Palynziq from the other alternative that might be on the horizon. Now, we're very excited about the opportunity to potentially be able to bring this to adolescents, ages twelve and up, because they also will be able to have these, these benefits from Palynziq. In addition, we're currently generating quality of life evidence that will strengthen the value proposition of this product, and we will use these data to go in and potentially expand access into new countries that we have not yet been into, or importantly, those that were previously inaccessible. So that's it on enzyme therapies. Let's move over to skeletal conditions. And this is an area that, just like we've done so with enzyme therapies, we intend and have the ambition to build a leadership position here, but in a much larger therapeutic area. Now, we want to continue to build on that really positive experience that we've had with Voxzogo and achondroplasia, to then move into other areas and treat thousands, potentially more children in the next decade across six growth-related conditions. Now, as Alexander spoke to, our TAPS, our Total Addressable Patient Populations, are rather large. But I want to repeat that these are both the diagnosed and the eligible patient populations, and this does not take into account access, competition, or any of the other things that might take cuts at this. But it's important to note that each of these conditions has a very nuanced component to it, and therefore, we have a specific go-to-market strategy for each that will take all of this into consideration. But even with all of those nuances and caveats, we are still confident that this represents a greater than $5 billion opportunity by 2034. Now, we have been asked by many, perhaps some of you in this room, whether or not we believe that we will be able to truly grow this business in the face of competition. And the short answer is yes. Yes, we do. And I'll tell you precisely why. I think that we are truly confident in our outlook across these multiple skeletal conditions based on what we've been able to do to date. So far, Voxzogo has become the standard of care, and this is due to the incredible data we have, our broad age label, as well as the positive experience that we're seeing, quite frankly, in the compliance rates that you see there on the Board. But we also know that this is something that it's so important that we have an approved therapy that can treat from infancy. You saw on Hank's slides how important it is to treat patients very early, and we know that families are starting very early in infancy so that they can maximize benefit, given that we know the greatest deficiencies happen in that first five years of life, and if it's not caught, you can't catch up. We're also clear, and we hear in our market research, that any of those families and children and treaters that are having a positive experience with Voxzogo, they're more likely to remain on Voxzogo if other options come to pass. And so that means that switching to another therapy, if there's another option for them, is a high bar. Further strengthening our belief in our growth outlook is our patent portfolio that we have in key geographies that covers long-acting CNP. Taken together, the confidence in our outlook is really underpinned by the opportunities that we have today in achondroplasia and in the near term, as well as with new indications in the future. Let's talk a little bit about achondroplasia and how we anticipate expanding on our leadership. The bulk majority of our growth between now and 2027 in skeletal conditions is with achondroplasia. It's de-risked, and we have a clear line of sight for how we intend to achieve that ambition. There's ample room for expansion, and let's be honest, we're really only at the beginning of this global launch. Now, we know that Voxzogo will be the only approved product for achondroplasia and will have the broadest age label possible from infancy, and so really, our growth strategy is based on expansion in current markets, as well as continuing to launch and grow into new markets, so if you look over there on the far left, that's our international strategic markets. In there, you have markets like Japan, Germany, and Italy, where we have gained very high penetration in a relatively short amount of time, and this is in part due to strong execution at the country level, but also because this is areas where treatment is more centralized and straightforward, and we've been able to really gain high penetration quickly. Also in Japan, it's important to note that that is the only country that has a current approved treatment, which is growth hormone. You've heard, Hank speak to that earlier. And this kind of shows what can happen if you have an established treatment paradigm, as well as a product like Voxzogo that has such great efficacy by comparison. So we'll continue to grow in those markets, albeit at a more measured pace, by really focusing on treatment at infancy. Moving over to the U.S., we know that this is our largest single market, and we have a lot of room to grow there. And again, we have clear line of sight on how we intend to do that. So what we're really focused on there is building or increasing our prescriber base, so this is across geneticists, pediatric endocrinologists, and general pediatricians, to ensure that they have relevant current information on Voxzogo, on Voxzogo treatment, and that every child with achondroplasia knows where a local care team can be, where a treater can be. We're doing this with digital, digitally driven, excuse me, data-driven insights and using digital channels to make sure that we're getting relevant information out there as quickly as possible. We're also ensuring that we continue that momentum based on the recent expansion of the age and our label, and we've got a lot of momentum going, and we're going to carry that forward. And then moving over to the other international markets. This is an area where we do have penetration. We know that there are some under-penetrated markets that we're focused on, but also it's important to know that we're currently in 44 countries with Voxzogo, and our plan is to expand into at least 20 more by 2027. And so here is where we're really leveraging that 20+ years of experience across 80 countries to ensure that families seeking Voxzogo treatment can obtain access. Now, moving over to the potential new indications in our pipeline. This is our first opportunity where we're gonna think about expanding that leadership position in skeletal conditions with hypochondroplasia, potentially in 2027, where we know there's still a high unmet medical need, as Hank spoke to. And also pending positive data, we'll seek approval in ISS in 2030, followed by Noonan syndrome, Turner syndrome, and SHOX deficiency simultaneously in 2031, where we know that there's still an unmet need despite growth hormone treatment. And I'll share a little bit more about how we're gonna go into each of these. So hypochondroplasia. So this is still an area of great unmet need, as we've all said here today, and really there's no treatment available outside of Japan, where growth hormone is indicated. Now, as Hank alluded to, there's a similar phenotype to achondroplasia, but it can also overlap with ISS. And so it's oftentimes there's a lot of heterogeneity in the severity of the condition, and it can oftentimes go undiagnosed, where some of these patients aren't even diagnosed until early childhood or later. And while we believe that the genetic prevalence of hypochondroplasia is similar to that of achondroplasia, you'll notice there that we have a much, a smaller, total addressable patient population, because what we've done here is that we know that there's high phenotypic heterogeneity and therefore a lower diagnosis rate. So we wanted to make sure that there we're only accounting for the most severe and likely to be diagnosed. So this really, for us, though, is an opportunity. We see it as an opportunity, and let's be honest, it plays to BioMarin's strengths. We have the opportunity here to build awareness of this condition and the diagnosis of it, so that we can ensure that patients are being diagnosed earlier and then treated if an option becomes available to them. To do this, we're gonna build on our experience, our relationships, and the infrastructure that we've built with achondroplasia to drive awareness of this lesser-known condition. Specifically, we'll have educational programs regarding the unmet medical need, the burden of illness, and the diagnostic paradigms. We expect to have our phase III study enrolled by early next year and approval in 2027, pending positive data, which would make Voxzogo the first targeted treatment approved for children with hypochondroplasia. Next, the next potential approval would be with ISS. Now, this is an area that I want to be clear, that we are only intending to pursue Voxzogo, Voxzogo development for ISS in the U.S. only. This is because there are only a small handful of countries that actually see this as a true medical need, and the U.S. being the biggest of those markets. Now, you can see that the TAP of this one is rather large at 190,000, and I just want to be clear that this is only reflective of the U.S. children aged zero to 15 and diagnosed with ISS, with the more severe presentation of it. So that's defined by being greater than two and a half standard deviations below average height. Now, what's interesting in the U.S. is even though this is in that growth hormone is indicated here and it's seen as a real condition, about a third of payers support treatment with growth hormone, and based on our market research, we see approximately 10%-20% of patients that are treated with growth hormone. And but what we know is exactly what you saw from Hank, that efficacy, that effect of growth hormone can wane over time, which is where we see the true unmet need, and quite frankly, where we intend to target at the outset. Now, Dr. Dauber did show some recent data at the Pediatric Endocrine Society earlier this year that does give us hope for Voxzogo as a potential treatment for ISS. And it will likely be the only other treatment on the market beyond growth hormone, because we do know, as Hank alluded to, FGFR targeted inhibition is not expected to be a viable pathway, and we don't see other novel agents on the horizon. So while it might not be the case forever, we do believe we have a significant head start. And then the last of the three conditions between Noonan syndrome, Turner syndrome, and SHOX deficiency. I recognize that there are medical differences across these conditions, but the ways in which that we would position and approach commercialization would be similar, so I'll talk to them together. So again, this is an area where we have growth hormone approved, but we do know that in the case, especially of Noonan, Noonan syndrome and Turner syndrome, there is a hesitancy to use growth hormone based on some of the cardiovascular complications that are seen with these conditions, not to mention the risk of chronic growth hormone use over time, and so we do believe that this is an area that can really be compelling for Voxzogo. Now, looking at it, and I want to be very clear about this, again, to look through the lens of where could we have the most impact with Voxzogo, we wanna make sure that we are treating patients with the highest unmet need. And so with that, and as a lens, looking at these three conditions and ISS, we have decided that we will position Voxzogo following treatment with growth hormone. So that means if there's growth hormone intolerability or that waning effect that we see over time, that's where we intend to position Voxzogo. And this really, I think, allows us to enable... to deliver that profound impact that Voxzogo is known for. But not to mention, it also helps us to maintain the value. Now, we're excited about Voxzogo. I think you can hear that very clearly here, but we're also thrilled about the potential that we have with BMN 333, which is a next-generation product and a longer-acting CNP, with the potential for weekly administration. Now, we do know that there are many areas that 333 could add benefit to both children, families, and their caregivers. But what we really know that is the potential for that greater efficacy, based on the fact that it has a longer half-life than Voxzogo and therefore would have that prolonged, treatment exposure. Now, it's of course, essential, and we hear this very strong in all of our market research, that the safety profile be as good as or better than that of Voxzogo. And so we do plan to initially study 333 in achondroplasia and hypochondroplasia, and we'll of course, consider other skeletal conditions of high unmet need in the future, if appropriate. And what we would do, again, is leverage that leadership that we have with Voxzogo, the infrastructure, the relationships, et cetera, and really ensure that patients have access to this potentially improved CNP later in the decade, should our data be true. Now, I think you guys can see it and hear it, that our overarching goal across all the skeletal conditions business is really to reach as many children as possible who can benefit from our transformative therapies, and we're only at the beginning of this journey. But I think that the word transformative takes on a whole new meaning when you see it through the eyes of a child and a family experiencing the profound impact that Voxzogo can offer. Now, this is Chinara. She's a child with achondroplasia from Sri Lanka, and she was initiated on treatment at six months old in one of our studies. Now, the picture on the left is Chinara at three years old, and on the right, you see at her - at her current age of five. And it is really hard not to see the visual impact of her treatment. But I think what's most meaningful is actually what we've recently heard from her mother. Chinara is proudly going around stating that she's independent, and she can take care of herself in ways that she... that her mom knows she would not otherwise have been able to do without Voxzogo treatment. And it's probably the things that many of us at her age took for granted. It's things like washing her hands in a sink, sitting on the same chairs that her friends do at school, climbing on the rope structure in the playground. These are all the things that's giving her the life that she's really enjoying and something that we're really proud of to hear. I think you can probably hear it. I'm extremely proud and honored to be a part of the work that we do here at BioMarin. We have an incredible past in transforming the lives of patients, of redefining treatment paradigms, and importantly, of building markets and countries, you know, or one country at a time, excuse me. What I'm more excited about is the future and the promise that we have ahead. With that, I'll hand it over to you, Alexander, to close us out. Thank you very much, Cristin. I hope you've all can see why we're so excited about BioMarin's future. So I came to BioMarin very simply to build a great iconic biotech. I mean, all the building blocks were there. I think you can see with this plan. The strategy is going to realize this, to bring value to more value to all of our stakeholders: employees, patients, and shareholders. The first nine months has not just been about assembling this plan. I hope you can see that we're already well underway in terms of the doing and putting this plan into place, making big decisions and difficult decisions to deliver this plan. Prioritizing our pipeline, the Roctavian strategy, the decisions around the five new indications for Voxzogo and the progress we've made there. Difficult but important decisions about structure, organizational model, and cost transformation. We've also made significant and many changes to our leadership team, and now we have the team in place to take this strategy forward and to deliver for all stakeholders. Bottom line, this plan is already well underway to being realized, and I think you can be confident that this is not just about a plan going forward. We're talking about the future, but based on our performance so far in this nine months, the decisions we've made, you can be confident that this team is gonna deliver. So in summary, this is the differentiated, compelling investment thesis for BioMarin. First, top quartile biopharma revenue growth. Second, doubling of non-GAAP operating margin. Third, prioritized innovation, focused on innovation that delivers the most for all stakeholders. Fourthly, optimized cash flow and capital allocation. And with that, we'd like to transition to Q&A. I'd like to invite up Greg, Cristin, and Brian to join me on the stage. Hank is gonna join us virtually. Just give us a moment to get the chairs up on stage. And if I could ask people who'd like to ask a question, we're only gonna be taking questions in the room. The folks who would like to ask a question, if you could please introduce yourself with your name and your organization, please. Thanks. Sorry. Good to see you again, Alexander. Hope you had a good run this morning. I did. He ran by me in Central Park about twice as fast as I was going. Thanks. Paul Matteis from Stifel. I wanted to ask a little bit more about the assumptions in the long-term revenue guidance. Specifically, can you share as to whether in your internal model you are contemplating competition, garnering some share? And then second, do you need to have successes from the higher-risk portion of your pipeline outside of Voxzogo in order to get to that long-term CAGR? Thanks. Great. Thank you very much, Paul. Brian, I'm gonna hand it over to you to answer. Yeah. Thanks, Paul. Appreciate the question. I'll work backwards. So, as I mentioned in my remarks and as indicated on the slide, we do assume some contribution from the launch of the pipeline products. However, because they're coming later in that cycle, and are, you know, just in their early launch phase in this overall timeframe, they are a smaller contributor. It's part of why we kinda gave not a specific range, but talked about the long-term CAGR expected growth rates in terms of that mid-teen. It allows for some variability in timing and whatnot. And I'm sorry, the first part was- Competition. Oh, competition. We do, we do have a competition assumption in this guide. Do you think you can quantify or, like, speak to at this time? Not at this time. I would just refer to Cristin's comments that we're confident that Voxzogo has the ability to actually grow through competition for the reasons noted. Thank you. Hi, Ellie Merle, UBS. Thanks so much for taking the question. In terms of Voxzogo, just curious how you're thinking about pricing long term as you expand into a much larger population? And I guess on a related question, but perhaps clinically, do you have any reason to believe that the dose levels might be different across some of the different indications? There's some, you know, scientific literature that suggests some of them might be more responsive to Voxzogo, for instance. So curious how you're thinking about that. And then last question on pricing with Voxzogo, just what are your assumptions in terms of the length of exclusivity here? And if the weekly formulation were to not be successful, how long do you think you would be able to get sales in these expansion indications? Thanks. Great. Okay, so I'm gonna ask Cristin, if you could- Pricing. - handle the pricing questions. Yeah. And then, Hank, if you can hear us, I hope you can. If you could handle the dosing questions, that would be great. Yeah. So thank you very much for the question. We, of course, as we were looking at these potential opportunities, did a lot of pricing research. I don't know if that's mine. Did a lot of pricing research and feel very good about where we've netted out. I will say that, you know, there is, we are very clearly positioning ourselves after growth hormone use in some of these bigger indications, which I think is in part because that's where we believe the highest unmet need is, and of course, that helps to retain value there. We have looked at what would be, as you expand, especially in European countries, you do take a little bit of a discount based on expansion, and we've built that into our model. I think that we've done the right amount of research and feel good about where we've landed on the model, and again, I'll just emphasize with the confidence around the greater than $5 billion in 2034. ... Hank, can you hear us? Can you... Yep. Thank you. Yep, yep. As regards dose and other indications, in fact, that is why we're going to do a phase II dose ranging studies in idiopathic short stature, and in the bucket of Noonan's, SHOX and Turner's. From Dr. Dauber's data, he saw really dramatic increases in annualized growth velocity, in just those few patients that were reported, so that reinforces the need to establish the proper dose. I omitted, by the way, if you give me one minute of liberty, to welcome Greg Friberg. I did want to especially say thanks to Greg for taking on the continuing journey. Greg is the... is a translational physician who has the same sense of urgency and passion for making a difference in the lives of other patients. And so welcome, Greg. Back to the room. Thank you, Hank. ... Can you hear me? Oh, perfect. Yes. Could you speak further to how de-risked the program is based on the data you've seen to date, and recognizing the clinical trial requirements and the TAM that you provided, what is your understanding on the addressable commercial opportunity here? And then with the Duchenne program, that's where we're gonna see data in 2025, maybe help us understand what we should expect and your level of confidence based on what you've seen to date. Okay. Hank, did you hear those questions? Otherwise, I can summarize. I did. I did. Great. Salveen, our confidence is. Well, first of all, dystrophin levels from SRP-5051, from Dyne, have all been in the low-mid 5%, somewhere around there. And as I showed you from our preclinical studies, we're capable of getting up to 50%, 40% preclinical. Now, the key question is translatability. And the thing that's hard to handicap in that regard is the impact of going to the second site. Now, those other programs have not reported intramuscular concentrations of their drug, nor have they reported, at least to my knowledge anyway, the amount of nuclear translocation from the internalized drug into the nucleus where skipping can occur. Whereas we've documented that. We've documented muscle concentrations and nuclear trans and accumulation in the nucleus of the cell. So, we don't fully know why they're unable to get to higher levels of dystrophin. Maybe site one is saturable, maybe there are problems in delivery, intracellular delivery, but our confidence is driven by actually measuring all of those steps, leading to substantial exon skipping and dystrophin production. As I said, 5% has been about where they are, and we'll look at our first biopsies and see where we are in the early part of the year. There was an ISS question. Yeah. Sorry, Hank, did you hear the ISS question as well? Nope, sorry. Okay, it was about the data you've seen in, we've seen so far with ISS in terms of the proof of concept and our confidence then, in terms of the total addressable population we're talking about and our ability to penetrate, you know, that large market opportunity. Yeah. Well, again, our confidence in improving outcomes in children with ISS derives from genetic data that I showed you, the master regulator of bone growth, the fact that patients who are exposed to CNP end up being taller than average stature. And then the preliminary data that we've seen, not—it's. The data are not preliminary, but it's a relatively small number of children who have, you know, who have mutations that are that would be considered ISS. As our understanding of the condition of ISS evolves, we actually realize that ISS is actually a collection of either rare monogenic mutations or the accumulation of relatively more minor polymorphisms that contribute to short stature. But regardless of the background of the etiology of the condition, we expect that CNP will have a profound effect, particularly in those children who have more severe forms of statural impairment. And then, David, do you want me to? Really quickly, I'll just reiterate on ISS that, you know, when you look at that TAP, as you'd specifically asked about, what we know from market research is only about 10%-20% of patients seek treatment. And so we've taken that into consideration, as well as then looking at how many of those patients will either be intolerant, like they'll have intolerability issues with growth hormone or have a waning effect over time, and that would be the patient population we'd be targeting. Hi, Phil Nadeau from TD Cowen. Three questions from us. First, on business development, thanks for outlining your strategy. We're curious to hear you characterize your sense of urgency for doing business development. Obviously, there's a lot of expansion opportunities in your current portfolio, but the late-stage pipeline's maybe a little bit more thin than it has been in the past. So curious to hear a little bit more about your desire to do the deals. Second, on the $500 million of cost savings, could you break that down between R&D and SG&A, roughly? Then last, on the enzyme therapy growth, one thing you didn't mention is pricing. What role will price play in the acceleration of growth, and has BioMarin's pricing strategy changed for that portion of the business? Thanks. Great. Thanks very much. I'll handle the BD one, then transition to Brian, and over to you, Cristin. So with regard to BD, you know, we're very excited to have James Sabry joining us. You know, he's, we, you know, we've constantly been screening potential opportunities, just like any company does. We have not done, as and many people here know, we have not done late-stage transactions. We've focused really our BD activity on early-stage stuff. We really see that opportunity to expand that perspective. And you know, James will be joining at the beginning of October. You know, we're gonna make sure he really gets to understand what is our right to win. You know, the deep scientific expertise we have in genetic medicines, together with our right to win from a manufacturing and a commercial standpoint. You can tell it's gonna be really grounded on that we're gonna be focused on. So really want to get him on Board and for him then to really see those opportunities. And you know, I think this is a real opportunity for us. We've got these capabilities and this right to win. We're generating cash. We've got a very exciting plan without it, and I hope that really comes across from the numbers we share. But on top of that, if we can do really smart deals with our right to win, let's do it and produce even more impact for patients and value for shareholders. Brian, I'll hand over to you. Yeah. Thanks, Alexander. Thanks, Phil, for the question. We're not breaking out today the cost efficiencies among the G&A or P&L line items. There's probably a bit of triangulation you can do from, you know, last year's margin, kinda the way this year is playing out into those 2027 targets. Some of them will be very clear, like, you know, COGS efficiencies. Those are gonna affect, obviously, gross margin directly. The portfolio prioritization decisions, those are mostly research and development impacts, global business services and procurement. That's gonna be across the enterprise. So, it's part of why we showed that chart and that table. You know, you can probably start to bridge it a bit yourself, and we'll look forward to giving more color and updates, by the way. That's part of why we wanted to provide that level of specific detail today on our operating margin plans, so that we can both update you on our progress along the way here, and you can hold us accountable to these targets. Thanks. I just wanted to add on to Brian's comments. I mean, you saw the hexagon slide with all the different cost transformation efforts that we have rolling out from now, some already done, some future-oriented. You know, for example, you know, global business services, that is the one that's the furthest out. That is actually really quite small in terms of its contribution to the $500 million. The stuff we've already got eyes on, already made decisions on, things like org model, R&D prioritization, et cetera, those are underway, and we have enormous confidence. So, I would just say the procurement efforts, this is really bringing to BioMarin, you know, industry-standard, best-in-class procurement practices that haven't yet been done at BioMarin. It's been very much focused on getting these products to market and growing a biotech. We're now at the point of maturity, where it's really important that we do these sort of best-in-class industry sort of practices. So these are very, very achievable, these operating expense expectations that we have in this plan. Cristin, over to you. Thank you for the question, Phil. So on the pricing component of enzyme therapy, so first I want to start off by saying our pricing philosophy has not changed. We believe in setting the price at what is commensurate with the value of the innovation. But speaking specifically to the growth trajectory for enzyme therapies, we really did focus a lot of that work on demand generation. So really, it's the bulk of that growth is coming from volume. There is a pricing component, but it is certainly not a large contribution there. Maybe I'll just shamelessly add something to Phil, your part on COGS, since I'm here. We've been working at this for the last couple of years, and so those COGS efficiencies that Alexander and Brian were talking about are now just flowing through the P&L. They've already happened, yield improvements, all the things you can think about. So they're starting to flow through now, but they actually were started several years ago. So that's why the confidence is relatively high on executing that. Cory Kasimov, Evercore ISI. So I wanted to ask about the expansion of Voxzogo, and really appreciate all the color you provided here today. So when you consider this $5 billion- plus opportunity with modest penetration, can you speak a little bit more to what you mean by modest penetration? And then maybe also talk about your expectations, with regard to the typical patient's kind of urge to seek treatment in these other indications beyond achondroplasia, maybe how that might eventually compare with what we see in achondroplasia today. Thank you. So yeah, so I appreciate the question. Thank you very much. So with regard to the urgency to treat, I think that that is something in particular beyond achondroplasia. I think that that is something that we will likely see grow over time. And I say that because that's precisely what we've seen in achondroplasia and you see in different disease areas, which is when there's a really valuable treatment option available, you see that urgency to either switch from a current therapy or, go on to something de novo, I think, enhance over time, and that's precisely the type of market development activity that we wanna do in the preliminary stages of development. Now, specifically to achondroplasia, penetration, and what have you, I'm sorry, the specific question was how we see the penetration now? Yeah, you talked about sort of modest penetration in that $5 billion-plus number. Yeah. If you can kind of speak a little bit more to what you mean by modest penetration? ... I mean, at current state right now, our global penetration is under 20%. If you look at it globally, amalgamation across all countries. We believe that we can drive higher penetration, especially in some of our strategic markets, where we can, based on the importance of this treatment, based on what we're seeing in our market research, as well as in the conversations we're having, where people are really starting to see the impact of the therapy, especially as we mature a little bit, following our launch. We're seeing that grow over time, and we anticipate we can get higher penetration, in particular, much higher penetration, in particular, like markets like the United States, where we have now the infancy label, we can now expand on that, and we're gonna see a difference in the penetration over time. In the international bucket, where we're talking outside of what we've called those strategic international markets, that will always be more limited by nature. But we're really kind of focused in different ways at the different pockets of the countries. Thanks very much, Cory. I'll just add, you know, we've tried to be very, very realistic when it comes to the TAPS for each of the indications. You can see, for example, for hypochondroplasia, where we talk here about a TAP that's lower than the prevalence that has been discussed up to this point. You can see it with ISS. We've really looked at the diagnosis rate, looked at the severity cut by that population as Cristin talked about. So we feel very comfortable with these TAPS, and then, you know, that walk down, you know, I think the potential for skeletal conditions to be in excess of $5 billion, we feel really quite confident about. Hey, good afternoon. Thanks for taking my question. I'm Debjit from Guggenheim. So just two questions for me. Firstly, on your BD strategy, the $1.5 billion that you're sort of earmarking, is that a 2027 kind of a number, or is that going out to 2034? And when you think about BD, what kind of risk are you willing to take? And are there specific indications that would be more logical fits to the pipeline? And then on Voxzogo, U.S. penetration is a lot lower than, say, Japan, Germany, etc. Is that a pressure from Little People of America? And as you think about expanding into Noonan's, etc., where there is growth hormone use, do you think that materially moves the number to higher penetration? Thank you. Great. Thanks very much for the two questions. So I'll handle the first one, and I'll ask Cristin to handle the second one. So with regard to BD, the $1.5 billion target number is really to give you a sense of kind of what we're gonna be prioritizing for the next several years with regard to BD. So really focused on making sure that we're really building the muscle. We don't wanna, we don't wanna run before we can walk here. We think, again, we've got a really good right to win, and the assets are gonna be more valuable to us than they're sitting right now. So we're gonna get James in here, and he's gonna really understand that, and we're gonna start to build that muscle and see the value that we can create. Maybe handing over now to Cristin. And I think specifically in terms of the penetration in the U.S., I think one of the major headwinds relative to the other markets where you see much higher penetration has been honestly in the way that care is coordinated in the U.S. So you have geneticists, you have your pediatric endocrinologist, and you have general pediatricians, all of whom are seeing patients and children with achondroplasia. And so what we've really tried to focus in on, and I think that we're really zeroing in to some meaningful strategies, is how we generate the right level of awareness across these different types of treating physicians and importantly, drive the right referral patterns. So if it's a general pediatrician who may not be comfortable or as aware of treating with Voxzogo, make sure that they know where a local treater is in order to ensure that that child is put into the right treatment center. So we've really been focusing in on that and ensuring that we have that broad awareness and appropriate understanding of the treater base. In the U.S., I'd say that that's been the biggest challenge, not to mention then the recent expansion that we got with the label in terms of the age group. We are having conversations with LPA, very much listening to what they have to say and believe that we've built that into our plans. And what we hear from talking to advocacy groups is really important to them, is not just height. Exactly But it's all the other health benefits. You saw Hank's slide with the data from Johns Hopkins is really telling. You can see why it's so important to them beyond the height, these very serious comorbidities associated with achondroplasia. And you can also see from us, from this presentation and going forward, the amount of data that we're generating that shows the impact of treatment on those other really important aspects. So this is gonna be, we believe, really important, together with the expansion of the age population and making sure that pediatric endocrinologists, and there's a real treatment home for patients. These are gonna be the things I think that give us a lot of confidence that we'll be able to continue to expand our penetration in achondroplasia. Hi, Whitney Ijem from Canaccord Genuity. Just to follow up on the achondroplasia, hypochondroplasia market research, how much of a lever is the once weekly dosing, as we think about the competitive dynamic and the longer-term share assumptions that you're making? And then a follow-up on the BD side, I guess, anything you can speak to at the moment in terms of whether or not or how modality agnostic, I guess you're being as you think about that, particularly in the context of the IRA. Thanks. Okay, thanks very much. So in the market research. Thank you for the question. In the market research, we see very, very clearly that efficacy and safety are what always reigns supreme. So long as, you know, they're having that positive experience, we see that that bar for switching becomes much higher simply because that efficacy and safety and the patient years we have behind it is of utmost importance. Below that then becomes dosing frequency and route of administration. So those things do become important, assuming all else is equal or better with efficacy and safety. With regard to BD and modalities, you know, as I mentioned this, it's a really compelling strength of this organization's capabilities. You know, Greg's organization, the research organization, we can handle multiple different modalities. We've got a great track record. We're able to do that from large molecules to small molecules, peptides, and proteins. So that is not a screen for us. Greg's organization has shown that they can produce those things and produce them reliably, and we can ensure they can get through the clinical trial development and get to patients for years thereafter. Hey, good afternoon, Jessica Fye, JP Morgan. A couple of questions on Voxzogo and 333. So when you say that 333 is intended to enable higher CNP exposure to potentially yield greater growth, is that higher peak exposure, higher AUC, or maybe both? And how much window do you think you have to do that while avoiding hypotension? Is there confidence that you can go higher there safely? And then maybe following up on Ellie and Salveen's questions, for Voxzogo and ISS, where you talk about that 190,000 addressable patient population with Z-scores at least 2.5 standard deviations below average. I think you mentioned that about a third of payers cover growth hormone for the condition. Do you expect that proportion could be higher for Voxzogo? To the extent you're not going after growth hormone in ISS, can you talk about your confidence in preserving price? Thanks. Okay. So first part, Hank, did you hear the question with regard to peak AUC? I did. Good. I did. So, the concept of the long-acting is to avoid high levels of Cmax, which could trigger cardiovascular effects, and achieve a better level of growth through sustained exposure and higher AUC. And then with regard to the question, ISS. So, to your point, I do think that we might see more coverage when a very effective treatment option comes onto the horizon. That could be, that is not what we put into our assumptions, but that's certainly something that could be. And based on our payer research, based on what we believe the TPP, the target product profile, could be of Voxzogo, we feel confident in the pricing assumptions we've put into the model. That we could in fact, That we are because we're targeting those patients for whom growth hormone therapy is not effective, that this does allow us to have some value preservation. Really, this is the starting point- Absolutely ... for this point where we are in the development of Voxzogo in ISS. So obviously, we're one of the arms in the phase two study is growth hormone. When we look at the proof of concept, the data looks really good, but we need to see comparative data. So we think, again, this is a realistic starting position. Obviously, we need to, and this is very much part of your question, we need to make sure we balance the penetration, but also take into account the value proposition and the impact on price. So we think this is a good going-in position, and then, you know, let's see how well Voxzogo performs compared to growth hormone. Joe? Joe Schwartz at Leerink Partners. I heard you say that BMN 333 has similar chemistry to other approved drugs for prolonging half-life and maybe getting weekly dosing. Can you talk about what the chemistry employs exactly and/or what those drugs are? And then, how does Pemazyre's potency against the mutant variants that are most common in hypochondroplasia, ISS, Noonan’s, et cetera, compared to those which are most common in achondroplasia? And have you seen any data or been able to generate any data that gives you any insight into the relative potency of the FGFR3 inhibitors across these different indications? Thanks, Joe. Hank, did you hear those questions? I did. Thank you very much, Joe. So the concept of BMN 333 is there's a fatty acid that would bind it to albumin. There's a linker that connects the fatty acid to BMN to CNP, and that linker is hydrolyzable. We haven't disclosed what the linker is, although its chemistry is similar to a linker that's been in humans and actually had a lot of dialogue with the FDA about that, and they seem confident in the approach that we're taking. Now, your questions about the... If I understood them, about CNP's effect over a range of different types of mutations in hypochondroplasia. Now, the important thing, if I got that question right, is that CNP's action is independent of what's going on in the FGF side, but operates at a different level of the pathway, and therefore, is expected to be effective across that entire range of mutations. As regards the potency of different FGFR inhibitors on different types of mutations in hypochondroplasia, that's actually been published on, and the dominant mutation that occurs in hypochondroplasia is expected to be somewhere around two- to fourfold less sensitive to the current generation of FGFR inhibitors. And so what that could mean is that if you wanted to get a similar effect of an FGFR inhibitor against the common mutations in hypochondroplasia, you might have to raise the dose two- to four- or higher fold. That, of course, is when you're gonna really start to see alterations in phosphate balance. That all, taken together, all of that is why we're extremely excited about how CNP pathways can affect beneficially hypochondroplasia and beyond, because of its operating through a different pathway in which high gains can be safely achieved. Thank you. Mm-hmm. We have time for one more question. Two more questions. Okay, great. Gena Wang from Barclays. So two questions. I know we talk a lot about Voxzogo as a main driver. So what is your defensive strategy if a competitor long-acting CNP also show similar, say, efficacy and a safety profile? And a second question, I know you talk about, you know, the potential BD strategy. You put price tag less than $1.5 billion, and giving a lot of the criteria you list out, does that mean the acquisition target could potentially be early-stage asset? Great. So I'll handle both questions. So with regard to competition, what gives us confidence against a potential long-acting competitor, I think, you know, is our start in the market, our capabilities. As Cristin outlined, what physicians and parents want is to start treatment as early as possible. So that gives us a further extension of leadership in the market to really establish ourselves. In addition, and I think this was, you know, has not been picked up so far in the questions, is our confidence in our intellectual property. So it was on one of the slides, we saw that there were opposition proceedings that we participated in, where our intellectual property around our CNP- 38 patent was upheld by the European Patent Office. We also saw, we also, in the United States, sought the re-examination of our claims with regard to our patents. And we're very confident from these two things in our intellectual property with regard to long-acting forms coming on the market. So whilst we... You know, what we know right now, and we've seen, of the Ascendis program, gives us confidence that this, that they would be infringing our intellectual property should they come to the market in United States or Europe. Hi, this is Katherine Wang, here for Akash Tewari with Jefferies. For your DMD corrector, BMN 351, what's the potential for accelerated approval here, given it looks like Dyne is going after AA? Additionally, what's the bar regarding expression for AA and to being materially better than the current products in development? And also, do we know if the full-length dystrophin your product is creating is more functional? Thank you. Great. Thank you very much for the question. Hank, I hope you heard that. I did. You know, so the, I think the key to achieving an accelerated approval will be several fold. One fold is to have compelling evidence of increase in dystrophin. And part of compelling is the magnitude of the increase, and what you're seeing so far are much smaller levels of dystrophin increase. And I think another element of compelling is gonna be the accompaniment of functional effects that are as unequivocal as they can be. I think when you look at people walking around with the, what would be the skipped wi-- you know, in the wild, these people have levels of dystrophin that are north of 10%. And so I think it's gonna... I think, you know, you can get a regulatory approval today with, you know, modest levels of dystrophin increase in the 5% range, with modest evidence of functional benefit. But I mean, I think if you really want a facile approval, much higher levels of dystrophin together with much more objective evidence of functional benefit are gonna be really compelling at a health authority level. And I have to say, not just in the United States, most of these products that we're talking about are not yet approved in Europe, and I think higher levels of dystrophin expression together with more compelling functional evidence is gonna compel regulators around the world. Great. And with that, if there are additional questions, please don't hesitate to reach out to our investor relations team. Thank you all so much for attending today. I hope you're excited about the vision and outlook for BioMarin. We look forward to keeping you updated on our journey forward to deliver much more for patients, for our employees, and for shareholders. Thank you very much.