Hey, everyone. Thank you for joining us today for the Amicus Therapeutics Fireside Chat here at the 45th Annual TD Cowen Healthcare Conference. I'm covering analyst Ritu Baral, and with us from Amicus today, we have CEO Brad Campbell. Brad, thank you for joining us today. So let's start with PomOp, or Pombiliti, Opfolda. The launch is for Pompe. The launch is now one year out. What sort of trends are you seeing right now? Yeah, so maybe I can start just by thanking you, Ritu, for hosting us here at TD Cowen. It's a great schedule. Great to see everybody here in Boston. Maybe before we dive in, just framing a few things that we're trying to orient investors to this year. I think, you know, last year was really a lot about the launch. There were some macro issues, not public policy issues that are going on now, but different macro issues in our industry that we were dealing with last year, and we were really pleased with the outcome, with the progress, with the performance last year. I think this year, as we've come into 2025, our focus is really reminding investors, number one, of what a great base of business we have, the growth that we are expecting for the year. A lot of that fueled still by a Galafold franchise that we expect to see 10% to 15% growth in its seventh year of commercialization, lots of excitement around the IP runway there now, which we could talk more about, and then, of course, Pombiliti Opfolda is still a really important part of the story. Getting into the meat of the launch now, we're looking at, we think, 65% to 85% growth there. And all of that with continued financial management and getting to the first time, we believe, to GAAP profitability in the second half of this year, so lots of important growth on the horizon, but also, I think, turning a milestone from a financial perspective, but with all that as backdrop, thinking about Pombiliti Opfolda and the launch there, a few things that we're really excited about. The first is that we announced at the end of the year last year, we had 220 patients who had been treated or scheduled for treatment, and so one of the questions that we had as we went through the year last year is, you know, is this launch continuing to go at a pace that you'd like? And I think with the numbers we shared at the end of last year, the answer is very much yes. Some important trends on the reimbursement side of things, you know, two places that we're focused. First is we announced coming into the year a number of new countries that we arrived to reimbursement in Europe, and I know we'll dive into that in more detail, but also in the United States, getting the time to insurance down to 30 days or less, which was really our goal for that process. So I think that's going really well. One thing that we continue to look at is breadth and depth of prescribers. So around the world, making sure, number one, you're getting new physicians to prescribe, but also the physicians that do prescribe, seeing second, third, fourth prescriptions, and we're seeing that expand as well. And then I think, importantly, building the body of real-world evidence. And I know you were at World and saw some of that at our symposia. We'll continue to see that as an important part of the story. We should talk more about how we're using that from marketing, from a medical affairs perspective. But I think those things all give us great confidence that, you know, the launch is going well and it'll be a great driver for us this year. So on the last two points that you mentioned, Brad, I want to say this delicately. There has been an 800-pound gorilla in the space in Pompe. Of course. Yes. Of course. Yes. For years, Sanofi Genzyme. They have given many, many research clinicians who also happen to be treating physicians lots of dollars for research and patient group and, you know, patient groups and support. You know, they are well-established, well-loved. Oftentimes, there's a sense of loyalty, I think, is the best way of putting it. And when you go into that space, understanding that there are physicians who are much more familiar with the Sanofi Genzyme drug, much more comfortable with their Sanofi Genzyme relationship, because that's a classy way of putting it. How are you seeing that evolve going back to your comment on number of prescribers? Yeah, look, I think clearly, originally Genzyme and then Sanofi Genzyme and some others were pioneers in this space and, to your point, did a ton of further research and new treatments. And so they do have a rich history in the space. I will note that the original Genzyme team that became part of Sanofi has largely moved on at this point. So I do think it's a new company, new identity, et cetera. So I do think that's part of it. But I think if you look at Fabry as an example, of course, we've been competing against Sanofi Genzyme in the Fabry space for, you know, seven or eight years now. And sure, in the beginning, you're very much defending your technology, you're defending your company. But we've clearly shown that over time, we've been able to, I think, drive broad adoption of our products wide, because they're differentiated, because they have great data, and because I think we also are not afraid to drive important scientific questions. I think you did it. You had it. You had a great note coming out of World. Where were we focused at World? We were focused on new data on Galafold coming out of our registry. We were focused on driving the conversation still on the relationship of phenotype-genotype in that disease. We were focused on finding new patients. And then in the Pompe space, I think very much now with multiple new therapies, we were focused on, again, new data, real-world evidence. And I think that body will grow over time. We were focused on what should you be monitoring, and that's a we should talk more about that. For sure. What you should monitor now that you have choices. And so I think, look, I very much respect the folks that have come before us, but I fully believe we have a better product. I think the data illustrates that. And I think over time, how do you win? You win with data. And I think data and experience. And I think we're on that journey. And I'm very confident that in the end, this will be the leading product in the Pompe space. Given the indication in the US is for treatment experienced patients, naive patients are part of the European label. Correct. In-clinic evaluation of patients is very important to your Pompe opportunity. Yeah. Can you walk us through what the average neuromuscular expert measures and assesses during their Pompe patient visit? And how often in your market research do Pompe patients actually come back and get monitored? Yeah. And I do think, you know, that's an important part of we've all heard, we've talked a lot about this idea that physicians feel like once they put a patient onto a new medicine, that they want to give it at least a year or two to understand if it's working or not or having an effect or not. And I think part of that is that typically what they've been monitoring is 6 minutes walk and forced vital capacity, which are far less sensitive measures that do take more time. You know, you're not going to see a difference, you know, from this month to next month in your 6 minute walk unless something's really negative. Right. I I mean, those are FDA endpoints. Those are FDA endpoints. Exactly. Not like day-to-day endpoints. Exactly right. And so part of the journey is driving the conversation around what should we be measuring to see what really is happening, maybe at a more granular level. So I do think that's part of the timing factor there. Patients are usually coming in sometimes every six months, more likely every 12 months. And so you do have some time between visits. There is not great consensus around what you should be measuring. And that's one thing that we're working very hard with the physician community is to really identify what is a more sensitive, perhaps less invasive, maybe more relevant to the patient themselves as it relates to what you should be following. The places that we are starting to hear some traction, though, and I think you'll continue to see is more listening to the patient in terms of how they feel, fatigue, pain. Also, important milestones like, have you lost the ability to go upstairs or are you having a harder time getting to work? Those kinds of things. So I think you're seeing a broader understanding of the importance of what's going on with the patient and less around like a 6 minute walk test. Is there a practical PRO scale that can be used? Yeah, there are a handful of PROs that are fairly practical. You know, none of them are perfect. Some of them are borrowed from other diseases, like Duchenne as an example. But I do think that there is enough out there. And if you look at our phase 3 data, actually, we showed quite good. It doesn't all translate to the label, but in terms of the publications where the physicians can go look, we had great benefit on a number of those other measures of disease, including the PROs. So I think over the next kind of now that you have choice and it forces physicians to think more, you know, subtly around what's going on with their patients, I think you'll see a growing utilization of some of those outcomes. The Holy Grail would be more of like a biomarker that could be followed easily. You've got CK, you've got Hex4, which are generally measures of muscle damage. You also have Hex4 is a glycogen, you know, metabolite. So it's an indirect measure of glycogen. I mean, there's ALT, ASTs too, right? Exactly. Which are also indirect measures. Exactly. So those are helpful, but probably not dispositive. What you are seeing is, I think, a greater appreciation potentially for MRI to look at not just glycogen, but also fat infiltration. There's a whole group that's been looking at that. You'd need, you know, I think, more readily available, less costly ability to access MRI to be able to do that. But I think the ability to measure it is increasing. So there's an opportunity there. But I do think, you know, the near-term answer is much more around just asking the questions in a more consistent way and following, again, things like fatigue, pain. Some of the time get up and go kind of measures, but also just asking, you know, how are you feeling and have you lost or gained any function since the last visit? Some of the big ones, again, are sort of, you know, going from not needing very much ventilation to needing more BiPAP or CPAP to not walking with assistance to walking with assistance, the inability to go upstairs or something. You know, those kinds of things, I think, will become a more serious part of the conversation with physicians. About who's declining. Exactly. Therefore appropriate. Or perhaps who's improving. Got it. Got it. What's the time frame generally that these assessments are made over? You know, what we've seen, at least, and this is all anecdotal, so we have to see this now, you know, get translated to the literature, but we've heard of responses, you know, kind of almost immediately, and if you look at the data from the phase three study, you know, on the more typical measures of like 6 minute walk, it was, you know, from the beginning you started to see those impacts and then they were sustained over time. Awareness, like, decline happens over what period? Kind of gradually. You know, so declines, I think, you know, you see like FVC is a good one. It used to be believed that, you know, 1% or 2% decline in FVC over time was stable anyway. And so I think that's where reframing expectations for therapy. That's why even our approved materials with the FDA for our promotional materials say improvement is possible. That's just a reframing of the expectation of therapy. Now that takes time, right? And we're kind of on that journey. But to me, the ultimate outcome is I'm not going to wait a year or two years to let some of those things decline. I'm actually going to use the best thing I can use right now. And we believe that's Pombiliti Opfolda. So actually, I can even have the possibility of gaining function instead of kind of waiting for some decline and then making a switch. Has coverage been largely squared away in the US? We had heard something earlier from doctors about getting the Pombiliti part covered versus the Opfolda part covered. Is anything left to optimize in time to fill? No. Like I said, we are down to 30 days or less from an insurance process, and then it's just a matter of the physician scheduling the infusion with their patients. The good news is we do have a hub, and so in those instances, and we, you know, we won't name that person, but we know who you're talking about. There are sometimes challenges with paperwork between the site and with us. So, you know, when we have those things, we work through them, and that's part of the value of having your own case manager, but that's not an insurance issue. That's an administrative issue. I see. Which is, you know, sometimes you have human error. So we work through that. But no, there's no on the insurance side of things, we've gotten great coverage for both products, Pombiliti and Opfolda, and we have no concerns about that going forward. So Genzyme has been sort of counter-detailing the fasting requirements around, you know, we've had doctors who say this is no big deal, but we keep hearing about it. On the investor side is a question. How are you addressing that? And how are patients handling that in the real world? Yeah. Part of me is sort of, you know, I think it's no accident that instead of coming after the efficacy of the drug, they're coming after the logistics of the drug, right? So maybe they can't fight one thing, so they're fighting something else. The good news is both the research we've done and the conversations we've had with physicians and patients say that it is not an issue. In fact, we had a poster at World that was the patients coming out of the technical POM-07 study. How did they report the physicians and patients? How did they report their experience with fasting and the drug, et cetera? And over 90% of them said that it was either very convenient, convenient, or neutral to their previous experience. Over 90%. So the vast majority of physicians and patients are saying this is not a big deal. Small minority, you know, maybe needs some more education. Interestingly, you know, we've focused a lot on with Galafold, the every other day dosing mechanism. And there is actually a fasting period around Galafold as well, which is not a big deal now because everybody knows how to do it. But in the beginning, it was a question mark. And the way you deal with that is just through these amazing nurses on the staff of the sites. Because once they understand how to help the patients navigate it, you know, it becomes just part of their routine. Remember, these patients are oftentimes taking some sort of concomitant medication, whether it's Benadryl or NSAIDs or something else. And so taking another pill within all of that sort of regimen really becomes a non-issue. And like I said, over 90% said that was the case coming out of the study. On your Q4 earnings call, you noted that 40% of current Nexviazyme patients are approaching this 2 year treatment mark. That, our survey suggests, is really, really, really critical to their self-assessment for how they're doing on the therapy. Do you have any market insight on how those patients are doing based on talking to clinicians? And, you know, what's the willingness? I mean, it's a psychology question, right? What's the willingness to tolerate decline in these patients and in the clinicians? And that's, you know, that can be different. Yeah. I think, you know, look, historically, when you only have one option, which was, you know, Lumizyme or Myozyme, the physicians and the patients were doing everything they could. And so I think their tolerance for some modest decline was very high because absent that. What were they going to do? What were they going to do, right, so there is a behavioral shift here, right, and so I think if you look at now the switch in the United States where they had such a head start, I think they're kind of mentally going through that same process, which is, hey, at least I'm going to give it a little bit of time, you know, and, you know, honestly, how do you begrudge that decision initially, right, because they finally have a choice, they finally were able to put somebody onto a new thing, and yes, there's another new thing, which I think many physicians point to and say, look, the data look better to me. But I might as well give this a chance because we never, so the psychology to me in the near term makes good sense. You know, I think that it very much will depend on time, which, like you said, we are getting to that bigger bolus of patients coming into a 2 year period, which everybody said like that's enough to see how for most patients things are going. But I also think it's going to come down to data and experience. And that's why we've started to show case studies, which I think are individually interesting and compelling. And I think that will continue to grow. But what we're really excited about is in the shorter term, you're starting to have some physicians who have large cohorts of patients. So this is in Europe in particular, the UK, where they've actually had, you know, 10, 12 or more patients on Nexviazyme and 10 or 12 patients on Pombiliti Opfolda and followed them side by side. And so I think towards the end of this year, you're going to start to see publications and posters with like the first ever side by side or head-to-head comparison in a real-world setting. And what we're hearing is that that, you know, that should look very positive and favorable. Of course, we've got to see it in print first. But to me, that'll be the next step, which is investigator cohorts. And then I think the last step, which will take a little bit more time, is we do have a registry where we have Naive and Switch and competitor patients in the registry. And those are regulatory commitments. And we'll be able to publish on those things over time as well. So I do think you'll have a build of evidence to support why, again, switching earlier does make sense. Because if you can have a benefit by switching, then I think you should be doing that as soon as you can versus kind of waiting a year or two to see what happens on another drug. I hope those posters, which seem really important, are not at World Muscle because apparently investors are not welcome there to appreciate them. If they are, we'll share it with you. How about that? Excellent. Because I think those will be very important to the marketing and, sorry, the marketing effort going forward. Given Genzyme was, how should I put this, at their commercial presence at World, the absence of their Nexviazyme materials, messaging, symposiums was noted. Let's put it that way. Agreed. Any additional thoughts on what that changing competitive dynamic, the counter-detailing dynamic? What have you noticed? You know, I don't want to speak directly for a competitor, but I would encourage people to look at sort of what they're saying and what they're focused on from a corporate perspective and maybe telling as relates to where they're not focused. But I think we have established, I think, Amicus as a credible partner in the scientific community. And I think that that really leads to trust and leads to being able to have these conversations and hopefully be able to help physicians understand how best to use our products. Can you walk us through the major regulatory submission and reimbursement agreements for PomOp outstanding in 2025? Yes. So the biggest regulatory commitment, there's some stuff at the margins that aren't that important, but the biggest regulatory commitment is the registry. And so, and again, that's a collection of naive, switch, and naive patients who go on to PomOp, switch patients who go on to PomOp, and then naive patients who are on a therapy and patients who are on a competitive therapy. So it's like all cohorts of patients over time. And that's a pretty, as you know, it's a typical commitment for orphan drugs in Europe and the United States. So we will continue to do that to monitor safety and efficacy across multiple parameters. But it'll also be an important publication generator. The other important part of our commitments are our pediatric commitments. And so there you have three. Expansion trials. Correct. Yep. Yep. So So we have three cohorts that we're looking at. The first is 12 to 17. That trial has already read out. It was primarily safety and PK, and it was all positive. We'll look to start submitting those data to regulators in the second half of this year. So you could start to see labels in late 2026 or 2027. Then we have a, sorry, and that's pediatric late onset, 12 to 17. We have another pediatric late onset cohort, which is, I guess, 0 to 12, where similar study, PK and safety, that's about a year behind. And so that'll roll on about a year after that. And then we're also doing an infantile onset study. And that one, again, is about a year or so behind. And so the reason, number one, those are regulatory commitments because we studied primarily adults in our phase three studies. But the other reason why that's important is because one of the themes, I'm not sure if you picked up on it or not, but one of the themes that we heard loud and clear at World was this growing cohort of, especially in the US, late onset pediatric patients identified through newborn screening. Identified early, asymptomatic for now, and whether they are worth treating or not. Right, and maybe they're not worth treating now or next year or even three years from now, but I think three to five years from now, you're going to start seeing more and more of that cohort being treated, and, you know, if you look at, of course, Dr. Kishnani and others who have been looking very carefully at that phenotype, what they're finding, and this doesn't surprise me, is that actually you have progressive symptomatology at a very young age. And again, if you have a therapeutic option that you believe can change the course of the disease, then why wouldn't you intervene early, so I think, you know, it won't be part of our story, you know, next year, maybe even the year after, but I think sort of year three, four, five, that could be a really interesting growth driver for us. All right. Let's move to Galafold because obviously it is a big part of your revenue base. Yes, it is. What are the biggest levers as you see it right now for continued growth for Galafold 2025, 2026? Geography seems to be tapped out. You're pretty much expanded worldwide. So how are these growth drivers evolving? So we're probably in about 90% of the commercial footprint that we aspire to. We're still pretty early in the launch and commercialization in some Asia-Pacific countries and in Latin America. Turkey is a big market where for just a thousand different reasons, mostly government and macro reasons within Turkey, we still haven't gotten to reimbursement yet. So we're approved, but we don't have reimbursement. That's actually one of the largest by population countries. The price point's relatively small, but that'll be part of that 10% growth. We just got on the national reimbursement for Singapore, which has a reasonable population. We haven't baked any growth into China into any of our forecasts. So there is a possibility at some point to access that, but it's about 10%. So that's a small driver, but it does, you know, that'll still contribute. The biggest two places then are the dynamics we've been looking at, which is switch population. We have about a 65% share of the treated amenable population, which means we still have 35% or so to switch. We get to 90%-ish peak market shares in our core market. I think there is still some growth there. The other opportunity, of course, is in the naive population, which treatment naive, I should say, which I think is worthy of exploring a little bit because there's both a diagnosed untreated pool as well as a newly diagnosed pool. I think both of those segments are actually important in different ways. Got it. In the last five minutes, I do want to talk about your business development strategy and your internal pipeline. What sort of internal pipeline development is underway and what sort of timelines are we talking about? Yeah, so one of the things that you may remember that we developed a deep expertise in is protein engineering, and the question is then how best you deliver those proteins with Pombiliti. It was by enzyme replacement therapy. We put a lot of research behind AAV-delivered protein therapeutics and for lots of reasons, which is our historical, we've moved away from that as an option. However, we do think there's potential for delivering therapeutic proteins with non-viral mechanisms, whether it's LNPs or whether it's RNAi or some other approach. We think there are ways still that could be helpful for these disease areas or modified ERTs, etc. The work we're doing internally right now is exploring whether we can take our novel constructs and deliver them by some, you know, reasonable mechanism. Now, Simon, who's sitting in the audience, is our CFO, has given us very, very, very little dollars to do that in the near term. But my hope is that, call it, you know, end of this year, next year, you could have something that comes out of that work that would be line of sight to a clinical candidate. Understood. So I think that's probably an early 2026 story. I also think there are some very early technologies externally that could be interesting as well. And again, in that kind of same timeframe, my hope is that coming out of, you know, either internal or external research in 2026, we've got something early to talk about for Fabry and Pompe. As you think about internal and external focus, are you still focused on de-risked late clinical development? For sure. Oh, like, and what therapeutic area? Are Are you going to maintain this almost ultra-rare focus? Yeah. So I think what we've committed to, and it's an important part of the story, is number one, we do think we've built a core business that is sustainable, profitable on its own, and will deliver great revenue growth for the company. Clearly, though, you know, from a biotech investment perspective, you know, we don't just invest in sort of steady, you know, revenue growth in this industry. We also want to see development. And so we are focused on late-stage de-risked, either peri-commercial or late clinical assets that can slot into our global infrastructure and leverage what we've already built so that we're. The Sales force. The sales force. It could be the sales force, certainly the country organizations. You know, a lot of companies who thought that they could attract the capital to build a global infrastructure in this market are probably having challenges with that. So you can imagine licensing deals where we can leverage our global infrastructure. You can imagine, you know, small tuck-ing kinds of things. So maybe you're thinking less sort of like who's the same call point or which programs have the same call point, thinking more, you know, what's out there that isn't being promoted in Europe and could slot into your very successful European sales operation. Yeah. And I think it's commercial areas that we can confidently be successful. And what I mean by that, of course, Fabry and Pompe, but we don't think there's anything late stage that's going to get approved there. But neuromuscular, cardiovascular, rare renal, maybe rare neuro, certainly metabolics, genetics, things that we understand the commercial model. It may not be the exact same call point, but it's certainly the same kind of specialized centers. We understand the reimbursement model, the pricing model, and we would be able to, with, you know, very little incremental spend, we would be able to bring those assets in and get a lot of leverage out of what we've built. So I think that I think the idea is, you know, whatever we do next, if you see that, you're going to say, "Oh yeah, that makes perfect sense. I'm confident Amicus can really add value there, and it makes sense why the counterparty, you know, wasn't able to access the same value. Great. I think with that, we are at time. Excellent. Brad, thank you very much. Thank you, Ritu. It's very insightful. Yeah. I appreciate it.