To this fireside chat with BioMarin. It's my pleasure to host. I'm Joe Schwartz from the BioPharma Equity Research team at Leerink Partners. I'm pleased to be joined by Brian Mueller, Chief Financial Officer, and Cristin Hubbard, Chief Commercial Officer. Thanks for joining us.
Thanks for having us, Joe. Good morning.
Excited to be here.
Before we get into individual products, Brian, can you frame what's driving BioMarin's next phase of growth, particularly the mix of near-term commercial execution, upcoming pipeline milestones, and portfolio expansion?
Yeah, of course. Thank you, Joe. We're really excited about 2026 at BioMarin. We're coming off a strong performance year in 2025. We grew total revenues 13% in 2025. Within our business units, we grew our Skeletal Conditions unit, which include VOXZOGO revenue at 26% last year and Enzyme Therapies at 9%. Looking ahead to this year and beyond, I think we'll frame it up, Joe, is there's three pillars to our corporate strategy: growth, innovation, and value commitment. On the growth side, we're continuing to plan for strong growth from both of our business units. The midpoint of our guidance is high single digits for both Skeletal Conditions and Enzyme Therapies.
We are also very excited, and look forward to the assumed closing of the Amicus acquisition in Q2, which is gonna bring two high-growth products into our commercial portfolio, with an outstanding strategic fit, in rare genetic conditions. On the innovation side, we're very excited to have a number of programs advancing. Just recently, we announced the approval of PALYNZIQ in adolescents. I'm sure we'll get to it, and Cristin can elaborate on the opportunity there. We're expecting two phase III data readouts this year, one in VOXZOGO being examined in hypochondroplasia. This would be the second indication after the current approved indication of achondroplasia. BMN 401 for ENPP1 deficiency. This asset came to us through the Inozyme acquisition last year.
We're also advancing our, additional clinical stage pipeline, asset BMN 351 for Duchenne muscular dystrophy, BMN 333, which is, BioMarin's long-acting, CNP for achondroplasia, as well as our, early-stage research programs. On the value commitment side, you know, we transformed the company over the last couple years with a significant focus on, efficient cost allocations and disciplined, expense management while growing the top line. This has led to leveraged growth. If you look through some of the, special items in our 2025 P&L, we're growing earnings per share at the midpoint of our guidance at approximately 3 x revenue. Also looking to, our third year of operating margin expansion and, cash flow growth.
We're making great progress across all three pillars of the strategy, and we think creating a lot of value for shareholders.
Great. Yeah, we appreciate that overview. Let's talk about VOXZOGO. I'm wondering, since you're having such strong new patient starts and patients under age two now, how do you think about stickiness and whether you have any strategies to forestall switching once new options become available and you know, we have patients in multiple age segments, and how do you think about those dynamics?
Yeah. This is something that we've been doing a lot of thinking about, obviously. First and foremost, I'd be the, you know, the first to say that more options are great for patients. It, it certainly gives them the ability to choose what is right for them. What we hear a lot of, Joe, is we're going out there and really, you know, understanding what today's market and the future market can look like, is that at the end of the day, the decision-makers for a switch are going to be the parents, the caregivers.
Physicians tell us very often that they are there to provide any factual truths, to lay out the options that are there, but at the end of the day, it's gonna come down to that caregiver and that family and the decision that they choose to make for their child. What we see in much of our market research, in addition to the conversations that we're having, is that, for the patients for whom there is, you know, efficacy that is being seen, that that's gonna be a high burden to switch. They've gotten used to their daily injections. They've gotten used to whatever their routine is.
That we're seeing on average about 2/3 of KOLs, physicians, and caregiver research telling us that the chances of switch, if the patient is doing well on therapy, are low and not as compelling. I think that really at the end of the day, what it comes down to is efficacy matters, safety matters, and so has over 10,000 patient years of that data to hold behind it, and then convenience comes third.
That's really helpful. As you look at the achondroplasia market, do you have a sense of how many patients are attracted to a value proposition, primarily based on growth and how many decision makers view growth as a surrogate for other health benefits and how many individuals are just not interested in treating this condition?
While I wouldn't say we have rigid numbers in terms of the buckets of specifically that, I will say that this landscape has evolved, and you would expect it to. VOXZOGO was the first treatment ever available for achondroplasia outside of growth hormone. We're seeing this landscape evolve. As more data is being generated, as more publications are being made, we're certainly seeing there be more focus on the benefits beyond height. AGV was of course what we had agreed to with the regulators, and that was the most visible sign of the product working. At the end of the day, what is most compelling to families, to physicians, to those who treat achondroplasia is the broader health story, and that is precisely where we're building that body of evidence, and we're really moving the needle on that front.
Great. can you talk a little bit more about that? What kind of efficacy on proportionality, if that's the right way to think about this, that there might be read-through from that? Obviously, BioMarin has the most experience of anyone in this space. be great to hear some more about the strategy to communicate those benefits.
Yeah. We've continued to publish, for instance, at ASBMR in 2025, we've continued to publish our body of evidence, and we are seeing areas such as foramen magnum benefits. We are seeing, you know, symptomatic spinal stenosis benefits. We're certainly seeing proportionality, where we have statistically significant data to show that proportionality is improved by treatment, including things like leg deformities, so tibial bowing, like any of the kind of various things that could affect their gait and their mobility at the end of the day. In addition to overall quality of life data, where you see also the kind of the more just overall life improvements and how they feel on the day to day.
We're seeing all of these things benefit in our longer term data, and we are continuing to publish on those and really share that story with physicians and families alike.
Okay.
Just to add, you know, this is an area where BioMarin will always be in the lead.
Yeah.
We started our VOXZOGO development program more than 15 years ago. We've got patients who have been on the therapy for 10 years now. You know, the drug was approved in 2021. It was a conditional approval. One of the post-marketing commitments to file for full approval was this long-term data set where we followed a number of patients through final adult height. We now have that data, and we'll be filing it this year, and we'll see if that turns into something on a label amendment. At a minimum, we're always and this is the level of publishing that Cristin mentioned.
Mm-hmm.
We're generating the longest and most robust data set.
Right. Okay. That makes sense. BMN 333 showed much more free CNP than VOXZOGO. I'd love to, as you embarked on a phase II/III seamless design trial, discuss the strategy there to generate height as well as other health benefits. How much of a proportionality benefit or anything else do you think it would take to encourage patients to switch from VOXZOGO or maybe one of the newer options to BMN 333?
You start.
Yes. Thanks, Joe. Our strategy with BMN 333, which, I touched on, is BioMarin's program for a long-acting CNP. It's really important to note that BMN 333 is not designed as just a convenience strategy. It's designed to be superior to VOXZOGO and the competition based on the data we've seen. To your question, you know, we think that the phase II/III seamless design study that we're enrolling will have the ability and the power to detect both the annualized growth velocity, target as well as benefits beyond height. It's 120 patients designed to statistically detect a superiority to VOXZOGO at the 90% level.
Okay. Switching gears to hypochondroplasia, the next potential opportunity for VOXZOGO. How do your early indicators of market demand in hypochondroplasia compare to where you were at a similar stage of launch in achondroplasia?
I'll start here. We're really excited about being able to turn over the card and see the hypochondroplasia data coming up here soon in the first half of 2026. The reason for that is that we have high confidence in the science. We saw really strong signals in Dr. Dauber's sponsored trial, and therefore are very much hoping to see that continue in our phase III trial. Importantly, when you ask the question about kind of what's the excitement around this, how do you see this playing out, I think the biggest and best proxy that we have to date in terms of the excitement around this indication is how quickly our phase III trial enrolled.
It went well beyond our expectations in terms of speed of enrollment, which oftentimes is a very good proxy for the excitement level. The work that we're doing today and the work that we think is very, very important for hypochondroplasia is in and around education and the diagnosis of this condition. While we believe the prevalence to be very similar to that of achondroplasia, we know that we have that we look at much lesser in terms of the TAP, the total addressable patient population. The reason for that is because it's not diagnosed at the rate that achondroplasia is.
We're doing a lot of our work today focused on disease awareness in addition to really figuring out how we can enhance the diagnosis journey and also shorten it because many of these patients are on average diagnosed around the age of five or six. Similar to achondroplasia, we wanna ensure that we're really getting patients treated as early as possible so that diagnosis journey is very important.
Mm-hmm. We hear that there's a wide, or fairly wide spectrum of severity in hypochondroplasia. You know, at the one end of the most severe end, you know, some patients might already be on VOXZOGO, we hear that there's some proportion of the market that's milder. What's your understanding of the patient population in terms of, you know, the, the addressable market that knows they have the disease and is severely afflicted enough that they might be motivated to treat it?
We certainly, as you said, there's a range there, and that is in large part why the diagnosis happens oftentimes later. It's when these children start to fall off the growth curve that they start to ask these questions in and around what might be happening, should we get a genetic test, et cetera. That is specifically why we are so focused on ensuring that people understand some of those early signs of the condition and importantly what that pathway to getting diagnosed can and should be. There are a significant proportion of these patients who would be eligible for treatment with VOXZOGO should those data turn out to be positive and importantly in the way that we design the trial, a very significant proportion.
The bigger challenge is gonna be ensuring that they are diagnosed early and that they are seen as eligible.
Okay, great. Just one more question, given we're almost halfway through the first half of the year, when is the hypochondroplasia phase III data expected?
Go ahead.
We have a few months left before the-
First half
-first half, so.
Understood.
Stay tuned, Joe.
Okay.
There is-
Great. We will for sure. Okay, great. Well, congratulations on the recent Amicus acquisition. I, it seems like a perfect fit for BioMarin. I guess to start, you've highlighted that Galafold is currently available in around 40 countries and BioMarin operates in around 80. I'm wondering, beyond simple geographic expansion, how much of the projected accretion in 2027 relies on just deeper country penetration versus other dynamics?
We are really excited about being able to say more as soon as we close, and we'll give far more detail at that point in time. I think it's important, you know, to address your question specifically. We really do believe that there's the opportunity for both country expansion, given that, as you said, Joe, they're currently in 40 countries and we have a larger country footprint of 80, but we also know that there's opportunity for deeper penetration in the markets in which Galafold already exists. We say that because we know one of the biggest opportunities for Galafold and Fabry is really in and around diagnosis.
Given that that is such a sweet spot for BioMarin to really be able to drive diagnosis of disease and then get those patients on therapy and have them stay adherent to said therapy, there's a big opportunity for both expansion into new countries and deeper penetration in the ones they're already in.
Mm.
We're looking and there's teams working diligently on and precisely what those plans will look like right now.
Great.
Yeah. Thanks, Cristin. I'll just jump in, Joe, since you touched on accretion. I'll share that through these levers, again, subject to closing of the transaction, as we get deeper into the integration, we believe that there's opportunity to unlock even more value, from Galafold and Pompe. When we built our model to support the deal, of course, that's something that, you know, we have to have high confidence in to be able to make a share price bid and be confident in the value of the acquisition. What I mean by that is, you know, higher confidence usually means, you know, some base level of measured conservatism as well. Through these expansion opportunities, we think that we're actually gonna be able to unlock more value over time.
Interesting.
In our comments at closing around accretion, which was, you know, should we close the transaction in the second quarter of this year, you know, because we'll be incurring significant interest expense and just integrating the company, which comes with some cost, we think that the transaction could be, you know, slightly dilutive in calendar 2026, but accretive for its first 12 months and substantial accretion starting next year.
Mm-hmm.
That's again, based on that deal model.
Okay.
We'll say more upon closing, assuming we close.
Okay. Understood. Look forward to that. Amicus on their own did a great job with Galafold and penetrated the amenable Fabry patients well, and it seemed like they were starting to get good traction with Pompe. And I'm just curious at a high level, you know, what kinds of operational skills does BioMarin bring to the table to take things to the next level for those kinds of products?
I think very similar to what we just discussed with Galafold, I think that with Pompe, there's an even bigger opportunity. They're currently reimbursed in 15 countries. Going back to the fact that we have a much, you know, larger country footprint, that's gonna be an exciting opportunity out the gates. I think what's really important specifically for Pompe is the continual publication of real-world evidence that demonstrates the value of Pompe relative to those patients who have come off another enzyme therapy. Amicus has done a great job at starting to generate and publish those data, and that is something that we will very much look to continue so that you can generate a faster switch for those patients who are progressing in their disease.
Yeah. It seems like there's a nice opportunity for Pompe. It's just getting started. And that takes me to my next question. Manufacturing has been a skill set that, you know, we associate with BioMarin doing in a really high-quality manner, and Pompe is a challenging product to manufacture. What is your plan on that front? I think they currently manufacture it in China. They had talked about doing second source manufacturing. Has BioMarin settled on the strategy for manufacturing that product?
Thanks, Joe. I'll take that one. Yeah, that question unfortunately falls into the category of, we need to close the transaction to be able to say more. During this period of time, it's, you know, really important that the two companies continue to operate as two independent entities. There's some integration planning that we can do ahead of closing, but that level of, you know, deep integration-
Yeah
-with respect to manufacturing strategy is something that'll we'll have to wait to talk about. But the premise of your question is the right one, which is that BioMarin is a world-class manufacturing entity, and we've got a great track record across our portfolio, both the commercial portfolio and our and the research and development portfolio of manufacturing globally, and look forward to bringing that skill set to the Amicus assets.
Yeah. No, good. That makes sense. Okay. Moving on, I guess, we're looking forward to seeing the next data cut for BMN 351. We have MDA going on now as we speak. Can you give us an update on what the next data cut will be for the first dose cohort and when we'll see data from the second dose cohort and what you hope to see there?
Yeah, thanks. There's 3 doses, 6, 9, and 12 mg. So far we've announced data from the 9-mg dose at 26 weeks where we observed a mean dystrophin expression of 5%. The key next data point will be watching the higher dose and the 12 mg reach its, you know, next couple of milestones. Beyond dystrophin expression, we're also gonna be looking at clinical benefits, which is really important in this community. We're doing both the North Star Ambulatory Assessment as well as forced vital capacity. You know, hopefully seeing a correlation between that dystrophin expression and the clinical benefits will be something else we're looking for.
Remind us of the threshold for you deciding to advance this program?
We're aiming for 10% dystrophin expression. Again, I would point to the clinical benefits that we're observing and we'll look at the totality of the data to decide, you know, how to move forward.
Mm-hmm. Okay. Great. Let's touch on the Inozyme programs, given you have pivotal phase III, ENERGY 3 data expected also in the first half. Can you talk a little bit about what you hope to see on that front?
You wanna start?
Yeah. Again, another program that we're very excited about and feeling very much that it fits right into BioMarin's sweet spot in rare disease, and that is really in being in a rare condition, ENPP1 Deficiency, where there is not otherwise a treatment. We're very excited to see the pediatric data here coming up soon. What we've estimated, and you can imagine, the data are quite a wide range, but we believe that the total addressable patient population to be in and around 2,000-2,500 patients worldwide. Our job, again, will really be to ensure that we can find those patients, get them diagnosed, and get them on treatment as quickly as possible. Now, as I'd said, this is just an estimate.
As we found on the NAGLAZYME story back in the day was that you can estimate something, but then when there's a treatment available, it's amazing how much you learn about the condition and how many more patients and physicians are coming out to be getting diagnosis because importantly, there is actually an option which raises awareness. We saw that quite a bit with the NAGLAZYME story. I don't know if you wanna elucidate on that.
I will. Thanks, Cristin. This is a profound data point, I think, you know. First of all, you know, doing incidence calculations in ultra-rare disease is difficult as it is, but it is often the absence of a therapy that leaves these patients unidentified. Once a therapy exists, with the improvement in diagnosis and disease awareness, you can really, you know, start to bring those patients in. You can look back at our 10-Ks on this. NAGLAZYME was approved approximately 20 years ago, and we used to cite global prevalence of the disease as 1,100 patients in existence. Here we are now, 20 years later, we probably have almost 150% of that number actually on commercial therapy.
Mm-hmm.
It's, you know, and this is again, this is what BioMarin does.
Right. Still growing.
Mm-hmm.
Okay, great. Well, maybe a couple, more commercial questions to round out the discussion. I can't resist but go back to VOXZOGO. Can you discuss what underpins your assumption that VOXZOGO revenues in the second half of this year are expected to be greater than the first half? Is that entirely due to OUS orders? I know there might be several moving parts because we might have the emergence of some competition, can you just give us some insight into your crystal ball on that front?
Yeah. Thanks, Joe. I'll take that one. That timing and, you know, we shared on our Q4 2025 call that, first of all, we'd see a similar, you know, lower first quarter as we did last year in 2025. That for the full year, VOXZOGO revenues would be weighted to, you know, both the back half generally and then even more specifically Q4. This is entirely order timing and largely international order timing. 75% roughly of VOXZOGO's revenue comes from outside the U.S., and most of those international customers are single national payer healthcare systems.
Whether it be the way that their cash flows and budgeting works or their procurement model, we've observed this trend before, where the purchasing patterns again across dozens of these countries, just happens to be, you know, weighted to the second half of the year. What's really important to know and we point to this across all of our portfolio when we experience some of this quarter-to-quarter volatility on revenue, is that we've continually to steadily add patients quarter after quarter. We expect that to be the case here in 2026, it really is just the timing-
Mm-hmm
-that drives that dynamic.
Okay, great. Well that's helpful. Well, thank you so much for the update today. We look forward to following more progress at BioMarin.
Thank you, Joe.
I appreciate your time. Thank you.