BioMarin Pharmaceutical Inc.

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 Biomarine Pharmaceutical fourth quarter and full year 2025 conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one again. Thank you. I would now like to turn the call over to Tracy McCarty, Head of Investor Relations. Please go ahead.

Thank you, Operator, and starting on slide two. To remind you, this non-confidential 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 10Q, 10K, and 8K 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 three and introducing Biomarin's management team joining today's call, Alexander Hardy, Chief Executive Officer, Brian Mueller, Chief Financial Officer, Kristen Hubbard, Chief Commercial Officer, and Greg Freiberg, Chief R&D Officer. I will now turn the call over to Biomarin's CEO, Alexander Hardy.

Thank you, Tracy. And moving now to slide five. 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, an 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 Voxogo revenues. Importantly, enzyme therapies revenue has grown at a 9% CAGR over the last five years, demonstrating the durability and reach of this $2 billion plus franchise across our 80 country footprint. With VoxOgo 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 this 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 BMN401 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 Gallifold for the treatment of Fabry disease and Pombility and Alfolda for Pompe disease to our commercial portfolio and is expected to close next quarter. This transaction presents a particularly compelling opportunity to further build on Amicus's success by leveraging our scale and global capabilities to serve even greater numbers of patients. In addition to the expansion of Biomarin's portfolio from acquisitions, we're particularly excited to build upon Voxogo's leadership in achondroplasia with a potential addition for treatment of hypochondroplasia. Because CNP is the master regulator of bone growth and supported by the one-year results from the investigator-sponsored study, we are excited to see and share the upcoming pivotal results with Voxergo for the treatment of hypochondriplasia in the coming months. We look forward to the possibility of adding hypochondriplasia to our global skeletal conditions treatment offerings by early next year. On top of Voxergo indication expansion, based on the very encouraging PK data recently shared, we're preparing to begin enrollment in our Phase 2-3 study for BMN 333. We believe this next generation long-acting CNP therapy has the potential to set a new standard of care and to demonstrate superiority compared to any candidates under development for achondroplasia. Those are just a few of the anticipated pipeline highlights expected this year. so you can understand our enthusiasm for what's ahead in the coming months. Turning to innovation. During the period where we are de-levering the financing associated with the announced acquisition of Amicus, we will remain actively engaged in business development activities targeting pipeline assets. This is an important component of a larger pipeline expansion plan, a plan that both accelerates our financial performance and further diversifies our portfolio to drive durable, long-term growth. In closing, we are pleased that the transformational work implemented over the last 24 months has already delivered significant results and positions us for even more revenue growth, profitability, and pipeline expansion. Prior to any contributions from the amicus assets, this year we anticipate Biomarin's enzyme therapies will deliver high single-digit growth, and Voxogo will continue along its trajectory towards blockbuster status. Following the completion of the transaction, we anticipate that integrating Gallifold and Pombility and Upfolder will enable both medicines to reach more people around the world living with Fabre and Pompei, significantly enhancing our 2026 outlook and enabling accelerated revenue growth through the 2030s. With that, I will turn the call over to Brian to provide additional financial updates. Brian.

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 seven, 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 Voxogo delivering 31% year-over-year growth and Enzyme Therapies achieving 13% year-over-year growth in the fourth quarter. Palanzic revenue increased 25% in Q4, marking its fourth consecutive quarter of 20% or higher year-over-year revenue growth. For the full year, Voxogo revenue increased 26% over 2024, totaling $927 million and underscoring the strong global expansion since its launch over four years ago. For the full year 2025, approximately 73% or nearly $680 million of the $927 million of total VoxOgo 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 Palazic and 7% growth for Vimizin, underscoring the durability and strong demand for these established brands. As expected, Q4 revenue benefited from the timing of large orders in both Voxogo and enzyme therapies. In Q4, we recognized revenue from an approximately $30 million contracted government order for VoxOgo, 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 VoxOgo, Palantzeek, and Vimezen. Now moving to slide eight. As an update on our plan to divest Roctavian, we recently made the strategic decision to withdraw it from the market. As a result, during the fourth quarter, we recorded approximately $240 million in special items on a GAAP basis. Approximately half of that amount relates to an inventory write-off that does not get adjusted out of non-GAAP income. Biomarin reported $3.15 of full-year 2025 non-GAAP diluted earnings per share And looking past the 2025 IPR&D and Roctavian charges included in non-GAAP income, our underlying business earnings per share grew by approximately 34%. This performance contributed to $828 million in full year 2025 operating cash flow, a 45% increase versus full year 2024. Further demonstrating the strength of our operating model, and providing meaningful capital to reinvest in innovation. We are pleased to see the operational transformation implemented over the last 24 months drive this level of profitability. Together with our revenue growth plans, Biomarin is positioned to sustainably grow profitability and cash flow while still investing in the business. As we prepare to close the amicus acquisition, we were pleased to secure approximately $3.7 billion of debt financing consistent with the strategy that we shared upon announcement of the transaction. Confidence in the strength of Biomarin's business and financial outlook supported a positive credit ratings outcome and helps drive demand for all components of the capital raise, which enabled favorable pricing across the capital structure. Now moving to slide nine. Looking ahead to full year 2026, we are providing initial guidance that reflects Biomarin's growth expectations, excluding any post-close contributions from the announced acquisition of amicus. Please note that currently available Biomarin consensus estimates include a combination of revenue estimates, some that include Gallifold and Pompability and Opfolder revenues, some that do not. We plan to provide updated guidance on the combined business following the close of the acquisition, expected in the second quarter of 2026. And we request that you wait for those details prior to updating BioMarin's models with the post-closed amicus contributions. Turning to 2026 guidance items, we expect enzyme therapies revenue of between $2.225 billion to $2.275 billion, and Voxogo revenue of $975 million to $1.025 billion. We expect continued high patient demand across both the enzyme therapies and Voxogo in 2026, resulting in high single-digit growth rates of both business units at the midpoints. Outside of enzyme therapies and Voxogo, we are expecting significantly lower Royalty, Gouvan, and Roctavian revenue in 2026, which affects year-over-year comparisons of total revenue. We estimate those revenues to be between $100 million and $125 million in 2026, representing a 3% headwind to total revenue growth when compared to 2025. Taken together, We anticipate 2026 total revenues in the range of $3.325 billion to $3.425 billion. Again, this excludes any contributions from the amicus products. And while we will wait for the acquisition to close to provide more details on 2026 revenues for the combined business, we are expecting a meaningful uplift to our 2026 total revenue growth rate once the transaction closes. We anticipate 2026 non-GAAP diluted earnings per share in the range of $4.95 to $5.15. Please note that our guidance reflects approximately 25 cents per share of pre-closed integration preparation costs and interest expense related to the amicus transaction. On non-GAAP operating margin, Our underlying organic operating margin expectation without the amicus transaction is approximately 40% for 2026, consistent with our previously communicated target. In the announcement of the amicus transaction, we share that we expect the amicus acquisition to be modestly dilutive in 2026, which we expect to be a slight headwind to operating margin that could drive it slightly below 40% for the year. Aside from the impact of the amicus transaction, we recognize that over the last two years, BioMarin has been able to solidify its revenue growth potential and transform its cost structure to realize the potential of a strong operating margin profile well into the future. I will also comment briefly on quarterly dynamics in 2026. Coming off our strongest revenue quarter on record, We expect similar trends in 2026 as those observed in 2025. For example, we expect the first quarter of this year to be the lowest total revenue quarter of 2026, with both total revenues and Vox Ogo revenue expected to be on par with Q1 2025. Q1 non-GAAP diluted earnings per share will have the additional impact of the vast majority of the pre-closed amicus costs just described, resulting in it being our lowest anticipated ETS quarter for 2026. For both Voxogo and enzyme therapies, we anticipate large international order timing to contribute to higher revenue in the second half of 2026 compared to the first half and weighted to Q4, similar to the 2025 dynamic. Our underlying business has consistently produced profitability growth that has outpaced top-line growth, and today's guidance reflects our commitment to continue to grow the business, operational efficiency, and prioritize reinvestment and innovation. Thank you for your attention, and I will now turn it over to Kristen for a commercial update. Kristen?

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 rates. With 22% year-over-year revenue growth, Allen Zeek again outperformed expectations. As the only approved enzyme replacement therapy for PKU, Allen Zeek stands alone in its ability to enable people with PKU to reach physiologic fee 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, Palenzec is expected to remain the primary growth driver in today's enzyme therapies portfolio, supported by the anticipated adolescent label expansion, with a U.S. PDUFA target action date of February 28th and an anticipated European approval later this year. Excitement is building among the treating physicians and families around the value proposition that Palenzec 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 healthcare 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 Palanzeke 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. Voxogo continued to be a standout growth driver, delivering 26% year-over-year growth in 2025. It's particularly gratifying to know that well over 5,000 children with achondroplasia worldwide were being treated with Voxogo at the end of 2025. Now, going forward, with Voxogo in its fifth year of commercialization, our growth strategy is focused on a multi-pronged approach. First and foremost, we are driving new starts globally across all ages, with a particular emphasis in children under two years of age, an age group where we do not expect another approved product for the next several years. Next, in highly penetrated countries, which have become incident markets, our priority is to continue to find and start treatment-eligible infants going forward. In addition, we see meaningful opportunity to more deeply penetrate larger countries where we already have established commercial presence and large growth potential remains. And finally, we are expanding uptake in fast-growing, newly launched markets where significant pools of eligible patients exist and streamlined care pathways are enabling access. To provide more context on the results that these strategies are producing, I'll share a couple of recent examples illustrating Biomarin's deep global capabilities, commercial scale, and more than 20-year track record serving patients around the world. In a recently launched country in the Asia-Pacific region, Voxogo reached approximately 40% penetration within seven months of launch. This success stemmed from early non-promotional pre-launch activities and strong relationship building with clinicians. We ensured that there was a focus on patient identification beforehand and strong support for each patient's experience throughout the journey. In another example, in a mid-sized European country, Voxogo achieved approximately 70% penetration within 12 months of launch. This was driven by early non-promotional engagement with clinicians and patient advocacy groups to build strong relationships with local stakeholders and drive momentum and awareness of VoxOgo. We tailor our approach to meet the needs of the patients and the respective country's ecosystem. We will build on these successes to drive deeper penetration in existing markets and to prepare for new country launches in 2026. These strategies are crucial to our growth outlook with VoxOgo, since roughly 75% of total revenues are generated from countries outside of the United States. In the United States, we are driving increased penetration across all age groups, supported by investments in data, digital, and field force. We're seeing particularly strong momentum in the under two-year age group, reflecting international guidelines for achondroplasia, recommending early diagnosis and treatment with Rofsogo as soon as possible, and long-term data supporting its safety and efficacy from infancy. Approximately half of the new starts in the fourth quarter were children under age two. Since we believe Voxogo will be the only approved therapy in this age segment for the next several years, driving new patient starts in children under two is a key pillar of our growth strategy. With the potential full approval of Voxogo on the horizon, we believe families and caregivers will have even greater confidence in Voxogo's established safety and efficacy profile when considering treatment for their infants and children with achondroplasia. In conclusion, I'm incredibly proud of what our teams have accomplished and energized by the opportunities ahead. I will now hand it over to Greg for an R&D update.

Thank you, Kristen. We have a very busy year ahead for R&D with multiple meaningful milestones. Moving to slide 14, as Kristen mentioned, we are preparing to submit the full approval package for Voxogo 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 Voxogo treatment for more than 10 years, underscoring the value of Voxogo across all age groups, including meaningful impacts on quality of life and anatomic outcomes. In addition to linear growth, Voxogo'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 genovarm 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 plan 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, BMN333 is our long-acting CNP therapy for achondroplasia. We previously shared our plan to initiate a combined phase 2-3 study in the first half of this year. Today, we are pleased to share more details on the Phase 3 study design and powering assumptions. The Phase 3 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 Voxogo. This translates into a growth increase of 2.25 centimeters per year over placebo, an effect size that would represent a clear best-in-disease effect. This represents a floor, not a ceiling. We also anticipate that this would translate into greater benefits and other measures of health and wellness for achondroplasia, including proportionality and health-related quality of life. Our goal is to establish BMN 333 as the new standard of care for achondroplasia and potentially for other skeletal conditions. Now turning to slide 16, we have several additional exciting highlights expected across the pipeline in 2026. To note a few, we anticipate phase 3 data readouts for Voxogo in hypochondriplasia and for BMN401 in ENPP1 deficiency, both serving as key steps towards potential approvals as the first genetically targeted therapies for each of their indications. We are approaching the U.S. SBLA action date for Palenzec for the treatment of adolescents with PKU. Given the unique clinical benefits of Palenzec, We believe families with teenagers seeking treatment will be particularly interested in a therapy that can deliver potent fee reduction, as well as the potential to enjoy an unrestricted diet. Our PDUFA action date is February 28th, and we look forward to sharing that outcome when it becomes available. Finally, BMN351 for Duchenne muscular dystrophy demonstrated 5% mean absolute dystrophin expression at week 25 in the nine milligram per kilogram cohort, a level that translates to a predicted 10% absolute level at steady state. We are currently enrolling in a 12 milligram per kilogram cohort and plan to share those results in the second half of the year. Full results for the six and the nine milligram per kilogram cohort will be presented in an oral presentation at the Muscular Dystrophy Association meeting in March. In summary, 2026 will be an important year of many data readouts, clinical advancements and regulatory activities across our R&D portfolio. We'd like to thank all of the patients, families and caregivers whose dedication and support enabled the advancement of these programs. Thank you for your attention today. We will now open the call to your questions. Operator?

At this time, I would like to remind everyone in order to ask a question, press star then the number one on your telephone keypad. We encourage everyone to limit yourself to one question. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of Mohit Bansal with Wells Fargo. Your line is open.

Great. Thank you very much for taking my question and congrats on all the progress. Just, you know, I want to understand the dynamic in the Echondroplasia 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 and above placebo with BMN 333, do you think injections could be the first-line therapy there before or after? Thank you.

Thank you, Mohit. This is Greg Freiberg. I think I'll take the first half of your question and then I'll hand it off to Kristen. 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 one year. Of course, this is one-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 Voxogo can deliver value here is that Voxogo, not just having one year of data, has a tremendous amount of supporting evidence behind it. You know, we talk about the 10,000 patient years of safety and We also, of course, have a deep wealth of information with regard to evidence beyond height, whether it's foramen magnum, physical function, tibia bowing, quality of life. All of this data, again, creates a real, you know, 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 of that we care most about, because the growth is a surrogate for the health and wellness of these patients. And again, going back to Voxogo, we do believe that that increase in growth would, in all likelihood, again, lead to a best-in-disease profile that patients, payers, and physicians would value. So with regard to the market dynamics, I'm going to hand it off to Kristen.

Yeah, thank you so much, Greg, and thank you, of course, Mohit. I do think, you know, 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 Voxogo 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 we 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. Are 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 Voxogo, 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, 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 that is going to play out as we see this dynamic continue.

Excellent. Thank you.

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

Hey, thanks for taking the question. I'm hearing you guys on the switcher dynamic and the comment that, you know, if patients are doing well, there'll 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 Voxogo experienced. And I think, you know, their commentary is that there actually is a decent amount of parents and patients out there that are interested in switching to something. Let me 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. 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.

Thanks so much, Chris. And this is Greg Freiberg 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 Exxon 51 skip amenable patients. Now, what we also know from the program is that the 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, you know, 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, we'll have it before the end of the year and And in the meantime, we will be presenting our complete six and nine milligram per kilogram data at the DeShane's 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 Voxogo, 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 Oxogo, 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 Kristen, a chance to share her perspective.

Yeah, 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 and 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 Voxogo continues to work year over year, data that we published going seven 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 Voxogo. 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, of markets. We've got some which are larger markets, which we have highly penetrated, and these have become incident markets. So really where we intend to grow Vox Sogo 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 Voxogo 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 Voxogo is there and will continue to grow therein. 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 an important story for VoxOgo and all.

Your next question comes from the line of Phil Netto with TD Cullen. Your line is open.

Good afternoon. Thanks for taking our question. Another question on VoxOgo, but on hypochondriplasia. Can you help us frame the upcoming results? What magnitude of growth velocity increase do you think would be meaningful in hypochondriplasia 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. Thanks, Phil. This is Greg again. I'm going to take a first stab and, again, hand it to Kristen 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 Voxogo 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 hypochondriplasia 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. Yes, sir?

Yeah, so I think, you know, 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 hypochondriplasia, 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 an 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 pre-launch non-promotional work. We're educating on signs and symptoms requiring further evaluation and genetic testing for hypochondriplasia. 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 hypochondriplasia, that we can get out there and tackle that early. To remind you, the total tap size 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've 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 and help to grow.

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 deficits.

Your next question comes from the line of Akash Tiwari with Jefferies. Your line is open.

Hi, this is Phoebe on for Akash. Thank you for taking our question. One on VoxOgo again, just following on the infogratinib 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 VoxOgo with the final adult height and how you expect that to impact patient preference? Thank you.

Hi, Phoebe. This is Brian. I'll take the first part of the question on 27 and any impact from the InfraGrad 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 range. This is in line, we assumed, to competitors and comparable data to VoxOgo.

Thanks. And this is Greg Freiberg, 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 frame and 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 builds on that confidence. There are some other tactical, 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 Salvin Richler with Goldman Sachs. Your line is open.

Thanks for taking our question. This is Tommy on for Salvin. We just wanted to drill a little bit more into the factors assumed in your Voxogo 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 it as the preferred option for new patients from switching, given that the long-acting competitor will have a bit of a head start here. Thank you.

Hi, Tommy. It's Brian. I'll start with the first part of your question. Thank you. In terms of the VoxOgo guidance for 26, you know, 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 market 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's 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. Kristen, 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 in said country. But at the end of the day, our priorities remain the same. And these profiles that we've seen so far are very much in line with with what we anticipated. And importantly, where we intend to continue growing patient demand is what I've said. It's in that zero to two population and ensuring that we're really protecting switching. Yep.

And 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 competence 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 those powering assumptions were aggressive or conservative. And I would argue that they're somewhat conservative. Our animal model data, as well as our PKPD model or dose response model, suggests that any one of the doses that we're putting into phase two could potentially deliver the profile we're looking for.

Your next question comes from the line with Barclays. Your line is open.

Hey, guys. Thanks for taking the question. What's your latest expected timing for the data readouts from the Phase 2 Panoply Basket Study for VoxOgo? And second, just to ask a bit more on the VoxOgo 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 VoxOvo. Thanks.

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 timeframe, as we've stated previously. No updates in that regard. And that refers to ISS and the Noonan's Turner shocks. program. Our canopy study, of course, also includes hypochondriplasia, which we're excited to turn the card over in the first half of this year.

And thanks, Ali. This is Brian. I'll start with the first part of your guidance follow-up. We're not delineating further the 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. Vox Ogo is 50 on the market. We are satisfied with being 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 we're expecting to have the infant market in the US, even if competition comes to market. So that will remain 100% Vox Ogo. And Kristen's already touched on the level of opportunities ex-US. 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. Just give you a little bit more color on those. They're in a number of markets. When you get into five years on the market, And the product is very well established and has broad usage. You know, you tend to go under, you know, 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 you 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 know, 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 VoxOgo in those markets and overall.

Helpful. Thanks. Your next question comes from the line of Corey Kasinov with Evercore ISI. Your line is open.

Hi, this is Addy on for Corey. I had a question on BMN 333. Based on the preclinical data and initial, you know, first, should we expect the safety profile to largely mirror Vox Sogo? Or are there any meaningful differences emerging that could differentiate the profile one way or the other?

Thank you. Thank you for the question, Addy. Our preclinical models, in this case the cinnamolgus monkey models in particular, have not demonstrated any additional safety concerns for 333 over Voxogo 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 Voxogo. And again, that's opened this therapeutic window that has allowed us to go to 3, 5, 7X, and higher AUC exposures. And again, we're quite hopeful if that recapitulates what we've seen in the efficacy animal models that we're going to have a best in disease profile.

Your next question comes from the line of phone. Matt is with Stiefel. Your line is open.

Great. Thanks so much. 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 Bomarin'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 so much.

Thanks very much for the question, Paul. Yes, I mean, these two products, our intention is, post-close, that 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 for when you add those into Biomarin. So more to come, Paul.

Okay. And if I can just ask one quick follow-up, thank you, Alexander. 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, you know, I guess I'm not by any means asking you to give kind of guidance or context here, but From our end, it seemed, you know, like as Alexander alluded to, this isn't all that. It's fairly straightforward. So where were you coming from on that point?

Yeah. Thanks a lot, Paul. 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 biome remodels and some not. Thanks for the opportunity to clarify that. It had nothing to do with the direction of what we see and some of those that are including it.

Your next question comes from the line of Joe Schwartz with LeRinc Partners. Your line is open.

Great. Thanks so much. 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, you know, diagnosed yet. I think amicus had some pilot programs to do this. at a few centers, and I was just wondering if Biomarin had the opportunity to see the results of these pilot programs and if, you know, they're along the lines of what you expect to roll out. Could you just talk a little bit about your initiatives there?

Thanks. Thanks for the question, Joe. It's Kristen. So, you are indeed exactly what you just said, that there are – they've been running pilots. There's different models. Just to reiterate that we are in the process now of really diving in between sign to close, really understanding what's going on, what makes sense given what we already have in our company versus what's 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 Gallifold and PalmOp, as Alexander has already spoken to, is certainly how it fits to, you know, 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 PalmOp. But then when you're talking about PalmOp, 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 Breyer with Cancer. Your line is open.

Good afternoon, guys, and thank you for the question. I have a few follow-ups on Vox Sogo. 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 and just cadence of quarterly Vox Sogo revenue this year. And then a quick follow-up on hypochondriplasia. 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 hypochondriplasia 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 quarters. I appreciate the question. Yeah, 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-downs 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, you know, kind of just making their way through their budgets. There's a number of factors, but we've seen this in Q4. It was exacerbated, seen this before for Q4, 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 VoxOgo patient additions, it is amazing how clear of a straight line the steady patient additions have been quarter after quarter over the last several years, frankly. But yet when you look at revenue, it bounces around a bit 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 lagging 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 VoxOgo 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 hypochondriplasia, 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 about our go-to-market plans as we move further along in the process.

Your next question comes from the line of Jason Drewberry with Bank of America. Your line is open.

Hey, guys. Thanks for taking my question. Am I just on the phase three powering in the 2.25 centimeter per year. Is that a threshold effect? You know, if when you're doing your phase two dose 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, you know, if it looks like you're on a trajectory for say two or 2.15, is it still worth moving forward in the Phase III with BMN3-3. So I just wanted to clarify if that's a threshold effect and a go-no-go threshold in the dose-ranging work.

Yeah, 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 was statistically significant, but clinically meaningful. We will have a chance to look at our phase two 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 competence 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 state 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 Voxogo 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 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 will 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.