BioMarin Pharmaceutical - Q4 2025

Transcript

Operator (participant)

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. 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 Tracey McCarty, Head of Investor Relations. Please go ahead.

Traci McCarty (Head of Investor Relations)

Thank you, operator, 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 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 US GAAP. You can find the related reconciliations to US 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, 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.

Alexander Hardy (CEO)

Thank you, Tracey. 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, 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 five 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 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 BMN-401 for ENPP1 deficiency. This is a condition for which there is no approved targeted therapy, 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 and Pombiliti and Opfolda 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 Voxzogo'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 Voxzogo for the treatment of hypochondroplasia in the coming months.

We look forward to the possibility of adding hypochondroplasia to our global skeletal conditions treatment offerings by early next year. On top of Voxzogo indication expansion, based on the very encouraging PK data recently shared, we're preparing to begin enrollment in our phase II/III study of 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 Voxzogo will continue along its trajectory towards blockbuster status. Following the completion of the transaction, we anticipate that integrating Galafold and Pombiliti and Opfolda will enable both medicines to reach more people around the world living with Fabry and Pompe, 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?

Brian Mueller (CFO)

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 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, 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 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 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.

Looking past the 2025 IPRD 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. Helps drive demand for all components of the capital raise, which enabled favorable pricing across the capital structure. 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 Galafold and Pombiliti and Opfolda revenues, and 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. We request that you wait for those details prior to updating BioMarin's models with the post-close Amicus contribution.

Turning to 2026 guidance items, we expect enzyme therapies revenue of between $2.225 billion and $2.275 billion, and Voxzogo revenue of between $975 million and $1.025 billion. We expect continued high patient demand across both the enzyme therapies and Voxzogo in 2026, resulting in high single-digit growth rates of both business units at the midpoint. Outside of enzyme therapies and Voxzogo, we are expecting significantly lower royalty, Kuvan, 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-$3.425 billion. Again, this excludes any contributions from the Amicus products. 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-$5.15. Please note that our guidance reflects approximately $0.25 per share of pre-close 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 shared 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 impacts 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 1st quarter of this year to be the lowest total revenue quarter of 2026, with both total revenues and Voxzogo 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-close Amicus costs just described, resulting in it being our lowest anticipated EPS quarter for 2026. For both Voxzogo and enzyme therapies, we anticipate large international order timing to contribute to higher revenue in the 2nd half of 2026 compared to the 1st 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 Cristin for a commercial update, Cristin?

Cristin Hubbard (Chief Commercial Officer)

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. 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, 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 therapy portfolio, supported by the anticipated adolescent label expansion, with a US 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 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 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 Phe levels.

The opportunity for adolescents to use Palynziq may provide dramatic Phe 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 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 Voxzogo at the end of 2025. Now, going forward with Voxzogo 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. 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, Voxzogo reached approximately 40% penetration within 7 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, Voxzogo 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 Voxzogo. 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 Voxzogo, 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 2-year age group, reflecting international guidelines for achondroplasia, recommending early diagnosis and treatment with Voxzogo as soon as possible, and long-term data supporting its safety and efficacy from infancy. Approximately half of the new starts in the 4th quarter were children under age 2. Since we believe Voxzogo will be the only approved therapy in this age segment for the next several years, driving new patient starts in children under 2 is a key pillar of our growth strategy. With the potential full approval of Voxzogo on the horizon, we believe families and caregivers will have even greater confidence in Voxzogo'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.

Greg Friberg (Chief Research and Development Officer)

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 in 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 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, 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 are 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 best in disease effect. This represents a floor, not a ceiling. We also anticipate that this would translate into greater benefits in 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. Turning to slide 16, we have several additional exciting highlights expected across the pipeline in 2026.

To note a few, we anticipate phase III data readouts for Voxzogo in hypochondroplasia and for BMN 401 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 US sBLA action date for Palynziq for the treatment of adolescents with PKU. Given the unique clinical benefits of Palynziq, we believe families with teenagers seeking treatment will be particularly interested in a therapy that can deliver potent Phe reduction, as well as the potential to enjoy an unrestricted diet. Our PDUFA action date is February 28, we look forward to sharing that outcome when it becomes available.

Finally, BMN 351 for Duchenne muscular dystrophy demonstrated 5% mean absolute dystrophin expression at week 25 in the 9 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 6 and the 9 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?

Operator (participant)

At this time, I would like to remind everyone in order to ask a question, press star, then the number 1 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.

Mohit Bansal (Managing Director and Co-Head of Therapeutics Research)

Great. Thank you very much for taking my question. Congrats on all the progress. Just, you know, like, want to understand the dynamic in the achondroplasia market now that, you know, we have data for the oral medicine also out there. How do you see this market evolving with the availability of weekly as well as oral at some point? Then, the last part of the question is basically, if you do deliver 2.25 centimeters or above growth velocity, above or, and above placebo with BMN 333, do you think injections could be the first-line therapy there before orals? Thank you.

Greg Friberg (Chief Research and Development Officer)

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 one year. Of course, this is one-year data. We'll need to see both durability as well as safety data over time. The read-through, of course, in terms of how we believe Voxzogo can deliver value here is that Voxzogo in it, 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 for Foramen Magnum, physical function, tibial bowing, quality of life. All of this data, again, creates a real, you know, confidence that, that, that data is something that patients can rely on. With regard to BMN 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, that, that increase in growth in all likelihood, again, lead to a best in disease profile that patients payers and physicians would value. With regard to the market dynamics, I'm going to hand it off to Cristin.

Cristin Hubbard (Chief Commercial Officer)

Yeah, thank you so much, Greg, and thank you for the Mohit. I do think, you know, and as we've said before, I think having more options is certainly important for patients. We're going to see how that continues to play out. I think Greg has done a nice job articulating what we've seen in the recent data releases. 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 we can do for patients. 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, the, the longest term benefit, and we have that in 10,000 patient years across all age groups, actually in the pediatric space. 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. 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, the patients and the caregivers who are actually driving the switch. 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.

Mohit Bansal (Managing Director and Co-Head of Therapeutics Research)

Absolutely. Thank you.

Operator (participant)

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

Chris Raymond (Managing Director and Senior Biotech Analyst)

Hey, thanks for taking the question. I, I'm hearing you guys on the switcher dynamic, and the comment that, you know, if patients are doing well, there, there'll be a limited motivation to switch. 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. I think, you know, their commentary is that there, there, there actually is a decent amount of parents and, and patients out there that are, are interested in switching to something. Let me just talk about what you're seeing more broadly. You know, is there a demographic or some attribute other than just, you know, performance that, that might drive this decision or, or, or desire to switch?

You know, I, if I can maybe ask a question on BMN 351. I'm kind of struck by, you know, this is-- this drug is mentioned in your, your commentary, but just looking at the dystrophin data, it looks, you know, pretty differentiated, if not superior to what's out there. Let me 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 way points on that drug, please. Thanks.

Greg Friberg (Chief Research and Development Officer)

Thanks so much, Chris. This is Greg Friberg again. Let me take your second question first. I, 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 PK/PD model, predicts roughly 10% at steady state. That is a, a, an unprecedented number for the exon 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. 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. 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. 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 95th Centile data.

We expect that this next tranche of data will have it before the end of the year. 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. 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. 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. I think I've gone through some of the package there that, that goes through, again, some of those data points. With that, though, from the commercial perspective, I want to give Cristin a chance to, to share her perspective.

Cristin Hubbard (Chief Commercial Officer)

Yeah, thanks for the question, Chris Raymond, and you know, 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, in which we operate. 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. 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 seven years out, which really matters to these, to these caregivers, these patients, and importantly, the physicians.

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 decision. Now, importantly, when I think about the markets, you know, we've got, we've got very different, you know, 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. Really, where we intend to grow Voxzogo there is going to be really in newborns, where our label enables us to. 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 or 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. We think that the value proposition of Voxzogo is there and will continue to grow therein. 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. 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, and important story for Voxzogo and all.

Operator (participant)

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

Phil Nadeau (Managing Director and Senior Biotechnology Research Analyst)

Good afternoon, thanks for taking our question. 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? 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.

Greg Friberg (Chief Research and Development Officer)

Thanks, Phil. This is Greg again. I'm going to take a first stab and again, 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. Dobber's data, for example, is showing slightly larger, more like a 1.8 centimeter growth of AGV in the hypochondroplasia patients. 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. We believe we've designed the right study.

It's a question of reaching the endpoint and turning it over, and we're very excited to see the data. Cristin?

Cristin Hubbard (Chief Commercial Officer)

Yes, I think, you know, once we see the data, the scientific rationale will have been proven. But I, 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. 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. When I think about what the biggest opportunity is, and, 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. 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 hypochondroplasia. We're really talking a lot about the burden of the condition to, to really, enhance that, that sense of urgency to treat. We're, 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. All in all, we really are working at ensuring that diagnosis, diagnosis, which I think will be the biggest problem statement for hypochondroplasia, that we can, that we can get out there and tackle that early.

To remind you, the, 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 there and help to grow-

Greg Friberg (Chief Research and Development Officer)

Yeah.

Cristin Hubbard (Chief Commercial Officer)

The space.

Greg Friberg (Chief Research and Development Officer)

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.

Operator (participant)

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

Speaker 16

Hi, this is Phoebe on for Akash. Thank you for taking our question. One on Voxzogo, again, just following on the infigratinib data, where does this fall in your scenario analysis for your 2027 revenue outlook? 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? Thank you.

Brian Mueller (CFO)

Hi, Phoebe, this is Brian. I'll take the first part of the question on 27 and any impact from the infigratinib data. We don't have new updates on 27 at this time. I, 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 2 competitors and comparable data to Voxzogo. Thanks.

Greg Friberg (Chief Research and Development Officer)

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 seven, eight, nine, 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 builds on that confidence. There are some other tactical, I think, benefits that come along with full approval.

Most importantly, again, we see this as our opportunity to put forward what we see as a leading evidence package for achondroplasia.

Operator (participant)

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

Speaker 15

Thanks for taking our question. This is Tommy 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. Also for BMN 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.

Brian Mueller (CFO)

Hi, Tommy, it's Brian. I'll start with the first part of your question. Thank you. In terms of the Voxzogo guidance for 2026, you know, first of all, just to note, we're really pleased to have grown the product 26% in 2025, its fourth year on the market. With respect to the range, the $975 million-$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 2027. I'll also share that we're being guarded on a couple of routine market access renegotiations in 2026. These are normal course of business.

The product's fifth year on the market, those will resolve this year, but we're being measured on those. 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, new patients?

Cristin Hubbard (Chief Commercial Officer)

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, these profiles that we've seen so far are very much in line with what we anticipated. Importantly, where we intend to continue growing patient demand is, is what I've said, it's in that zero to two population and ensuring that we're really protecting switching.

Speaker 15

333.

Greg Friberg (Chief Research and Development Officer)

Yep, this is Greg. With regard to the BMN 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 BMN 333 can have a superior growth profile over all the available agents. 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.

The question I think, behind your question was whether that those powering 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.

Operator (participant)

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

Gena Wang (Managing Director of Biotech Equity Research)

Yeah, thanks for taking the question. Just what's your latest expected timing for the data readouts from the phase II CANOPY basket study for Voxzogo? 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 US growth versus ex-US growth over the course of the year? 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. Thanks.

Greg Friberg (Chief Research and Development Officer)

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. That refers to ISS 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.

Brian Mueller (CFO)

Thanks, Ally. This is Brian. I'll start with the first part of your guidance follow-up. You know, we're not delineating further the individual growth dynamics in the US and ex-US. Again, we've discussed before about growing in all markets. You know, by the way, even, you know, with competition coming to market, Voxzogo is 50 on the market, we are satisfied with be able to, you know, confidently guide to a high single-digit growth rate in 2026, and at the midpoint, having the product reach blockbuster status. You know, 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, you know, 100% Voxzogo, and Cristin's already touched on the level of opportunities ex-US.

We'll keep you updated from quarter to quarter on the growth dynamics, but not breaking it out further at this time.

Alexander Hardy (CEO)

Hi, Ellie, this is Alexander. I'm just going to come back to your, to the question about the reimbursement processes that Brian mentioned. Just give you a little bit more color on those. They're, they're in a number of markets. You know, when you get into five years on the market, and the product is very well established and has broad usage, you know, you, you, you tend to go under, you know, formal reimbursement processes. 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. 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, where it's going to be happening in 2026, you know, you obviously have a price reset on your, on your entire population. Then in front of you, you have the potential to, to reach many more patients. It's a, it's a very exciting actual opportunity for Voxzogo in those markets and overall.

Gena Wang (Managing Director of Biotech Equity Research)

Helpful. Thanks.

Operator (participant)

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

Speaker 14

Hi, this is Addie on for Cory. 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 Voxzogo, or are there any meaningful differences emerging that could, that could differentiate the profile one way or the other? Thank you.

Greg Friberg (Chief Research and Development Officer)

Thank you for the question, Addie. 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. Again, that's opened this therapeutic window that has allowed us to go to 3, 5, 7x, and higher AUC exposures. 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.

Operator (participant)

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

Paul Matteis (Managing Director)

Great. Thanks so much. I, 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, a brief try. Just as it relates to the integration of the business, Alexander, you reorged 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. How do you think about Amicus fitting into that going forward? 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.

Alexander Hardy (CEO)

Thanks very much for the question, Paul. Yes, I mean, these, these two products, our, our intention is, post-close, that these are going to drop right into our enzyme therapy business unit. I mean, it, they, they just fit perfectly. The, the entire go-to-market model is, is exactly the same as our, as our current portfolio. The, the opportunities and the, the opportunities for us to, to drive synergies on the top line, as well as synergies in terms of the way that we operate are, are, are tremendous. You know, we're, we're looking forward to, to sharing more post-close.

We're on track right now for a 2nd quarter close, and then we'll, we'll share more about our specific plans and, our, our expectations for what these, 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. More to come, Paul.

Paul Matteis (Managing Director)

Okay. If I could just ask one quick follow-up. Thank you, Alexander. 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? 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 seems, you know, like, as Alexander alluded to, this isn't all that... It's fairly straightforward. Where were you coming from on that point?

Greg Friberg (Chief Research and Development Officer)

Yeah. Thank, 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. It had nothing to do with the direction of what we see and some of those that are including it.

Operator (participant)

Your next question comes from the line of Joseph Schwartz with Leerink Partners. Your line is open.

Joseph Schwartz (Senior Research Analyst)

Great. Thanks so much. 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 and at a few centers, and I was just wondering if BioMarin had the opportunity to see the results of these pilot programs and if.

Brian Mueller (CFO)

you know, they're on, along the lines of what you expect to roll out. Could you just talk a little bit about your initiatives there? Thanks.

Cristin Hubbard (Chief Commercial Officer)

Yeah. Thanks for the question, Joe. It's Cristin. You are indeed, it exactly what you just said, that 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, what's going on, what makes sense, given what we already have in our company versus what's going on over there. At the end of the day, we are running as two independent businesses at this point in time, 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 Pompe, 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.

Also importantly, the really big opportunity there is to increase the diagnosis rates for both Galafold as well as Pompe. Then when you're talking about Pompe, 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.

Operator (participant)

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

Olivia Brayer (Director and Senior Biotech Analyst)

Hi, good afternoon, guys, and thank you for the question. 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. Then a quick follow-up on hypochondroplasia. When do you think we could realistically see that launch and uptake in those patients?

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, the competitive headwinds in the achondroplasia market next year?

Brian Mueller (CFO)

Thanks, Olivia. This is Brian. I'll start with a little more color on the quarters. I, I appreciate the question. Yeah, a few brief things there. First of all, we've always experienced these kind of bolus orders, and, and the potential volatility of quarterly revenue. By the way, we've typically seen step downs from Q4 to Q1. We do-- I, I think we, especially after this year, we, we definitely observed some Q4 buying globally. It, it isn't always, inventory levels. It, it could be, in some cases, of single national payers, you know, kind of just making their way through their, their budgets. There's a number of, of factors, but we've seen this in Q4. It was exacerbated-- seen this before for Q4, exacerbated, here in 2025.

Another item I'd share is. 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 steady patient additions have been quarter after quarter over the last several years, frankly. Yet, when you look at revenue, it bounces around a bit because of these, because of the order timing. In fact, while Q4 had a, you know, a bolus effect, there's actually some markets where it was kind of a catch-up because revenue was flagging patient additions. That's number one, and number two is, I think we're gonna continue to observe that this year. I'll share, and this should also help you all estimate the proportions of revenue for Voxzogo.

We expect that the quarters will be similar to last year. I already said that Q1 is on par with Q1, but we also expect a lot of it to be backloaded to Q4. Any confidence, any assumptions around the competition are fully baked in.

Cristin Hubbard (Chief Commercial Officer)

With regard to your second question, 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. What that means is hopefully approval is coming 2027, and we would expect to see immediate revenue impact at that point in time. 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.

Operator (participant)

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

Jason Gerberry (Managing Director)

Hey, guys. Thanks for taking my question. Might just on the phase III powering and the 2.25 centimeter per year, is that a threshold effect? You know, if when you're doing your phase II 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? I think in your earlier comments, not to get too hung up, I think, on that 2.25 number. You know, 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?

I just wanted to clarify, if that's a threshold effect, and a go, or no-go threshold in the, in the dose-ranging work.

Brian Mueller (CFO)

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, you know, alpha numbers behind that as well. 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 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.

Those numbers, and announcing them again, I think they state appropriately our ambition of what we think a meaningful, and, and clinically relevant improvement over what is already a, a well-established, safe and effective therapy in Voxzogo would look like.

Operator (participant)

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

Alexander Hardy (CEO)

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.

Operator (participant)

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