Voxzogo. So talk about the growth trajectory sort of today, with respect to, you know, underlying patient demand, maybe have manufacturing be a consideration there, and then we'll get into sort of line extensions and the future. Okay, great. Yeah. So I think Voxzogo has the potential to be, you know, in the history books for biotech. I mean, this is the proverbial, you know, pipeline in a molecule. And we're only in its first indication. We only have got so far penetrated, you know, around a third of achondroplasia globally. So the launch has been going extremely well. It's obviously driving the growth of BioMarin, but we're really at the beginning of this journey. The achondroplasia launch has been successful. I think that the thing that I'm particularly excited about right now, which is driving and accelerating our growth, as you can see in our Q1, was the expansion of the indication to zero to five. We now are having babies being put on Voxzogo within days of birth. The soonest after birth I've heard so far is within nine days of birth. And this is great from a clinical outcome standpoint. Obviously, the earlier start, the more time you have before the growth plates to close. But also, obviously from a revenue and a competitive standpoint, this is really exciting because, if a patient is doing well on Voxzogo, I think it's very unlikely that a parent or a HCP will want to switch. And you can see the majority of the growth in patients is now in that younger cohort, and it isn't at the expense of the older cohort. They're all growing. And we're really—again, we're only a third penetrated into achondroplasia, so there's a lot more progress to be had there. And then you mentioned manufacturing. You know, the opportunity in achondroplasia was actually underappreciated by the company, and unfortunately, we didn't have the manufacturing capacity we needed. The team has been really focused on making sure we've got the capacity we need. In the middle of this year, we'll be on track to no longer have supply constrain our results. And actually, our long-term plans for the manufacturing, we're moving them all forward. We've made really good progress. So what we said in January would be our peak capacity next year will actually achieve by the end of this year. And the plans in the years out, as our lifecycle management, which is obviously the next topic we're going to talk, as we come forward with the new indications, we're going to have plenty of capacity to be able to meet demand. Great. Before we get into additional indications, talk a little bit about the lifecycle management with respect to the injection frequency, kind of next gen Voxzogo. Yeah, that's in our R&D prioritization. I was really pleased to see on the merits of the molecule. We did the prioritization based molecule by molecule. What are we most excited about in our pipeline? And also, what should we stop and reallocate the resources on what's most promising? And you saw the results of that in Q1, we announced that. And one of the programs we prioritized was actually the follow-on compound to Voxzogo. So it's BMN-333, which is going to be a long-acting formulation of Voxzogo. It's early on, I'll be clear on that, but we think there's a path to development and approval at least two years prior to Voxzogo LOE. The minimum TPP we have in mind, target product profile, is at least as safe as and effective as Voxzogo, and that's a very high bar, and I'm sure we'll maybe get on to touch on that in a moment, but with the potential for once-weekly dosing. So, I think that is gonna be... It's gonna be exciting. It's gonna be critical from a business standpoint, that as we build up in all these indications to maximize Voxzogo, then we have a molecule coming well before LOE to be able to transition patients in the business over to. Yeah. I guess, can you just kind of tell, remind us of where you are in terms of the additional label expansions for Voxzogo? What should we expect to see this year? What should we see trials starting, as well as design of the pivotal trials? Yes. So, you know, I think this is a very, very important topic to sort of elucidate because I think only a couple of analysts have even hypochondroplasia, and we have all these other indications now planned and making progress on. So hypochondroplasia is the next indication. We're already into our pivotal studies for that. So we'll start the 52. We've, we've, we're well underway with the natural history run-in study for the registrational study. We've got very, very compelling phase II results. Actually, the growth values achieved in that were even better than we achieved in achondroplasia, and the scientific rationale is clear. We've got very clear feedback from the FDA. So, moving into the 52-week treatment arm, middle of this year, aiming for approval in 2027 for hypochondroplasia. So that is in its pivotal studies, and that is well underway, and, again, a really, really high confidence, high probability of success and regulatory success with that. Then, at Q1, we announced that we were moving forward with idiopathic short stature conditions. This is a huge indication. So achondroplasia, just for folks to know, is about 21,000 patients globally. Hypochondroplasia is about the same, around 21,000 patients. Idiopathic short stature conditions is about 600,000 patients. We have clarity from the FDA with regard to the endpoints, with regard to the comparator, with regard to the duration. We have kicked off our Phase 2 study, and we'll do a Phase 2 study and then roll into a Phase 3. And then we have the pathway conditions, and there was also data on pathway conditions in ISS at the Pediatric Endocrine Society, showing really good efficacy and a compelling safety profile. We're in discussions with the FDA about the regulatory pathway, pun intended, for the pathway conditions. That I think will be a really pretty straightforward, probably a basket study. And you know, the exciting thing from a commercial or revenue standpoint is this is human growth hormone is already used, but it's very unsatisfying results. We have every reason to believe, and we've seen data, and it's been shared publicly, that Voxzogo is effective. That will be the next up. So we are, you know, with hypochondroplasia, we're on track. ISS is now loaded and firing, and next up is pathway conditions. So, you know, a whole raft of new conditions, many, many times larger than achondroplasia is ahead of us. No, it's very exciting. I guess, how do you prioritize additional indications? We saw some results at PES, and of course, they look very exciting, so there's a lot to do. Yeah. You know, that's been the focus over the last 5 months, is accelerating those plans. So the existing plans, hypochondroplasia, how can we actually complete those studies and the regulatory process quicker? And then, ISS was, you know, is the largest, and it's obviously a diagnosis of a range of different short stature conditions. And you know, getting clarity from the FDA on that was really important. So that, I think, represents probably the most challenging to navigate. Obviously, a very large population. You wanna make sure that you've got a very compelling value proposition, because you don't obviously want to erode the value that you've created in these other conditions. I mean, the reality is that achondroplasia, the pathway conditions, the level of the severity of the disease is much greater than the majority of ISS patients. So figuring out what is the proportion of the ISS patients that we're gonna be targeting in our study, and again, we have that clarity now. I guess last question here: How do you think about... So you have age expansions, you have additional indications. How does this impact the competitive landscape? Yeah, you know, as we're successful, we're attracting competitors. People see the potential of these diseases. We're establishing... I mean, these, there's no treatment options in achondroplasia or hypochondroplasia with a first. And so it's inevitable there's gonna be competitors. The big thing is getting into these diseases, establishing a leadership position, creating a lot of data, quality of life data, safety data, to really establish yourself prior to competitors. When and if competitors come, they will start in the older kids. If they're lucky, they'll be able to get down to zero, but they won't start out with having the indications from birth. And all of our market research shows that a patient is, a baby that started at birth, within days of birth, and is doing well on Voxzogo, which, the majority of patients do very well, the patients and the, the healthcare provider are very reluctant to switch. So, you know, the, just in terms of the competitive dynamics and the, what's important to both patients and, and caregivers is really, really clear, also from our market research, that safety is a non-negotiable. So a really established safety profile where you're dealing with pediatric rare disease, that is a non-negotiable. Then it's efficacy, and only when those two things are equal, then it's convenient. So I've just... I mean, I think that probably makes sense to people logically, but it's really important to understand those things. So that's why BMN 333, that's why the minimum target profile is as safe and as effective as Voxzogo, which is not a low bar, then convenient. So I'm assuming that if as you target the larger indications, ISS and others, you'd want to have the once-weekly three, three, three fully de-risked? I mean, is there a way... I wasn't sure how you prioritize, you know, the optimization of dosing with, you know, with label expansion in a meaningful way. Yeah. We'll share more about what the different indications and the sequencing will be for 333, but we obviously want to go fast- Yeah. faster to market as quickly as possible. Okay. If its Target Product Profile looks as compelling as we think it is in the preclinical data we've seen, then we'll wanna go as quickly as possible. There are other indications which I haven't mentioned, which we also think CNP could be really important for. Yep. So this is, again, this is very much still we're only at the of the potential of... Right ... of Voxzogo. And I, it's also probably worth highlighting that the FGFR3, ISS and the pathway conditions, mechanistically, there's no scientific rationale. So competition won't be able to follow us into those indications as well. Makes sense. Well, let's switch gears to Roctavian. So, you know, over the course of the, you know, past couple of years, you've spent the, you know, clinical investment, and now you have the commercial investment. You're in, you know, a few major geographies, and you're just starting to see some traction there. But I think investors, you know, have been anticipating this for a while. So help us with where this fits today and maybe in the future in BioMarin's strategy, you know, for, you know, for, obviously not as, not as core as likely as Voxzogo, but overall growth. Yeah, I think for investors should look at Roctavian as a sort of covered bet. Certainly, that's the way we look at. Here we are in Vegas, covered bet. I don't really know. I'm not a big gambling person, so I'm probably not using. But what I mean by it is that, you know, in terms of our plan and our long-range plan, Roctavian is not core to that plan. The guidance that we gave this year, we have a very conservative view on Roctavian, and we're not dependent on Roctavian results. We'll see whether Roctavian manages to take off. I think, you know, there's obviously patient and physician interest in the proposition of living with hemophilia without being reminded you constantly getting treatments. I think that's, you know, that's a compelling proposition. But that site readiness and patient-level reimbursement in multiple different geographies is proving to be challenging. So what we've said is, you know, either we're gonna see this ramp, and it's gonna take a little bit of time to a reasonable level of sales, or we will contemplate either divesting it or partnering it. Okay. So, we will see, but it's again, BioMarin, with or without Roctavian, is a really compelling proposition. Yep. And just remind investors of the geographies that you're still, you know, wouldn't say investing in, but you're following closely. I think you're probably not going to invest in a global launch, you know, at the, based on, you know- That's right. The levels that you did. That's right. We need to- Twenty two ... We need to see the proof of concept from a commercialization standpoint. I mean, obviously, you need to whilst this has been a long journey, and I think a source of pride to have the first gene therapy in hemophilia A is not an insignificant accomplishment. We have to be very focused now about proving the commercial value and the return to investors from this. So we have decided to, in this first five months, to really focus down on three geographies where we have national-level reimbursement. That's the United States, where we have 275 million lives, where payers have said or have got a policy in place to cover Roctavian. Germany, where we have national-level reimbursement and a price, and Italy, where we have, since January, national-level reimbursement and price. So now we wanna see in those geographies, can we see the patients go on therapy at the bottom of the funnel? So, a very focused effort around that, pulling through patients at the bottom of the funnel. Can you speak a little bit about the commercial spend right now and how you might see that moving forward? Yeah. We're spending about $50 million or so a quarter on Roctavian. It's not around half of that, approximately, Brian, right, is marketing and sales. The remainder is R&D. So, that is obviously there's long-term regulatory follow-ups required. We have to follow the patients after the clinical studies, et cetera, et cetera. So it's about 50% of the $50 million per quarter. One of the options that we could have is, and that we're exploring right now is if that ramp is a lower ramp, so not even a revised expectation, but something smaller, is there a level of promotion which is attractive from a profitability standpoint? So, I think that might be, with a very focused effort, that might be a path forward. Helpful. I guess if you're thinking about as well, the 340B centers and the sites, what's the hold up there? Are you seeing any progress in terms of their discussions and actually getting patients on treatment? Because we saw a patient treated in Wisconsin, was it? Green Bay, yes. Green Bay. Yeah. Yeah. Yeah, so, you know, United States, most hemophiliacs are treated at Hemophilia Treatment Centers, which are 340B institutions. They are, in many cases, part of larger health systems. So there's really two things that need to happen for the HTC. They need to agree the split of the economics, the 340B spread with the parent institution, and then they then also need to then contract with the payer around the specific patient. So there's really a two-step process they need to do. So that's what we'll need to start to see these centers doing. This is that there are some challenges, obviously, with gene therapy and high-price therapeutics. There's an additional complexity when you add in 340B, when there's a lot of economics to split between the provider and the payer. I'm sure everybody's getting an education on 340B with this as well and, you know, the U.S. healthcare system in action. ... Where are we in Germany with the national payers and those subgroups as well? Yeah, so in Germany, what has transpired is, whilst we have national reimbursement, and that's usually green lights down the track for patients to then be starting to be initiated. We've seen some of the sub-insurers, which represent various percentages of patients. Usually, it's organized in Germany by types of industries, et cetera, these sub-insurers. And some of them are putting roadblocks in the way of use of Roctavian. So, they're either going back to the providers or they're coming to us, and they're saying: "Look, you know, we're, we need more assurances," or they're trying to hold the providers accountable, which is... There is that possibility in the German healthcare system that they say to the treatment center: "Look, if this patient doesn't do well on gene therapy and needs to go back on prophylaxis, then you're gonna be on the hook." And not surprisingly, the centers are like, "What?" So this is something we need to work through. It's unprecedented in my experience, but we've got a number of different things what we're doing to try and unblock that. You know, this is, it's gonna be something we need to figure out. And Italy right now looks like it's green lights. So the Italians, starting in January, we'll see how many patients flow through. Quite a few patients in process there. Again, we'll have to see. Bottom line for investors is that, you know, regardless of Roctavian, we're confident of the outlook for BioMarin this year, next year, and in the years to come. Can I ask you about the independent of the Roctavian decision, should investors look at the delivery, the AAV technology, as foundational? In other words, is the Roctavian decision going to be affected, going to affect the other pipeline elements within BioMarin that use AAV, or are they sort of independent, kind of evaluated, you know, processes? I wish there was a simple answer to that. I'll be kind of as quick as possible. There are various aspects of gene therapy which are important to consider. As I mentioned, there are long-term monitoring costs. Yep. So as soon as you start dosing patients, you're signing up for years and years of very expensive follow-up. But you know, the challenges on the commercialization of Roctavian are really indicative of the treatment landscape in Hemophilia A. Yep. They're not indicative of gene therapies. So there is still, I think, attractive science, patient impact, and commercialization case for, for gene therapies. We still have some gene therapies in our, in our pipeline. We did stop some of them, but they were based on the merits of those particular molecules. Uh, right. There's no blanket, you know, Roctavian read-through onto other gene therapies. Okay. And just along those lines as well, when you think about the strategic review and, and what you guys are gonna be, you know, communicating to investors, what are the, the sort of levers, or what are the, the inputs for the pipeline? I know you, you've prioritized or deprioritized a few things previously, but are there, you know, indications that you think are more sort of exciting? Are there? Is there potential to bring in other assets, or is it just a function of sort of culling some of the things that look suboptimal? Yeah. So with the portfolio prioritization, we are prioritizing some molecules we think are really, really exciting. Yep. You know, and we'll learn more, we'll communicate kind of the milestones. But for example, DMD 351 exon skipper in Duchenne muscular dystrophy, we've started the proof of concept studies. You know, if those are successful, we have a high bar. BioMarin does this extremely well. It set a high bar, proof of concept. You know, we could potentially file off that study and get to market, you know, in the next several years. So that's very, very exciting. But when we did the prioritization, it was to reallocate some of those resources to things we wanted to accelerate, and that was also includes Voxzogo lifecycle management. As we lay out these different indications we talked about, Alex, you know, they will drive the growth of BioMarin into the mid-2030s. Yep. So, you know, there, there's plenty of growth potentials around that, pun intended again. I'm full of puns this morning. The other aspect I would say is, and you mentioned it, is, you know, we want to. We're in a period of high growth, which we think, you know, will continue for the next several years. We obviously want to sustain growth at a high level. Yep ... out through 2030. We know that's how you build a great company, and you create a lot of value for shareholders. And when we look at what we're prioritizing from our pipeline, when we look at Voxzogo lifecycle management, again, which will drive growth through the mid-2030s, but we wanna actually make sure we're sustaining really high levels of growth. We see this as an opportunity for really focused external innovation and deals, leveraging our capabilities. I mean, we're in over 70 markets. We've figured out how to commercialize rare disease assets around the world. That is not trivial. We know how to get good prices for rare disease, demonstrate the value, get good prices. We know how to access those markets.... You know, there are plenty of companies who have no idea how to commercialize rare disease assets in the United States or around the world. That would be a natural sort of tuck-in for us, maybe on a product-by-product basis rather than necessarily M&A. And then, you know, whether it's Voxzogo or DMD, you know, utilizing our capabilities, our presence in these markets, are there other opportunities which really are logical, but very importantly, that create value to shareholders? We're in a-- This is not like a large pharma, where we have a big patent cliff and revenue is dropping off in the next several years. This is about sustaining high levels of growth and doing really focused business development that really makes sense in terms of taking advantage of the capabilities and our footprint globally. Right. And just along those lines, the core ERT business, I know it's less of a focus for investors, although it does provide, you know, revenue, it provides, you know, obviously, profitability. It's stable. Are there... Within that portfolio, are there assets that you feel like have been underinvested, that you could, you could grow a little bit more? In other words, could something rise out of that, that becomes one of those priorities, or is it, is that less likely? You know, I think this is another aspect of BioMarin, which I think is not fully appreciated, is this ERT and Palynziq business. You know, you say stable. It's actually, as you know, it's growing- Yeah. As you well know, and no end in sight. I mean, this is, this is fantastic. I mean, no inflation reduction impact, no competitive threats that we think are, are gonna dent this growth. And, you know, several billion dollars. I think this Palynziq has additional growth opportunities. We see potential next generation, follow-on in our pipelines around that. We think that's an attractive area. I think the ERT business overall, yes, that, you know, that's gonna be one of the things that the new chief commercial officer, who starts next week, that's one of the responsibilities she's gonna have, is to, is to look to see are there additional growth opportunities. But I think it's probably mainly in the optimization area, in that many of these drugs have been launched for 10 years. You know, can we keep these patients on drug more, more efficiently and effectively? It's a very, very different business and opportunity than Voxzogo, where it's basically blue sky prospecting these new indications. Revenue, operating margin, that will be very, very specific, and then long-term financial aspirations, which will be a little bit more qualitative. To give you an idea of kind of where we're aiming for, the strategy underpinning that, we'll give you the Voxzogo lifecycle management. So very specific, how we see those indications playing out, the milestones. You'll be able to track along with us the progress towards those milestones. We'll give you the size of the opportunities for those indications, which is really critical to your question, Alex. What is the size, what is the value, potential revenue, of those? We'll have our innovation strategy as well, which obviously is really critical, what we're excited about in our pipeline. The role of external innovation, and then we will be very clear on operating margin, kind of how we're gonna achieve that, down to specific initiatives and how they're gonna contribute to us achieving that higher level operating margin. And lastly, capital allocation strategy. 'Cause we're in the enviable situation where obviously cash flow positive, generating cash. It's important we're very clear to investors kind of how we're gonna spend that capital going forward. So, I mean, if you're not planning to be there, you should be. I mean, it's gonna be, it's gonna be great. Makes sense. Well, thanks, Alexander. Appreciate the conversation. Look forward to the Analyst Day. Thanks very much, Geoff. Thanks, Alex.