BioMarin Pharmaceutical Inc.

Good afternoon and welcome everyone to the Biomarin Pharmaceutical First Quarter 2026 conference call. Today's conference is being recorded. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press the star key, followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one again. At this time, I would like to turn the conference over to Tracy McCarty, Head of Investor Relations. Please go ahead.

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

Thank you, Tracy, 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, Galifold for Fabry disease and Pombility and Opfolder for Pompe disease. The acquisition accelerates our anticipated year-over-year 2026 revenue growth to 20% at the midpoint of today's updated guidance. This 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 one 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 Gallifold and Pombility and Opfolder to our commercial portfolio, and DMX-200 for FSGS in phase three 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 Palenzec adolescent label expansion in the United States. which Kristen will discuss in more detail. We expect enzyme therapies will deliver robust growth in 2026, further supported by the addition of Galifold and Pombility and Opfolder to the portfolio. Moving to our skeletal conditions business unit, we saw strong patient demand for Boxergo, with new patient starts increasing across all regions in the first quarter. In the US, the majority of new patient starts were from the underage two cohort. These results reflect our focused investments in increasing adoption of Oxogo, particularly among younger patients. Building on our leadership in achondroplasia, we are pleased to have submitted the SNDA full approval of Oxogo. 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 VOXOGO in hypochondriplasia and BMN401 for ENPP1 deficiency, those 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 pursuing regulatory next steps following the two upcoming pivotal data readouts. The addition of Gallifold and Pompility and Opfolder 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 10Q, which we expect to file in the coming days. Now moving to slide seven. Total revenues in the first quarter were $766 million and increased year over year, supported by increased patient demand across both enzyme therapies and Voxogo. 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 Vimizin, Naglizide, and Brynura. Palantir's 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 this stocking dynamic to normalize and anticipate year-over-year revenue growth for Palanzeke in full year 2026 as growth in new patients starts in the under 18-year-old population, gains momentum, and patients continue to titrate to their maintenance dose. La Togo revenue was supported by new patient starts across all regions and in line with the expectations that we shared on our prior quarter earnings calls. Looking ahead, due to anticipated order timing and consistent with 2025, we expect Voxogo revenue to be higher in the second half of 2026 compared to the first half. Kristen will provide more color on commercial dynamics in a moment. Turning now to slide eight, 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 Nagozyme manufacturing capabilities. 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 Inzyme transaction in the second half of 2025. Development activities for Voxogo for hypochondriplasia, 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 Voxogo, and partially driven by pre-closed costs associated with the amicus acquisition. First quarter non-GAAP diluted earnings per share was 76 cents 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-closed costs associated with the amicus acquisitions resulted in a $0.20 earnings per share impact to our non-GAAP earnings per share result. Looking past those elements helps 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 nine 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 Gallifold and Pompility 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 Boxogo, 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 diluted 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 get some perspective on timing of the updated guidance, we expect order timing for the historical Biomarin products and two full quarters of Gallifold and Pompility and Opfolder 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-closed 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 two-thirds 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 Gallifold and Pombility and Opfolda, and setting the stage for accelerated near and midterm growth. Thank you for your attention. I will now turn it over to Kristin for a commercial update. Kristin?

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 Voxogo. We look forward to providing a more detailed commercial update on our plans to maximize the potential of both Gallifold and Pompility and Upholda next quarter. Our initial priorities therein are focused on driving diagnosis in Fabry and switch in Pompeii. This will support increased penetration in countries where Gallifold and Pompility and Upholda are marketed, while we concurrently 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 Vimizem, Naglazyme, and Brunera. Across the enzyme therapies portfolio, we continue to see strong patient demand and adherence. Turning to Palenzeke, in the first quarter, we continued to expand the underlying patient base, and physician engagement remained strong. Importantly, following the FDA approval of Palenzi's age 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 healthcare providers treating adolescents during this critical stage of their development. Since approval, we have observed meaningful enrollments and new patient starts in people under the age of 18. From a prescribing standpoint, adolescent uptake is being driven by both physicians with significant experience prescribing Palanzeke, 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 Palanzeke, so we would expect to see the results of positive early prescribing over the coming quarters. Palanzeke continues to stand alone in its ability to enable people with PKU to reach physiologic fee 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 Palenzi can have for additional families over time. Turning now to Vox Sogo on slide 12. As discussed, first quarter results reflected expected order timing dynamics following a strong Q4, particularly in international markets. Importantly, we observed strong growth in patient additions globally, the number of children being treated with Voxogo 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, Voxogo progress continued, supported by ongoing patient additions across all regions and 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 two years of age, where international consensus guidelines for achondroplasia recommend early diagnosis and treatment with Voxogo 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 two-year-old age segment. In Q1, over half of new patient starts were from children under age two, a greater proportion compared to last quarter. Additionally, we have seen an approximate 10% decrease in the average age of children initiating VoxOvo treatment in the under two segment, narrowing the window between diagnosis and treatment starts. Internationally, building on our global expansion into 55 countries to date, our strategy remains focused on reaching more patients in 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 VoxOgo'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 VoxOgo into hypochondroplasia. As we get closer to the phase three 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 three 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, Kristen. 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 Vox Sogo 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 three ongoing long-term extension studies that illustrate these sustained benefits of Vox Sogo over time. Consistent and cumulative improvements in arm span Z-scores were observed across all age groups over the six to eight 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 eight years of follow-up. In addition to anatomic measures of benefit, we also presented data demonstrating Voxogo'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 Voxogo's well-established long-term safety profile. Taken together, this extensive body of evidence reinforces Voxogo'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 Voxogo 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 VoxOgo'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 hypochondriplasia, we believe the healthcare provider community is looking forward to a targeted therapy that addresses this skeletal condition, and we are confident in the scientific rationale for Voxogo 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 3 pivotal trial. We look forward to sharing these Phase 3 top-line results in the second quarter. In parallel, enrollment is progressing very well in our Phase 2 study in children under the age of 3, highlighting early interest in Voxogo as a potential option from infancy in hypochondriplasia. We also expect phase three top line data for BMN401 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. BMN401 has the potential to be the first disease targeted therapy for ENPP1 deficiency. The ENERGY3 study in children aged one to 12 includes two co-primary endpoints, The first is change from baseline and plasma measures of inorganic pyrophosphate through week 52. The second is change in the RGIC, or Ricketts 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'd 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 2-3 study. We are rapidly progressing this program with the goal of establishing BMN 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 Duchenne's 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 six and nine 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 six-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?

Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press star 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star 1 again. We'll go first to Sean Lehman at Morgan Stanley.

Hi, this is Mike on for Sean. Thank you for taking our questions. I guess I 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 and hypochondriplasia, and how does that maybe inform or influence your expectations heading into the top line?

Yeah, thanks for the question, Mike. This is Greg Freiberg. Yeah, 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 in that cumulative data suggests, again, that in addition to growing growth growing bone length and stimulating endochondral bone formation, that yes, that bone is healthy and, you know, 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, the data at PEF highlights the fact that hypochondriplasia, 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 has 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.

Thank you so much. That's really helpful. And then just maybe circling back onto the intro comments, regarding the integration of Amicus, you alluded, maybe there's like a roadmap for future growth acceleration. We were just wondering if you could help to comment, I mean, specifically for Pumbility North Boulder, what levers do you see for driving increased switch rates in that market? Thank you.

Yeah, thank you so much. This is Kristen 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 being high-growth products to add to our portfolio. As we've mentioned before, but I'll expand a little bit, for Gallifold 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, you know, 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 Pombility and Opfoldis 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. We'll share more on that on our Q2 call.

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

Thanks for taking your question. This is Tommy on for Salveen. Just a quick one on Doxogo, wondering if you've seen any early signals of different behavior from competitor entry, whether it be switching or in new patient ads. Thank you.

Yeah, thank you for the question. This is Kristen 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 zero to two population based on the consensus guidelines, and we're seeing real momentum there, not only where our new patient starts weighted and more than half of them being in that zero to two population in the first quarter, but But we're also seeing a reduction in the time we have from diagnosis to treatment in that population. That's reduced by 10% already. So we know that that real focus therein is working. In addition, we're focused on the patients that are already on treatment and making sure that 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 Voxogo and continue to have a positive experience in terms of the benefits. So we're very pleased with how Q1 went and look forward to continuing on that trajectory.

We'll go next to Paul Matisse at Stiefel.

Great. Thanks so much for taking my question. Just kind of previewing your update next quarter as it relates to the Amacus integration, I was wondering if you could set the stage for us on 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 views 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 profitability outlook as well. Thank you.

Hi, Paul. Thanks. Appreciate the question. And yeah, we wanted to highlight today having, you know, just closed the transaction a week ago, you know, 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 eight 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 that 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 a billion dollars each for Gallifold and Pompility and not Folda. But as we developed 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. It'll 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. We'll look forward to sharing more, but we're off to a strong start.

We'll move next to Ellie Merle at Barclays.

Hi, this is Jasmine on for Ellie. Thank you so much for taking our question. So just for Voxogo and hypochondriplasia, what's the latest on what you're thinking will be good data and what you're looking to see on AGVs? And also, how are you thinking about the contribution to VoxOga revenues from hypochondriplasia 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.

Thanks, Jasmine. This is Greg Freiberg. Maybe I'll take the first part and then hand it off to my colleague. With regard to the VoxHCH study, 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 anthropomorphic 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 hypochondriplasia 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 Kristen.

Thank you. And so overall, our goal, of course, is to continue the growth of Voxogo into the midterm, and hypochondriplasia provides an important component of that. Really where we're focused today on our pre-launch activities is in and around diagnosis. We have shared before that the total addressable patient population globally is at 14,000, and 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 hypochondriplasia patients that have been identified, that we're getting physicians to understand the genetic testing and make sure that they're putting orders for that, and really the idea being that patients get diagnosed at a much earlier age. So our goal today is to improve upon that and make sure that we have identified patients.

And Jasmine, 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. You know, there's probably three 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 genetic side to reclassify so-called VUSs, variants of uncertain significance. And so in that world, we're anticipating, again, that there will be patients available and ready for this therapy should it become available.

Just 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 non-promotional pre-launch activities, we're already seeing a 90% increase in the number of hypochondriplasia 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 Corey Kasimov at Evercore.

Hi, this is Addy on for Corey. Thanks for taking the question. I had a question on the guidance increase. The 500 million from midpoint increase in guidance. Can you frame that, you know, the contribution from data for power is that conservative relative to these 600 million revenue that generated in fiscal year 2025? And what are the key assumptions for, you know, adding these two assets into the guidance?

Hi, Eddie. 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, yeah, I'll frame it up for you. First of all, you know, 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 eight 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 that, you know, both Gausbold and POMOP together are off to a strong start in 2026. So with that being said, again, 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 is 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 onto 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 Fai at J.P. Morgan.

Hi, this is Joseon for Jess. Thanks for taking our questions. How should we think about the adoption of Bugzogo in hypochondriplasia relative to chondriplasia? What do you see as the similarities and differences between these markets? And second, can you help us bridge the disconnect between the 20% year-over-year patient growth in one cue? versus a 3% revenue growth? Is it entirely explained by larger orders in the fourth quarter last year? Thank you.

Yeah, 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 acondroplasia, but I think as I'd 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 Kristen, from a medical standpoint, if I could just comment, hypochondriplasia children are not born with the same growth 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, uh, in the hands of the right physicians, um, who again can know what to do for them. Uh, that seems like a real early success and we're looking forward to continuing to help shape that community and, uh, make, uh, make these, these therapies, should they become available actually, uh, in the hands of the physicians who treat the patients.

Thanks, uh, Greg and Kristen, I'll take that revenue timing, uh, fluctuation, uh, question, uh, I appreciate you pointing that out because it is important to emphasize that the disconnect between that underlying patient demand growth and 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 Palantik and Voxogo. 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 impact. Price drivers in there, by the way, it is entirely order timing dynamics.

We'll move next to Phil Nadal at TD Callen.

Good afternoon. Thanks for taking our questions. 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 note that there's going to be some data from BMN 333's Phase 2-3 trial in 2027. Can you provide a little bit more details around what data will be released at that time? Thanks.

Thanks very much, Phil. This is Alexander. I'll take the first part of your question and hand it over to Greg for the second part. So with regard to the ITC, I mean, overall, we believe that issuing an exclusion order at the ITC 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 Sendus' product infringes our patent. on or about August 21st. At that point, if the full commission decides to review the decision, then the final decision is expected on or about December 21st. So this is a little bit of, you know, where we are and what can we expect going forward. I will also add that, you know, on completion of the ITC process, we would expect to also enforce our patent in the federal district court, where, of course, monetary damages are available. And I'll now hand it over to Greg.

Thanks 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 1, 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 2-3 study in children with achondroplasia. This is a multi-regional 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 two portion where one of three doses of BMN 333 will be administered to the children, and there'll be one arm that has Voxogo 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 six-month time point, and we'll be using that data along with other measures, anthropomorphic measures, other measures of safety and well-being, to make a decision based on a Bayesian analysis of which dose we should bring forward into a phase three to run head-to-head against Varxogo. 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.

Yeah. Thanks. Uh, just a question on the, 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, um, and the decision to go with a superiority trial versus non-inferiority. Um, I think I've heard what you guys have said around 333 providing two to three times free CNP and that that should translate into higher efficacy, but maybe just strategically, um, If a non-inferiority trial could show that data, why take the risk and run a superiority study? Thanks.

Yeah, thanks for the question. This is Greg Freiberg. And, you know, our goal with BMN 333 is to evolve this space, not just make a more convenient version of Voxogo. I'll just highlight that that 3x target was an at least 3x. We're actually testing a 3x, a 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, you know, 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 10 times the size. in order to show non-inferiority versus even, you know, a drug like Voxogo. 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 two portion. And if there need to be adjustments, if the Bayesian 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, actually, as Greg said, this is Alexander, you know, we think the opportunity and the need here is really around superiority in terms of efficacy, HEV, and all the benefits beyond linear growth. Um, but also, you know, by, by, uh, this design of a study, we, we actually have, uh, an active control, uh, with Vox Ogo. So the size of the study is smaller than it would be if it was in a non-inferiority design as Gregor was already covered. But we also think the proposition to both caregivers and physicians means that, you know, this should be a study that's very attractive, uh, to, uh, potential patients to, to, uh, to, um, 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.

Yeah, placebo-controlled studies, when they're 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.

Great. This is for Mohit Bansal. Thank you for taking our question. So we just have a, I just want to double click on the BMA-CC3 a little bit. I think you guys discussed that BMA-CC3 targeting, you know, improvement in aconchoplasia. But just wondering whether a competitor that is also advancing their weekly DMP analog together with the growth hormone and potentially reporting a higher AGV. Just how should we think about BioMarin's view of this, you know, evolving treatment landscape and the role that 3C3 could potentially play over time? Thank you.

Thanks for the question. This is Greg Freiberg 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 is 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 to three 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 longstanding. 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 Larrink Partners.

Great. Thanks very much. I was wondering if we could get some more perspective on your guidance raise for the enzyme therapies business. We see it increased by $500 million, and we estimate that Amicus generated around $450 million in revenue for Gallifold and Palm Op in the comparable eight 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.

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 eight months of 2025, you know, there's, you know, There's some missing 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 four months of the year for both Gallifold and Pompility and Uphold. So again, not reported. This is internal management data. We're not disclosing it because it didn't go through the usual, you know, 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. So I'd encourage you to anchor to that rather than trying to calculate some intra-quarter math.

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

Hey, guys. Thanks for taking my questions. 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 ascendance's 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 as a follow-up, just on POMOP, 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.

Thanks very much for the questions. Unfortunately, I'm not going to get any details of the ATC, the potential you know, 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 Kristen for the second part.

Yeah, thank you very much for the question around POMOP. And you're absolutely correct in that currently we are reimbursed in 15 countries. And what we've been doing, you know, before the transaction was closed, what we've been doing is significant and deep dive discovery sessions, really looking at the business in each market for both Gallifold and Palm 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 Gallifold as well as Palm Op. Given that Palm Op is much earlier in its launch trajectory, you can imagine that there'll 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 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 BioMaria. 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 Palenzyk launch in adolescence will continue to build. With Voxergo, a 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.