For Q&A?
Yeah.
Usually, they stand up here.
Okay.
All right. Great. Good morning, everyone. Welcome. My name's Jessica Fye, and we're continuing the 44th Annual J P Morgan Healthcare Conference today with BioMarin. First, you're going to hear a presentation from the management team, and then we're going to go into some Q&A, so if you're here in the room, you can raise your hand, someone will bring you a mic. If you are not, you can submit a question on the portal, and it'll come to an iPad up here, and I can read it off. Before we get started, I have to read this. It says, "Please note that J P Morgan has a role on the potential transaction involving Amicus and is subject to restrictions.
As a result, I will not be discussing the transaction during this session nor taking questions from the audience on that topic during Q&A." So with that out of the way, let me pass it over to BioMarin CEO, Alexander Hardy, for the presentation.
Thank you very much, Jess, and thank you all for joining us this morning. Two years in the role as CEO of BioMarin, we've been busy as a team working on transforming BioMarin and setting the path for another era of significant growth, and really excited to update you on our progress and our plans today. I'm going to be talking about BioMarin's future plans, and so please take note of the forward-looking statement. Okay, so BioMarin is a leader in genetically defined conditions with an extraordinary track record of innovation. We have six first-in-disease treatments, many best-in-disease treatments, and this is all driven by the capabilities we've built over almost 25 years of our history. Capabilities such as our geographic footprint in 80 countries, our track record from a global regulatory and approval standpoint, our really impressive R&D capabilities, and our in-house manufacturing.
That has driven not only tremendous progress for patients with these conditions, but has also delivered an extraordinary and strengthening financial outlook of growth on the top line and increasingly growth on the bottom line. And this is only further strengthened by the changes we've made over the last several years and most recently the Amicus transaction. But very importantly, what is our focus at BioMarin? What all the employees every day think about is our purpose to be the biotech leader that translates the promise of genetic advances and discovery to really make a profound difference on the patients that are depending on us. This is what motivates us every day. By doing this really well, we actually also create an enormous amount of value for our other stakeholders. So what have we been doing over the last 24 months? Well, we've been very, very busy.
These are the pillars that we outlined at our Investor Day in September of 2024, and I'll briefly summarize our progress on each. First, with regard to innovation, we prioritized our pipeline to focus on the things in our pipeline which we believe have the most transformative potential for patients. That focus is great to see. I n the next 12 months we're going to see a lot of different readouts, and Greg Friberg, our head of R&D, will be up next to tell you a little bit about our significant progress, and we have some important updates to share today with you all. It's great to see the fruits of that focus, acceleration of key assets like 333 and 351, and that ability now that we have with regard to BD to supplement our internal innovation with external innovation.
Our second pillar, growth, we've really been able to significantly drive our growth rates. Today, we'll be announcing our preliminary 2025 revenue, and if you look at our CAGR over the last two years, we've achieved a 15% CAGR during that period. This has been driven by our enzyme therapies business unit. We've refocused into business unit and our enzyme therapies with additional focus. We've really achieved very significant growth, growing at approximately a high single-digit growth rate. And then our skeletal conditions and our drug Voxzogo is now in 55 countries. We are the standard in achondroplasia, and we're looking forward to pivotal data in hypochondroplasia this year with a potential launch, if approved, in 2027 of hypochondroplasia.
Just as a reminder, this is the first of five additional indications we're going to be seeking with Voxzogo, so we're really only at the beginning of the impressive growth potential of this asset. And then our third pillar, value commitment. As a team, we've been really optimizing BioMarin's ability to operate at scale. Cost transformation, where we identified $500 million of costs to take out of our ongoing and forward-looking business operations, has allowed us to dramatically increase profitability and also, therefore, improve our cash flow, generating a really compelling balance sheet. And we talked to you all about our capital allocation strategy. Very, very proud of the team at BioMarin for putting that to work and completing two M&A deals in 2025, doing what we said we were going to do, do value-creating deals for all of our important stakeholders.
When I take a step back and look at this progress over 24 months, I am incredibly proud of the team at BioMarin. Many of the leadership team are sitting here in the front row. We have delivered on and executed in terms of our financial performance, all at the same time while transforming fundamentally BioMarin and setting us up for a really, really exciting future. That is really impressive. I really can't think of companies that have managed to do those two things at the same time, and it's a tremendous credit to the employees of BioMarin. So that is the past and the present. Let's talk about the future. What are our priorities for 2026? And I will start to bring in some of the new news today. It's very, very exciting. So our first priority is to accelerate revenue.
We've already had an impressive level of revenue growth over the last several years. We're aiming to build upon that with Voxzogo in achondroplasia and then, as I already mentioned, the growth in hypochondroplasia, which is ahead of us. Our enzyme therapies are performing extremely well. We have the potential addition of an important indication expansion for Palynziq in adolescents. And then, of course, the Amicus integration, which you can expect I will be talking about, it's going to come in the next few slides, is going to be a really important addition to our growth rates out into the future years. But secondly, this is the lifeblood of biotech, is innovation. We've really got an exciting year from a catalyst standpoint ahead of us. We have two phase 3 data readouts this year. We also have, announcing today, a filing for full approval for Voxzogo in achondroplasia.
We have completed the post-marketing requirements for that drug, and we're going to be seeking full approval. Greg will share more details. There's a lot more additional that we're aiming to do with that regulatory update. We also have two label expansions expected in the next 12 months, and we have two data readouts which are really important in terms of our pipeline molecules for 333 and 351 and Greg. Again, Greg will share more details in a moment. And then finally, our priority, the third priority for us, is strengthening our pipeline. We're very excited about our innovation engine at BioMarin, but we're supplementing that with external innovation.
This BD capability that has secured us two important M&As in 2025, while our current or short-term focus is deleveraging following the financing of the Amicus acquisition, our focus from a BD standpoint will be earlier stage pipeline deals to supplement our growth outlook in the longer run. So a very, very exciting 2026 ahead of us. So let's talk a little bit about the Amicus transaction. I'm going to be quite brief here. We announced this, obviously, on December the 19th, equity value of $4.8 billion. Why is this really exciting? I mean, this is an incredibly compelling transaction for BioMarin, and we believe for patients with Fabry and Pompe disease around the world. Because it's, first and foremost, this is an exceptional strategic fit. These two drugs just drop perfectly into our enzyme therapy business.
It's a perfect match with what BioMarin does really, really well in our track record of success in enzyme therapies built over 20 years, so exceptional strategic fit. The second compelling proposition from this acquisition is this further accelerates and diversifies our revenue growth. We've got a compelling revenue growth picture of BioMarin alone. Adding Amicus further strengthens that growth outlook and diversifies our revenue base, so following this acquisition, we'll have four major growth drivers within our portfolio. This is pretty compelling and quite differentiated versus the rest of the sector, and because of the very much the similarities in mission and purpose between Amicus and BioMarin, we're able to realize significant financial benefits from this transaction, and we're confident of our ability to begin to be accretive within 12 months post-closure of the deal and to be substantially accretive beginning in 2027.
All in all, an exceptional fit, bringing exceptional value to all of our stakeholders. But let's talk about the two key products that are part of the acquisition of Amicus. The first is Galafold, Galafold in Fabry disease. This is the only oral therapy in Fabry disease. The proposition that we have here is to build upon Amicus's tremendous success. Galafold has been a very successful launch. Amicus is an extraordinary company that's done a great job, but in our hands and with our capabilities, we believe we'll be able to reach more patients around the world. The simple point is that at the moment, Galafold is available in around 40 countries around the world, and we'll be aiming to bring it into our 80-country footprint over a period of time. But this is more than just about numbers of countries. It's also about depth in countries.
We have BioMarin operations in many of the 80 countries, BioMarin employees, not only distributors. So we have a depth of capability which really we will put to work to really maximize the impact of Galafold and reach those patients. There's also a tremendous opportunity to increase the diagnosis and treatment rate of Galafold. Fabry disease, there's a prevalent population of about 100,000 patients globally. There's only about 18,000 of those patients that are actually diagnosed right now with Fabry disease. 12,000 of those are treated. So you can see here that we have an opportunity to increase the treatment rate and the diagnosis rate, increase the switch rate, and increase the naive patient initiation rate with Galafold. Again, building upon what Amicus has done, we believe we can do even more. With regard to Pombiliti and Opfolda for Pompe disease, there's also a significant opportunity here.
There is also the opportunity for us to maximize the impact of our global footprint. Pombiliti is available and reimbursed in 15 countries around the world, so you can probably very quickly see that there's a growth potential there with, again, the breadth and the depth. But with Pombiliti, we're also very, very excited about the really impressive data, real-world data that Amicus has been producing. This is really very important. This is really compelling in driving the switch where that is on label, driving the switch to Pombiliti. And then, in addition, there are tremendous opportunities for label expansions with the potential to increase the age population for late-onset Pompe disease, but also to expand this drug into infantile-onset Pompe disease. Bottom line is you can see here significant additional growth opportunities ahead for Pombiliti as well as Galafold.
But in terms of growth drivers, it's important not to look past Voxzogo. Really impressive growth rate over the last several years as we also expand this out into our geographic footprint. Now, today, we're announcing the 2025 preliminary revenue of $920 million for Voxzogo. Translated on a quarter-by-quarter to quarter basis, fourth quarter of this year, that would effectively mean a growth rate of 27% year over year. So you can see Voxzogo is growing extremely well and very strongly. And this is even before we expand out into those additional indications. And then, of course, you've got the geographic growth opportunity as well. We're in approximately 55 countries out of our 80-country footprint, so there's also the opportunity to bring Voxzogo to more patients around the world.
In terms of our enzyme therapies business, as I already mentioned, we've been achieving high single-digit growth rates up to this point, but we're really at an exciting point because ahead of us are really some exciting growth opportunities. We have BMN 401, which we acquired as part of the enzyme acquisition, with pivotal data reading out this year and potentially first indication next year, and then, of course, on top of that, we've got the Amicus drugs, Galafold and Pombiliti contributing to our growth rates in the future. Now, I'm sure this is probably going to be a question. You're not going to hear from us today what we project that future growth rate's going to be, but you can imagine that we're confident we can do a lot better than we were saying of a high single-digit growth rate.
Let us integrate, complete the transaction, close the deal, integrate Amicus, and we will then provide you additional color on a really exciting growth rate and potential for our enzyme therapy business unit going forward, so my last slide before I hand over to Greg. This is the overall outlook for BioMarin, and it's a really compelling outlook. Today, for 2025, we're also announcing our estimated preliminary revenue number of $3.2 billion for 2025. When we look ahead to this year, of course, with the closure of Amicus projected in the second quarter, we'll be adding, on top of our growth rate this year, we hope, Pombiliti and Galafold, and again, when we provide additional outlook following closure, we'll provide the guidance as to what that looks like, but what I'm particularly excited about is when you layer all of this on top of each other.
You layer on top the 401, the momentum we've already got with Voxzogo in the enzyme therapy business, add on top of it Pombiliti and Galafold from the Amicus acquisition, and then pipeline assets like 351 and 333. We think we're well on the way of achieving our ambition of targeting sustained double-digit CAGR from now into the 2030s, and this is enormously exciting. So with that, I'm very pleased to hand over now to Greg, our head of R&D, to provide some clinical updates.
Thank you, Alexander. It is an absolute privilege to be able to represent the countless individuals who work in the R&D group at BioMarin and have prepared much of this data for us. As Alexander highlighted, we've got a busy 2026 when it comes to events from R&D. Three major data readouts, including the newly announced filing for full approval for Voxzogo this year, adolescent expansions, six new phase two indications where we're doing indication evaluations in a variety of skeletal conditions, and then, of course, two pipeline agents, BMN 351 and 333, which will have some data that we're going to share with you today. First of all, with BMN 351, this is our antisense oligonucleotide for Duchenne muscular dystrophy. We have turned over the cards for the first two cohorts, and we have seen encouraging dystrophin responses.
The study is continuing as planned, and with the 12 milligram per kilogram cohort initiated, as we've noted, we're hoping to have that data and be able to present a more totality of information before the end of the year. So what did we exactly see? What you see on the left is actually a depiction of the actual data. These are mean absolute dystrophin numbers from patients on the study. They were treated at 9 and 6 milligrams per kilogram, and you see a clear dose-dependent dystrophin response in the data that we've seen. The findings were consistent across multiple assays. That's Western Blot as well as Mass Spec. MassSpec is what's shown here. It's the better assay to look at quantification. And just as a reminder, we look at these numbers without the double correction for histologic adjustment for muscle content.
That 5% number certainly was a number that gave us what we thought were encouraging results that this study demands continuation. We know that the tissue half-life for this chemistry is longer than what's seen for the so-called morpholinos, so we expect that these numbers, as you see in gray depicted on the left, will continue to rise over the course of the next six months. Now, what will we see by the end of this year? What we're going to see is, of course, dystrophin expression at the next dose level, the 12 milligrams per kilogram, but we're also going to see long-term safety data both for that 12 milligram per kilogram cohort, but also the 6 and the 9. Those patients are all remaining on treatment.
Of course, for a weekly administered chronic therapy, that benefit-burden argument is something that we want to flesh out with more granularity. Finally, we'll also get a first glimpse at functional data. The intermediate endpoints looking at dystrophin expression, I think we're all familiar with that this is a good start, but ultimately, functional measures, including stride velocity 95C, that's the kind of data that I think will be really transformative for this community. You can expect to see these full results for the six and the nine milligram per kilogram cohort in an oral presentation at the Muscular Dystrophy Association meeting in March. Moving to BMN 333, we have mentioned that the early results supported the initiation of the phase two-three study in achondroplasia.
As a quick reminder, we had wanted to develop and engineer a long-acting product that would allow us to reach multiple-fold increases in free CNP AUC as compared to another long-acting CNP agent. Our target was to see a 3x increase, and what you see today is the data that we're newly releasing that actually not only did we beat that 3x margin in three consecutive cohorts, cohort four, five, and six, but the highest increase that AUC by over 13-fold. So clearly, what you have there, these aren't necessarily going to be the doses we bring into phase two, but it gives us a range to work with, a very clear range where it's not just a small amount of increase, but a dramatically improved exposure to free CNP that we believe we will be able to offer patients with achondroplasia.
So the next stop is to initiate the phase two-three study. That study is going to initiate shortly in the first half of this year. We're actively working currently. It will be a combined phase two-three study where in the first stage, one of three doses, high, medium, and low of BMN 333 will be benchmarked straight up against Voxzogo. Once we have a winner from that arm, we anticipate moving rapidly into phase three and doing a head-to-head against Voxzogo looking for superiority. AGV, of course, is the primary endpoint here. That's growth-related, though that's not what patients, again, are most interested in. We've learned a lot from Voxzogo. We're going to come back to this in a moment, but we will be measuring a variety of factors in this study, including, of course, proportionality, anatomical changes, and importantly, mobility changes as well.
So more to come there, and we anticipate that this could be potentially on the market as soon as 2030, and we're, of course, trying to accelerate that with every lever that we have at our disposal. Quickly, just wrapping up, BMN 401, first in disease, ENPP1 deficiency, cohort turning over in the 1 to 12-year-olds mid-year, and, of course, we're working on other age groups as well, looking forward to that data and building upon the legacy that Enzyme has nicely prepared. As Alexander noted, hypochondroplasia also. We talk a lot about achondroplasia, but whether we look at Dr. Dauber's phase two data or, again, our own experience, we're quite hopeful that this is going to be an active, safe, and effective therapy that is Voxzogo for hypochondroplasia as well.
We recruited the study very quickly, and we'll be turning the cards over for that phase three study in the first half of this year. That's just the beginning of the journey. We're also working to prepare the community, make sure that they understand the disease and, again, the genetics behind it and so forth. So more to come there. I'll just wrap up in terms of the regulatory updates. On Rare Disease Day, February 28th is our FDA PDUFA action date for the adolescent expansion in Palynziq. The results were quite effective, similar to what we've seen in adults, both in terms of decreasing phenylalanine levels, but also the opportunity to increase native intact food that these adolescents could consume.
This is important, of course, because before these individuals go off into adulthood, having this window from 12 to 17 years with the support of their community and their family is really important to be able to get them to a point where this would be a therapy that they could benefit from maximally. So more to come there. I'll just wrap up by highlighting that it will be a catalyst-rich year for R&D. We've talked about the phase 3 cards turning over. We've talked about age expansion. We've talked about pipeline data being revealed, but I do want to highlight and end on this Voxzogo submission for full approval. So this is something that in the first half of this year that we will be filing with the FDA.
We've engaged with regulators about structure and format, and it will be our opportunity not just to talk about final adult height, not just to talk about length, but really about the health and wellness of patients. We have a comprehensive and consistent wealth of data. There's over 10,000 patient years of safety data, and, of course, patients as old as having been on the therapy for as many as 10 years. We want to be able to show the data that really supports the value of this molecule across all age groups, including some of those factors we noted previously when we talked about certainly quality of life, but also anatomical changes. In particular, we have some foramen magnum data that we're very excited to share later this year. This data won't just be for regulators.
It will also be for public presentation, and we expect a rich set of presentations that we'll be able to show this year to show the value of currently the only available and approved therapy for achondroplasia, that being Voxzogo, so with that, I want to hand it back to Alexander.
Thanks very much, Greg. It's really exciting to see all the catalysts that you and your team are going to be realizing this year. It's going to be tremendously exciting to see the difference we can make for patients across so many important genetically defined conditions. Just by way of closure, first off, we provided some preliminary financial data today. In the appendix to the presentation, you will see a summary of that, so you have that information in writing. In addition, information about EPS and Roctavian. So please refer to the appendix for that.
But in closing, I hope you can see the progress we've made, the refresh strategy, the execution against that, and now we're in a period of realization of the enormous potential that BioMarin has as a leader in genetically defined conditions, the potential to achieve sustained double-digit CAGR growth rates on the top line, a period of tremendous R&D excitement and catalysts, and we're going to aim to supplement that with external innovation from our really impressive BD capability. And as a team, we're going to continue to execute, deliver significant profitability, and cash growth. And with that, I'd love to hand it back to you, Jess, for questions on anything apparently except Amicus.
Great. Thank you. And as a reminder, if any questions in the room, just raise your hand, or you can always submit them on the portal. Maybe just starting with Voxzogo, what are the specific drivers that factor into how you're thinking about Voxzogo's growth in achondroplasia kind of from here?
Yeah. Thanks very much, Jess. I mean, Voxzogo is still in a phase of growth in achondroplasia. We're in 55 countries. We're still expanding the number of countries. We have important launch countries happening within our global footprint of 80 countries. In addition, we have opportunities to further penetrate in currently developed markets where we already have a presence. We have the advantage of the zero to two indication, the infant indication. This is extremely important. The guidelines now, the international global guidelines for the treatment of achondroplasia, talk about the importance of diagnosing and treating patients as early as possible. So often, the diagnosis is actually made before birth. The treatment decision in many cases is made before birth, and increasingly now, the treatment is initiated within weeks or months of birth.
And the advantage of our indication, which we will sustain for, we believe, several years while other potential competitors have to generate that data and seek approval, is very, very important. So there's lots of room for additional growth, and this is even before, obviously, we talk about the five subsequent indications we're developing Voxzogo for.
So you mentioned at the beginning having, I think, hit whatever amount of data it is you need to bring to the FDA to seek full approval for Voxzogo. Can you just elaborate on kind of what that is that you've collected and when that filing could go in?
Yes. I'm going to ask Greg to elucidate further on that, but I would say this is very, very important. Beyond the regulatory milestone, the treatment of achondroplasia efficacy and safety are critically important. And when we talk about efficacy, it's actually sustained durable efficacy. So to be in this position where we're able to provide full final adult height is extremely important, not only from a regulatory standpoint, but we believe in terms of the treatment decision of physicians and caregivers in the treatment of achondroplasia. But Greg, over to you.
Yeah. From the standpoint, the drug's been on the market for nearly five years now, so we have a lot of data. The 10,000 patient years of safety data, of course, every year we update the FDA, but this particular time is our opportunity to also look at different efficacy endpoints. I can refer you to the post-marketing commitments that are public in terms of some of the data that were required there. Clearly, final adult height, which is a bit of a misnomer, it's really five years' worth of treatment and how much height folks who reached a certain age group have achieved. But also, it's an opportunity for us to look at data, whether it's body morphometry, looking at anatomic changes, that's both in the spine as well as tibial bowing.
We've presented some of this data, though we've also uncovered some new findings, some new presentations that we're looking forward to later this year. In particular, this isn't just an update for, for example, the older children. It'll include all of the ages, including the infants, and in particular, we're hopeful that the data with regard to the foramen magnum is something that will, at least when we present it, will be of interest to the community, so these are, I would say, a comprehensive and a consistent set of data that really show what that value argument is for Voxzogo. It's one thing to be an investigational therapy and to have that promise. It's another thing to have the data.
I think that physicians and patients care about that, and certainly the payers care about that, and we're looking forward to being able to present this wealth of data as the year continues.
What has patient retention looked like thus far with Voxzogo, and what do you think it'll look like once there are additional players in the market?
The adherence rates on Voxzogo are currently extremely high. I mean, obviously, across 55 countries, there are different data sources, but we've talked hitherto of adherence rates of approximately 90%, which really speaks to really how important a therapy this is, but also how caregivers, the family, build the daily injection into their routine. Looking ahead to when and if these currently investigational therapies, if and when they're approved, it's great there will be further treatment options available for caregivers and HCPs, but there is going to be a decision to be made, and it's going to be a shared decision in many cases between the caregiver and the HCP. I've already talked, and I think it's very, very important. We will sustain for several years. It's likely that infant indication to zero to two population, so we will be the only option for several years for the patients.
Most commonly now initiated in these first months and couple of years of life. But for patients who are already on therapy, that switch decision will be a conversation between the HCP and the caregiver. And as is very similar to many of these pediatric rare diseases, the factors are safety, efficacy, and convenience. You've already heard from Greg the wealth of data, the long-term data, and the benefits beyond height from an efficacy standpoint. That's going to be part of that conversation. The established safety profile, we have 10,000 patient years' worth of safety. It's very, very clear and very understood and a very positive safety reputation. And then they'll consider potentially convenience, but that will be a third factor in any decision.
I think we fully expect, and it's built into our plans, there'll be some patients that will switch to more convenient formulations, but those other factors of safety and efficacy will remain paramount, and as a company, we continue to focus on generating that really compelling evidence, which is important, as well as advancing BMN 333. You saw the data here, the PK data. You see now why we're so excited about this molecule and the potential for this to actually be an advance from an efficacy standpoint with those higher free levels of sustained CNP, so we think that that will be a real game changer and an opportunity for us to further advance the treatment of achondroplasia in the longer run.
Can you recap the status of your various strategies to delay competition for Voxzogo and just talk about how BioMarin plans to kind of defend its market position in the event these other products do gain approval?
Yeah. Yeah. We feel very strongly about the work that we did for many, many years to really identify the role of CNP in the treatment of achondroplasia. So we are going to vigorously defend our intellectual property. This is an important year in 2026 with regard to that. We have petitioned the FDA with regard to the orphan drug exclusivity associated with achondroplasia, requesting that the FDA delay the approval of any, I should say, of the product currently under review until the expiry of our orphan drug exclusivity, which is remaining three years left. But in addition, we have other intellectual property litigation ongoing. This year, you can expect the decision from the U.S. International Trade Commission in the United States, as well as other litigation activities in the U.S. and in Europe potentially.
So maybe kind of stepping back, the company's undergone significant changes, right? You've implemented a lot of change over the past just two years. How and maybe when do you envision those changes translating into a valuation more aligned with your growth outlook?
I think that's happening as we speak. I mean, I think it's been a work in progress of big, big changes that we've made. I think we very quickly made significant improvements in our profitability and in the growth rates on the top line for our enzyme therapies and the Voxzogo business unit, but now I think the most important thing with regard to valuations is sustained long-term revenue growth, and I think with the strength of our business units, supplemented now by these wonderful products developed by Amicus, Pombiliti, and Galafold, in our hands, the possibility for them to reach even more patients. They're growing assets with very, very high significant potentials. We believe that in our hands, we believe that ramp and that peak is going to be higher. When you add that in and the combination, we think that's really compelling.
We think that investors are now starting to really, they've seen the changes, and I think we believe you can really see the results projected now into the future.
Maybe with the last kind of minute here, you started out the presentation talking about BioMarin's unique attributes, capabilities that are differentiated. So what would it take for another company to build that?
Yeah. I mean, it's taken BioMarin, and it's a huge credit to the organization and leadership over the years. It's taken BioMarin over 20 years to build those capabilities. It does take time. It also is about relationships and reputation in many of the markets we operate. This is not something that you can do overnight. So I think it will take time, and it will take focus from any potential competitor or anybody looking to build a presence in these genetically defined conditions.
Great. Perfectly out of time, so we'll stop there. Thank you.
Thank you very much. Thank you for attention.