Good afternoon, everyone, and thank you for joining us for our next session of Baird's Global Healthcare conference. I'm Joel Beatty, one of Baird's biotech analysts, and I'm really pleased to have this session with BioMarin Pharmaceutical. With us today, we have CFO Brian Mueller. Brian, thank you so much for joining us today. Yeah, thank you, Joel. Thank you for having us, and thanks. Thanks, everyone, for joining. Cool. So, you know, obviously, you know, today you had your R&D Day, which I was really excited about, knowing that you'll be in town around the time of our conference. And then, the heartbreaking aspect of it is I haven't even been able to catch up on it myself yet. But, I'd love to hear more about it from you and maybe what to focus on for people that haven't seen it yet but would like to go do so. Yeah, thanks for asking. It's fresh on my mind since we just wrapped it up about an hour ago and made our way over here. So thanks. And I guess first, just a plug, I'd encourage you all to, you know, check out the replay. The slides will be on our website within a day. But yeah, I'd love to give you a few highlights. So just, you know, background as to how we got here, maybe that's worth just a few seconds. You know, BioMarin has always been high science, innovative therapy, you know, working on translating genetic discoveries into transformative medicines, you know, frankly, before it was a big, a big thing in the sector. Going back, you know, 20 years ago, there were just a couple of rare disease companies, you know, it was us and Genzyme and Shire. And since then, over time, we've built this portfolio of eight internally developed products, but also built out this infrastructure, not just commercial and manufacturing, which are very robust and global, but this R&D engine. It all starts with our core four research scientific attributes or principles, which are understanding the true cause of disease and dysfunction, usually a genetic cause. Developing a therapy that is targeted to that cause, not palliative, not somewhere else on the pathway, but targeted to the condition. Best example of that is our enzyme replacement therapies, which is a $2 billion business. You know, genetic mutation, patients don't make a certain enzyme that's part of the metabolism. We've got a recombinant human version of that enzyme, weekly infusion, and it does what it otherwise would have done if it was in the body naturally. Next is the third principle, is clearly discernible endpoints. Can we measure whether the drug is working clearly? Do we have well-understood biomarkers, relevant biomarkers? And then the fourth is truly transforming disease. Not a marginal impact, but striving for normalization. So that's how we built this business, and I bring it up as a backdrop because I think you really will see the fruits of that approach and now the resources and capabilities that we have. Firstly, just to note, for those that follow the Roctavian gene therapy program for severe hemophilia A, we shared the seven year phase II data. So that, you know, has, in the past, been released about every... Early in the summer. We shared it today. So it was a phase II study, but with durability being one of the questions around gene therapy for hemophilia A, to have seven years now in these 13 patients, continue to see factor levels stabilizing and bleeding control. 11 of 13 patients in those studies are still off of prophylaxis, the standard of care, so that was a great highlight. We reviewed, again, some deep science and rationale around the development program for seven assets, including two new assets. You might be familiar with our pipeline and some of the assets we've been talking about over the last year. Today, we announced another gene therapy for cardiomyopathy and another monoclonal antibody program for long QT syndrome. So, seven assets reviewed, and then the last major component of the pipeline was the, or is the, indication expansion opportunities for Voxzogo and Roctavian. These are our two potential blockbuster products that we're launching now, each with a, you know, indicated label that we think could derive individually over $1 billion of revenue. Each of those assets has significant, life cycle management, indication expansion opportunities. I actually wrapped it up with a few words around how this fits into our business strategy. We've built this base business of over $2 billion in revenue, which is profitable, cash flow positive, and the beauty of it is, at the same time, we think we can, you know, invest in the business in this next generation of innovative assets. We think we can do that while still achieving the profitability goals that we have, call it sort of the virtuous cycle. So I commented on that today in our long-term strategy around building a high, high profitability, high-value growth enterprise. So tune in. Terrific. Well, yeah, look forward to watching that full R&D day, and that's also a terrific framework for the rest of our discussion here today. Maybe it'd be good to dive into some specific agents from here, and maybe first I'll begin with Roctavian, which was recently approved. As far as maybe Europe, I believe we've heard that the first patient was dosed there recently. Could you tell us more about kind of the status of the launch there, and does the first patient being dosed mean we should start looking for more of a trajectory there? ... Yeah, great, great question. We know there's a lot of focus on that. You know, just a reminder that, you know, pricing and reimbursement in Europe, often by design, is a very structured process that typically can take 12 or 15 months or longer. So we filed our top few pricing and reimbursement dossiers in Europe late last year, so we're getting towards the end of those processes, but still negotiating final price in Germany, France, and Italy. Those are the top three markets that we're prioritizing in Europe. It was great to get that first patient in Germany dosed. But important to note, while we're working through those, you know, final pricing and reimbursement discussions, there has been a lot of work that happens on the ground, educating physicians, getting sites ready. Part of the Roctavian patient journey is getting the test for antibodies to the AAV5 vector. This is a companion diagnostic that was approved along with with Roctavian. That test is available, and we're seeing dozens of patients put their hand up. Doctors encourage their patients to pursue Roctavian, start that eligibility testing. So we've got, again, dozens of patients have made it through that part of the process. So the demand signal is there. Sites and physicians are ready, so now it's just a matter of that final pricing reimbursement, which again, takes long by design. Yeah, yeah, that, that makes sense. And then I guess for the U.S., we've also seen recent approval. Can you walk through... You know, I guess it's kind of those same dynamics you're seeing about, patients being tested for AAV5. Are you also seeing that in the U.S., or is there a little bit differences in timing or just what you would expect from the dynamics of the market? We are. We are seeing similar dynamics. Now, there's two, two big things that are different in the U.S. from a launch standpoint. The first is that you don't have that same structured, single national payer pricing and reimbursement. It's important that we set a responsible WAC price, which we think we've done because of the value proposition for Roctavian, which actually has the potential to deliver value back to the system if patients stay off their costly standard of care for up to several years. And then secondly, is the ability to market directly to consumers in the U.S. We can't do that in Europe. We're really reliant on the physicians to engage with their patients, and I think we can engage with the patient communities there, you know, the associations, but not, not direct, to consumer marketing, if you will. So we're leveraging those two things in the U.S.: the ability to price, and then, the ability to set a price, and then the ability to market to consumers. Now, the other parts of the U.S. launch, some of the dynamics that we're seeing are, good payer engagement. That's another key stakeholder group. So while we set the price, it's important that, early on in the launch, we see payer policy coverage policies being issued, and we are seeing that. There were several payer policies issued, in the first few weeks of launch. This is just the tenth week of launch. So I can share that several coverage policies have been issued favorable to Roctavian, meaning that they're consistent with the label. They use terminology like medically necessary. So good to see that level of engagement from payers. Lots of interest from physicians and patients. We've held a few dozen Roctavian-branded patient engagement sessions, which have been well-received. Lots of inbound calls from both doctors and patients. So we feel like the interest and the momentum is there. And then the last piece of sort of logistics in these early days of launch are getting the hemophilia treatment centers up and running both logistically ready to dose Roctavian and all the contracting necessary. Because while we have payer coverage policies, the local practice economics are important. So what's the, you know, mechanisms and contracting required between the site and that ultimate payer? That's also in process. But again, good progress. Just to share, you know, there's 140 hemophilia treatment centers in the U.S. It would be either inefficient or impractical to approach all of those immediately, so we're starting with a smaller number of what we believe will be HTCs that are both ready the earliest and then have early good throughput for patients. Terrific. And I guess with that in mind, how do you see the... Well, actually, I guess, so, you know, in talking with physicians, you know, sometimes we'll hear that, while the profile for Roctavian looks really great, you know, though this is also an area where prophylaxis can be quite great too. When we think about that dynamic, how do you position Roctavian in the market, or how would you respond to that, to physicians? Yeah, great, great question. And again, I probably should have made this comment as part of my R&D update or R&D Day update. The other key segment of today wasn't just those BioMarin program reviews, but there were two panel sessions with some outstanding key opinion leaders in both the, you know, short statural growth disorder area, so, you know, pediatric endocrinologists, and then hematologists and folks that practice medicine with hemophiliacs, familiar with standard of care, familiar with gene therapy. Definitely that's a... That was another key highlight today. Two things I'd say directly to your question, Joel. One is our data. Our phase III study wasn't designed as a comparator against placebo. We compared to the standard of care, prophylactic factor VIII. or recombinant factor VIII prophylactically. And in our phase III study, the largest gene therapy study ever conducted, 134 patients, we now have three years of data from that study. Over 90% of the patients are still not using their prior medicine and off the standard of care. Significant bleed rate reduction, and that includes, you know, not just overall total bleeds, but what's most important to physicians and patients are these joint bleeds and spontaneous bleeds. And again, just, you know, more than 90% reduction in overall factor usage, even if there was, you know, a use before you, you know - Even if, even if your Roctavian's working, you might still take an injection just to feel right before you go to the dentist that day, something like that. So we've got a strong data package. Then the reason why that reminded me about the panel is the real promise of the value of Roctavian is the... Aside from the efficacy and what we hear anecdotally about, you know, the quality of life impacts, it is the freedom from their therapy, and if their bleeding is under control, it's almost a freedom from their hemophilia. Again, the burden of therapy, while it is effective, to your point, is burdensome, you know, up to several injections a week, carrying around medicine when you need to travel, anxiety if you're managing through peaks and troughs. What level of activity can I do this day? When did I take my last factor infusion? So that, those are the conversations, those are, that's the experience of the patients in the clinical trial. Those are the conversations that are happening between the docs and the patients. It will just take some time. This is a pioneering, innovative therapy. We've only been, you know, like I said, 10 weeks into the launch. So, I think this is the type of launch where, as the knowledge and experience and confidence in the product, in the data, grows, so will the, you know, the ultimate commercial uptake. Great! And maybe in thinking ahead, what's the opportunity for Roctavian beyond the initial indication into additional indications? Yep. Thanks. Great question. It's big, and the reason is, you know, severe hemophilia A is a larger rare disease indication globally. We do plan to launch the product, you know, throughout our global footprint. However, I'll talk you through a couple of these. Our phase III clinical trial entry criteria were rather strict and excluded significant populations within total severe hemophilia A. So first is being just severe, which is under 1% naturally occurring factor, but, you know, if you're under 2% or under 5%, that's severe or severely moderate, which still requires a lot of maintenance. So can we, you know, do some additional clinical work to get into that population? The delivery mechanism for the transgene is an AAV5 vector, and that AAV5 vector occurs in nature. Many of the global population have been exposed to it. I think we understand that it is more prevalent around agricultural areas. You know, approximately one-third of the population has been exposed to the AAV5 vector, which means their bodies have naturally occurring antibodies to the vector. They were excluded from the trial, but still represent a significant amount of severe hemophiliacs, again, a third of the market. So we've got several ideas, and these were covered today at R&D Day, to either dose through or around or have other mechanisms to quiet down those AAV5 antibodies to let the transgene be effective. So that's another big population or big portion of the population. Then the last significant portion of the population that was excluded from our trial, but we've got research or reason to believe that there may be ways to navigate them scientifically, is the presence of either prior or active inhibitors to Factor VIII. That being known as the inhibitor population, this is... You know, these folks can even, you know, regular factor may not have the same level of effectiveness in those patients because of these natural inhibitors. And so, we understand that between the prior and active inhibitor population, the larger portion of those is prior inhibitors, and some of these patients may have had their Factor VIII inhibitors a very long time ago. So that might be an eligible population where we can start to dose these patients, see if Roctavian's effective, and have a pathway forward. Interestingly, the FDA label does not contraindicate prior inhibitors. It's got a statement that this product has not been shown to be effective in prior inhibitor population, but we feel like that is an open door to, for us to do more research, generate the data, in that population. And then likewise, even for active inhibitors, there might be other ways to either quiet those down or dose around them. So as I mentioned, each of those has significant pieces of the population, 25%-30% of total hemophilia, that's where these, you know, indication expansion opportunities really get big. Terrific. And I guess maybe from here, let's step back and look at the pipeline as a whole. I guess from a gene therapy standpoint, it seems like, you know, gene therapy even more maybe than some other areas, is an area where you know, technical expertise is really important. And as you mentioned, BioMarin's run the largest program of a gene therapy, largest clinical trial. You know, how can that be leveraged and, you know, what's the status of BioMarin's gene therapy pipeline? Thanks. Yeah, again, ties into R&D Day today, where we touched on a couple of things that I'll share. You know, first of all, is just that. There's a lot of leverage, you know, maybe starting from the end and working backwards, you know, we've shown with some of the other approved gene therapies being much smaller indications, we've shown that we were able to navigate, you know, a complicated clinical and regulatory pathway to get a large indication gene therapy approved. Like I said, working back, we've developed absolutely the world-class gene therapy manufacturing in CMC. This was a decision at BioMarin years ago when we saw the promise of first Roctavian and the importance of controlling your own manufacturing. There's a lot of other gene therapy programs that stumble when they're either need to scale up what was a small batch, you know, preclinical or clinical gene therapy manufacturing process, or move it in-house because you used a contract manufacturer. We made the early decision to invest in our own dedicated gene therapy manufacturing facility. It's on our manufacturing campus in Northern California, and since then, have only, you know, gotten better and improved and invested in that capability. For example, starting up a pilot plant, which is literally 40 yards away from the main manufacturing plant. In the pilot plant, we can create small, you know, either experimental, you know, technical development batches or clinical batches of gene therapy product. But the process and even a lot of the equipment in the pilot plant is the same, so when it comes time to transition that process or product into our commercial plant, it's much lower risk. Our gene therapy plant has a significant amount of capacity, and we are moving some of our other gene therapy candidates into that facility. So manufacturing CMC, a lot of expertise, clinical, regulatory, a lot of expertise. We got Roctavian to the finish line. We think this will bode well for not only our other BioMarin candidates, but potentially being a partner of choice for some of the other gene therapy programs out there that are still trying to work through these issues. The other thing I'd say is, while we're motivated and believe that we have a lot of potential now with this gene therapy modality as a platform, BioMarin is still not a dedicated gene therapy company. We grew up that base business I referred to earlier around complex biologics. We've got small molecule expertise, oligonucleotides. Again, we had experience with a compound for DMD. We used that research to get into a version 2.0 of a DMD oligo, which we hope to enter the clinic soon. So, we're not quite modality agnostic, but we've got deep, rich technical expertise across several modalities and like that optionality in the pipeline, because not everything may work out. And so to be able to pivot and invest in the right places as well is important. Great. Let's jump to Voxzogo, which we've seen a strong launch from since it was approved. And then recently with earnings call, you mentioned a supply issue, and maybe could you clarify how much impact that could have or if there's a point in time that we could kind of learn all that's resolved and behind us? Yeah, thanks. Important topic. Thanks for the question. So first, maybe to start with just a little bit of more detail on that, supply constraint itself, because there's a couple important points to make. Number one, this is a, fill finish constraint, where we use a contractor for the final fill and finish of the vialed product. It's not a, bulk drug substance issue. We make our own, bulk drug substance, on again, that same Northern California campus in a dedicated suite with a significant amount of bulk drug substance capacity, even for the future. It's also not a quality issue, with, with either the, the drug product or the drug substance. So, so again, contractor, fill finish, constraint. It's also important to note that this is a constraint on growth. We noted that even though, we're managing tight supply right now, and that shows up in the form of, you know, maybe lowering order volumes for some of those customers or countries that may have typically wanted to order several weeks, two months of product at a time, we're trying to limit some of those orders. But when I say constraint on growth, we're still planning to add hundreds of new patients in the second half of this year, and grow the product significantly last year. I can share an update. JJ, our CEO, made the comment on, on our Q2 call when we were talking about this constraint, that even in this constrained environment, our supply plan should allow us to achieve roughly $570 million. That was consensus at the time for next year. He talked about it in terms of 2024 consensus that we can meet that demand. So I'm happy to report that our team and by the way, our partner, have been hard at work since then, and we have secured some additional slots, and we're now at a point where even more supply is available, to be able to provide between $600 million and $700 million of revenue next year. That's not guidance. I'm just talking in terms of supply, but it gives you an idea, given this year's guidance of $400 million-$440 million, that even in this constrained environment, the product is, you know, growing a lot. And by the way, you know, the constraint showed up because the demand was even higher than what were high expectations. We had expectations that this would be a robust launch, and you can imagine our supply chain teams, you know, having product on hand at a level significantly higher than that, in case it was better. So it was even higher than that. So we had a strategy already to increase the volume capacity because we talk about Voxzogo as a potential billion-dollar opportunity. So the situation is we just had to pull that strategy now and accelerate it by basically a full year. Right now, we're still sharing a line with another customer. Part of the, you know, mitigation or future strategy is to get a dedicated line. So that, that's all, that's all in the works now. ... Great. Yeah, I think the additional capacity sounds like a, perhaps a challenge to the sales force to sell that additional supply, and maybe even a challenge to us analysts to reconsider our consensus as well. Maybe. We'll see. I'll ask you to wait until we comment officially on 2024. But again, the uptake has just been very strong. You know, side note is one of the questions going into this Voxzogo launch, again, achondroplasia, the most common form of dwarfism, or cause of dwarfism. You know, there were questions about, you know, whether parents and physicians would put their hand up, and whether there was really gonna be a willingness to treat? And we saw that there absolutely was, and some of the patients, or some of the physicians, including on the panel today, you know, literally talked about phones ringing off the hook and things like that. So it's been really positive. Great. Any thoughts on the opportunity for Voxzogo, as BridgeBio is advancing an agent in this space as well? Yeah, of course, we're watching the competitive landscape and appreciate that several months ago, a competitor showed some data that did show incremental growth from their compound. A couple of things I'll note there are that you know, Voxzogo for us has been a 10-year journey. And even in the late-stage development, from starting our phase III to approval took five years. So a small amount of patients, six months' worth of data, we would just wanna see more, more data, more patients, longer term. You know, one of the things we like about Voxzogo, beyond the robust data package, Voxzogo's safety profile through tens of thousands of injections, is the nature of the compound. So CNP being a peptide, which is a natural regulator of bone growth, hits exactly the right place in that pathway, and we think that's why we've seen this durable, robust effect from Voxzogo over time. And by the way, why we think it'll work in a significant number of additional patients in other genetic short stature indications. So we appreciate that we've established yet another big market and understand, you know, why competitors would be interested, but very, very early days as far as we see it. Got it. For additional indications for Voxzogo, I think this first indication, you've had two years of data to support approval. Is that same two years of data needed, or can it be reduced for additional indications? Yeah, great, great question. We're still working through parts of that, and we did talk about it today. There's sort of three different flavors. I'll be brief; I know we're running on time. So first is Hypochondroplasia, which has a similar... It's a mutation in the same gene as achondroplasia, has similar manifestations, slightly different, slightly less severe, but definitely some severe short stature there. This is where we recently announced that because of its similarities to achondroplasia, the FDA did agree to a one-year study, a pivotal study, which we're now starting. So that's an example where there's less work to do. We can leverage all that work we did with Voxzogo for ACAN and essentially have a new phase III asset, which is a similar size indication. The other two, which require more work, are other known genetic short statures, and these were also part of the investigator study that Dr. Dauber was on our panel today. This is SHOX, Noonan syndrome, NPR2, ACAN disorder. These are other genes with no mutations, but specific mutations that cause the short stature and other manifestations. There we might have some additional work to do to, you know, both work with the regulators and establish the clinical program. The third, which is interesting, is idiopathic short stature. This is more unexplained short stature, not a specifically no mutation, maybe a number of, you know, genetic, you know, career or, you know, mutations across a number of genes. This is the indication that human growth hormone is approved for in the U.S. And, but again, because CNP is a natural regulator of bone growth, there's reason to believe that it could or should work in these other indications. Slightly more complicated development pathway. We might have to do a head-to-head study with growth hormone, but we're talking a massive amount of patients. I mean, growth hormone is predicted to be an $8 billion-$10 billion market by the end of the decade. So stay tuned. We'll keep you updated, but, you know, it's a high priority with, with a lot of potential. Great, well, looking forward to that and, you know, perfect timing that we've- Okay ... kind of run out of time. But I'll, I'll leave it to you, Brian, for any closing remarks. Well, thanks for the interest and support. We'll look forward to keeping you updated on our progress. Again, we feel like we're executing on this strategy of leveraging this profitable, growing base business, launching two potential blockbusters, and reinventing or reinvesting in the future. So catch that R&D Day replay. Thank you. Thanks, Joel. Thanks, everybody.