Hello everyone, thank you for joining us and welcome to the BioMarin third quarter 2026 conference call. After today's prepared remarks, we will host a question and answer session. If you would like to ask a question, please press star 1 to raise your hand. To withdraw your question, press star 1 again. I will now hand the call over to BioMarin's Head of Investor Relations, Tracy McCarty. 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 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, Alexander Hardy, Chief Executive Officer, Cristin Hubbard, Chief Commercial Officer Greg Friberg, Chief R&D Officer, and Brian Mueller, Chief Financial Officer. I will now turn the call over to Alexander to provide our quarterly highlights. Alexander?

Thank you, Tracy, and thank you all for joining us today. Starting on slide five, strong demand across our diversified portfolio of innovative therapies drove 32% year-over-year growth in the third quarter, surpassing $1 billion and many more. Also last week, we announced the addition of a new investigational Fabray asset to our clinical portfolio. Recently renamed BMN450, the fourth new asset added to our pipeline in 2026. This highlights the focused and deliberate expansion of Biomarin's clinical stage pipeline. BMN450 has the potential Thank you for joining us. They totaled more than $200 million in combined revenues in the quarter, while at the same time, the pace of the Amicus cost synergies realization exceeded our expectations. We are energized by the addition of our Amicus colleagues, and we're working together to expand the reach of both Gallifold and Pompility and Opfolder, bringing these therapies to more patients around the world. I am also pleased with the continued global expansion of VoxOgo as the number of children treated increased by 17% worldwide. Building on this momentum, we are pleased to share that May 30th, 2027 is the PDUFA date for VoxOgo for the treatment of hypochondriplasia, the first targeted therapy to potentially be approved for the indication and a potential and the seventh first in disease medicine for Biomarin. The team is well prepared for strong launches in hypochondriplasia in the US and Europe, and we anticipate both regions will benefit from our global leadership in skeletal conditions. Before I turn the call over to Cristin, I want to say a few words about the work we are doing to expand our pipeline, including the most recent addition to our clinical portfolio. BMN 450 is a phase 1-2 compound that builds on our Gallifold experience and has the potential to expand the therapeutic reach to those with Fabry whose variants are not amenable to Gallifold. The Amen 450 is a strategically compelling addition to our metabolic conditions BU, addressing treatment burden and a priority unmet need with a differentiated, long-acting, subcutaneous profile. It also reflects our growing commitment to the Fabry community, building on the Amherst acquisition, as well as the expertise and relationships established with Gallifold. In summary, we delivered strong financial results in the third quarter and made meaningful progress across every part of our business. In a moment, Brian will speak to some expected order timing dynamics and geopolitical headwinds that we are observing, resulting in today's updated guidance. In 2026, we have delivered on the strategic expansion of our innovative pipeline, including the addition of BMN 450, BMN 440 for hypophosphatasia, BMN 430 for a new syndrome, and BMN 820 for FSGS. Our business development execution, having delivered five deals in two years, demonstrates our capabilities across the value chain as a rare disease leader operating at scale. Our commercial portfolio is now more diversified and more resilient following the successful acquisition of Amicus, as well as our pipeline with the more recently acquired earlier stage assets. We look ahead with enthusiasm for what's to come as we advance the next wave of therapies from our clinical stage pipeline and to reporting on a number of key updates in 2027. Combined with the strength of our more diversified commercial portfolio, we are confident in our ability to create lasting value for patients and all of our stakeholders. And we look forward to updating you on our progress. I will now turn the call over to Cristin for more detail on our commercial performance. Cristin.

Thank you, Alexander. The third quarter again showed the strength and growing diversity of our portfolio. Our team stayed focused on expanding diagnosis Increasing access and helping more patients start and stay on therapy. Now turning to slide seven. We have begun to implement the initiatives that we outlined last quarter for Gallifold and Pompility and Opfolda. For Gallifold, those levers are expanding diagnosis and treatment and deepening market penetration globally. For Pompility and Opfolda, there are increased patient switching and global market expansion, complemented by improvements in diagnosis and treatment. New geographies take time, so this quarter we focused on the fastest levers, finding and treating more patients in existing markets. We are pleased with the progress we've made in a short amount of time. Both medicines delivered strong revenue in the quarter. Gallifold was $152 million, 10% higher than the $138 million Amicus reported for the third quarter of 2025. Pumbility and Opfolda revenue was $49 million. 58% higher than the $31 million Amicus reported for the same period last year. The number of patients treated with GalaFold increased by approximately 13% year-over-year, with growth across both established and newer markets. For example, in the quarter, one international market increased patients on therapy by 20% year-over-year, reflecting the ongoing success of Family Cascades testing initiatives bolstered by expanding newborn screening programs. The number of patients on Plumbility and Afolda increased by approximately 69% year over year. Switching continues to be supported by its differentiated clinical profile, as we help physicians better identify disease progression on prior therapies. The expanding body of clinical and real-world evidence reinforces that profile, including the five-year Propel extension data presented at the World Muscle Society Congress in October, which Greg will speak to in a moment. We are also seeing an increasing penetration in Europe. Pompility in Op Fulda is now the market share leader in terms of patients on therapy in four markets. This leadership reflects the growing confidence in the profile of Pompility in Op Fulda. In the third quarter, we also began supporting patients in certain European markets who are affected by recent supply constraints for other Pompe therapies. We have released additional supply so that patients who need it can get treatment without interruptions. As a result, patients who switched to Pompility and Opfolda during the quarter due to supply constraints represented a meaningful share of new patient starts in these markets. We would expect to see some additional patients in the fourth quarter due to supply constraints for the other Pompe therapies, with the revenue benefit from this dynamic building in 2027 and beyond. Now, we can't predict how long the constraints for other Pompe therapies will last or if it will result in material revenue increases from Pompility and Opfolda, but reliable supply from Biomarin could become a factor in treatment choice. Now turning to slide eight, total metabolic conditions revenue was $744 million and grew 44% year over year, driven largely by the first full quarter of GalaFold and Pompility Not Fold Up. The number of patients on therapy grew across every one of our marketed metabolic conditions brands. Moving to the other products and metabolic conditions, the quarter reflected continued patient demand along with the order timing patterns we have consistently described. Reflecting Palenzeke's distinct product profile, patients on therapy increased 9% year-over-year globally, led by the adolescent launch in the U.S., and we observed minimal switching to BH4 analogs. In fact, we've been pleased that some patients who switched to oral therapies have returned to Palenzeke treatment. Revenue grew 2% as the U.S. order timing normalized after a strong second quarter. It can take many months for a patient to titrate to a maintenance dose, so we expect the adolescent revenue contribution to build into 2027 and beyond. Zim is Zim grew 18% year over year, benefiting from orders outside of the U.S., while Maglazyme revenue was lower, as expected, following order timing benefits in the second quarter. Because order timing shifts between quarters, Our full-year metabolic conditions guidance is the best indicator of expected underlying performance. Turning to slide 9. In the third quarter, Voxogo revenue grew 12% year-over-year to $245 million, despite a large order previously expected in Q3, now anticipated in Q4. Patient demand outpaced revenue in Q3, as the number of children treated with Voxogo globally increased approximately 17%. More than 75% of revenue in the third quarter was generated outside of the U.S., and we expect this segment to be a leading area of expansion in achondroplasia. We are pleased to share that we recently received approval to treat children with achondroplasia in three additional international markets with Voxogo. Briefly on the U.S., children under two represented the majority of new patient starts in the quarter, and approximately 85% of the U.S. children remained on Voxogo as of the end of September. based on our switching data. We observed that the pace of switching trended downward each month during the third quarter. When we surveyed families about why they stay on Voxogo, they say it's because they are confident it is working for their child and because daily dosing has become an established, well-tolerated routine. Further confidence for families and treaters comes from the growing body of clinical and real-world data supporting Voxogo's long-term safety and efficacy profile as reflected in the data package we submitted for full approval. Beginning in the fourth quarter, we plan to focus our updates on Voxogo revenue rather than providing U.S. switching metrics. As Voxogo's market mix changes with the anticipated launch for hypochondriplasia next year, along with continued international expansion in achondroplasia, U.S. switch data becomes less relevant to Voxogo's overall revenue performance. Leadership in achondroplasia sets the foundation for a potential launch of Voxogo in hypochondriplasia. where we estimate a global total addressable patient population of approximately 14,000 children. Our launch preparation is focused on three things. First, we are sharing the evidence. The first full phase three results published in the New England Journal of Medicine evidence and presented as a late-breaking oral at SB showed statistically significant improvements in growth velocity, height, and arm span. Our medical affairs team is increasing diagnosis and patient identification, helped by the first international consensus recommendations for diagnosing hypochondriplasia published this quarter, and by disease education that has reached more than 1,200 pediatric endocrinologists and geneticists in the U.S. And third, we're laying the foundation for rapid access, engaging payers early on the pivotal data and building on Voxogo's established coverage and real-world experience in achondroplasia. With the potential addition of hypochondriplasia, we remain confident in Voxogo's durability. More than 5,000 infants and children in 58 countries have been treated with Voxogo, and its evidence base continues to expand. Together with the potential of BMN 333, should data be supportive, these opportunities underpin our ambition to remain the leader in skeletal conditions. With that, I'll turn the call over to Greg for an R&D update.

Thank you, Cristin. Turning to slide 11, we are quite pleased to have four new assets under development, having leveraged externally sourced innovation to add multiple new programs to our pipeline this year. These additions span preclinical through phase three development, setting the stage for some exciting potential updates in the coming quarters. Today, I have the opportunity to provide more details and talk about our newest addition, BMN 450, A potential first subcutaneous enzyme replacement therapy for febrary disease, having just announced the license agreement last week. I'm also excited to share a little more detail on BMN 440, the first potential oral treatment for hypophosphatasia. And finally, I'll review the five-year outcome data for pumbility and upfolda that were presented at the World Muscle Society, further underscoring the benefit of this therapy for those with late-onset Pompe disease. Now moving to slide 12 and BMN 450, which we are thrilled to add to our growing clinical pipeline. It is an investigational, long-acting ERT for Febre disease and is designed to extend the half-life and improve stability relative to currently available ERTs. Approved ERTs for Febre are all administered by intravenous infusion, and BMN 450 has the potential to be the first subcutaneous ERT in the space. giving patients and physicians an option to reduce the treatment burden. Importantly, we believe BMN450 also has the potential to be mutation agnostic and to address a broader patient population than that of Gallifold, which is indicated for the estimated 35 to 50% of patients with amenable mutations. We are encouraged that in preclinical studies, BMN450 demonstrated differentiated efficacy across key measures, including renal function, vascular health, and peripheral nervous system outcomes, which may offer potential for an improved therapeutic profile. It has received orphan drug designation from the FDA and is currently in phase 1-2 testing. Entering at phase 1-2 is fortuitous, as it allows us to shape the program moving forward, including the selection of dosing and patient populations. We bring deep experience developing and manufacturing ERTs, and the regulatory pathways for ERTs in Febre are well established. Following the ongoing study, we will assume sole responsibility for subsequent clinical development, manufacturing, and commercialization outside of Korea. We look forward to updating you as the program progresses. Now turning to slide 13 and BMN 440, which we added in the third quarter through the Alesta acquisition. Because the disease and the mechanism may be new to many of you, I want to spend a moment on each. Hypophosphatasia, or HPP, is a rare genetic condition caused by mutation in the ALPL gene that codes for the enzyme tissue nonspecific alkaline phosphatase. When this enzyme is deficient, inorganic pyrophosphate, or PPI, accumulates upstream and acts as a direct inhibitor of bone mineralization, leading to fractures and exerting both direct and indirect effects on muscle, leading to weakness. PPI reduction is known to track with clinical benefits on bone health and mobility in patients. BMN 440 is a direct inhibitor of the ENPP1 enzyme directly upstream of PPI and thus can be thought of as a substrate reduction therapy for HPP. Preclinical data support this approach. At ASBMR in October, Data from a mouse model of later-onset HPP showed that oral treatment with BMN 440 reduced PPI and normalized the phosphate-to-PPI ratio. It also improved bone mineralization, muscle strength, and mobility measures. The promise of this approach is to deliver an oral alternative to ERT therapy for pediatric and adult-onset HPP, with the added potential to better address systemic symptoms that bone-selective ERTs cannot. This is especially important because adult onset patients are often affected by muscle weakness, pain, and fatigue more so than bone problems. At ASBMR in October, a study with adult HPP patients demonstrated that the burden of this condition in adults extends beyond the skeleton to physical functioning, fatigue, sleep, and pain. There are no approved therapies for adult onset HPP in the U.S. or Europe. BMN 440 is now in a phase 1-2a study in healthy volunteers and adults with HPP. We expect data in 2027 that will characterize pharmacokinetics, pharmacodynamics, and safety, establishing an initial human proof of mechanism and informing dose selection and design for our next study. Turning to slide 14. At the World Muscle Society Congress in October, we presented five-year data for the Propel open-label extension study in adults with late-onset Pompe disease. This analysis followed 82 people who received POMBILITY and OPFOLDA continuously from the start of Propel. Most had received prior enzyme replacement therapy, having received it for an average of 7.6 years per year previous to enrollment. Over five years on POMBILITY, OPFOLDA, Motor function was maintained and pulmonary function remained relatively stable. In ERT-experienced patients, six-minute walk distance was maintained, while in the ERT-naive patients, it actually improved over time. Reductions in creatine kinase, a marker of muscle damage, were sustained for the duration and there were no new safety signals. These data support durable outcomes through five years in patients who had already been treated and add to the growing body of evidence supporting the rationale of switching to POMBILITY and UPFOLDA. Sustaining motor function and limiting pulmonary decline for five years in a progressive disease like late-onset Pompe is quite clinically meaningful. As a reminder, POMBILITY and UPFOLDA is indicated in the U.S. for adults who are not improving on their current ERT therapy, so long-term results in this population are especially relevant. With that, I will turn the call over to Brian. Brian?

Thank you, Greg. Please refer to today's press release for detailed third quarter 2026 results, including reconciliations of GAAP to non-GAAP financial measures, as well as our upcoming Form 10-Q. As Alexander and Cristin have already covered the key revenue details for Q3, I will cover the financial impact of our two recent business development transactions, some revenue timing and geopolitical dynamics that we are observing, and the expected associated earnings per share impacts in 2026. Turning to slide 16. We were pleased that third quarter revenue exceeded $1 billion, a first for BioMarin. Also on revenue, beginning this quarter, royalty and other revenues include amounts earned from Ascendus under the global settlement that we announced in August. Third quarter results include the Alesta acquisition. which closed on August 31st and drove approximately $290 million of pre-tax expenses or approximately $1.48 per share on a pre-tax basis, mostly related to acquired in-process research and development or IPR&D. The impact of the ELESTA charges on pre-tax income for Q3 and the full year results in a timing-related tax element Thank you for joining us today. Non-GAAP diluted earnings per share during the quarter was 23 cents, which reflects the IPR&D charges related to the Alesta acquisition. Also underlying the results, revenue grew 32% year over year, while non-GAAP SG&A expense increased 12%. The non-GAAP SG&A increase primarily reflects the addition of amicus, including the commercial teams that support GalaFold and Pompility and Upholda. Turning to slide 17 and our updated full year 2026 guidance. We are updating our full year total revenue guidance range to between $3.8 billion and $3.9 billion. The driver of the change is order timing and not underlying patient demand. During the third quarter, a single international customer indicated they intend to defer multiple expected orders. totaling approximately $70 million. Certain of these orders are already under contract for shipment and we expect to fulfill the majority of the orders between late Q4 and Q1, 2027. However, we cannot predict the exact timing. And while this type of order movement is normal for our large global business and one of the reasons that we don't guide quarterly, the magnitude and timing uncertainty A second factor is the prolonged conflict in the Middle East. We have been managing through moderate disruption thus far in 2026. However, customer liquidity and customer cash flow disruption have increased over the last two months. We are sharing this dynamic today because on a full-year basis, we are usually able to offset various headwinds and tailwinds in our business, However, with just two months to go in the year, there are less of those available. Both the expected order timing just discussed and the observed Middle East disruption are reflected in today's updated guidance. To be clear, this guidance change is not driven by patient demand in these markets, and our updated guidance is based on timing of revenue between Q4 and next year. The underlying business is performing strongly as underscored by third quarter results today. We're also updating non-GAAP diluted earnings per share guidance to a range of $2.80 to $3.10, reflecting the two business development transactions that were not included in our August guidance, as well as the bottom line impact of today's updated revenue guidance. The Alesta acquisition reduces full-year non-GAAP diluted earnings per share by approximately $1.55, and the BMN 450 license agreement reduces it by approximately $0.32. The Alesta impact reflects approximately $320 million of acquired IPR&D and ongoing operating expenses this year, including transaction and transition costs. The BMN 450 impact reflects approximately $83 million of primarily upfront acquired IPR&D expense and ongoing operating expenses, which we expect to record in the fourth quarter. We recognize that the bridge from our Q2 to Q3 guidance is complex. Excluding the two recent business development deals and today's updated revenue guidance due to order timing, The midpoint of our updated earnings per share range is effectively unchanged from August, reflecting the delivery of our underlying business profitability goal. In summary, the third quarter reflected strong top line execution across a broader portfolio, and we continued investing in future value creation through the acquisition of new clinical assets. At the same time, amicus cost synergies are ahead of schedule, and we continue to expect approximately $220 million of non-GAAP cost synergies to be realized fully in 2028. Thank you for your attention. We will now open the call to your questions. Operator?

We will now begin the question and answer session. Please limit yourself to one question and one follow up. If you would like to ask a question, please press star one to raise your hand. To withdraw your question, press star one again. We ask that you pick up your handset when asking a question to allow for optimum sound quality. If you are muted locally, please remember to unmute your device. Please stand by while we compile the Q&A roster. Your first question is from the line of Jessica Fai with JP Morgan. Your line is now open. Please go ahead.

Hello, this is Adam on for Jess. Thank you for taking our question. I just wanted to ask, and sorry if I missed this, but the PR says you Realize Accelerated Cost Synergies in 3Q While Maintaining the 220 Non-Q Target for 2028. Could you elaborate on that? And what should investors carry into the 2027 OPEX assumptions as we model that out? Thank you.

Hi, Adam. This is Brian Mueller. Thanks for the question. And yeah, you heard that accurately. You know, we came out in the Q2 report in early August with our long-term views on the amicus integration. We quantified the synergies and started to talk about the accretion of the deal. And those metrics were partially dilutive post-acquisition here in 2026. Substantial accretion beginning next year in 2027 and then growing to full synergy realization in 2028. The integration is going really well. We're executing, really proud of both the BioMarin and Amicus teams, and now we're one team. And the cost synergies are ahead of schedule, so we're not – updating or quantifying any additional metrics at this time. We'll talk more about the 27 accretion when we guide to 27, but we can say that the cost synergies are ahead of schedule. We initially said that within the first calendar year post-closing, the deal would be accretive. We can now pull that forward and be confident that the deal is accretive actually within nine months. and still a quarter to go here, but I'll also share that we're currently tracking to even calendar year accretion in 26. Thank you.

Your next question is from the line of Sean Lammon with Morgan Stanley. Your line is now open. Please go ahead.

Hi, Alexandra and team. I hope everyone's well. On POMOP, the patient growth was around 69%, but you've acknowledged that uptake benefited from the competitor supply constraints. Alexander, can you quantify the underlying growth, excluding that disruption? And I might have missed it. And how many of those starts are likely to remain durable once competitor supply normalises? Thank you.

Thanks very much, Sean. I'm going to hand it over to Cristin.

Thanks so much, Sean, for the question. This is Cristin. Yeah, as you noted, the performance in the third quarter for POMOP was indeed strong. Revenue up 58% and patients up 59% year over year relative to what Amicus reported in the same quarter. And I think what's really important to note on POMOP is that the switching really is based on the clinical profile of the medicine. Now, we're watching this growing body of clinical and real-world evidence You saw in the prepared remarks the Propel Extension Study that Greg spoke to, which I think has been a really important momentum builder for us. But as noted, we have also seen what we called a meaningful share of new patient starts based on the supply shortage we're hearing from other Pompe therapies. Now, this is happening in certain European markets. We aren't sure how long this will last, nor the depth of the problem. But what we've done is worked really hard to ensure that we have additional supply So that we can not only support our patients that are on Pondability and Opfolda, but importantly, any new patients that want to come on as a result of these shortages. So we really do think that this is an important moment for Pondability and Opfolda. We're building great momentum and it's just the beginning of some of the initiatives we put in place. I do want to note, however, that revenue Your next question is from the line of Ellie Merle with Barclays. Your line is now open. Please go ahead.

Hey guys, thanks so much for taking the question. Just on the achondroplasia space, something we've been hearing about recently from, I guess, one of the more outspoken competitors in the space is just around the safety of inhibiting FGFR2 in the developing brain and potential implications of that. I guess, do you have any thoughts on the debate here and how this could play out commercially, even just from a perception perspective? And then just second quick follow-up, for BMN 440, an interesting opportunity there. Could you elaborate what would constitute proof of concept at the data next year?

Thanks. Thanks, Ellie. This is Greg Friberg. I'll take a stab at both of those. Yeah, with regard to I think the comment you made about FGFR2 inhibition in the brain, you know, my thoughts are much more philosophical, which is, you know, drug development is hard. I think that when we are looking at small versus large molecules, they have their risks, they have their opportunities, they have their challenges. But really, this issue of whether or not a small molecule crossing the blood-brain barrier leads to any sort of untoward side effects, these are hypothetical at this point. I would just comment that the FDA has established guidance on how they look at this. They take structured processes. They evaluate the risk benefit of these drugs very carefully. And we know that that's incredibly important, particularly in children who are going to be on these treatment for multiple years. At the end of the day, clinical data is the antidote to all of these potential concerns. And really, from that standpoint, we're quite proud of the data package that we have with Voxogo. We've got, as Cristin commented on, over 5,000 patients, 10,000 patient years, 50 countries, We know that the benefit-risk profile is one that we can stand behind. We like to say it's the best-in-class evidence package. That, of course, has given us the opportunity to put forward the full approval data package that has additional information that will be ruled on by the FDA with the February 28th PDUFA date. I really can't speculate beyond that how the FDA will view this, but certainly, The idea of a chronic safety and efficacy package that we bring with Voxogo, we see that as a winning argument that we will be putting forward and continuing to publish on for patients and physicians. With regard to your second question, 440, and the proof of concept data, we have an ongoing Phase 1-2 study right now. As a quick reminder, this is a single-dose and a multi-dose study rolled together. It's in both healthy volunteers as well as a subset of HPP patients. And the data that we will have to present publicly next year will include both PK as well as what we're calling proof of mechanism data. So this is data, again, looking at enzymatic activity and biomarker activity. What will come thereafter, once we've been able to select doses and schedules, will be a phase two study that will look at harder clinical endpoints. More to come, but we're really excited about this opportunity. As a quick reminder, as a small molecule, a substrate reduction therapy for HPP, the promise and the opportunity here isn't just that we have a more convenient therapy, but potentially one that also reaches compartments like the muscle and the bone that can affect, particularly the adults, the kind of side effects and adverse events from their disease that are really burdening them the most. That is Muscle pain and limitations of mobility that again, some of the more bone targeting large molecules may not be able to.

Your next question is from the line of Corey Kasimov with Evercore ISI. Your line is now open. Please go ahead.

Hi, this is Adi on for Corey. We noticed the January pitufa for PharmOp in adolescents. Is that opportunity already included in your 1.2 billion peak sales outlook or would it be upside? And also more broadly, now that you've had more time with the acquired business, where else do you see the biggest opportunity to bring more Febre and Pompe patients onto treatment beyond switching from existing therapies? Thank you.

So we do believe that there's a lot of opportunity here to continue to, and did you ask specifically about PalmOp or also GalaFold? Sorry, just so that I'm clear on the question, PalmOp specifically.

Yeah, for both of them. For PalmOp, we noticed that all the SND has already filed. So yeah, it's on both.

Yeah, so we believe that opportunity is relatively small in the scheme of things. but we believe that the overall opportunity on Pombility and Opfolda is quite a bit bigger. In so much as I just mentioned in the previous comments, we really are seeing momentum build for this therapy. Not only is it the evidence that we're seeing but also importantly on just the experience. So where we see the opportunities where we can really help build this is certainly to share The real-world evidence as we generate it, certainly, you know, the adolescent is a catalyst opportunity, I should say, for Palmbility, not Folda. But really, as we continue to expand this, not only in the indication that we have today, but as we geographically expand this as well. So, the real switching opportunities here are to make sure that the data continue to be generated and that we educate on that meaningful data. that we importantly empower both physicians and patients to understand when their current treatment might be waning or they might be, they aren't doing as well on the treatment that they're on and so that they're advocating on their own behalf to ensure that they get that switch to happen. And then as I'd mentioned, I think that this geographic expansion, given that Pombility-Napalda is still in its early days, it's important that we continue to build momentum in countries not only where we are today but importantly in the countries we aren't yet And so our regulatory team, our commercial teams in the field are preparing for this, which will help to build that growth into the future.

Thank you.

Your next question is from the line of Paul Matisse with Stifle. Your line is now open. Please go ahead.

Hey, thanks so much for taking my questions. I appreciate it. I wanted to ask a couple on BMN 333 data next year. Understanding that your thesis here is that you could show clinical superiority, I was wondering what would be an outcome next year that would definitively de-risk that profile and make you confident in going that path for a pivotal study? And then maybe just as a second question to that, let's say this drug does show good clinical activity, but maybe the question around power for superiority looks a little bit riskier. Would you still forge ahead with maybe some sort of non-inferiority or equivalence path? Thanks so much.

Thanks, Paul. This is Greg. I'll tackle that one for you. With regard to the 333 study that's ongoing, just as a reminder for folks, we are running the Phase 2 portion of our combined Phase 2-3 program, which is looking at a variety of doses. In this case, it's three doses of 333 and looking at the AGV at six months. or greater, and trying to determine how that compares to the control arm of Voxogo. That not only will be studied within the protocol, but also will be supplemented by a wealth of historic data, again, that we have at our disposal. Now, again, it's not a question of whether a dose response exists, but it really is a question of the shape of that curve. We know that those three doses are going to give us have significantly increased AUC exposures of free CNP and will allow us to test this hypothesis. So we have a Bayesian model that's in place that will determine a posterior probability, not only of those three doses, but really looking at it with regard to exposure response as well. And while we're not releasing what the math behind that model is, We feel that, again, if we meet those criteria, we will have a good degree of confidence that moving forward with a superiority study, testing the winner dose against Sparxogo is a very good bet. That being said, you know, again, what we know so far is, of course, that we've been able to get not only PK, but increases in PD as well with the cyclic GMP. And we're quite confident, again, that we have the right molecule and we're running the right study. Just for posterity's sake, since you're asking the question, you know, should it not be achieved? Our phase three study also will provide an opportunity to consider alternative hypotheses like non-inferiority or less frequent dosing, and that would not materially slow down our development timelines. That's not our hypothesis. We think that we have the right study and the right molecule. We're looking forward to turn over the cards to that initial dose ranging study sometime next year.

So Greg, just to clarify, next year's readout is not really a growth velocity readout. It's more of a PKPD readout. Is that right?

It is a growth velocity readout. In this case, the PD is AGV. It's six-month or greater data. Please clarify, Paul.

No, thank you. Please go ahead.

Yeah, I was going to say it's AGV indeed. So the PD is AGV. Technically, that's an intermediate endpoint and final is all tight, which we're thrilled to again have for Voxogo would be the primary endpoint for full approval. But when I mentioned PKPD, I meant exposure response with regard to AGV.

Thanks for clarifying.

Your next question is from the line of Alex Hammond with Wolf Research. Your line is now open. Please go ahead.

Hey guys, thanks for taking the question. So since the full acquisition, you've added BMN 440 as well as 450, both early stage clinical assets. Isn't that now the template or would you use that 4 to 5 billion of firepower you expect in mid-2027 on another commercial or late stage deal? I guess after these deals, what gaps remain in your pipeline? Thank you.

Hey, Alex. Thanks very much for your question. Yeah, as you can tell, we're very excited about the deals we've done and to add four assets to our pipeline in 2026 so far. We continue to remain focused on clinical stage deals at the moment. So, you know, programs that fit with our capabilities around genetics, around Regulatory expertise around manufacturing, around commercialization. Particularly, as you can tell, interested in assets that fit with our business units, so skeletal conditions and metabolic conditions. But we're interested also in other genetic conditions, but clinical stage assets, absolutely. As Brian said, the accretion has been very impressive, the implementation of the amicus acquisition, and our firepower is increasing. So we will continue to do these clinical stage deals for the foreseeable future.

Your next question is from the line of Philip Nadu with TD Cowan. Your line is now open. Please go ahead.

Hey, this is Rishi on for Phil. Thanks for the call tonight. Really great progress. Two questions for me. First is, so UB Well was given a positive opinion from the CHMP of the EMA last month. So with the possible launch in Europe, or approval in Europe coming up. How do you anticipate this to play into the competitive dynamics with Voxogo as quantitatively as possible? And then my second question is you've previously, moving on to hypochondriplasia, You've previously given metrics on your efforts to increase diagnosis rates and reduce age of diagnosis, saying 90% increased in diagnosis rates, 70% reduction in the age of diagnosis. Just do you have any updates on those metrics now? Thank you.

Thanks for the question, Richie. So I'll take those. So UVA Well in Europe I can say that we are very much anticipating the launch there, have that into our plans. Our competitive readiness, of course, assumes that. We've not given guidance for the next year. And so in the next year, we'll be able to provide more color on that. But I will say that we are ready for it, have it in our baseline plans, and are looking forward to seeing what that looks like. Now, on the second one, on the HCH metrics, what we have shared is, you know, the real focus areas as we're nearing the launch. As you know, the PDUFA is coming in May in the U.S., and we're really focused on right now sharing the Phase 3 data, making sure that we're increasing diagnosis, and then ensuring rapid access, so having the right conversations with payers. Now, with regard to the specific metrics that you've asked for, we don't have an update on those today, but I will say that as we get closer to the launch timing, We very much will be sharing more on our plans and specifically the metrics that we'll be tracking and sharing as we move forward. So very excited about that as we move into next year.

Thank you. That's very helpful.

Your next question is from the line of June Lee with UBS. Your line is now open. Please go ahead.

Sorry, thanks for taking our questions. The BMN 333 has a bit of a moving target as we're expecting longer follow-up data from the combination of the equal human growth hormone and CMP by year-end. What would you be most focused on and how would you position 333 vis-a-vis the competition? Thank you.

Thanks, June. This is Greg. Maybe I'll take a stab at that. Really, you know, our thoughts with regard to the growth hormone combination are consistent. with what we've been communicating in the last few quarters. I think the question is not whether adding growth hormone to an achondroplasia patient's regimen would result in a spurt of additional growth. The question is whether or not that would be, number one, safe, of course. Number two, whether or not it would be persistent, whether or not, again, that would be an increase that would continue over time. and of course the larger question which gets back to the root of why growth hormone is not typically used in achondroplasia patients to begin with is whether or not the final adult height of these patients will be impacted. The concern of course is that growth plates may close prematurely over time. These are hypothetical risks but it highlights the fact that additional data is needed. Now when you slice and dice the data every three to six months it's hard to get a look at that. That being said, again, the last look at the data did suggest that perhaps those effects were starting to wane with the addition of growth hormone to CNP. Our feeling with 333 is that having a single agent, again, one that for, remember, patients who are not growth hormone deficient, a single agent that gives you similar results would be preferable. That is also consistent with the thesis of what we think that 333 can deliver. Again, higher levels of CNP. We're looking to optimize and have the best in class CNP that if there were a future state where combinations were available, you'd always want to combine with the best CNP anyways.

Thank you.

Your next question is from the line of Olivia Breyer with Cantor Fitzgerald. Your line is now open. Please go ahead.

Hi, good afternoon, guys, and thank you for the questions. Brian, on the updated revenue guidance, can you maybe just help us better understand what's happening with that single customer's ordering patterns? Not sure whether you're able to disclose which country it is, but do you still expect growth from Voxogo in 2027, no matter how that ordering timing actually shakes out, whether it be in late 4Q versus the early 1Q of 2027 timeframe that you mentioned? And then on hypochondriplasia, congrats on the PDUFA. So assuming a summer launch, anything you guys can say at this point about how quickly you expect that to meaningfully contribute to Vox Sogo sales? And is that something that you think you'll be ready to quantify come January? Thank you.

Thanks, Olivia. It's Brian. I'll start with your first question and then let Cristin comment on hypochondriplasia. For those of you that know the company well, quarterly order timing dynamics in our business is very common, something that we regularly manage through. We've got this diverse global business. Two-thirds of it is outside of the United States. That international business is largely single-payer national healthcare systems that tend to order large quantities on an inconsistent basis. but they roll up to this robust business that we have. And over the course of any given year, again, these dynamics are something that we consistently manage through. There are usually puts and takes over the course of the year. And, you know, we'll comment on those at the quarters and, you know, perhaps adjust expectations as necessary. However, at this point in time with this, you know, single customer that flagged their intention to defer these handful of orders that total $70 million for the fourth quarter. It was just large enough and uncertain enough for us to recognize the uncertainty in today's guidance update. But very important, as I mentioned a few moments ago, it's not tied to patient interest in the therapy. It's entirely timing. Some of the orders are contracted for shipment. It's just that the contract runs into, you know, January in that instance. So, just timing before Q4 and Q1 and kind of the lack of offsets here. So, we just wanted to share the update and take a measured approach here.

And, Olivia, with regard to your second question about hypochondriplasia, so, yeah, very excited about this as we near into next year. and specifically, you know, the team working on diagnosis and patient identification. Our medical affairs teams are out there now. We're educating on the phase three data that we have. We're educating on the condition itself and what we're really working on both in our customer interactions but also importantly using different sources of data and being able to stitch some of that data together because we have more access to data in the U.S. We are working on identifying patients and offices and finding out where they actually are. So what we will do as we near the launch and we gear up for it early in next year, we will be sharing more about specifically what our expectations are around that and how we feel like we'll be able to deliver on it and report out on it as we move forward.

Okay, that's helpful. Can you guys actually comment on whether you expect Voxogo to grow in 2027 or is it too early given the dynamics with the ordering patterns?

Yeah, thanks for the reminder there, Olivia. We do expect Voxogo to continue to grow in 2027. And there is an element which includes the HypoCon land launch, offsetting some of the potential loss of share to the current and additional and other potential competitors. But just a reminder that more than 75% of the Vox Ogo business is outside of the US. We're continuing to launch in new markets. We're continuing to deeply penetrate some of those international markets. We will remain the only chondroplasia therapy with a label for patients, children under two years old. and in that exclusivity over what we believe is at least the next couple years with the importance of starting therapies early from birth for the international treatment guidelines, that sets up this potential switch market. And so we've got a number of growth drivers and plan to continue to invest and grow Vox Ogo.

Okay, great. I appreciate it.

Your next question is from the line of Chris Raymond. with Raymond James. Your line is now open. Please go ahead.

Yeah, thank you very much. Yeah, I wanted to maybe ask a similar question. The last one was asked maybe a little bit more explicitly. So Brian, I heard you say that there was a $70 million order from Q3 that got shifted. Full year 26 guidance was lowered by 25. So the math, I guess, Is it as simple as saying, so Q4 should benefit by 45 million and Q, and I know you guys don't guide to 27 yet, but should we also then think then there's an additional benefit of 25 million in Q1, 27, just given this shift? And you mentioned that it spans both Q4 and Q1 of next year. And then maybe a follow-up to that question is on 333, Just hearing what you're saying about the option maybe to size the phase three portion to look at non-inferiority, what kinds of unmet needs are you thinking about addressing under that scenario if you have a phase two data set that maybe points to non-inferiority as the right way to go for 333? Thanks.

Thanks, Chris. This is Brian. I'll start. So first, just to clarify one element, because I think you touched on some of the Q3 to Q4 dynamics as well. Just to be clear, Cristin mentioned an order that shifted from Q3 into Q4. That was, again, a single large international customer. And that order actually was Vox Ogo. So that's part of the Vox Ogo Q3 being a little less than expectations this quarter. That's, again, a single order. But that one is planned for Q4. and it's different and not included in the 70 million that I referenced. That is another batch of orders that was previously expected in Q4 where the customers now flag that they may take delivery of those in Q1 or early 27. In the latter, the 70 million is the driver for today's guidance update. You know, we took a risk adjusted approach. We still have a chance to deliver some of these orders. So that's the lowering of the midpoint, but separate from that first item in Q3. Hopefully that helps.

Yeah, I just want to make sure I understand. So lowering Voxogo by $25 million for the full year, the assumption is that some of that will spill over into Q1. Is that correct? Can you just clarify?

Yeah, through this lowering of guidance, which allows and recognizes the uncertainty for some of the Q4 slippage, if you will. And by the way, A little more than half of that 70 million is Vox Ogo in this market. So yes, if those slip out of Q4 into Q1, they would benefit Q1 or early 27. But we'll talk more about 27 when we guide to 27. In these types of markets, if there's a If there's a timing deferral of a quarter, that could play forward into the next year where follow-on orders get delayed. So we're still building up the revenue plan for 27.

And Chris, this is Greg again. With regard to your 333 question, I think your question behind the question, of course, is what is the compelling value argument that we bring with 333 to the table? And We firmly believe that the superiority argument, the pharmacodynamics that we can bring forward give us a chance, again, to demonstrate that there is more growth to be had and more pull-through to markers of health and wellness with a molecule like 333. Out of an abundance of politeness, since I think it's four consecutive earnings calls that I've gotten a question about the non-inferiority, I answered it, you know, again, for directness sake, but We would believe that we would need to add something beyond simple convenience to make a value argument for what society would value from 333. Thanks.

Your next question is from the line of Joe Schwartz. Your line is now open. Please go ahead.

Hi, thanks very much. I have a couple of questions on 333. With only about 10 kids per arm in Phase 2, What growth advantage over VoxOga would convince you that it's real? And how does the model you've used to power phase three address the potential for growth velocity to plateau if it doesn't increase commensurate with the CGMP increases you've seen at some point over the curve?

Thanks, Joe. Let me answer the question this way. We believe that the size of the study that we put in place and the models that we're using. Again, we'll be looking at AGV for the individual cohorts, but we will also have the ability to match that to exposure analysis, that we're gonna have more than enough statistical power based on our model to have comfort moving forward to phase three. You had a second part of the question as well though, can you remind me?

Yeah, I guess what it's getting at is that Other CMPs have not seen growth move up in line with the CGMP increases that have been seen because there's been a plateau. And I know that you're hoping that exposure plus more activity at the receptor might be able to move beyond that. But I'm just wondering how, if at all, the phase three powering is planning for that potential to play out.

So the phase three is powered off an effect size. Again, as I was mentioning, the phase two will give us confidence that, yes, we have a dose that can reach it. And just to take a step back, the big question isn't whether there's a dose-response relationship to increasing levels of free CNP. It's really about the shape of the curve, where and if a plateau occurs, and of course, whether you can push your way up that curve. I think the direct answer to your question is we've picked three doses that give us sufficient increases in AUC for free CNP. That's roughly 3x, 5x, 7x. That's, again, probably a conservative estimate in terms of free CNP. These are doses that have not been tested in humans to this point. So again, that kind of spread of exposure, we do believe that we will definitively ask the question, Thank you. This concludes the Q&A portion of our call. I will now turn the call back to Alexander Hardy for closing remarks.

Thank you.

Thank you, operator. We delivered another standard quarter with 32% top line growth and the first quarter in our history in which total revenues surpassed $1 billion. Our focused and deliberate expansion of Biomarin's clinical stage pipeline is delivering results with four new programs added in the last 12 months and spanning preclinical through phase three development. We expect our leadership in skeletal conditions to support a strong launch of Vox Ergo for hypochondriplasia following its potential approval next May, which should mark Biomarin's seventh medicine. If you look ahead with enthusiasm, we advance the next wave of therapies from our clinical stage pipeline, prepare to report on a number of key updates in 2027. Combined with the strength of our more diversified commercial portfolio, Thank you for your continued support and look forward to keeping you updated on our progress.

This concludes today's call. Thank you for attending. You may now disconnect.