BioMarin Pharmaceutical - Earnings Call - Q1 2025

Executive Summary

• Q1 2025 delivered solid growth and margin expansion: total revenue $745.1M (+15% y/y), GAAP EPS $0.95 (+107% y/y), and non-GAAP EPS $1.13 (+59% y/y), with non-GAAP operating margin at 35.7% (+1,190 bps y/y).
• Results modestly beat S&P Global consensus: revenue $745.1M vs $738.7M* and non-GAAP EPS $1.13 vs $0.95*; strength was driven by 40% y/y VOXZOGO revenue growth and lower operating expenses from 2024 cost transformation and portfolio reprioritization.
• Guidance reaffirmed: FY25 total revenue $3.10–$3.20B, non-GAAP op margin 32–33%, non-GAAP EPS $4.20–$4.40; VOXZOGO FY25 revenue expected at $900–$950M.
• Management flagged order timing and H2 weighting (VOXZOGO revenues to be more weighted to H2), implying potential Q2 volatility despite sustained patient growth—an important near-term trading dynamic.

Consensus estimates marked with * Values retrieved from S&P Global.

What Went Well and What Went Wrong

What Went Well

• VOXZOGO momentum: revenue up 40% y/y to $214M, driven by global demand and expanded access to 49 countries; management expects H2 weighting as ordering patterns normalize across OUS markets.
• Profitability outpaced revenue growth: GAAP operating margin 30.0% (+1,640 bps y/y) and non-GAAP operating margin 35.7% (+1,190 bps y/y), reflecting 2024 cost transformation and R&D reprioritization.
• Cash generation: operating cash flow $174M (+271% y/y) and total cash/investments ~$1.8B, supporting reinvestment in pipeline and commercialization.
  “Non-GAAP operating margin reached 35.7%… driven by strong revenue performance and a spending reset as we prepare to invest more aggressively across R&D and SG&A in the coming quarters.” — CFO Brian Mueller.

What Went Wrong

• Sequential VOXZOGO revenue disconnect: management highlighted flattish revenue trends from Q4 → Q1 and potentially into Q2, despite increasing patients due to multi-market order timing—creating near-term optical pressure.
• KUVAN headwind: product revenue fell 31% y/y to $25M due to ongoing generic competition post loss of exclusivity.
• Tax rate impact: higher tax provision associated with increased taxable income partially offset profit growth.

Transcript

Operator (participant)

Good day, everyone, and welcome to the BioMarin Pharmaceutical First Quarter 2025 Conference Call. Just a reminder that this conference is being recorded. I would now like to hand things over to Ms. Traci McCarty. Please go ahead, ma'am.

Traci McCarty (Group VP and Head of Investor Relations)

Thank you, Operator. To remind you, this non-confidential presentation contains forward-looking statements about the business prospects of BioMarin Pharmaceutical, including expectations regarding BioMarin's financial performance, commercial products, and potential future products in different areas of therapeutic research and development.

Results may differ materially depending on the progress of BioMarin's product programs, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market, and developments by competitors, and those factors detailed in BioMarin's filings with the Securities and Exchange Commission, such as 10-Q, 10-K, and 8-K reports. In addition, we will use non-GAAP financial measures as defined in Regulation G during the call today.

These non-GAAP measures should not be considered in isolation from, as substitutes for, or superior to financial measures prepared in accordance with U.S. GAAP, and you can find the related reconciliations to U.S. GAAP in the earnings press release and earnings presentation, both of which are 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.

On the call from BioMarin Management today are Alexander Hardy, President and Chief Executive Officer, Brian Mueller, Executive Vice President, Chief Financial Officer, Cristin Hubbard, Executive Vice President, Chief Commercial Officer, and Greg Friberg, Executive Vice President, Chief R&D Officer. I will now turn the call over to BioMarin's President and CEO, Alexander Hardy.

Alexander Hardy (President and CEO)

Thank you, Traci, and good afternoon, everyone. Thank you for joining us today for our First Quarter 2025 Results update. We are pleased to have delivered strong financial performance and revenue growth of 15% in the quarter. On the bottom line, non-GAAP earnings per share of $1.13 represented a 59% year-over-year increase, reflecting significant profitability expansion, nearly 4x the rate of top-line growth. This performance highlights the fundamental value of our transformative medicines and the strength of our business, both of which are key attributes that distinguish BioMarin.

These results pave the way for record full-year performance in 2025 and boost cash generation for reinvestment in innovation and expansion. Last September, we announced changes to BioMarin's strategy and operating model. Since that time, we have been focused on implementing these changes while at the same time delivering strong growth and profitability.

Looking ahead, we expect to see the continued implementation and benefits of this transformation deliver even stronger results and innovation in the coming quarters and beyond. Turning briefly to external dynamics impacting the sector, we believe BioMarin is well positioned to manage through uncertainty across a number of areas. As the preeminent innovator of medicines that treat rare conditions, BioMarin is less exposed to macroeconomic conditions impacting other sectors. Because so many of our medicines are treatments for children, we have limited exposure to policies impacting Medicare, which covers roughly only 2% of our U.S. patient population.

In addition, BioMarin's core fundamentals also provide a level of insulation from external unknowns. Increasing cash generation, our extensive global revenue base, with approximately 2/3 of our total revenues originating from outside the United States, along with our established global commercial, regulatory, and manufacturing capabilities, position us well in an evolving and dynamic market environment. Moving to the specific uncertainties around potential pharmaceutical tariffs, we are analyzing potential exposure and mitigation tactics under multiple scenarios.

As BioMarin's medicines address relatively small patient populations around the world, we manufacture products that address these rare indications in single locations, either in the U.S. or Europe. Based on our current understanding, we believe that the global scope of our business model, with approximately two-thirds of total revenues generated from outside of the United States and a significant level of U.S.-based manufacturing, will provide some protection from potential tariff impacts should innovative medicines for rare conditions be targeted.

Important to note, BioMarin has immaterial exposure to U.S. tariffs for China, Mexico, and Canada across its global supply chain operations and product sales. Turning now to potential new products and expansions, we're making good progress on our innovation strategy. I am pleased to share that we recently completed enrollment in our pivotal phase III study with VOXZOGO in children with hypochondroplasia, paving the way for a potential launch in 2027. With PALYNZIQ, based on the positive pivotal data we announced in April 2025, we are on track to submit applications in the second half of this year in the United States and Europe for the treatment of adolescents.

In addition, we expect to share early clinical results later this year from both BMN 351 for Duchenne muscular dystrophy and BMN 333, a long-acting CNP, two candidates that may provide highly differentiated treatment options for the conditions they target.

Finally, we expect to fortify our internal innovation with business development, as we feel that BioMarin's established global capabilities, coupled with the external environment, create opportunities that will support our growth agenda. In summary, we believe we are well positioned to manage through ongoing market uncertainty based on the global demand for our innovative medicines. Through BioMarin's strategic transformation implemented over the last year, we have set ourselves up to deliver significant value creation for all our stakeholders in 2025 and beyond. Thank you for your attention. I will now turn the call over to Brian to provide our financial highlights for the quarter.

Brian Mueller (EVP and CFO)

Thank you, Alexander. Please refer to today's press release for detailed first quarter 2025 results, including reconciliations of GAAP to non-GAAP financial measures. All 2025 results will be available in our upcoming Form 10-Q, which we expect to file in the coming days. We are pleased with BioMarin's strong results across the business in the first quarter of 2025. First quarter 2025 total revenues rose 15% to $745 million compared to the same period last year. VOXZOGO's demand fueled growth, with global revenue reaching $214 million, a 40% increase year-over-year and continuing its strong growth trajectory since approval four years ago.

Revenue from the Enzyme Therapies business unit grew 8% year-over-year to $484 million, with substantial contributions from PALYNZIQ, which grew 22% compared to the first quarter of 2024. As I mentioned in February 2025, we expect total revenues to be higher in the second half of this year compared to the first half due to anticipated order timing dynamics across the portfolio. These dynamics apply to VOXZOGO as well, with the product now available in 49 countries.

While a significant volume of new patients have started VOXZOGO therapy in recent quarters through today, we note that quarterly VOXZOGO revenues, looking back to Q4 2024 and anticipated trends through Q2 2025, have revenues slightly disconnected from patient growth and appearing relatively similar quarter-to-quarter. Importantly, we continue to expect VOXZOGO full-year revenues to be between $900 million and $950 million, which at the midpoint represents 26% full-year growth. Moving to expenses, in the first quarter of 2025, non-GAAP R&D expense was $147 million and lower than the same quarter in 2024.

Operating trends in the first quarter of this year were consistent with those in the fourth quarter of last year, reflecting the impact of BioMarin's R&D reprioritization. Looking ahead in 2025, we plan to increase R&D spend on our pipeline priorities and the VOXZOGO new indication. In the first quarter, non-GAAP SG&A expense of $183 million decreased year-over-year, also due to the impact of the cost transformation initiative, including reduced activities related to the company's focused ROCTAVIAN strategy announced last year, where we observed reduced expenses due to these dynamics in the quarter.

Noting that Q1 is typically a lower spend quarter for BioMarin, throughout the remainder of 2025, we expect SG&A expense to increase as we invest in the strategic priorities of the newly formed Skeletal Conditions and Enzyme Therapies business units. Moving to profitability, non-GAAP operating margin reached 35.7% for the first quarter of 2025, an expansion of 11.9 percentage points year-over-year. These results were driven by strong revenue performance and a spending reset as we prepare to invest more aggressively across R&D and SG&A in the coming quarters.

For R&D, this will include global applications for PALYNZIQ adolescent approval, expansion of our BMN 351 and BMN 333 studies, as well as our clinical programs advancing multiple new indications with VOXZOGO, just to name a few. For SG&A, this will include investments in VOXZOGO and enzyme therapy global commercial expansion activities and commercial launch preparations for hypochondroplasia and PALYNZIQ in adolescents. Over the coming quarters, increased spending on R&D and SG&A is expected to result in slightly lower non-GAAP operating margin in Q2 through Q4 2025.

However, we expect that quarterly non-GAAP operating margins will balance out over the course of the year to our full-year non-GAAP operating margin guidance of between 32%-33% that we reaffirmed today. Strong non-GAAP operating margin flowed through to the bottom line, resulting in first quarter non-GAAP diluted earnings per share of $1.13, an increase of 59% year-over-year. Consistent with prior quarters, non-GAAP diluted earnings per share grew at a rate higher than revenue grew, reflecting BioMarin's focus on operational efficiency and our value commitment to shareholders.

Following my comments on the timing of both revenue and expenses in 2025, non-GAAP earnings per share is not expected to be a smooth progression from quarter to quarter. As implied with the strong Q1 result in our reaffirmed 2025 non-GAAP earnings per share guidance, earnings per share could decrease in certain quarters compared to this first quarter, but accumulate to the expected double-digit growth for the full year. Please note that while this reiteration of guidance reflects the impact of the currently enacted U.S. tariffs, it does not reflect the impact of potential future pharmaceutical tariffs.

BioMarin's increasing profitability continues to generate cash, with $174 million of positive operating cash flow in the first quarter of 2025, a 271% increase over Q1 2024. This trend is expected to continue and provides the opportunity to execute on our top capital allocation priority of investing in innovation and future growth to positively impact our patients, employees, and shareholders.

In conclusion, we are pleased to begin 2025 with another strong financial performance that gives us confidence that BioMarin will continue to execute on all of the elements of our revitalized strategy. I will now hand the call over to Cristin, who will speak to our commercial performance. Cristin?

Cristin Hubbard (EVP and Chief Commercial Officer)

Thank you, Brian. The team's focus on commercial execution led to another quarter of strong growth across the business. Starting with VOXZOGO for the treatment of achondroplasia, we were very pleased to have delivered 40% year-over-year revenue growth with strong contributions from across the globe. As of the end of the first quarter, children across 49 countries had access to VOXZOGO treatment, and we are making strong progress toward our goal of opening access in more than 60 countries by 2027.

In the United States, we are focused on implementing initiatives targeting new patient uptake, which we expect will drive continued expansion beginning in the second half of the year. Commercialization efforts include increasing field personnel to broaden the prescriber base and implementing activities to further drive the adoption of VOXZOGO treatment. Outside of the U.S., we saw continued strength across all markets. Taken together, we expect these U.S. and O.U.S. dynamics to result in higher VOXZOGO revenue in the second half of 2025 compared to the first half of 2025.

As our global presence treating achondroplasia expands, with strong momentum contributed from recently published international guidelines, which recommend diagnosis and early treatment with VOXZOGO, we are well positioned to enter the hypochondroplasia market in 2027, pending support of phase III data next year. We are focusing on our global launch preparations and will keep you apprised as progress unfolds. Moving to our Enzyme Therapies, we are pleased with this business unit's performance in the first quarter, where total enzyme therapy revenues increased 8% year-over-year.

Starting with specific dynamics in the quarter, we saw continued strong growth with PALYNZIQ, increasing 22%, and ALDURAZYME up 40% year-over-year. VIMIZIM, our second-largest revenue contributor, was uneven compared to the prior quarter, typical of ordering dynamics with our mature global brands. Now, the strength of PALYNZIQ is based on the opportunity for potent and durable Phe reduction to international guideline levels. The unrestricted diet potential that PALYNZIQ offers is an important product characteristic that we think will bring tremendous value to the adolescent PKU population should we get approval next year.

We are pleased with the growth of the Enzyme Therapies products in the first quarter and expect full-year contributions from this important business unit to remain robust. In summary, the team executed well in the first quarter, and we look forward to continued strong performance throughout the remainder of 2025. Thank you for your attention, and Greg will now provide an update in R&D. Greg?

Greg Friberg (EVP and Chief R&D Officer)

Thank you, Cristin. As Alexander mentioned, we recently completed enrollment in our pivotal study for VOXZOGO in hypochondroplasia. We will be sharing the 52-week results next year and will be seeking approval for 2027 should the data be supportive. Also new today, we are pleased to share that we have reached an agreement with the FDA on an overall clinical development plan for BMN 333. Assuming the phase I data are supportive, we plan to initiate a registration-enabling study in 2026, supporting our previously stated ambition for 2030 approval date. We will continue to engage with regulators around the globe to refine our plans in the coming months.

In the ongoing phase I study in healthy volunteers, we've enrolled multiple cohorts and look forward to sharing initial pharmacokinetic data in the second half of the year, with detailed data to be presented at a scientific venue in the first half of 2026. We're also pleased with the numerous data updates across the portfolio so far this year.

In March 2025, at the American College of Medical Genetics and Genomics meeting, we shared data demonstrating favorable safety and strong adherence in real-world clinical practice with VOXZOGO in children under three with achondroplasia. No treatment-related adverse events or dose interruptions were reported among these 63 children followed for up to two years. The study's safety results, including an infant as young as one month old, add to the growing body of evidence supporting early treatment initiation with VOXZOGO, consistent with international treatment guidelines published in the journal Nature Reviews Endocrinology earlier this year.

Also, at ACMG, PALYNZIQ data demonstrating the importance of sustained Phe reduction and the positive impact this can have on health-related quality of life outcomes were presented. Most notably, mood and attention scores for patients achieving sustained Phe levels less than or equal to 120 μmol per L were significantly better than those at higher levels, suggesting that sustained Phe in the normal range is both achievable and may provide additional benefits for adults living with PKU.

These significant and sustained reductions in blood Phe levels, coupled with the opportunity for an unrestricted diet, are unique characteristics of PALYNZIQ, the only enzyme substitute therapy for the treatment of PKU. These benefits demonstrated in adults with PKU give us continued confidence in the treatment profile of PALYNZIQ, including for adolescents, as supported by the positive pivotal data in the 12 to 17-year-old group, as announced in April 2025. We plan to submit for regulatory approvals in both the United States and Europe in the second half of the year.

Turning to BMN 351 in Duchenne muscular dystrophy, we plan to publicly present our first clinical update in the second half of this year, including 25-week muscle biopsy data for four patients treated at the 6 mg per kg dose cohort. We have done extensive PK/PD modeling based on preclinical data to determine what value at 25 weeks will predict muscle dystrophin levels of 10% or higher at steady state, which we anticipate to occur out at 52 weeks or later.

The model takes into account the tissue half-lives for several chemical species, including for BMN 351, for the skip product production, and for generation of dystrophin protein. These values were informed by our experience with BMN 351 in preclinical mouse and non-human primate studies, as well as from prior human experience with other phosphorothioate oligonucleotides. The model tells us that levels at 25 weeks can be expected to rise 2x-3x higher by the time steady state is reached.

We also want to measure how these patients feel and function. To do so, we have included several functional measures in this study, though we anticipate such measures will be most informative once steady state is reached. The next update on this program will be shared at a scientific congress in the second half of this year. Thank you for your attention today. We look forward to keeping you apprised of our progress as we continue to advance our high-impact candidates through the pipeline. We will now open the call to your questions. Operator?

Operator (participant)

Thank you, sir. Everyone, just a reminder that it is star one if you have a question. We'll go first to Phil Nadeau, TD Cowen.

Phil Nadeau (Managing Director and Senior Research Analyst of Biotechnology)

Hi, good afternoon. Thanks for taking our questions. Two financial ones. First, on VOXZOGO, you mentioned a couple of times about H2 being larger than H1 and also the revenue in the quarters through Q2 being relatively similar. We're just curious whether does that mean a decline in Q2 revenue? It does look like revenue grew a bit from Q4 to Q1, so if revenue is approximately in the intermediate between those two, maybe there'd be a down quarter Q2.

Second financial question on exposure to tariffs. I think your guidance as to the current tariff situation is very clear. Could you give us some sense of how your financials could be impacted should the U.S. impose a 25% tariff on EU pharmaceuticals, and then maybe should that situation be retaliated against with a 25% tariff from the EU on the U.S.? Thanks.

Brian Mueller (EVP and CFO)

Thanks, Phil. This is Brian. I'll take both of those. Appreciate the questions. First, on VOXZOGO, I think you heard accurately in terms of the trends we're observing coming out of Q4 last year here in Q1 and then into the first half of this year. We had previously commented that we expected most of the VOXZOGO revenue growth to come in the second half of the year.

The first thing I'd point to is what we're observing are global order dynamics, which are different from what shows up in the enzyme therapy business from time to time that the quarters would be a handful of those large bolus orders from select international customers that can either accumulate to an anomalous quarter or be missing from a quarter. It's less that and more just the dynamics of VOXZOGO being available in now 49 markets. It does not take much for some of the purchasing patterns between, again, the end of 2024, Q3, Q4 into Q1, Q2, for those to look flattish. Importantly, at the same time, we are steadily increasing patients from quarter to quarter.

It is just an accumulation of dynamics across all of those markets. We see it flip in the second half of the year when we expect revenue to increase more substantially. That is the key VOXZOGO matter. On tariffs, you heard accurately. Because we have immaterial exposure in our business to China, Mexico, and Canada, we do not have a material impact, and our reaffirmed guidance today includes any modest or immaterial impacts from tariffs in those regions. In terms of potential future pharmaceutical tariffs, we are modeling all scenarios and evaluating all of the potential mitigating tactics.

We're going to hold off on speaking to specifics, including quantifying any of those scenarios until we have more clarity and announcements and certainty in terms of what pharmaceutical tariffs could look like. I can assure you that we're not just looking at all scenarios, but all potential levers. Many of those are in the same categories that you're hearing some of the larger biopharmas discuss on their Q1 calls. That includes global supply chain strategies, which also for us includes our global manufacturing network, managing inventory levels, our global intellectual property rights.

Lastly, monitoring potential global tax reform in connection with or in response to the overall tariffs. We've got a dynamic global business. Our products are sourced from both the U.S. and outside of the U.S. I'll share that we are a net exporter of product from the U.S. due to our significant California-based manufacturing site.

Just a reminder as well that from an overall exposure to U.S. sales imports, most of our sales are outside of the U.S. Roughly 1/3 of our total sales are U.S. sales and 2/3 outside of the U.S. Those are potentially insulating factors should we see pharmaceutical tariffs. We're going to hold off on speculating on any details at this time. Appreciate your interest, though.

Phil Nadeau (Managing Director and Senior Research Analyst of Biotechnology)

Fair enough. Thanks for taking our questions.

Operator (participant)

The next question is from Salveen Richter Goldman Sachs.

Tommie Reerink (Biotechnology Equity Research Associate)

Thanks for taking our questions and congrats on all the progress. This is Tommie on for Salveen. Just wondering if we can get an update on your interest and maybe timing for BD after all of the meetings that you had in January 2025. When we think about the data that you'll give us for BMN 333 this year, can you maybe characterize the level of detail we'll get before you kind of present the full data at a congress next year? Thank you.

Alexander Hardy (President and CEO)

Thanks very much, Tommie. I'll handle the question on BD and then hand over to Greg. Yeah, we're continuing to be very excited about the potential for BD for BioMarin based on our strong capabilities and also, obviously, the state of the capital markets. We've been approaching it very methodically. We've got a great team and capabilities in place. We've got a very clear strategy, which we outlined and communicated to the outside world last year. We've been looking systematically at opportunities. Just to reiterate, what we're looking at is things which are completely lined up with what BioMarin is really good at.

Genetically defined conditions. We're looking at clinical stage assets in particular, as well as obviously earlier assets, but we've always done that. Particularly highlighting ones that align with our business unit structure, where we really think we have a strength and a right to win. Everything is very much on track. We continue to focus on doing at least one business development deal this year. We are looking forward to providing updates as and when that makes sense. Obviously, as the market continues to develop, it only creates more value from our perspective and makes those deals even more attractive from an investor standpoint. With that, I'll hand over to Greg.

Greg Friberg (EVP and Chief R&D Officer)

Thanks, Alexander. With regard to BMN 333, just as a quick reminder, we have an ongoing phase I study. It is in healthy volunteers, not in patients. The primary purpose of this study, of course, will be to look at single-dose safety, but also the PK profile. That is the data. Again, we're actually marching right through the study very efficiently. We're several cohorts in at this point. We anticipate before the end of the year that we'll be able to provide a top-line update with regard to whether or not that data is supportive of us moving forward. The more detailed PK data and totality of the phase I, we anticipate in the first half of next year, we'll be releasing that publicly.

Operator (participant)

The next question today will come from Joseph Schwartz, Leerink Partners.

Jenny Gonzalez-Armenta (Equity Research Associate)

Hi, this is Jenny on for Joe. Thank you for taking our question. I think for previously, you guys have mentioned that VOXZOGO has penetrated just under 20% of the market in achondroplasia as of the second quarter last year. Can you talk a little bit more about what strategies you're implementing to drive further adoption among patients? Is this something that you're going to have to reach out to physicians? What are the main areas of possible improvement here and how you see this trending over time? Thanks.

Cristin Hubbard (EVP and Chief Commercial Officer)

Yeah, thank you so much for the question, Jenny. This is Cristin Hubbard. Great question about the penetration of VOXZOGO. We have several strategies that we are in the process of implementing that I think will certainly help us to further drive growth. In particular, when I think about the U.S. market, which is our largest single-market opportunity, where we're really focused on is driving adoption across all age groups. Now, as we've previously reported, we've had quite an uptick in numbers in the 0-4 population. Just to remind you that we just got that label expansion at the end of 2023.

Our new patient starts have been very strong in the 0-4 age group, in which case this is very well aligned with the consensus guidelines that we saw come out earlier this year, which recommends early diagnosis and early treatment with VOXZOGO. We have strategies and tactics in place targeting that age group, starting at infancy. Of course, we do not want to forget about the importance of slightly older patients, so in the 5+ age group. That is where we are definitely still targeting. There is still opportunity there in the U.S. to continue to target those patients.

I will say that our strategies in particular are really in and around driving awareness of the medicine, of the fact that there is a treatment option available. We are looking at investing in initiatives that will help us there. This will, in large part, help us to expand the prescriber base. What we're looking at is really making sure that we're expanding the prescriber base. This is true across various specialties, but where we see the most growth in terms of prescribers is in the pediatric endocrinologists, which is very in line with our strategies to expand there.

We're also investing in increased field personnel, again, to target prescribers to ensure that we're driving awareness and adoption therein. When we think outside of the U.S., where we're looking at is continuing to look for those kind of access pathways, awareness pathways, but also importantly, we'll continue to open new markets. We'll expand further penetration. I should say [crosstalk]

Oh, I was going to say, and lastly, I think that all of this has really been enhanced in our ability to do this, to execute in a focused manner because of the business unit structure that we've put in place. This has been a really exceptional way for us to really drive into the market insights, leading to strategy and execution in a really focused and agile way. Thank you. Next question.

Operator (participant)

Thank you. Up next is Akash Tewari, Jefferies.

Zaki Molvi (Senior Associate of Biotech Equity Research)

Hi, this is Zaki on for Akash. Thanks so much for taking the question. Just on the DMD corrector BMN 351, when we looked at the recently published mouse data, it looks like there's some mild liver signals in those mouse models at the higher exposures and some inflammation in the liver and muscle in those mice. Given those safety signals, how are you thinking about your ability to dose chronically? Is there any data that you're collecting that we can see in the upcoming readout that could potentially make us more comfortable on safety? Thank you.

Greg Friberg (EVP and Chief R&D Officer)

Yeah, thanks for the question. This is Greg Friberg. These observations are class effects for the ASO categories. From that standpoint, we're not surprised to see at high dose levels in some of our toxicologic studies that we're seeing some of these end-organ toxicities. We're watching them very closely. In fact, we selected a chemistry type, this phosphorothioate instead of other available chemistry classes because we do believe that this is a case where it's all about opening that therapeutic window. Again, there are two ways to address the therapeutic window. One is to limit toxicity.

The other way is to drive the potency of the molecule. We've engineered this molecule to try to really take advantage of, like we've talked about previously, this novel skip site and some other chemical factors, again, that get the drug where we want it to be.

Those are the open questions, I think, for almost any molecule in this space. We are watching patients very closely for a variety of toxicities. We will be presenting our data from our 6 mg per kg cohort in the second half of this year. You can expect, in addition to dystrophin assays on muscle biopsies, that we would present the totality of our safety data that is available at that time.

Operator (participant)

The next question today is from Jessica Fye, JPMorgan.

Jessica Fye (Managing Director and Equity Research Analyst of Biotechnology)

Hey, guys. Good afternoon. Thanks for taking my question. BioMarin continues to execute across the business. However, the market seems worried about long-term competition for VOXZOGO. Can you talk about how you think you can best address the market's perception of VOXZOGO's long-term value, particularly beyond 2030? Thank you.

Cristin Hubbard (EVP and Chief Commercial Officer)

I'll start on the commercial execution here in the near term. If you want to talk about some of the life cycle management, I think that that would be probably a nice add. Thanks for the question, Jess. I certainly recognize where you're coming from in terms of the market perception. What I can really say is that with VOXZOGO, we're really focused in terms of our strategies and where I think that this is going to be something that will be quite powerful for us, is really focused in and around this notion of a start-and-stay treatment paradigm. Really getting patients to start.

Again, reminding everybody that our label starts at infancy, which I think is a unique differentiator here in the near term, it's really based on our ability to help families and prescribers feel comfortable with the growing body of evidence, which includes 6,000+ patient years of efficacy and safety data. We've got a tremendous, and I know, Greg, you can speak to some of this, growing body of evidence on the overall health benefits that go far beyond height, which I think is really important to treaters and families alike. We've got this broad label in terms of starting at infancy, which I think aligns nicely with the consensus guidelines.

Importantly, we have a growing footprint in countries outside the United States, reminding everybody that only 10% of the total addressable patient population is in the United States. We have an incredible commercial footprint that goes into many, many countries.

As you guys know, we are now in 49 countries we have VOXZOGO access in, and we are looking to build that into greater than 60 countries by 2027. We see the growth trajectory as something that we can maintain. As you know, we have given full-year guidance to a little over 25% at the midpoint for the year. We will continue with a 25% CAGR out into the future. Greg, I do not know if you maybe should speak to some of the life cycle options we have as well.

Greg Friberg (EVP and Chief R&D Officer)

Yeah, thanks, Cristin. From an R&D perspective, we are going to continue to try to leverage, again, that 6,000 patient year. It's about 4,000 individual patients and growing experience to actually put the data out there with regard to how we're improving the health and wellness of these patients with achondroplasia. We get caught up in, I think, AGV numbers sometimes, but we have to remember that the burden of disease that we really want to address are things that go well beyond that.

Data with regard to craniofacial volume, foramen magnum size, body proportionality, quality-of-life data, and of course, bone strength and bone integrity, these are the kind of data that we have already put out, but we're also going to continue to grow and put out. What patients and their families want is they want a safe and dependable drug. We think that that's exactly what VOXZOGO is. It's a targeted therapy that's tailored for these patients with achondroplasia. Again, that long-term experience, we're going to continue to publish that. We're also developing the molecule in other stature-related disorders.

I think we've spoken about that previously, but we think that there's an opportunity here to continue to develop the agent. We also, of course, are invested in our next-generation agent, which is BMN 333. Our goal with BMN 333 isn't just a more convenient version of CNP. It's to actually increase the free CNP exposure that we can reach in the patients. That recent agreement with the FDA moving forward into what a pivotal plan might look like, we see that as an incremental positive. We're very much looking forward to the PK data that we'll see later this year. Again, a lot of confidence that VOXZOGO is a safe and effective therapy.

Jessica Fye (Managing Director and Equity Research Analyst of Biotechnology)

Should we expect the same endpoint for BMN 333 in a pivotal trial as for VOXZOGO?

Greg Friberg (EVP and Chief R&D Officer)

We are envisioning that we will do a comparative effectiveness study versus VOXZOGO, and we will be looking at similar endpoints to what has been studied in previous examples.

Jessica Fye (Managing Director and Equity Research Analyst of Biotechnology)

Thank you.

Operator (participant)

The next question comes from Paul Matteis.

Paul Matteis (Managing Director and Head of Therapeutics Research)

Hey, thanks so much for taking my questions. I had one for Brian and one clinical question. Brian, I wanted to just clarify as it relates to VOXZOGO over the past couple of quarters and then what you're seeing going into 2Q. Has the net price on a global basis of the drug changed? Just curious if the net price has gone down a bit as you've diversified into other markets and your expectation there.

As it relates to this BMN 333 pivotal, that was super interesting to kind of hear the color on the comparative design. Are you looking to actually show superiority? Is it going to be powered for non-inferiority? I mean, maybe it's too early to say, but given your conviction that higher exposure may drive greater efficacy, what do you see the opportunity to show there? Thank you.

Greg Friberg (EVP and Chief R&D Officer)

Yeah, this is Greg. Maybe I'll take the 333 question because it's a quick answer. Yes, we are looking for superiority in growth dynamics from a higher exposure of CNP.

Brian Mueller (EVP and CFO)

Thanks, Greg. Thanks, Paul, for the question. Mine is likewise a quick answer because it is a great question. When you talk about demand increasing and not seeing the same correlation in revenue for these couple of quarters, we are not observing, not seeing any pricing dynamics. It's truly just the lack of correlation market by market that just happens to show up here in Q1 and possibly in Q2. No price factoring in.

Paul Matteis (Managing Director and Head of Therapeutics Research)

Makes sense. Thanks very much.

Operator (participant)

The next question is from Ellie Merle, UBS.

Jasmine Turner (SVP of Wealth Management)

Hi, this is Jasmine on for Ellie. Thanks so much for taking our question. What's the latest on timing for VOXZOGO in other growth disorders like ISS and SHOX? How quickly do you think that you could move BMN 333 here? Would you want to wait for VOXZOGO clinical success here before studying BMN 333 in these indications, or is that something you'd want to do sooner? Thank you.

Greg Friberg (EVP and Chief R&D Officer)

Thank you for the question. This is Greg Friberg again. With regard to the Noonan's, Turner, and SHOX basket that we have, as well as idiopathic short stature, both of those protocols are open for enrollment and are continuing to progress. We anticipate that we will have data from those programs that would enable us to begin pivotal studies in 2027. We remain on track for those goals. With regard to the role that BMN 333 would play in additional indications, just as a reminder, we still are working through with BMN 333.

Once we've moved beyond healthy volunteers, there will be both dose ranging as well as the effectiveness studies to come thereafter. That is the agreement, again, that we referred to with the FDA. Long way of saying that these reveals of information are actually going to line up quite nicely so that we can make decisions when we have the complete profile for BMN 333 to determine what the future plans would be. Right now, the discussions with BMN 333 that we've been talking about have been achondroplasia related.

Jasmine Turner (SVP of Wealth Management)

Thank you.

Operator (participant)

The next question is from Cory Kasimov of Evercore ISI.

Hi, thanks for taking our question. This is Adi on for Cory. I wanted to ask you if you can share how the U.S. versus ex-U.S. sales have evolved in the first quarter for VOXZOGO and what trend do you expect to see going forward into the rest of the year?

Cristin Hubbard (EVP and Chief Commercial Officer)

Yeah, thank you so much for the question. This is Cristin. And as you know, last quarter, we gave specifics on precisely that, which is the U.S. versus outside U.S. revenues for VOXZOGO. And we did that strictly so we could clarify the significant contributions that come from outside the U.S. Given that the ex-U.S. weight of the revenues is approximately 75% total of VOXZOGO revenues, we do expect this split to fluctuate just a little bit quarter-over-quarter. That goes back to what Brian had mentioned about ordering patterns becoming a little bit more bumpy as we turn into a more mature brand, which is very commensurate with other products in our portfolio.

Overall, we expect the split today to be roughly around 75%. In the long term, what we expect is that it will mirror that of our other products in our portfolio, which is where you have about 1/3 of the revenues coming from the U.S. and 2/3 coming from outside the U.S.

Brian Mueller (EVP and CFO)

Okay, thank you. I'll jump back in the queue for the rest of the questions.

Operator (participant)

We'll go next to Gena Wang, Barclays.

Gena Wang (Biotechnology and Mid- & Small-cap Equity Research Analyst)

Thank you. I have two sets of questions. First one is regarding also the VOXZOGO franchise. Maybe the BMN 333, can you help us understand because you have a healthy volunteer data and mainly is a PK data? How do you define that will be the top-line data you share with us that will be good enough that define it as a supportive to start your registration trial? Would you only identify one dose for your registration trial? Related question, I know there is a competitor running CNP plus a growth hormone study. Any thoughts there?

We know historically growth hormone did not work. Any thoughts there regarding CNP plus growth hormone study? The third part, very quickly on the manufacturing sites for VOXZOGO, do you have a manufacturing site both in the U.S. and the ex-U.S.?

Greg Friberg (EVP and Chief R&D Officer)

Thank you, Gena. First question with regard to BMN 333, you're correct. We will have PK data of all the species. We'll have not only BMN 333, but also free CNP levels. Our goal for that study is to see multifold increases in sustained exposure levels for free CNP. That data will then unlock what comes next. That next study, while we call it one protocol, which it is, it is a multi-part protocol that involves both a dose ranging portion as well as a comparative effectiveness portion.

In that regard, the data that we'll be revealing later this year will be the ungating to move into those patients with achondroplasia to do that dose ranging study to pick that final dose, again, that will be in the comparative effectiveness side. On the growth hormone side, I think you've actually framed it quite nicely. We would not be surprised at all to see that if you combine growth hormone with CNP in achondroplasia patients, that you would see an increase in AGV at 6 or 12 months, maybe even out at 2 years. Historically, the challenge for growth hormone hasn't been about those short-term benefits.

It's been about whether they translate into meaningful increases in final adult height. As you mentioned, they've been transient. That's been the challenge. This is, of course, why growth hormone isn't actually routinely recommended by expert guidelines or regulators around the globe, except for some unique regions. We also should remember that growth hormone, really in this discussion of height, is really not the most important measure that we should be talking about. The health and wellness of the patients is, of course, the most important factor.

We have not seen that with growth hormone, at least to this date, that the kind of evidence beyond height could be achieved in patients with achondroplasia. On the contrary, growth hormone really has added problems for patients. There has been acceleration of bone age. We have seen worsening proportionality at different times. Of course, I mean, you just look at the label, there are cardiovascular and metabolic disturbances.

One unique factor that has been brought up by some of the treating physicians, things like tonsillar hypertrophy that do not seem like they would be a big deal in most children, actually in children with airway obstruction can be a very challenging problem. Clearly, these need to be watched very closely with regard to growth hormone. What we are very pleased about with VOXZOGO is, remember, these kids are not even growth hormone deficient. What VOXZOGO brings is a targeted therapy.

We think, again, we've demonstrated the effects on all those areas beyond height. We talked about craniofacial volume and others in a previous answer, and all while maintaining bone health. That's what we think these patients need. That's what they want: a safe and dependable targeted therapy for their disease.

Brian Mueller (EVP and CFO)

Thanks, Greg. Hi, Gena. This is Brian. I'll take your question on VOXZOGO manufacturing. VOXZOGO drug substance is sourced from the United States. Thanks.

Operator (participant)

Thank you. Up next, we'll take a question from Kostas Biliouris, BMO Capital Markets.

Kostas Biliouris (Director and Biotech Equity Analyst)

Thanks for taking our question and congrats on the progress. Maybe one question for Greg on BMN 333. There is a recent presentation by Children's National Hospital at ESPE that shows that there is no really meaningful correlation between VOXZOGO PK and growth outcomes in hypochondroplasia. Given this data, I wonder to what extent will we be able to draw conclusions about BMN 333 outcomes based on the PK data that we will see in 2025? Thank you.

Greg Friberg (EVP and Chief R&D Officer)

Yeah, thanks for your question. I think when we talk about VOXZOGO PK, we also have to recognize the challenges when a drug has about a 30-60 minute half-life of actually getting the complete profile. Trough PK becomes very challenging. Trough PK, if you're going to measure a very low point, is easy. But measuring that full profile can be a challenge. There is a fundamental difference between the PK profile of VOXZOGO and what we expect to see in BMN 333. Of course, rather than a sawtooth pattern, we expect to see much more of a continuous release.

Fundamentally different approaches with the pulsatile versus the continuous coverage make it difficult to measure, I think, between the two and compare the PK profiles. What we can do is we can look at other long-acting CNP, both in preclinical models and the preclinical outcomes, and we can ask the question about sustained levels of CNP. That is what we have modeled from our Cynomolgus monkey models.

We believe that, again, if we can recapitulate what we have seen in those models against another long-acting, more continuous coverage and activation of NPR2, we think that, again, by seeing multifold increases above what has been demonstrated so far, that opens the opportunity to test the hypothesis is more better. Hopefully, that answered your question.

Kostas Biliouris (Director and Biotech Equity Analyst)

Thank you.

Operator (participant)

Mohit Bansal from Wells Fargo is up next.

Hi, this is Serena on for Mohit. Thanks for taking our question. Wanted to ask a question about BMN 351. In terms of the muscle dystrophin data expected in the second half, is that 10% dystrophin levels the only goal that should inform the future course of action for this molecule, or would you be looking at a bar for other parameters as well? Thank you.

Greg Friberg (EVP and Chief R&D Officer)

Thanks for the question. What we will have once patients have reached the 6-month time point is we, of course, will have a totality of safety data and PK on a variety of species. That includes not only the drug, but the muscle content of the drug because we're doing muscle biopsies. We'll also be able to look in the muscle at the skip product and the dystrophin. All of those factors will be there.

We have actually released an illustrative example that was connected to our release today of a model that we put forward. That model shows us that what we're going to see at the 25-26 week time point are dystrophin levels that, when predicted out at steady state, are going to rise 2-3 fold. They'll give us a line of sight whether that 10% at steady state will be achievable. We are also measuring in the study functional outcomes, which I think is the real question you're asking.

The challenge, of course, with functional outcomes is you need to wait till, of course, you reach steady state of the drug. We're looking at North Star. We're looking at six-minute walk test. We're looking at tride velocity 95C, all of those measures. We do anticipate that those will take longer than this initial first look. I also want to remind the audience that this is the first data from our 6 mg per kg cohort. We also have completely enrolled our 9 mg per kg cohort. Again, as in a relay race, that's trailing behind in terms of time. Our goal here is to identify a molecule that not only has potent dystrophin induction, but also can, of course, be administered safely in a chronic fashion.

Operator (participant)

Our next question is from Olivia Brayer, Cantor Fitzgerald.

Olivia Brayer (Director and Senior Biotech Analyst)

Hi, good afternoon. Thank you for the question. Greg, just wanted to clarify a comment you made earlier. Will we not see any level of phase II data from other short-stature indications until 2027? Or could we actually start to see some initial clinical characterization and maybe select patient groups just to help de-risk some of those new VOXZOGO indications? On the P&L, you guys are on track for over 20% EPS growth this year. Any comments on what kind of earnings power you think you could have as we get into the next few years?

Greg Friberg (EVP and Chief R&D Officer)

Why don't I take a quick stab just to clarify? With regard to the short-stature conditions, obviously, I mean, the Dr. Dauber study with VOXZOGO continues, and we do expect that that data will be updated over time. With regard to our own programs, what we're publicly commenting on is that we would have information to be able to initiate our phase III study in 2027.

It's possible that anytime proximal to that, depending again on speed of enrollment and so forth, we may have data. We're not committing, at least right now, beyond the 2027 initiation of a phase III. Clearly, we would need that data not only in-house, but we would be publicly presenting that data before we would initiate those phase III studies.

Brian Mueller (EVP and CFO)

Hi, Olivia. This is Brian on your profitability question. Thanks for that. Yeah, we are pleased with this strong start to the year on the bottom line with the $1.13 of earnings per share growth. Again, we are expecting, while revenues are planning to increase in the second half of the year, we are also planning to increase investments in both R&D and SG&A over the course of the year. By all means, we are confident in the full-year EPS guidance with this strong start to the year. We do believe that will continue. In terms of earnings power, I would point you to our long-term guidance that we remain confident in, at least today, excluding any potential impact of pharmaceutical tariffs.

Whether it be the goal of $4 billion of revenue by 2027 or our 40% and growing non-GAAP operating margin target next year, we did not give long-term earnings per share guidance. You can do the math along the trajectory of our OpEx line item goals over time and see that we are expecting significant earnings per share growth over the next several years. This year being 22% at the midpoint of our guidance is the trajectory that we are talking about.

Olivia Brayer (Director and Senior Biotech Analyst)

Okay. Thanks, guys. Helpful.

Operator (participant)

We have reached the end of the Q&A session. Our final question today will come from Vikram Purohit, Morgan Stanley.

Vikram Purohit (Biotechnology and Small & Midcap Research Analyst)

Hi, good afternoon. Thanks for fitting me in. We just have two quick clarification questions on BMN 333. Apologies if these topics were discussed and we missed it. Just to make sure we understand, for the pivotal program planned to initiate in 2026, would the bar for approval necessarily be superior efficacy versus VOXZOGO through the comparative effectiveness study that you're planning to run? Secondly, could you talk a bit about your plans to seek approval and define a plan forward ex-U.S. as well? Thank you.

Greg Friberg (EVP and Chief R&D Officer)

Yeah, thanks for the question. Just to clarify, the announcement today, again, was that we had reached agreement with the FDA and we're continuing to work with regulators around the globe. The study that we refer to that would initiate in 2026 is a combined phase II/III study. In that regard, we are doing dose ranging as well as the final comparative effectiveness versus VOXZOGO. We would be looking for a superior outcome with regard to the primary endpoint in that study versus the control arm.

Operator (participant)

Everyone, at this time, there are no further questions. I'd like to hand the conference back to the CEO for any additional or closing remarks.

Alexander Hardy (President and CEO)

Thank you, Operator, and thank you all for joining us today. As we described, our first-quarter performance highlights the fundamental value of our transformative medicines and the strength of our business, paving the way for record performance in full year 2025. In the face of external dynamics that are creating uncertainty across a number of areas, we think we are well positioned.

We remain laser-focused on what we can control, investing in the expansion of internal and external innovation, leveraging our extensive global revenue base, and our commercialization capabilities, and most importantly, continuing to deliver increasing value creation for all of our stakeholders in 2025 and beyond. We thank you for your attention. Look forward to speaking with you soon.

Operator (participant)

Once again, everyone, that does conclude today's conference. We would like to thank you all for your participation today. You may now disconnect.