Alrighty, I think everyone's just getting in. Day two of our London Healthcare Conference. Great to see everyone. Always really appreciative of the attendance. My name's Akash Tiwari. I'm a pharma and biotech analyst here at Jefferies. I have the pleasure of hosting the BioMarin Management Team. Alexander, why don't I hand it off to you for some intro remarks, and we'll get started. Great. Excellent. Thank you very much. Can folks hear me okay? Good. Thanks very much for joining us. Thank you for your interest in BioMarin. Actually, at the beginning of next month will be my two-year anniversary as CEO of BioMarin. I just wanted to, you know, this is always a period where you hit a milestone like this of a degree of reflection. We've done a lot of things, made a lot of changes. I think we're in a period of execution now of those changes. One of the things we've done, we reorganized the strategy around three pillars, around growth, driving growth from our existing portfolio, innovation, our pipeline, supplemented by business development, and then value commitment, realizing greater returns, increasing profitability, cash flow, free cash flow from improving our operations. We identified $500 million of cost transformation. A lot of that we've dropped to the bottom line to improve that cash flow, strengthen the balance sheet. We've also reinvested into the growth drivers, into that pipeline. We're now, as I said, into execution phase, growing that current portfolio. We're entering now a really interesting, and it's great to have Greg here, the Head of R&D, 14 months into the role. We're now into a period of pipeline readouts. What can you look forward to in that? We've got BMN 351 for Duchenne muscular dystrophy, where we're on the verge of, by the end of this year, we'll be sharing the top-line results of that program. At the beginning of next year, we've got the readout, the phase III data of hypochondroplasia of Voxogo, which will be another growth opportunity, the fourth of five additional indications that we're pursuing for vosoritide or Voxogo. We have the phase three readout for the 4.0.1 program. This is the program that we acquired as part of the INNERZYM acquisition. In addition, we have the pending approval by the FDA with an FDA action date of February 28 of next year of Palynziq in adolescents, which is an exciting additional growth opportunity for Palynziq. Palynziq is already growing at just over 20% this year. This will be another additional growth leg for that. There is a lot to talk about, Akash. I'm looking forward to hearing your questions. Thank you. Actually, I'm going to start, you know, we'll get to the guide, we'll get to the products, but I wanted to talk a bit about the unique BD environment we're seeing right now. You know, I've had two companies where there was a public offer and then there was a topping bid, and it is annoying for me to deal with, but nonetheless, you don't see that typically. I think the question I have for your team is, you know, there is this kind of dynamic of, you know, people who have cash and you have about $2 billion in terms of flexibility, but then you might be competing against a mega-cap company where they might have a limitless balance sheet, seemingly, in terms of getting an acquisition done. How does that concern apply to your team? Because, you know, you're new, how do BDs come in? You guys have talked up external acquisitions. Do you feel like it has been more difficult for you to identify assets that you find compelling and pay a price that makes sense? Or actually, that's not the case. Yeah, you know, we have built a world-class BD function. We do think that BD is a real opportunity for future growth to supplement our internal innovation. The space we're playing in, I mean, let's be really clear, we're focused on genetically defined conditions. We've defined that. That is an absolute requirement for anything we look at from an external standpoint. That is a segment that we see little, relatively little competitive pressure in terms of other people hunting after the same assets. They require very specialist expertise, just for the very nature that these end up being a little bit smaller opportunities or smaller opportunities than will move the needle for the big pharma players that are, you know, the actors in the play that you're watching and enjoying watching. We do not see that same context with the companies and the assets that we are talking to right now. Understood. And to me, you know, you're kind of thinking about like peak sales and risk adjustment. I can't help but think, Alexander, you're thinking, give me a Palynziq Voxogo-like opportunity that fits into this business unit approach, right? Genetic to sort of skeletal muscles, skeletal conditions, and then enzyme replacement. It seems like that's the kind of sweet spot. And then either pre-commercial or just launch. I mean, is that the right framework we should be thinking about in terms of external BD? Yeah, you've largely got it spot on, Akash. I mean, we're, you know, BD is about, for us, supplementing, you know, the growth rates in the medium term. That's what we're focused on doing. We don't need to buy revenue. We don't have any large loss of exclusivity events. We believe that actually assets are worth more in our hands than where they're sitting right now. There's lots of under-resourced genetically defined disease or rare disease companies. Why do I say that? Actually, the prevalent populations for these genetic conditions sit outside the U.S. and Europe. This is a footprint that we're in 80 countries. It's absolutely remarkable. We built that up over 20 years and occupied it with our enzyme therapies and Voxogo. That's where the patients are. These companies don't have that sort of geographic presence. I'll give you the example of achondroplasia, which is Voxogo's first indication. 68% of patients are outside the U.S., Europe, Australia, Canada, and New Zealand. 68%. You need that geographic footprint. We have that. Others do not. That is just one element of the capabilities. Our capability advantage is across research and our deep genetics capability, our development, our ability to design studies, regulatory endpoints for these sorts of conditions. Manufacturing, again, many of these small rare disease companies use contract manufacturing organizations. We have our own manufacturing capability across multiple modalities. We can do that more efficiently and effectively. I've already mentioned the commercialization footprint. I hope that this investor audience can see that, you know, there's a real value proposition. Right. As we announce deals, you'll be able to understand the value proposition of how this is going to actually be really good for the growth prospects for the company. Alexander, maybe just a point on that, because I remember last year there was this question of, would you do, you know, you have your long-term guide, would you do a deal that would impair that? I think your answer was like, look, in general, we want to keep our long-term approach. We think that's really important. If there's an asset that we think is super compelling, we're going to have to go for it. I think lost in that kind of nuances, and especially in what you just said, it's about acquisitions that are earnings accretive, right? Talk to me about the importance of, if you are in licensing assets, how does that change the long-term financial profile of the company? How, you know, coherent is that with your long-term guide as well? Brian, do you want to? Yeah, sure, I can start. First, maybe thanks for the question, Akash. Just to start on the financial elements of our transformation itself, those are on track. There's largely two. First is executing on revenue, which we've been doing the last several quarters. Then second was cost, where we've always had a sense of prioritization. It was important through this transformation to fully get cost under control, which we have. That comes with disciplined investments in the right places, as well as operating efficiency, which we're executing. We're, as Alexander mentioned, you know, two-thirds of the way through here now on a $500 million cost transformation. Importantly, you know, it's not just investments or prioritization and efficiency. During this time, we've been able to make actually incremental strategic investments across all parts of the business, whether it be global sales and marketing within the business units or to accelerate the pipeline assets. This was not outright cost reductions, but strategic investments. That is on track. Targeting 40% non-GAAP operating margin next year. That would be a more than doubling of our operating margin back in 2023, which was 19%. Excluding our in-process R&D development charges this year, our operating margin is 33-34% target. That is a substantial improvement. To your question, when faced with the choice of shareholder value creation and those long-term profitability targets, we will choose creating shareholder value. That could adjust where we land long-term margins, but these targets are, you know, solidly ahead of many benchmarks within the peer group. We think we can balance both achieving and sustaining profitability and reinvesting in the business. That's the goal. Okay. Understood. Now, maybe just kind of stepping back, and as a part of that kind of revised tweak guidance, I think there's a bit of confusion about Voxogo's trajectory both into next year and 2027. I'm just kind of thinking out loud. Would you agree if I were to say, I'm very confident, A, Voxogo is going to grow in terms of just net patient ads year over year in a manner that's quite similar to 2025. Number two, in 2027, there are scenarios that we can easily imagine that patient ads in achondroplasia, or sorry, hypochondroplasia, more than offset any competition you face in achondroplasia. How crazy is that framework for you? I would say that we believe that Voxogo is going to continue to grow over the next several years. There's still a lot of growth opportunities in achondroplasia, both in the U.S. and in that global footprint. And then, as you mentioned, you know, in 2027, if we're approved, we have the hypochondroplasia launch. So we think there's sources of growth and, you know, plenty of opportunity for the drug to continue to grow through this timeframe. You know, with regard to the, you didn't directly ask the question, but with regard to the 2027 guidance, you know, there's a lot happening, obviously. You know, this is the big question, is the competitive question around Vox. There's a lot happening over the next several years. We thought it was useful. We had this 2027 guidance. Rather than saying that's a point estimate, there's a whole range of scenarios. Sure. We decided the most useful thing was to communicate a range. That low-case scenario is not a scenario that we believe is the most likely. We said, okay, what if there are two competitors that take substantial share from Voxogo? What does that mean? Obviously, also backing out things like Roctavian. That translates to a number which is really in line, actually, with your own perspective on 2026. That is our low case. That is not what we believe is going to happen. We are confident, back to the first part, or your question in the first part of my answer, we are confident that actually Voxogo will grow over the next several years. Understood. You know, actually, I'm just thinking about this. There seems to be kind of a, you know, what I find kind of amusing, maybe a little sad, is you have other CEOs that are entering in the space, and they are convinced that there's going to be this kind of explosion for their programs. It almost implies not only is Voxogo's share just going to go to zero in a way that I just don't think maybe makes logical sense, but there's also just that there's just patients out there that we're not seeing, right? From my perspective, there seems to be kind of consistent patient ads we see in achondroplasia. In a lot of your markets, you're going from kind of a prevalence to an incident type of framework. You've done a good job talking about, you know, 70% of your patients are XU.S.. If you were to tell me, like roughly speaking, how much of the markets you're going in an incident market where you have a zero to two label versus a prevalence market where there's still kind of room to expand? Help us understand that. Yeah. So, you know, there are obviously different markets in different stages. You know, we're still launching. We're now in 55 out of the 80 countries. Again, that's part of how we're still growing. Obviously, those sorts of markets, new patients come from all different age groups. In more mature markets, this is very much an incident market. The majority of patients with achondroplasia in many countries are diagnosed, actually, you know, in some cases before birth, but within days or weeks of birth, it's very evident, unfortunately, the disease presentation. We will be, you know, we have the zero to two indication. To be determined how long it will take the competitors to get that indication. In many markets, that is the incident population. Yeah. Competitors will have to switch in the more penetrating markets. They will have to switch existing patients. And as you know, and I think you're intimating with your question, you know, switching patients that are doing well on a treatment as they are on Voxogo, you know, the safety profile is very well established. There's a lot of confidence amongst prescribers and caregivers around the profile of the product. You know, is not a straightforward proposition, I would say. And, you know, I think this is a topic that, you know, the implied valuation has got wrong. Yeah. This is not a zero-sum game. Again, in our low-case scenario, which is not the one that we believe is the most likely, we've taken that into account as it sits right on top of consensus that reality is going to be somewhere in between. And, you know, yes, there will be some patients to switch, but there will be many that decide to continue because they've seen great results with Voxogo. I'm going to dig into that. I think it's quite important as we get into the extended approval. That decision's coming up soon. Look, again, I have a horse in this race, but I can't just help but think it's hard for me. Like, I look at the multidisciplinary review for Voxogo. There are age-match analyses that were done. There are ways that the FDA cuts the data. Some of those analyses end up reflecting what's in the label. We're in this kind of, I think, surreal scenario where if it's 0.3 or it's 0.1, 0.5, 1.3 versus 1.5, there's a perceived meaningful difference in terms of impact to your franchise. Do you feel like there are scenarios where the ascendist label could show efficacy that looks numerically worse than Voxogo on an age-match basis? Greg, I'd love if you could comment on this in terms of switch. What is the label that you anticipate them getting, given that they did run a different clinical trial? Yeah, it's always a little bit tricky. I never like to speculate on how the regulators are going to view data sets. You're correct. They will be looking at individual patient-level data, both with regard to efficacy, but also with regard to safety analysis and how preferred terms are bundled, for example. Our experience would suggest that for accelerated approval, for example, the indication statement that we've received is a, you know, probably the most likely regulatory outcome, though, again, I don't want to speculate, again, where the regulators will end on that. Beyond that, you know, what we have in Voxogo is we have almost 10,000 patient years' worth of data at this point. That means, of course, not only are we talking about one year or two years of efficacy, but we can extrapolate that out to seven, eight, nine years. We can talk about tibial bowing in a meaningful way, intrapedicular distance for hopefully prediction and prevention of spinal stenosis. That is a data set that we want to continue to publish on. We want to own the information that we have. Voxogo is a safe and effective drug. All of that data is something that we think will be valuable, certainly to patients and physicians, absolutely to payers. Okay, so just to hit on that, we get into this question of full approval for Voxogo and, you know, final adult height and whenever when does that end up getting reached? Could you potentially make an argument to the FDA that we shouldn't just look at final adult height when you're thinking about that decision, but maybe more holistically looking at some of these other kind of secondary biomarker-driven endpoints as a part of a full approval decision? Could you be having that discussion with regulators right now? This is absolutely something that's on our mind. Final adult height is driven by a mathematical calculation and negotiation with regulators. Anytime we engage with regulators, it's an opportunity to put in front of them the totality of our data, which we think, again, will help prescribers and patients make an informed decision. We have a wealth of data from that 10,000 patient years' worth of safety and including following up on many efficacy endpoints. You can be assured that those are going to be active discussions. We are very much looking forward to having those discussions with regulators around the globe. Okay, understood. Maybe just lastly, you know, there is a regulatory and IP discussion to be had here. You know, you guys have seen my research. I'm personally a little skeptical that, you know, you had a citizen's petition that perhaps a citizen's petition would be able to block a competitor product from getting onto the market. To us, we dealt with this with Jazz and Abidel, where you had a once nightly, and that still got approved. I think one of the things that maybe doesn't get caught in that discussion was there are two separate decisions that get made by the FDA, right? There is a separate division that makes a decision on granting both exclusivity and designation. Then there's a separate part of the FDA that actually grants approval. I think if we look back at the Abidel scenario, there was a delay in outright approval as you waited for the actual ODE decision. Is that an angle we should be thinking about here with the citizen's petition? It's not just as binary as launch or not, but maybe potentially a delay. Again, you know, just like Greg, I don't really want to speculate on what the FDA will or will not do. You are correct. It is a separate part of the FDA. I think we're all, you know, professional. We've always been professional FDA watchers, but trying to understand kind of how decisions are made at the FDA right now. What I would sort of reframe this, this is, you know, we feel convicted under the importance of the orphan drug exclusivity to incentivize companies like us. We've now had, you know, six first-in-disease treatments. We know how important orphan drug exclusivity has been for the business case for ourselves and for others to make progress. We think we made a strong argument. We will only know, obviously, that outcome at the point of approval. We'll find that out at the same time as you do. It's not the only arrow in our quiver. We also have ongoing litigation in front of the International Trade Commission with regard to the U.S. We've got traditional IP litigation as an option in the United States on a point of approval. In Europe, there is also the possibility of additional IP litigation around new patents which are pending at the European Patent Office. We've got, you know, I think primarily the focus of this conversation has been competing in the market with very satisfied patients, additional indications driving additional growth, our global footprint, our indication zero to two. In addition, we have this myriad of ongoing litigation, which I think investors should keep one eye on. Understood. Now, maybe going into hypochondroplasia, can you talk about the size of that population relative to achondroplasia? Because, you know, there are degrees of severity with hypochondroplasia. And then number two, you know, the Dr. Daber data so far, I mean, it looks just as good in hypochondroplasia as it does in achondroplasia. What are, can you give us directionally your powering assumptions for that trial and what you expect on average growth height velocity? And then maybe lastly, you know, what investors love to know is, is there warehousing? Have you identified patients? Could this be a bolus launch? Because it's the same doctor. So how immediate is that commercial opportunity for you, let's say if you get approval in 2027? Okay, I think there's three questions there. I'll take the first and the third, and you take the second. Okay. With regard to the first, in terms of the size of the population, we think the genetic prevalence, and, you know, we have quite a good level of expertise here, is approximately the same as achondroplasia. Achondroplasia is about 24,000 patients globally. However, to your point, these patients present later. We think it's likely that it's going to be a more severe subset of these patients, which are really the addressable population. We would encourage you to use a figure of 14,000 patients. That's what we use internally as the addressable market. The work that we have underway right now is to really create awareness and understanding of the disease. You know, people talk about this relative to achondroplasia. I think the important thing is to talk about this relative to patients without those genetic mutations. There's around three to five times the level of healthcare utilization. These kids aren't just shorter, but they have a myriad of health issues. With regard to your third question, you know, there are clearly, this is the same prescribing universe. Pediatric endocrinologists are achondroplasia. They're very excited about the prospect of a first-in-disease treatment for hypochondroplasia. They do have patients that they have tried in some cases in the United States to get reimbursement for and have been unable to because there's no approved indication. There will also be, just like we're now seeing with achondroplasia, you know, the older patients are under the care of pediatricians in the community. The ability to reach and connect with those patients, this is a capability we have that we've developed over multiple drugs using it in achondroplasia where, you know, you get a ping of a diagnosis in a claims data saying that there is a hypochondroplasia patient at a particular pediatric practice. And then we go into action and encourage that patient to be referred into the specialists to get treated. They're already diagnosed to get treated. Very quickly, the study's powered to look for an AGV delta similar to what's seen with achondroplasia, 1.5 centimeters per year. That is conservative compared to the Daber experience, which saw more like 1.8 centimeters. I'll also add that the most powerful predictor of AGV change is AGV that you walk into the study with. If you're a slower grower, you have the chance to grow faster. We have refined for patients who are minus three standard deviations or less. Hopefully that will, again, make the powering conservative for what we're looking for. We're out of time. I'm going to stick one more question. I think it's quite important, Greg, can you just comment on how to do an apples-to-apples comparison with your DMD corrector data versus the Dyne and Avidity data sets? I think it's quite important. I think it's important to look at other exon 51 skippers. So that would be Dyne. Dyne has reported the 3.2%, again, not adjusted for muscle or fat content, but that 3.2%, they recently, I believe, commented that they believe over time that that will go up to about 4% at their next level. We will be looking similarly at an earlier time point than steady state. Our goal is that we have a level that will predict 10% at steady state. It's a different dynamic. It's a different timing with the phosphorothioate chemistry. It takes almost a year or more to reach steady state. A level of between 3% and 5% at six months will predict a 10% level out at steady state. Got it. Thank you so much. I appreciate it. Thanks, everyone, for joining us. Thank you.