Thank you for standing by. My name is Kate, and I will be your conference operator today. At this time, I would like to welcome everyone to the BioMarin Pharmaceutical Fourth Quarter and Full Year 2025 Conference Call. [Operator Instructions] I would now like to turn the call over to Traci McCarty, Head of Investor Relations. Please go ahead.

Thank you, operator. And starting on Slide 2. To remind you, this nonconfidential presentation contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including expectations regarding BioMarin's financial performance, commercial products and potential future products in different areas of therapeutic research and development. Results may differ materially depending on the progress of BioMarin's product programs, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market and developments by competitors and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, such as 10-Q, 10-K and 8-K reports. In addition, we will use non-GAAP financial measures as defined in Regulation G during the call today. These non-GAAP measures should not be considered in isolation from, as substitutes for or superior to financial measures prepared in accordance with U.S. GAAP, and you can find the related reconciliations to U.S. GAAP in the earnings release and earnings presentation, both of which are now available in the Investor Relations section of our website. Please note that our commentary on today's call will focus on non-GAAP financial measures unless otherwise indicated. Moving to Slide 3 and introducing BioMarin's management team joining today's call, Alexander Hardy, Chief Executive Officer; Brian Mueller, Chief Financial Officer; Cristin Hubbard, Chief Commercial Officer; and Greg Friberg, Chief R&D Officer. I will now turn the call over to BioMarin's CEO, Alexander Hardy.

Thank you, Traci. And moving now to Slide 5. Thank you all for joining us today to discuss BioMarin's fourth quarter and full year 2025 results as well as our outlook for 2026, which will be an exciting year. We are particularly proud to have accomplished our strategic goals for 2025, while achieving outstanding growth. In 2025, total revenues grew by 13% to a record $3.22 billion for the year and operational excellence led to strong profitability and increasing cash flow. This result was fueled by a 9% increase in enzyme therapies revenue and a remarkable 26% rise in Voxzogo revenues. Importantly, enzyme therapies revenue has grown at a 9% CAGR over the last 5 years, demonstrating the durability and reach of this $2 billion-plus franchise across our 80-country footprint. With Voxzogo, now in its fifth year on the global market, we're very pleased with the consistent strong growth already achieved and have deep conviction in our ability to continue expanding should another product be approved. BioMarin's 2025 performance and 2026 outlook highlight both our deep global capabilities and the vital importance of our targeted therapies to the patients we serve. Building on the strong foundation in 2026, we will expand our therapeutic and commercial reach with the addition of assets from two significant acquisitions announced last year. The first, Inozyme, strengthened our enzyme therapies portfolio with the addition of BMN 401 for ENPP1 deficiency. This is a condition for which there is no approved targeted therapy. So we're really pleased about the possibility of launching what could be our sixth first-in-disease enzyme therapy should pivotal data be supportive. We look forward to sharing that update in the coming months and to filing submissions soon thereafter. Our second acquisition, Amicus, potentially adds both Galafold for the treatment of Fabry disease,…

Thank you, Alexander. Please refer to today's press release for detailed fourth quarter 2025 results, including reconciliations of GAAP to non-GAAP financial measures. All 2025 results will be available in our upcoming Form 10-K, which we expect to file in the coming days. Starting on Slide 7. Our fourth quarter results reflect strong global demand, with total revenues of $875 million, representing 17% year-over-year growth. This strong performance was broad-based across our portfolio with Voxzogo delivering 31% year-over-year growth and enzyme therapies achieving 13% year-over-year growth in the fourth quarter. Palynziq revenue increased 25% in Q4, marking its fourth consecutive quarter of 20% or higher year-over-year revenue growth. For the full year, Voxzogo revenue increased 26% over 2024, totaling $927 million and underscoring the strong global expansion since its launch over 4 years ago. For the full year 2025, approximately 73% or nearly $680 million of the $927 million of total Voxzogo revenue was generated outside of the United States, reflecting BioMarin's differentiated global reach and infrastructure, deep rare disease expertise and ability to execute at scale. Full year 2025 enzyme therapy revenue increased 9% year-over-year, led by 22% growth for Palynziq and 7% growth for Vimizim underscoring the durability and strong demand for these established brands. As expected, Q4 revenue benefited from the timing of large orders in both Voxzogo and enzyme therapies. In Q4, we recognized revenue from an approximately $30 million contracted government order for Voxzogo, the magnitude of which we do not expect to repeat in Q1 2026. Additionally, in Q4, we saw stocking levels increase in the U.S. and select global markets for Voxzogo, Palynziq and Vimizim. Now moving to Slide 8. As an update on our plan to divest Roctavian, we recently made the strategic decision to withdraw it from the market. As a…

Thank you, Brian. I'll open by highlighting the outstanding work of our teams around the world. Their focus and deep expertise have been instrumental in driving another year of impressive commercial performance. Now moving to Slide 11 and starting with enzyme therapies. In 2025, enzyme therapies delivered year-over-year revenue growth across every product in the portfolio, leading to 9% growth, driven by new patient starts across all products and consistently strong therapy-adherence rate. With 22% year-over-year revenue growth, Palynziq, again, outperformed expectations. As the only approved enzyme replacement therapy for PKU, Palynziq stands alone in its ability to enable people with PKU to reach physiologic phe levels while reducing dietary restrictions regardless of severity. The performance further highlights our leadership in the PKU market having established invaluable partnerships with our stakeholders during almost 20 years treating people living with PKU. In 2026, Palynziq is expected to remain the primary growth driver in today's enzyme therapies portfolio, supported by the anticipated adolescent-label expansion with the U.S. PDUFA target action date of February 28 and an anticipated European approval later this year. Excitement is building among the treating physicians and families around the value proposition that Palynziq represents to the adolescent PKU community. This label expansion will enable young people with PKU to start treatment while living at home, supported by caregivers and under the guidance of their health care providers. Adolescence is a pivotal time where dietary therapy typically starts to become unsustainable for those living with PKU, which can result in rising blood fee levels. The opportunity for adolescents to use Palynziq may provide dramatic fee lowering, the ability to eat more like their peers for social inclusion and ultimately, a better setup for them to enjoy an independent successful life. Now turning to Slide 12. Voxzogo continued to be…

Thank you, Cristin. We have a very busy year ahead for R&D with multiple meaningful milestones. Moving to Slide 14. As Cristin mentioned, we are preparing to submit the full approval package for Voxzogo and achondroplasia. This submission will allow us to present a comprehensive story around final adult height as well as a broader health and wellness outcome data set. We have collected over 10,000 patient years of safety data, including data for some children who have been on Voxzogo treatment for more than 10 years underscoring the value of Voxzogo across all age groups, including meaningful impacts on quality of life and anatomic outcomes. In addition to linear growth, Voxzogo's broad evidence package demonstrates the treatment's impact on key complications associated with achondroplasia, including foramen magnum stenosis and symptomatic spinal stenosis as well as improvements in body proportionality, arm span and leg deformities like genu varum and tibial bowing. These extensive data also show clear functional benefits with improvements in measures of mobility, gait and quality of life. Together, these findings support our plans to submit the full approval package to the FDA and to continue sharing additional data through peer-reviewed publications and scientific forums later this year. Now moving to Slide 15. BMN 333 is our long-acting CNP therapy for achondroplasia. We previously shared our plan to initiate a combined Phase II/III study in the first half of this year. Today, we're pleased to share more details on the Phase III study design and powering assumptions. The Phase III portion of the study will enroll 60 patients into each arm and will have 90% power to detect a 50% increase in annualized growth velocity versus Voxzogo. This translates into a growth increase of 2.25 centimeters per year over placebo, an effect size that would represent a clear…

[Operator Instructions] Your first question comes from the line of Mohit Bansal with Wells Fargo.

Congrats on all the progress. Just one point just -- and the dynamic in the achondroplasia market now that we have data for the oral medicine also out there, so how do you see this market evolving with the availability of weekly as well as oral at some point? And then the last part of the question is basically, if you do deliver 2.25 centimeters or above growth velocity, above -- over and above placebo with BMN 333. Do you think injections could be the first-line therapy there before orals?

Thank you, Mohit. This is Greg Friberg. I think I'll take the first half of your question, and then I'll hand it off to Cristin. With regard to the recently released data for the FGFR3 inhibitor, our take there, of course, was that this was generally comparable to other CNP class effects at 1 year. Of course, this is 1-year data. We'll need to see both durability as well as safety data over time. And the read through, of course, in terms of how we believe Voxzogo can deliver value here is that Voxzogo not just having one year of data has a tremendous amount of supporting evidence behind it. We talk about the 10,000 patient years of safety. We also, of course, have a deep a wealth of information with regard to evidence beyond height, whether it's foramen magnum, physical function, tibial bowing, quality of life, all of this data, again, creates a real confidence that, that data is something that patients can rely on. With regard to 333 and the effect size, we've stated again what the powering assumptions would be, and we do believe that the 2.25 centimeters of growth not only are differentiating on a clinical level, but we have some preliminary market research that suggests as well that, that would be important. It's important not to get too caught up in the growth being the outcome that we care most about because the growth is a surrogate for the health and wellness of these patients. Again, going back to Voxzogo, we do believe that increase in growth would, in all likelihood, again, lead to a best-in-disease profile that patients, payers and physicians with value. So with regard to the market dynamics, I'm going to hand it off to Cristin.

Yes. Thank you so much, Greg, and thank you so much, Mohit. I do think -- and as we've said before, I think having more options is certainly important for patients. So we're going to see how that continues to play out. But I think Greg has done a nice job articulating what we've seen in the recent data releases. But what I do think is really important is to understand kind of where Voxzogo plays in this dynamic and in this landscape. First and foremost, it's really important and the data continue to show as do the international guidelines that treating early is the most important thing you can do for patients. And that is something that we really have been able to generate, not only does our label allow us to do that, but importantly, the evidence that we continue to generate supports this that treating early will provide the longest-term benefit, and we have that in 10,000 patient years across all age groups actually in the pediatric space. So I think that's a really important component. The other piece is going to be the switching dynamic or patients that are doing really well going to switch over to another therapy. And what we see and what we hear in our market research and what we have in our field interactions is actually a fair amount of reticence, the large majority of what we're hearing in the marketplace and in our market research is that for patients that are doing well on Voxzogo. There's not going to be a huge incentive to switch right away, especially because the long-term data for safety and efficacy hasn't yet played out for the other products, and that's really important. We've learned that HCPs and KOLs alike are not going to be the drivers of switch, they will provide the data that is out there, but they are going to be the ones that they will be the patients and the caregivers who are actually driving the switch. So this is where that long-term safety and efficacy data really comes through, and I think that is going to play out as we see this dynamic continue.

Your next question comes from the line of Chris Raymond with Raymond James.

I'm hearing you guys on the switcher dynamic and the comment that if patients are doing well, there will be a limited motivation to switch, but we were kind of surprised to learn one of your competitors is anticipating about half of their patients in their early achondroplasia trials will be Voxzogo experienced. And I think their commentary is that there actually is a decent amount of parents and patients out there that are interested in switching to something. Maybe just talk about what you're seeing more broadly. Is there a demographic or some attribute other than just performance that might drive this decision or desire to switch? And then if I can maybe ask a question on 351. I'm kind of struck by -- this drug is mentioned in your commentary, but I'm just looking at the dystrophin data, it looks pretty differentiated, if not superior to what's out there. Maybe just talk a little bit about your plan to communicate this. I know there's data, the full data is going to be at the MDA conference next month, but just talk about your plan to communicate the waypoints on that drug, please?

Thanks so much, Chris, and this is Greg Friberg, again. Let me take your second question first. I would agree with you. The data is quite encouraging from BMN 351. The 5% absolute dystrophin measure, again, which if you look at our PKPD model predicts roughly 10% at steady state, that is an unprecedented number for the exon 51 skip amenable patients. Now what we also know from the program is that data monitoring committee has allowed us, again, to go to a higher dose level and complete the study. So we see quite a bit of value to continuing the experiment for a variety of reasons. Number one, of course, the 12-milligram per kilogram level, we'll see whether we can see something superior to that number, knowing that within all these patients, there's some degree of variability. Number two, we'll obviously get to see more chronic safety data as well. And this is something, again, that in this field, of course, where benefit burden is key is something that we absolutely want to continue to follow. And finally, we'll get our first look at some functional data as well as we treat these patients for longer and look at, for example, the Stride Velocity 95C data. We expect that this next tranche of data will have it before the end of the year. And in the meantime, we will be presenting our complete 6- and 9-milligram per kilogram data at the Duchenne Muscular Dystrophy Association meeting in March, just a couple of weeks away. So we're sitting tight. And again, encouraged by what we've seen. We want to see more data there for this weekly IV administered antisense oligonucleotide. With regard to Voxzogo, your question is a nuanced one. It's one of whether or not, again, patients, physicians, their caretakers, whether they can have the confidence in the data package for the medicine that they're given in many cases, to very, very young infants. And of course, with Voxzogo, we have a wealth of data. We're looking forward to present that in our full evidence package that we'll be presenting for full approval to the FDA in the coming months. And I think I've gone through some of the package there, that goes through, again, some of those data points. With that, though, from the commercial perspective, I want to give Cristin, a chance to share her perspective.

Yes. Thanks for the question, Chris. And I'd be happy to kind of both dig in on the switching dynamic but also important on the market dynamic in the different geographies in which we operate. So again, going back to that notion of why switch, what we hear disproportionately is that above all else, efficacy and safety are the highest priority. Convenience is the third. So the fact that we have both kind of long-term safety and efficacy data but also importantly, durability. We are showing data now that shows that Voxzogo continues to work year-over-year data that we published going 7 years out, which really matters to these caregivers, these patients and importantly, the physicians. So I think that this is going to be in the near term, in particular, when there is more data in favor of Voxzogo, I think that, that's going to be part of the switch decisions. Now importantly, when I think about the markets, we've got very different categories or phenotypes, if you will, on markets. We've got some which are larger markets, which we have highly penetrated. And these have become ends incident markets. So really where we intend to grow Voxzogo there is going to be really in newborns, where our label enables us to. Then moving over to some of the bigger growth opportunities, I think we have where Voxzogo can really play a meaningful role. That's going to be both in countries that we're already in that still have meaningful opportunity ahead of us. Now let me be clear, these are more complex markets. They take a little bit more time. But we think that the value proposition of Voxzogo is there, and we'll continue to grow there in but also, as you heard me say in the prepared remarks, we have some exciting markets where they are fast growing, there's access pathways, and we're growing quickly in those. And so between all of this, when you look at kind of 75% of our revenues being weighted outside the U.S., I think there's an important value story and important story for Voxzogo and all.

Your next question comes from the line of Phil Nadeau of TD Cowen.

Another question on Voxzogo, but on hypochondroplasia. Can you help us frame the upcoming results? What magnitude of growth velocity increase do you think would be meaningful in hypochondroplasia patients? And can you talk about the dynamics of that market? Would you expect uptake as quick as in achondroplasia? Or are there other factors which could make it less rapid?

Thanks, Phil. This is Greg again. I'm going to take it for stab, and again, I hand it to Cristin at that point. With regard to the study, again, we're very excited that we'll be turning the card over in the first half of this year. The study is designed to measure an effect size roughly equivalent to what Voxzogo delivers for achondroplasia. That being said, that's a fairly conservative assumption. We know that Dr. Dauber's data, for example, is showing slightly larger, more like a 1.8-centimeter growth of AGV in the hypochondroplasia patients. And it's our goal and intent also to follow through, as I mentioned previously, not just measuring AGV, but also looking at measures of health and wellness for these patients. So we believe we've designed the right study. Now it's a question of reaching the endpoint and turning it over, and we're very excited to see the data. Cristin?

Yes. So I think once we see the data, the scientific rationale will have been proven. But I do think that the enrollment rate of the trial in and of itself shows the excitement level that could be here for hypochondroplasia, assuming that all plays out well. And I think that this is yet another example, though, of our leadership in skeletal conditions where we're out there defining area where nothing exists now. And so when I think about what the biggest opportunity is, and we've said it before, it's really in and around diagnosis. This is an underdiagnosed condition, and it doesn't quite have the infrastructure that is needed to ensure that, that can happen rapidly for these patients. So we're out there now doing a prelaunch non-promotional work. We're educating on signs and symptoms requiring further evaluation and genetic testing for hypochondroplasia. We're really talking a lot about the burden of the condition to really enhance that sense of urgency to treat. And we're working actually on establishing and disseminating guidelines for when to refer and test for these patients so that we can shorten that journey to diagnosis. So all in all, we really are working at ensuring that diagnosis which I think will be the biggest problem statement for hypochondroplasia that we can get out there and tackle that early. To remind you, the total TAP side that we understand it to be today is we expect that the prevalence is in and around that of achondroplasia. But because of these diagnosis rates being so much lower, we said that the TAP is around 14,000 patients. I hope that helps you to understand. We're really excited about this and think there's a lot of work there and help to grow space.

And that targeted patient profile includes what we studied in the clinical trial, which is those patients that are more negatively effective in terms of standard deviations for growth deficit.

Your next question comes from the line of Akash Tewari with Jefferies.

This is Siyue Wang on for Akash. One on Voxzogo again, just following on the infigratinib data, where does this fall in your scenario analysis for your 2027 revenue outlook? And additionally, can you talk about the importance of the full approval for Voxzogo with the final adult height and how you expect that to impact patient preference?

This is Brian. I'll take the first part of the question on '27 and any impact from infigratinib data. We don't have new updates on '27 at this time. I will say in response to your question, that the assumptions we made in the more competition impacted scenarios when we did update our views on that range, this is in line, we assumed two competitors and comparable data to Voxzogo.

And this is Greg Friberg. Just commenting on the full approval. This is a real chance for us to work with regulators to present our totality of the data set. We know that we have confidence in the 7, 8, 9, 10 years of safety and efficacy data that we have in achondroplasia. We will have the opportunity to also put in front of them those measures of health and wellness. I mentioned the foramen magnum data, the physical function, tibial bowing to see again whether or not it meets criteria for label inclusion. It's an important moment, having full approval, build on that confidence, there are some other technical, I think, benefits that come along with full approval. But most importantly, again, we see this as our opportunity to put forward what we see as a leading evidence package for achondroplasia.

Your next question comes from the line of Salveen Richter with Goldman Sachs.

This is Tommie on for Salveen. We just wanted to drill a little bit more into the factors assumed in your Voxzogo guidance, especially as it relates to new starts and potential switching in the context of upcoming competition. And also for 333, kind of your confidence in establishing as the preferred option for new patients from switching given that the long-acting competitor will have a bit of a head start here.

Tommie, it's Brian. I'll start with the first part of your question. Thank you. In terms of the Voxzogo guidance for '26, first of all, just to note, we're really pleased to have grown the product 26% in '25. Its fourth year on the market. And with respect to the range, the $975 million to $1.025 billion really just reflects a handful of scenarios. On the lower end of that range, you can assume a stronger competitive impact from the first competitor potentially coming to market in '27. I'll also share that we're being guarded on a couple of routine market access renegotiations in '26. These are normal course of business. Again, the product is fifth year on the market. Those will resolve this year, but we're being measured on those. And then at the high end of the range, it would just assume a lesser impact from those couple of swing factors in the guidance. Cristin, anything else to say on patient additions, and where they're coming from.

No. I mean, we're continuing to generate patient demand. And really, our priorities remain the same. Now our execution at a country level may look different depending on what choices are available inside country. But at the end of the day, our priorities remain the same. And these profile that we've seen so far are very much in line with what we anticipated. And importantly, where we tend to continue growing patient demand is what I've said, it's in that 0 to 2 population and ensuring that we're really protecting switching.

Yes, this is Greg. With regard to the 333 question, the ultimate issue here is whether or not convenience is the lever that we're focused on or whether or not patients, physicians, regulators can have confidence in the data package we put forward. We believe that we've designed the appropriate study to show that 333 can have a superior growth profile over all the available agents. And in that regard, really have an opportunity to differentiate itself as the most active agent in the field, not just for AGV, but also the pull-through of health and wellness as well. The study is certainly powered to detect the size difference that we mentioned there. But the question, I think, behind your question was whether that -- those prior assumptions were aggressive or conservative. And I would argue that they're somewhat conservative. Our animal model data as well as our PK/PD model or dose response model suggests that any one of the doses that we're putting into Phase II could potentially deliver the profile we're looking for.

Your next question comes from the line of Ellie Merle with Barclays.

Just what's your latest expected timing for the data readouts from the Phase II CANOPY basket study for Voxzogo? And second, just to ask a bit more on the Voxzogo guidance. Could you comment specifically on what the guidance reflects or how you're thinking about U.S. growth versus ex-U.S. growth over the course of the year? And then if you could just elaborate on that last comment that you're being guarded on a few routine market access conversations and sort of the implications for that for Voxzogo?

And this is Greg. Maybe I'll knock down the CANOPY question first, if that's okay. We're anticipating that we're on track for data in the 2027 time frame, as we've stated previously. No updates in that regard. And that refers to IFS, and the Noonan, Turner, SHOX program. Our CANOPY study, of course, also includes hypochondroplasia, which we're excited to turn the card over in the first half of this year.

Thanks, Ellie, this is Brian. I'll start with the first part of your guidance follow-up. We're not delineating further individual growth dynamics in the U.S. and ex-U.S., again, we've discussed before about growing in all markets. By the way, even with competition coming to market, Voxzogo's 50 on the market, we are satisfied with to be able to confidently guide to a high single-digit growth rate in '26 and at the midpoint, having the product reach blockbuster status, I'll remind you that the -- we're expecting to have the infant market in the U.S. even if competition comes to market, so that will remain 100% of Voxzogo and Cristin's already touched on the level of opportunities ex-U.S. So we'll keep you updated from quarter-to-quarter on the growth dynamics but not breaking it out further at this time.

Hi, Ellie, this is Alexander. I'm just going to come back to your question about the reimbursement processes that Brian mentioned to just give a little bit more color on those. They're in a number of markets, when you get into 5 years on the market and the product is very well established and has broad usage. You tend to go under formal reimbursement processes. And this represents actually an opportunity for us to broaden the access in those countries. Up to that point, they may well have been under a name patient single patient access type approach. So you go into a negotiation and you offset potentially a reduction in price but with the opportunity to significantly expand the population. Obviously, in the first year that it happens and there's two of these countries where it's going to be happening in 2026, you obviously have a price reset on your entire population. But then in front of you, you have the potential to reach many more patients. So it's a very exciting actual opportunity for Voxzogo in those markets and overall.

Your next question comes from the line of Cory Kasimov with Evercore ISI.

This is Adi on for Cory. I had a question on BMN 333. Based on the preclinical data and initial first -- should we expect the safety profile to largely mirror Voxzogo or are there any meaningful differences emerging that could differentiate the profile one way or the other?

Thank you for the question, Adi. Our preclinical models and in this case, the cynomolgus monkey models, in particular, have not demonstrated any additional safety concerns for 333 over Voxzogo as a free drug. The reality actually is that the profile for free CNP allows us to go up to much higher exposures when given in the form of 333 as compared to the daily administration of Voxzogo. And again, that's opened this therapeutic window that has allowed us to go to 3x, 5x, 7x and higher AUC exposures. And again, we're quite hopeful that recapitulate what we've seen in efficacy animal models that we're going to have a best in disease profile.

Your next question comes from the line of Paul Matteis with Stifel.

I'm not sure how limited you are, and how you can speak about Amicus and things going forward, but I thought I'd give it a brief try. Just as it relates to the integration of the business, Alexander, you, I guess, reorg BioMarin's commercial infrastructure with different business units, and this was kind of, I think, more in reaction to Valrox a number of years ago. But how do you think about Amicus fitting into that going forward? And how much do you think you can leverage a lot of the reps you have, the units you have existing relationships versus kind of building out a whole new way of selling some of these products?

Thanks very much for the question, Paul. Yes, I mean these two products, our intention is post closure, these are going to drop right into our enzyme therapy business unit. I mean they just fit perfectly. The entire go-to-market model is exactly the same as our current portfolio. So the opportunities and the opportunities for us to drive synergies on the top line as well as synergies in terms of the way that we operate are tremendous. We're looking forward to sharing more post close. We're on track right now for a second quarter close. And then we'll share more about our specific plans and our expectations for what these really exciting products that Amicus has done such a good job bringing to market what the pro forma looks like when you add those into BioMarin. So more to come, Paul.

Okay. And if I could just ask one quick follow-up. But Brian, I think you said earlier in the call, please don't update your models just yet for the deal. I think a number of models have been updated. Are you seeing anything in the way people are modeling this, that is missing the point that you want to make sure you guys can articulate your vision first, or I guess I'm not -- by any means asking you to give kind of guidance or context here, but from our end, it seems like as Alexander lists, it isn't all that -- it's fairly straightforward. So where are you coming from on that point?

Yes. Thanks a lot, Paul. I appreciate the opportunity to clarify that. The comment was based on entirely just the mixed bag of some analysts having post-close Amicus revenues included in their BioMarin models and some not. Thanks for the opportunity to clarify that had nothing to do with the direction of what we see and those that are including it.

Your next question comes from the line of Joe Schwartz with Leerink Partners.

So one of the levers you highlighted for longer-term growth when you announced the Amicus acquisition was some initiatives to identify patients who might have Fabry and Pompe that wasn't diagnosed yet. I think Amicus had some pilot programs to do this. And in a few centers -- and I was just wondering if BioMarin had the opportunity to see the results of these pilot programs and if they are along the lines of what you expect to roll out. Can you just talk a little bit about your initiatives there?

Thanks for the question, Joe, it's Cristin. So you are indeed exactly what you just said that there are -- they've been running pilots. There's different models. And just to reiterate that we are in the process now of really diving between sign to close, really understanding what's going on, what makes sense, given what we already have in our company versus going on over there. And at the end of the day, we are running as two independent businesses at this point in time. And so they're continuing their work on any of the pilots that they have ongoing. I think the real opportunities that we're excited about for both Galafold and Pom, Op as Alexander has already spoken to is certainly how it fits to -- it fits within our business unit model here on enzyme therapies. But also importantly, the really big opportunity there is to increase the diagnosis rates for both Galafold as well as Pom, Op. But then when you're talking about Pom, Op, really driving that switch. So important areas that we'll continue to work on, but we're in the process now of really diving in and understanding what's exactly going on.

Your next question comes from the line of Olivia Brayer with Cantor.

I have a few follow-ups on Voxzogo. First is just maybe can you talk about level of confidence in actually hitting the numbers that you laid out this year? Just in light of a weaker first quarter due to those ordering patterns that you highlighted, Brian. Anything more you can tell us on those ordering patterns, and why they might be so heavily weighted to the fourth quarter this year. I'm just trying to understand how having a new entrant on the market could impact some of those patterns and just cadence of quarterly Voxzogo revenue this year? And then a quick follow-up on hypochondroplasia. When do you think we could realistically see that launch and uptake in those patients? And any comments at this point just around how quickly you could start to see added sales from hypochondroplasia patients especially as you think about navigating some of the competitive headwinds in the achondroplasia market next year.

Thanks, Olivia, this is Brian. I'll start with a little more color on the quarter. I appreciate the question. Yes, so a few brief things there. First of all, we've always experienced these kind of bolus orders and the potential volatility of quarterly revenue. And by the way, we've typically seen step-down from Q4 to Q1. We do -- I think we -- especially after this year, we definitely observed some Q4 buying globally. It isn't always inventory levels. It could be, in some cases, of single national payers kind of just making their way through their budgets. There's a number of factors. But we've seen this in Q4, it was -- seen this before for Q4 was exacerbated here in '25. Another item I'd share is, and this is to your point about the competition, I mean two things. One, when we map our revenue to global Voxzogo patient additions. It is amazing how clear of a straight line, the study patient additions have been quarter-after-quarter over the last several years, frankly. But yes, when you look at revenue, it bounces around a bit because of these -- because of the order timing. In fact, while Q4 had a bolus effect, there's actually some markets where it was kind of a catch-up because revenue was flagging patient additions, so that's number one. And number two is I think we're going to continue to observe that this year. I'll share and this should also help you all estimate the proportions of revenue for Voxzogo, we expected the quarters will be similar to last year. So I already said that Q1 is on par with Q1, but we also expect a lot of it to be back-loaded to Q4, and any confidence, any assumptions around the competition are fully baked in?

And with regard to your second question, so as you've heard us say, we'll be presenting or sharing the top line data in the first half of this year for hypochondroplasia, and then our submissions will happen in the second half of this year. So what that means is, hopefully, approvals coming 2027 and we would expect to see immediate revenue impact at that point in time. And we'll share as we see the data, we'll share more on our go-to-market plans as we move further along in the process.

Your next question comes from the line of Jason Gerberry with Bank of America.

Just on the Phase III powering in the 2.25 centimeter per year. Is that a threshold effect when you're doing your Phase IIs ranging, if you're learning that perhaps that may be too ambitious of a target, would you just kind of adjust your statistical analysis plan. Is it -- I think in your earlier comments, not to get too hung up, I think, on that 2.25 number. So if it looks like you're on a trajectory for, say, 2 or 2.15, is it still worth moving forward in the Phase III with BMN 333. So I just wanted to clarify if that's the threshold effect in a go no-go threshold in the dose-ranging work?

Yes. Thanks for the question, Jason. And that 2.25 really comes from the sample size that we've laid out, that's 60 versus 60. There's some standard deviation, some alpha numbers behind that as well. But we wanted to share with you again what our ambition was, what we thought not only statistically significant but clinically meaningful. We will have a chance to look at our Phase II data. It's not a straightforward black-or-white situation. We're doing actually a Bayesian approach where we'll be looking at the totality of the data. And setting a certain threshold for confidence to move forward. Rather than get into the details there, I will just answer your question directly and say we would have the opportunity to potentially modify the protocol thereafter. But those numbers and announcing them again, I think they stated appropriately our ambition of what we think a meaningful and clinically relevant improvement over what is already a well-established, safe and effective therapy in Voxzogo would look like.

This concludes the Q&A portion of the call. I will turn it back to the CEO, Alexander Hardy, for closing remarks.

Thank you, operator, and thank you all for joining us today. We're particularly proud to have accomplished our strategic goals for 2025 while achieving an outstanding growth. In 2026, we will build on this momentum and expand our therapeutic and commercial reach with the addition of high-growth assets from two significant acquisitions announced last year. We also look forward to sharing a number of key regulatory milestones, data readouts and label expansions throughout the year, setting us up to deliver even more growth, profitability and pipeline expansion. We're energized by what lies ahead this year and intend to deliver again on an ambitious set of priorities, demonstrating our dedication to innovation and sustained growth in ways that we will believe patients, we will believe, we'll benefit patients, employees and shareholders. Thank you for your continued support, and we will speak to you soon.

Ladies and gentlemen, that concludes today's call. You can now disconnect. Thank you, and have a great day.