BioMarin Pharmaceutical Inc. ($BMRN)

Good afternoon, and welcome, everyone, to the BioMarin Pharmaceutical First Quarter 2026 Conference Call. Today's conference is being recorded. [Operator Instructions] At this time, I would like to turn the conference over to Traci McCarty, Head of Investor Relations. Please go ahead.

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

Thank you, Traci, and thank you all for joining us today. I am so pleased that we completed the Amicus acquisition last week, starting a new and exciting chapter for BioMarin with the addition of two innovative therapies, Galafold for Fabry disease and Pombiliti and Opfolda for Pompe disease. The acquisition accelerates our anticipated year-over-year 2026 revenue growth to 20% at the midpoint of today's updated guidance. The strengthening trajectory is just the beginning of BioMarin's enhanced longer-term financial outlook supported by our larger, more diversified commercial portfolio. Since announcing our plans to acquire Amicus late last year, we have been preparing for rapid integration beginning on day 1 with the goal of increasing the peak potential of these newly added products. Following the recent close of the transaction, we initiated our targeted integration plan, focused on leveraging BioMarin's operating scale and capabilities to drive diagnosis and treatment rates for patients with Fabry disease and late onset Pompe disease. Next quarter, we plan to share this roadmap as well as more detail on BioMarin's growth acceleration with the addition of Galafold and Pombiliti and Opfolda to our commercial portfolio, and DMX200 for FSGS in Phase III to our late-stage pipeline. Turning briefly to first quarter results and outlook for the remainder of this year and starting with enzyme therapies. I am pleased with the strong interest we are seeing from the PKU community following the recent PALYNZIQ adolescent label expansion in the United States. With Cristin will discuss in more detail. We expect enzyme therapies will deliver robust growth in 2026, further supported by the addition of Galafold and Pombiliti and Opfolda to the portfolio. Moving to our skeletal conditions business unit. We saw strong patient demand for VOXZOGO with new patient starts increasing across all regions in the first quarter. In the U.S., the majority of new patient starts were from the under age 2 cohort. These results reflects our focused investments and increasing adoption of VOXZOGO, particularly among younger patients. Building on our leadership in achondroplasia, we are pleased to have submitted the sNDA and full approval of VOXZOGO. We expect to hear the timing of our review in the coming months. I want to congratulate our regulatory team for the outstanding work that went into this comprehensive submission package. We also look forward to pivotal results for VOXZOGO in hypochondroplasia and BMN 401 for ENPP1 deficiency both later in Q2. In summary, we expect 2026 to be a momentous year for BioMarin. Our immediate focus remains on the seamless and rapid integration of Amicus to accelerate our growth trajectory this year and beyond, pursuing regulatory next steps following the 2 upcoming pivotal data readouts. The addition of Galafold and Pombiliti and Opfolda to BioMarin's portfolio of innovative medicines provides an opportunity to reach more patients around the world, creating significant value for all of our stakeholders in the near and longer term. As we enter this next chapter, I would like to express my appreciation to the employees of both BioMarin and Amicus, whose dedication forms the foundation of our shared mission to serve patients. Thank you for your attention. And I will now turn the call over to Brian to provide additional financial updates. Brian?

Thank you, Alexander. Please refer to today's press release for detailed first quarter 2026 results, including reconciliations of GAAP to non-GAAP financial measures. All first quarter results will be available in our upcoming Form 10-Q, which we expect to file in the coming days. Now moving to Slide 7. Total revenues in the first quarter were $766 million and increased year-over-year, supported by increased patient demand across both enzyme therapies and VOXZOGO. And as expected, those organic growth drivers were partly offset by order timing dynamics as well as lower revenue from Roctavian, KUVAN and royalties. Enzyme therapies revenue increased 6% year-over-year, led by growth in VIMIZIM, NAGLAZYME and BRINEURA. PALYNZIQ first quarter revenues were impacted by U.S. order timing which resulted in elevated stocking levels in the fourth quarter of 2025, as discussed last quarter. We expect the stocking dynamic to normalize and anticipate year-over-year revenue growth for PALYNZIQ in full year 2026 as growth in new patient starts in the under 18-year-old population gains momentum and patients continue to titrate to their maintenance dose. VOXZOGO revenue was supported by new patient starts across all regions and in line with the expectations that we shared on our prior quarter earnings call. Looking ahead, due to anticipated order timing and consistent with 2025, we expect VOXZOGO revenue to be higher in the second half of 2026 compared to the first half. Cristin will provide more color on commercial dynamics in a moment. Turning now to Slide 8. Cost of sales increased year-over-year in the first quarter primarily due to a $31 million charge associated with an unsuccessful process qualification campaign to extend NAGLAZYME manufacturing capability. Importantly, this did not impact commercial supply. While this event decreased margins and earnings per share in the first quarter, we expect this charge to be offset in full year 2026 non-GAAP diluted earnings per share guidance. Q1 non-GAAP R&D expense increased year-over-year, primarily due to spend to support BMN 401, our Phase III clinical program acquired in the Inozyme transaction in the second half of 2025. Development activities for VOXZOGO for hypochondroplasia, BMN 333 for achondroplasia and BMN 351 for Duchenne muscular dystrophy also contributed to higher year-over-year R&D expense. Non-GAAP SG&A expense also increased, partially driven by investments to support commercial expansion across enzyme therapies and VOXZOGO and partially driven by pre-close costs associated with the Amicus acquisition. First quarter non-GAAP diluted earnings per share was $0.76 and was significantly impacted by the drivers of increased operating expense that I just mentioned as well as the impact of Q1 revenue which we believe will be our lowest quarter of the year. The impact of the cost of sales charge and pre-close costs associated with the Amicus acquisition resulted in a $0.20 earnings per share impact to our non-GAAP earnings per share result. Looking past those elements helped to measure BioMarin's underlying business performance as well as how this Q1 result fits into our full year earnings per share guidance, which remains unchanged for the historical BioMarin business before layering on the Amicus business. Now moving to Slide 9 and our updated full year 2026 guidance, which now includes the Amicus financial outlook starting last week. We are raising enzyme therapies revenue guidance to a range of $2.725 billion to $2.775 billion for the full year 2026 inclusive of meaningful contributions from Galafold and Pombiliti and Opfolda, resulting in approximately 30% growth at the midpoint. Adding these high-growth products to our enzyme therapies portfolio increases our full year total revenue guidance to a range of $3.825 billion to $3.925 billion with the midpoint representing approximately 20% year-over-year growth in 2026. For VOXZOGO, we are maintaining our revenue guidance of $975 million to $1.025 billion, which continues to reflect high single-digit growth at the midpoint. On non-GAAP diluted earnings per share guidance, we are updating the guidance range to $4.85 to $5.05. As previously communicated, the acquisition of Amicus will be slightly dilutive for the full year 2026. We continue to expect the acquisition to be accretive to non-GAAP diluted earnings per share in the first 12 months after close and substantially accretive beginning in 2027. The Amicus P&L will be incorporated into BioMarin's financial results as of last week's closing of the transaction. In 2026, we expect to include the base Amicus operating expenses less initial cost synergies anticipated in 2026. As Alexander touched on, now that the transaction is closed, we have engaged more deeply with the Amicus business, and plan to share our outlook on both commercial revenues and cost synergies on our next quarterly earnings call. To give some perspective on timing of the updated guidance, we expect order timing for the historical BioMarin products and 2 full quarters of Galafold and Pombiliti and Opfolda revenues in the second half of the year to drive significantly higher revenues as compared to the first half of 2026. To provide context, we expect more than 55% of total 2026 revenues to be recognized in the second half of the year. And likewise, on the expected timing of our profitability, we expect Q2 non-GAAP diluted earnings per share to be just modestly higher than Q1, partially due to pre-close Amicus costs incurred in April, plus a higher amount of the 2026 Amicus dilution being weighted to the second quarter. Further, the revenue timing weighted to the second half of the year results in most of our expected profitability occurring in Q3 and Q4. These earnings timing dynamics drive approximately 2/3 of our 2026 earnings per share expected in the second half of the year. Briefly on evolving geopolitical uncertainties. We are watching the situation in the Middle East very closely and note that today's guidance reflects an allowance for a modest amount of disruption in that region in 2026. Looking ahead, we look forward to sharing with you our expanded financial outlook, enhanced by the addition of Galafold and Pombiliti and Opfolda setting the stage for accelerated near and midterm growth. Thank you for your attention. I will now turn it over to Cristin for a commercial update. Cristin?

Thank you, Brian. We were encouraged by the commercial execution across our portfolio so far this year, with strong patient demand across enzyme therapies and VOXZOGO. We look forward to providing a more detailed commercial update on our plans to maximize the potential of both Galafold and Pombiliti and Opfolda next quarter. Our initial priorities therein are focused on driving diagnosis in Fabry and switch in Pompe. This will support increased penetration in countries where Galafold and Pombiliti and Opfolda are marketed, while we can currently work on geographic expansion plans for both products. We look forward to updating you on our Q2 call. Now moving to Slide 11. I'll begin with an update on first quarter 2026 performance, starting with enzyme therapies. As Brian outlined, enzyme therapies delivered 6% year-over-year growth in Q1, led by VIMIZIM, NAGLAZYME and BRINEURA. Across the enzyme therapies portfolio, we continue to see strong patient demand and adherence. Turning to PALYNZIQ. In the first quarter, we continued to expand the underlying patient base and physician engagement remains strong. Importantly, following the FDA approval of PALYNZIQ label expansion to those 12 years and older in February, we have successfully launched in this age group and are seeing encouraging early momentum. We have observed broad interest and engagement from caregivers and health care providers treating adolescents during this critical stage of their development. Since approval, we have observed meaningful enrollments and new patient starts and people under the age of 18. From a prescribing standpoint, adolescent uptake is being driven by both physicians with significant experience prescribing PALYNZIQ as well as by clinicians who are newer to the therapy. Recall that it can take a patient many months to titrate up to their maintenance dose of PALYNZIQ, so we would expect to see the results of positive early prescribing over the coming quarters. PALYNZIQ continues to standalone in its ability to enable people with PKU to reach physiologic Phe levels while reducing dietary restrictions regardless of severity. With the U.S. adolescent launch underway and European approval expected later this year, we are excited about the impact PALYNZIQ can have for additional families over time. Turning now to VOXZOGO on Slide 12. As discussed, first quarter results reflected expected order timing dynamics following a strong Q4, particularly in international markets. Importantly, we have reserved strong growth in patient additions globally with the number of children being treated with VOXZOGO increasing by more than 20% year-over-year. With the competitor having recently entered the U.S. market, our focus has remained on executing our strategy, and we continue to see strong momentum. During the first quarter, VOXZOGO progress continued, supported by ongoing patient additions across all regions in ages, strong adherence and persistence globally and continued expansion of the prescriber base. Our teams are focused on driving new patient starts across all ages with an emphasis on children under 2 years of age, where international consensus guidelines for achondroplasia recommend early diagnosis and treatment with VOXZOGO as soon as possible. In the United States, we are encouraged to see that our efforts educating and engaging with caregivers and HCPs, are having an impact in the under 2-year old age segment. In Q1, over half of new patient starts were from children under age 2, a greater proportion compared to last quarter. Additionally, we have seen an approximate 10% decrease in the average age of children initiating VOXZOGO treatment in the under-2 segment, narrowing the window between diagnosis and treatment states. Internationally, building on our global expansion into 55 countries to date, our strategy remains focused on reaching more patients and regions that have further opportunity and treating infants in countries that already have high penetration rates. With our sNDA for full approval now submitted, we believe the depth and durability of VOXZOGO's clinical evidence can be further reinforced, strengthening its role in treatment decisions for infants and children with achondroplasia. At the same time, we're making progress in preparations for potential expansion of VOXZOGO into hypochondroplasia. As we get closer to the Phase III data and potential launch, our pre-commercialization activities continue to accelerate. Our initiatives in the U.S. are making a difference. More people are being diagnosed at a younger age, diagnosis rates are rising and more doctors are requesting diagnostic tests. We look forward to the Phase III top line results in the second quarter of 2026 and submitting to global health authorities in the second half of this year with potential approval in 2027. In summary, we are pleased with the strong patient demand observed across the portfolio with continued momentum in our core business units and a compelling set of near-term opportunities to accelerate growth. With that, I'll turn it over to Greg for an R&D update. Greg?

Thank you, Cristin. As expected, 2026 is shaping up to be an active year for R&D, and we're looking forward to delivering multiple meaningful milestones. Moving to Slide 14. We've built a comprehensive VOXZOGO evidence package that goes well beyond describing annualized growth velocity, highlighting long-term durability and clinically meaningful health outcomes for children with achondroplasia. Recently, at the Pediatric Endocrine Society Annual Meeting, we shared data from 3 ongoing long-term extension studies that illustrate the sustained benefits of VOXZOGO over time. Consistent and cumulative improvements in Z scores were observed across all age groups over the 6 to 8 years of follow-up as depicted on the left of Slide 14. On the right side, you again see consistent and cumulative gains in height and height Z scores with durable results out to 8 years of follow-up. In addition to anatomic measures of benefit, we also presented data demonstrating VOXZOGO's favorable impacts on quality of life measures. Importantly, these sustained efficacy findings are supported by a robust safety database now comprising more than 10,000 patient years of exposure, reinforcing VOXZOGO's well-established long-term safety profile. Taken together, this extensive body of evidence reinforces VOXZOGO's differentiated profile with no other achondroplasia therapy supported by this level of long-term data with regard to safety, efficacy and functional outcomes. Importantly, this data spans the full pediatric age population, and VOXZOGO remains the only therapy approved for use immediately from infancy. This allows for early treatment initiation and enables a long window to positively influence endochondral bone formation and all the potential downstream benefits to health outcomes. Together, these data formed a strong foundation for our full approval submission intended to fulfill our post-marketing requirement, which was submitted to the FDA in April and will afford us the opportunity to share direct evidence of VOXZOGO's long-term value with the community via peer-reviewed publications and presentations later this year. Now moving to Slide 15. The remainder of 2026 includes several anticipated pipeline updates, including two particularly important pivotal data readouts expected in the second quarter. Starting with hypochondroplasia, we believe the health care provider community is looking forward to a targeted therapy that addresses this skeletal condition, and we are confident in the scientific rationale for VOXZOGO in this indication. That confidence is grounded in the strong proof of concept and durability demonstrated in Dr. Dauber's investigator-sponsored study and in the rapid enrollment we observed in our own Phase III pivotal trial. We look forward to sharing these Phase III top line results in the second quarter. In parallel, enrollment is progressing very well in our Phase II study in children under the age of 3 highlighting early interest in VOXZOGO as a potential option from infancy in hypochondroplasia. We also expect Phase III top line data for BMN 401 in the second quarter of this year. As a reminder, ENPP1 deficiency is a rare, serious and progressive genetic condition affecting vascular, skeletal and soft tissue systems. BMN 401 has the potential to be the first disease targeted therapy for ENPP1 deficiency. The ENERGY III study in children aged 1 to 12 includes 2 co-primary end points. The first is change from baseline and plasma measures of inorganic pyrophosphate through week 52. The second is change in the RGIC or Rickets Global Impression of Change after 52 weeks of treatment, assessing improvement in skeletal health. Clinical experience with BMN 401 in older patients has shown that normalization of pyrophosphate is accompanied by improvements in bone mineral biomarkers, functional performance and patient and physician reported outcomes. In addition to these pivotal readouts, I also like to highlight progress with BMN 333, our long-acting CNP therapy. We are pleased to share that enrollment is underway in our global registrational-enabling Phase II/III study. We are rapidly progressing this program with the goal of establishing BMM 333 as a potential next-generation standard of care for achondroplasia and potentially for other skeletal conditions. Before closing, I'd also like to touch on BMN 351 for the muscular dystrophy at the Muscular Dystrophy Association Congress in March, we presented initial data demonstrating dose-dependent increases in dystrophin at week 25 in both the 6 and 9-milligram per kilogram dose cohorts. These findings were accompanied by notable decreases in creatine kinase, a biomarker of muscle injury and the prevention of functional decline as measured by the North Star Assessment and the 6-minute walk test when compared to historically matched controls. So far, we are encouraged by both the dystrophin expression levels and the functional improvements observed in our development program. Enrollment in the 12-milligram per kilogram cohort is ongoing and we look forward to providing an additional update by year-end as this program continues to advance. Finally, we would like to thank the patients, families and caregivers whose commitment continues to make this progress possible. Thank you for your attention today. We will now open the call to your questions. Operator?

[Operator Instructions] We'll go first to Sean Laaman at Morgan Stanley.

This is Mike on for Sean. I just wanted to touch on two things. First, looking at the recent data at the Pediatric Endocrine Society, can you help to contextualize the benefits you saw in bone mineral content in hypochondroplasia? And how does that maybe inform or influence your expectations heading into the top line?

Yes. Thanks for the question, Mike. This is Greg Friberg. Yes, in addition to measuring growth velocity across both achondroplasia historically and hypochondroplasia, of course, we're measuring a variety of factors of health and well-being, including bone biology and bone health. The dexa scans that were presented and that cumulative data suggests, again, that that in addition to growing bone length and stimulating endochondral bone formation, that, yes, that bone is healthy and a strength that we would like to see. And again, reiterates what we've seen in the other FGFR3-related mutation condition of achondroplasia as well. Going into the card flip for the Phase III study, we're certainly excited to see that data. The event is going to occur before the midway point of this year. So we mentioned that it's in the second quarter. We're eager to see those results. And again, I think it highlights that the data at PES highlights the fact that hypochondroplasia, while a unique and individual indication as compared to achondroplasia, the related biology suggests again that the hypothesis is a strong one. We've seen in Dr. Dauber's data from National Children's, again, we've seen the kind of growth that certainly would meet the criteria for a statistically significant improvement that our study is developed to measure. And with regard to that safety profile, we're not anticipating any unexpected events there as well. So fingers crossed, and we'll be updating you all when that data is available.

That's really helpful. And then just maybe circling back on to the intro comments. Regarding the integration Amicus, you alluded maybe there's like a road map for future growth acceleration. We were just wondering if you could help to comment. I mean, specifically for Pombiliti and Opfolda, what leverage do you see for driving increased switch rates in that market?

Yes. This is Cristin Hubbard here. And just having closed last week, I can say we are really, really excited about the commercial potential of both of these products, both in high-growth products to add to our portfolio. As we've mentioned before, but I'll expand a little bit, for Galafold specifically, we really do think that the biggest growth lever is in and around diagnosis. We know that a large proportion of the amenable patient population remains undiagnosed, and driving diagnosis is exactly where Amicus has really started to build momentum, but we feel that using BioMarin's capability in this regard, we can really continue to drive that forward. On the Pombiliti and Opfolda side, that's more about a switching opportunity. And we really do think that there's going to be a sizable opportunity here to build over the next few years as patients on their existing therapies begin to progress. So we're really working on initiatives that, again, Amicus has started, and that is around kind of starting new therapy, looking at patients that have identified their own progression and understanding what progression looks like. That's an area that we're really focused on, not to mention the continued generation of evidence to show the benefits of a switch. So again, these are areas that we feel confident in our capability at BioMarin and are very excited about the future trajectory. So we'll share more on that on our Q2 call.

We'll move to our next question from Salveen Richter at Goldman Sachs.

This is Tommie on for Salveen. Just a quick one on VOXZOGO. Wondering if you've seen any early signals of different behavior from competitor entry, whether it be switching or in new patient adds.

Yes. Thank you for the question. This is Cristin again. And as you heard in our prepared comments, our demand in the first quarter really does remain strong. Our enrollments in fact, exceeded. In Q1, our enrollments exceeded that in the average of second half last year, and that trend continued into April. So as we see it now, we're really excited. As you know, we're very much focused on the 0 to 2 population based on the consensus guidelines, and we're seeing real momentum there. Not only were our new patient starts weighted and more than half of them being in that 0 to 2 population in the first quarter. But we're also seeing a reduction in the time we have from diagnosis to treatment in that population. That is -- that's reduced by 10% already. So we know that, that real focus therein working. In addition, we're focused on the patients that are already on treatment and making sure that the -- those patients for whom they're doing well on treatment, we want to make sure that they understand the totality of the evidence that exists for VOXZOGO and continue to have a positive experience in terms of the benefit. So we're very pleased. Good how Q1 went and look forward to continuing on that trajectory. .

We'll go next to Paul Matteis at Stifel.

Great. Just kind of previewing your update next quarter as it relates to Amicus integration. I was wondering if you could set the stage for us and just what you might be providing as it relates to the duration of the revenue outlook? Would you talk about peak sales at all? Or update those us or anything else? And then secondarily, anything you can do on setting the stage on our expectations related to accretion, cost synergies, and again, the duration of the profitability outlook as well?

Paul, thanks. Appreciate the question. And yes, we wanted to highlight today having just closed the transaction a week ago, brief update on the integration to date, which a weekend is going well, and you saw the update of our revenue guidance today, adding our expected range of the 8 months of Amicus revenues, resulting in a $500 million midpoint and the updated guidance, which is 20% year-over-year. We also wanted to set the stage for the Q2 update. The transaction announcement, we discussed how the strategic fit between these two businesses was very strong. And that because of the both global and commercial and medical capabilities of BioMarin built over time in our existing portfolio, that these two medicines should truly have more potential within BioMarin. That was a key rationale underlying the transaction, and we've been making plans up to this point of closing. And now that we've closed, we're just digging in and engaging more deeply with the Amicus business. And that's why we're going to wait until Q2 to give this additional update, but it will include a number of details and metrics about the long-term potential, including our views on peak revenue. Just a reminder, based on our due diligence at the time of announcement of the transaction, we reiterated what Amicus had shared with respect to peak revenue potential of roughly $1 billion each for Galafold and Pombiliti and Opfolda. But as we developed that long-term business plans and strategies to expand both of these medicines, we think that has some potential to be higher. So that's what we'll share. We'll be -- it will be important for us to share some of the key metrics and tactics in terms of how we expect to achieve that long-term potential. So stay tuned, and we'll look forward to sharing more in Q2. And by the way, that will include some of the other financial elements as well, such as synergies, long-term profitability, accretion, et cetera. I will share that for today. We are reaffirming our previous expectation that while, as you saw in the EPS guide today, the Amicus acquisition is slightly dilutive to calendar '26, but accretive for the first 12 months following closing and then substantially accretive for beginning full year '27. So we look forward to sharing more, but we're off to a strong start.

We'll move next to Ellie Merle at Barclays.

This is Jasmine on for Ellie. So just for VOXZOGO for hypochondroplasia, what's the latest on what you're thinking will be good data and what you're looking to see on AGV? And also, how are you thinking about the contribution to VOXZOGO revenues from hypochondroplasia next year? So what do you think the cadence of uptake will be in this population? And can you talk a little bit about your commercial preparations.

Thanks, Jason. This is Greg Friberg. Maybe I'll take the first part and then hand it off to my colleague. With regard to the VOX HCH, we're turning over, of course, -- we'll be looking at the data in the second quarter of this year, absolutely looking forward to that. And of course, the success is a statistically significant improvement in growth as compared to the control arm. And in this world, of course, we're measuring a variety of other measures. We're looking, of course, at other anthropometric measures as well as, of course, the safety profile. And really any statistically positive improvement in growth, we think that that's a win for these patients. I'll just add that we've seen pretty dramatic I think, accelerations of recruitment, both for the older children as well as I mentioned in the prepared remarks, the infants on our hypochondroplasia study, really suggesting that this is a market that's hungry for a disease targeted therapy. Again, the biology is significantly similar to that of achondroplasia with regard to the mutation that drives this condition. And so from that standpoint -- and of course, built upon the data that Dr. Dauber has seen, we're quite excited to see what those end results will be. I think there was a question also about the marketplace, and I'm going to hand that one off to Cristin.

And so overall, our goal, of course, is to continue the growth of VOXZOGO into the midterm and hypochondroplasia provides an important component of that. Really where we're focused today on our prelaunch activities is in and around diagnosis. We have shared before that the total addressable patient population globally is at 14,000, and that assumes that we can continue to drive diagnosis and awareness of this condition. So our goal at this point in time prior to launch really is around increasing the number of hypochondroplasia patients that have been identified that we're getting physicians to understand the genetic testing and make sure that they're orders for that. And really, the idea being that patients get diagnosed at a much earlie. So our goal today is to improve upon that and make sure that we have identified patients at the time of a potential launch.

And Jason, if I could just add one other factor from the medical affairs standpoint. -- we're obviously actively working in the community even prior to seeing our data to really try to accelerate the number of patients that are diagnosed with this condition. There's probably 3 prongs to that. Of course, getting patients to be able to be referred sooner, to be evaluated, of course, more testing as well as we're doing work on the genetics side to reclassify so-called VUSs variance of uncertain significance. And so in that world, we're anticipating again that there will be patients available and ready for this therapy should become available. .

To throw out a few components, if I could, quickly. On the success we've had already, when looking at the diagnosis program that we're running to date and these kind of nonpromotional prelaunch activities, we're already seeing a 90% increase in the number of hypochondroplasia patients that we've identified as well as a 70% reduction in the age. So those are precisely the types of numbers that we're driving for and want to continue throughout our launch period.

We'll move to our next question from Cory Kasimov at Evercore.

This is Adi on for Cory. I had a question on the guidance increase. The $500 million from midpoint increase in guidance. Can you frame that the contribution from Galafold, Pom-Op, is that conservative relative to the $600 million revenue that generated in fiscal year 2025? And what are the key assumptions for adding these two assets into the guidance?

Ed, this is Brian. Thanks a lot for the question. I appreciate the opportunity to provide a bit more color on this important element of today's update. So yes, I'll frame it up for you. First of all, the $500 million represents a midpoint of a range that fits within the range of our existing enzyme therapies guide for '26, but I'll speak to the midpoint. From a timing standpoint, just a reminder that with the transaction closing last week, that $500 million midpoint represents mostly the 8 months remaining from May to December for this year. I will share in terms of your question around conservatism. I would say it's neither conservative nor aggressive. We think it's realistic. I'll share that we've analyzed the unreported period of Amicus product revenue from January through April. And when we looked at that versus consensus, January through April performance, while not reported was ahead of consensus. So both Galafold and Pom-Op together are off to a strong start in 2026. So with that being said, again, it's -- this is -- the transaction closed just a week ago. We'll come back next quarter with additional color, including the long-term potential I'll also share that since you commented on the $600 million reported for 2025, the range that's underlying today's update from an Amicus organic year-over-year growth rate standpoint, ranges from the high teens to the low 20s. So we think it's a really healthy growth. And we're excited that these assets are now part of our portfolio. And again, you see this 30% increase year-over-year as a result of layering this on to the BioMarin enzyme therapies and total revenue, 20% at the midpoint. So we're feeling good about it, and we'll share more going forward.

We'll go next to Jessica Fye at JPMorgan.

This is Jose on for Jess. How should we think about the adoption of hypochondroplasia relative to achondroplasia? What do you see as similarities and differences between these markets? And second, can you help us bridge the disconnect between the 20% year-over-year patient growth in 1Q versus a 3% revenue growth. Is it entirely explained by larger orders in the fourth quarter last year?

Yes. So I'll address the first part of the question in terms of how we see it in terms of uptake going in. I think we can consider it being similar to that of achondroplasia. But I think as I've mentioned kind of earlier, what is most important to us is ensuring that the amount of disease awareness, the urgency to treat and the diagnosis are really what we're focused on because we believe this is what accelerates that adoption curve. So our intention has been to drive as much of that so that we have patients identified at the time of our potential launch in the beginning of 2027. But importantly, that we continue on with that momentum because that ultimately is going to be what drives the shape of the adoption curve.

And Cristin, from a medical standpoint, if I could just comment. Hypochondroplasia, children are not born with the same growth gross deficit that the achondroplasia patients may be born with. And as a result, they often are diagnosed a bit later. They're referred and diagnosed. So that data point that we referred to earlier, which was one of our goals to try to shrink that number in terms of age of diagnosis is something that we see as a real positive sign that the work that we're doing to get these children in the hands of the right physicians who, again, can know what to do for them. That seems like a real early success, and we're looking forward to continuing to help shape that community and make these these therapies should they become available actually in the hands of the physicians who treat the patients.

Cristin, I'll take that revenue timing or fluctuation question. I appreciate you pointing that out because it is important to emphasize that the disconnect between that underlying patient demand growth in reported revenues is entirely order timing. There's a couple of different layers to that. One -- both of which we discussed last quarter, by the way. One was large international orders that were processed in Q4 that just didn't recur in Q1. Then the second was something that was somewhat unique to our business when looking back over the years, which was a modest amount of U.S. stocking impact from Q4 to Q1. This affected both PALYNZIQ and VOXZOGO. It wasn't significant, just about an extra week of inventory, but it was enough to show up as a variance in the quarter-over-quarter revenue. So this is why we wanted to emphasize the underlying patient demand growth. There's no significant price drivers in there, by the way, it is entirely order timing dynamics.

We'll move next to Phil Nadeau at TD Cowen.

Two from us. First, could you give an update on the ITC hearing and in particular, we're curious to get your thoughts on the ITC pretrial brief that was recently posted online. That's first. And then second, in the press release, there's a a note that there's going to be some data from BMN 333's Phase II/III trial in 2027. Could you provide a little bit more details around what data will be released at that time? .

Thanks very much, Phil. It's Alexander. I'll take the first part of your question and then hand it over to Greg for the second part. So with regard to the ITC, I mean, overall, we believe that assuming an exclusion order enforcing our IP is the most expeditious way to protect our IP in the United States. As you mentioned, we recently completed the ITC evidentiary hearing and post-hearing briefs are now being submitted to the presiding Chief Administrative Law Judge. So what happens next is we expect to receive a decision on whether product infringes our patent on or about August 21. At that point, if the full commission decides to review the decision and the final decision is expected on or about December 21. So this is a little bit of where we are and what can we expect going forward. I will also add that on completion of the ITC process, we would expect to also enforce a patent in the Federal District Court, where, of course, monetary damages are available. And I'll now hand it over to Greg.

For the question, Phil, about BMN 333. And as a reminder for those on the call, this is our long-acting CNP analog, again, designed to release continuous potentially higher AUC exposures of CNP when administered on a weekly basis. Again, as a reminder, in our Phase I, we saw over 10x increases in the AUC levels that we were able to achieve safely in the healthy volunteers. And we've recently initiated our Phase II/III study in children with achondroplasia. This is a multiregional clinical trial. It's currently open in a variety of countries around the world. We're enrolling as we speak. And our goal is to run the Phase II portion, where 1 of 3 doses of BMN 333 will be administered to the children, and there will be one arm that has VOXZOGO as well. There's no placebo on this study. What we will ultimately report out in 2027 is that we will be able to measure the annualized growth velocity at the 6-month time point, and we'll be using that data along with other measures, measures, other measures of safety and well-being to make a decision based on the analysis of which dose we should bring forward into a Phase III to run head-to-head against VOXZOGO. Again, looking for a superiority profile when it comes to AGV with the presumption that more AGV will drive more in the measurements of health and wellness that we're all familiar with.

We'll go next to Chris Raymond at Raymond James.

Yes. Just a question on the pivotal trial for BMN 333. I know this has come up before, but I guess I want to just ask maybe in a more pointed way and the decision to go with a superiority trial versus noninferiority. I think I've heard what you guys have said around 333 providing 2 to 3x free CNP and that, that should translate into higher efficacy. But maybe just strategically, if a non-inferiority trial could show that data, why take the risk and run a superiority study?

Yes. Thanks for the question. This is Greg Friberg, our goal with BMN 333 is to evolve this space. not just make a more convenient version of VOXZOGO. I'll just highlight that, that 3x target was at least 3x. We're actually testing a 3x to 5x and greater than 7x AUC exposure. And so from that standpoint, we believe strongly that BMN 333 is the right reagent to test this hypothesis. I'll also add that from a non-inferiority standpoint, it's a natural question to ask, wouldn't this be easier? From a pure mathematical standpoint, it's actually much harder and the study would be upwards of 10x the size in order to show non-inferiority versus even a drug like VOXZOGO. And so from that standpoint, there's a practicality of designing the study but I do want to reassure you that we will have an opportunity to look at the data after our Phase II portion. And if there need to be adjustments that the model gives us an update that tells us we should be reevaluating those would be potential opportunities. That being said, we are very clear with what we want out of this molecule. We want a superior CNP product that can be the cornerstone for future therapies for achondroplasia.

And I would just add absolutely, as Greg said, this is -- we think the opportunity in the need here is really around superiority. In terms of efficacy, AGV and all the benefits beyond linear growth, but also by this design of a study, we actually have an active control with VOXZOGO. So the size of the study is smaller than it would have been if it was in non-inferiority design, as Greg has already covered. But we also think the proposition to both caregivers and physicians means that this should be a study that's very attractive to potential patients to sign up to be included and therefore, speed of recruitment, which is extremely important. So we think that superiority profile we're aiming for from an efficacy standpoint, together with rapid trial recruitment and milestones being achieved is really a compelling proposition.

Yes. Placebo-controlled studies, when there are active safe and effective therapies are no longer really possible to run. It's not the right thing to do either.

We'll take our next question from Mohit Bansal at Wells Fargo.

This is Chen for Mohit Bansal. So we -- I just want to double-click on the BMN a little bit. I think you guys discussed that BMN targeting improvement in achondroplasia. But just wondering with a competitor that is also advancing their weekly CNP analog together with the growth hormone and potentially reporting a higher -- just how should we think about BioMarin's view of this evolving treatment landscape and the role that 333 could potentially play it over time.

Thanks for the question. This is Greg Friberg, again. And it is true. I think the data in combination with growth hormone, of which we've seen about 12 months of data, does show in the early studies that there is potentially additional growth to be had by adding in a second agent. But I want to caution you that it is early days for the combination. Growth hormone has been around for quite a while. And in achondroplasia, it's only approved in one market that I'm aware of that's Japan. And the reason for that is that growth that can be stimulated with growth hormone ultimately has not historically resulted in increases in final adult height. It's growth that gets uncorked but at the expense of potentially closing the growth plates earlier. And that remains an open question. I think we do need to see data at 2, 3 years or more, not only to see the safety, of course, growth hormone, while it has a manageable safety profile, does have its own set of challenges that need to be monitored by a physician. But we need to see whether or not those gains are long-standing. I want to reassure you that this is something that we're watching very closely. And if there are opportunities and levers that can help CNP do its job better, so to speak, we will evaluate those at the right time and place. We don't feel that, that is the correct time right now, and we're certainly interested in seeing additional data before the paradigm shifts. And this is consistent with what we've heard from many of our stakeholders as well.

We'll move to our next question from Joe Schwartz at Leerink Partners.

I was wondering if we could get some more perspective on your guidance raise for the enzyme therapies business. We see it increase by $500 million, and we estimate that Amicus generated around $450 million in revenue for Galafold and Pam-Op in the comparable 8 months last year. And that implies low double-digit growth around 11%, I think. But I heard you reference high double-digit percent growth, Brian. So I'm just wondering if you can help us reconcile that difference?

Thanks, Joe. Appreciate the question and your math there. I'd probably attribute the reconciliation difference that you're trying to get at with two elements. One, by doing a pro rata 8 months of 2025, there's certain -- there's some in variables there and a lack of precision that we couldn't do a strict apples-to-apples comparison. And then secondly, on a full year basis, again, I pointed to that strong performance for the first 4 months of the year for both Galafold and Pombiliti and Opfolda. So again, not reported. This is internal management data. We're not disclosing it because it didn't go through the usual external reporting process like a regular quarter does. But we thought it was important to add color to that full year. So I'd say it's more important and this goes to our own business as well when we think about some of these quarterly timing dynamics. I think it's most important to compare the full year annual cycle year-over-year, and that's where when we piece together the range that's implied today over that full year $634 million that Amicus reported for '25, we have a range of high teens to low 20s. I'd encourage you to anchor that rather than trying to calculate them intra-quarter map.

We'll move next to Jason Gerberry at Bank of America.

Alex, just to follow up on the ITC question. I'm trying to just get my head around, do you have any knowledge of the Ascendis' ability to do manufacturing workaround? And just help us think through scenarios if you get a positive ruling like, could a decision be stayed pending any sort of appeals? And then just a follow-up, just on Pom-OP, I believe you've inherited the asset basically launched into 15 country markets, and I think the goal is to get it into 80 country markets. So how should we think about the phasing of that now that you've got the asset either 2026 or 2027?

Thanks very much for the question. Unfortunately, I'm not going to hear any details of the of the ITC the potential scenarios around it. So I hope you can understand that we don't want to get into too many specifics, especially whilst the case is very much pending. So I'll hand it over now to Cristin for the second part.

Yes. Thank you very much for the question Pom-Op. And you're absolutely correct in that there -- currently, we are reimbursed in 15 countries. And what we've been doing before the transaction was closed, we've been doing deep dive into discovery sessions really looking at the business in each market for both Galafold and Pam-Op, really understanding what the dynamics are therein, but then importantly, looking at, as you've mentioned, our 80-country footprint and saying, where would the potential and the opportunity be. We're identifying opportunities for both Galafold as well as Pom-Op, given that Pom-Op is much earlier in its launch trajectory, you can imagine that there will be a larger number of countries to look at therein. But it's important to note that we're not necessarily going to put it into our entire 80-country footprint but importantly, look at where we believe the potential opportunities are and then have a cadence to that, that we'll share more of in the Q2 call.

And that concludes the Q&A session. I will now turn the conference back over to BioMarin's CEO, Alexander Hardy for closing remarks.

Thank you, operator, and thank you all for joining us today. This quarter, as you can tell, marks a really important inflection point for BioMarin. With the recent close of the Amicus acquisition, expanding our commercial reach, strengthening our 2026 revenue growth outlook to 20% and enhancing our ability to serve more patients globally. We're encouraged by the robust patient demand observed across our portfolio. In enzyme therapies, we anticipate that the momentum from the PALYNZIQ launch in adolescence will continue to build. With VOXZOGO, the consistent rise in new patient initiations, more than 20% year-over-year in Q1, especially among younger children, demonstrates confidence in its long-term safety and efficacy and highlights the importance of starting treatment as early as possible. With the integration of Amicus now well underway, several near-term catalysts ahead, pipeline readouts. We are focused on translating this momentum into accelerated growth, broader patient impact, meaningful value creation. We appreciate your continued support and look forward to updating you next quarter. Thank you.

And this concludes today's conference call. Thank you for your participation. You may now disconnect.