Morning. Welcome to day one of the Jefferies Healthcare Conference. My name is Dennis Ding, Biotech Analyst here. I have the great pleasure of having Amicus Therapeutics here with us. Welcome. Welcome. Thank you. Maybe to kickstart things, you know, talk about Amicus and kind of the journey you guys have been on over the last one or two years to get to where you are today. Maybe also give us an update as to where you are today in terms of the base business and how you think about the outlook later this year. Yeah. Maybe I'll kick off and then Jeff can comment. Really over the last couple of years since Bradley Campbell has been CEO, the goal has really been to do two things. One is obviously to continue to grow strongly the Galafold and Fabry franchise. I think really the journey of the last couple of years has really shown with the patient growth that we've continued to see for Galafold in sort of mid-teen growth rates now in the third, going into the third year of that, really demonstrates the sustainability of Galafold's growth going forward. It's all coming from volume. We see that patient growth continuing going forward. I think secondly, obviously the launch of POMBILITI OPFOLDA, you know, we had $70 million worth of revenue last year. The first quarter of this year was growing extremely strongly year on year. We did adjust our guidance really to reflect just sort of the timing of uptake of patients within the year. We are seeing very positive sort of growth in prescriptions in the last couple of months. We are feeling pretty optimistic about the outlook. Really the goal was to grow the revenues from those two products while at the same time becoming a profitable biotech. We have been on a journey really in the last couple of years to reduce losses, first to have sort of profitable full year non-GAAP profitability, which we had in 2024, transitioning now step by step to GAAP profitability. We have said that in the second half of this year, we expect to become GAAP profitable during the second half of the year. We will obviously take it from there on out. I think that's important because that also reflects, you know, improving cash flow over time too. Our view is, you know, we want to grow profitability and cash flow while also doing thoughtful either tuck-in or in-licensing type acquisitions. I think Dimerix, the recent deal that we announced in FSGS, clearly demonstrates that thoughtful approach to business development, something with potential blockbuster status in the U.S.. Actually, we've only paid $30 million upfront, almost like a call option to flip the card on that. Overall, it's, you know, as we go forward to the future, continue obviously to expand the current portfolio, but to step by step sort of leverage our infrastructure through business development in a thoughtful way that's balanced with not sort of overstretching the balance sheet in order to move forward. Yeah. Thank you, Simon. Just to quickly add, good morning everyone. And thanks to Jefferies for having us. You know, I've been with Amicus for quite a while. You know, external market dynamics aside, as Simon just hit on all the key points, really exciting time. We had $458 million in sales last year, 15%-22% growth, turning GAAP profitable, just got rights to a potential phase three blockbuster drug for FSGS, long runway on our current products, and a lot of new growth with new patients being diagnosed. From that perspective, we're extremely bullish on the future and really excited. You know, I know right now it's a little bit of an uncertain time just with external dynamics, but we feel we're in a really good position moving forward. Thank you. I think that's a great overview. Let's focus on Galafold for a second. I feel like, you know, it deserves some airtime because it is really the, you know, what I would call the engine behind Amicus, right? And it's growing double digits. There's still a decent amount of runway there. What do you think investors are missing here? Because when you look at the valuation of Amicus and you try to, you know, correlate that with the value of Galafold, it's, you know, there's clearly a disconnect there. What are your thoughts on that? Like, what is your message to investors about Galafold and the outlook? What I would say to you is I honestly think there are a couple of key components that are being missed. First and foremost, in terms of intellectual property protection, with the settlement with Teva to January of 2037, you have essentially provided certainty for investors for the next 12 years, which is honestly longer than some products even have sort of patent protection for in a growing market. Yes, we do still have to resolve the outstanding sort of Aurobindo challenge. The reality is in the vast majority of cases, once the lead ANDA filer has sort of settled, others fall into line. We'll have to wait and see. I think that really extends the runway and the value of this product. I think secondly, it's really important to bear in mind in the revenue growth versus profitability discussion that once you get about $400 million worth of revenue coming out of Galafold as a small molecule, pretty much everything else falls to the bottom line from a profitability standpoint because we're not building additional sort of infrastructure to support it. It's more driving growth through market opportunities. Thirdly, I think, you know, as you look at patient growth, we are now in the third year of mid-teenish type patient growth. Even in Q1, where we had a few one-offs in the revenue line, underlying patient growth was 14%. Our guidance this year continues to be 10%-15% growth. Each year that goes by is another year reinforcing the opportunities. I'll let Jeff maybe talk about what some of those opportunities are. You also have market share expansion. We're roughly 65%-70% market share in those markets where we are globally. In the major markets, we're more like 85%-90%. There is still good growth opportunities in those markets as well. Those are the things that I think are, you know, obviously it's our job to get that message out there, but key things that people need to understand. Maybe you can just comment on some of the things that reinforce that growth going forward. Yeah. Thank you, Simon. You know, I really think to me the main thing I'd appreciate with Galafold, in addition to the long runway we have, is there's just so many patients still out there that are not diagnosed. The diagnostic opportunity to grow the market is just huge. There's more patients not diagnosed than are diagnosed. There's a lot of tailwinds for diagnosis. Physicians have a better understanding of when to think about Fabry. All of the kind of cardiac or renal screening panels include Fabry on those panels when it's so easy genetic testing. There's newborn screening initiatives going on in the U.S. We have eight states that are screening over 500,000 newborns every year, diagnosing index Fabry babies and then looking at those family members. Just a lot of tailwinds. You know, Amicus is trying to invest in certain things like AI and how to use medical records to also try to find undiagnosed patients. Really we see just a huge opportunity to continue growing this market at significant numbers just through diagnosing new patients. The other interesting thing is if you look, like when we launched in 2016, there were about 10,000 Fabry patients, about 5,000 treated, 5,000 diagnosed and treated. Today it's 18,000. It's gone from 10,000 to 18,000 diagnosed patients and 12,000 are treated and 6,000 diagnosed and treated. You're seeing instead of 50% of people treated in the past, now you're seeing two-thirds of patients treated. In addition to a lot of diagnostic growth, we're seeing physicians start to treat patients more early. We're seeing more treatment of females. Huge opportunity there as well. The last thing I'd say that is an additional tailwind specifically for Galafold that I think is benefiting us and why you're seeing more growth for Galafold than other Fabry treatments is that in the pool of patients and families left to diagnose, they tend to have late onset Fabry because they haven't been diagnosed with more classical symptoms. A high, high majority of late onset Fabry is amenable. A lot of that growth that's coming is actually enriched for amenability, whereas traditionally it was 35%-50%. It's probably 50% plus on kind of the new diagnosis. Okay. Those are very interesting. Like, you know, it does seem like there's a lot of tailwinds in terms of diagnosis and education and earlier treatment and things like that. When do you expect those sort of, you know, dynamics to impact Galafold from a revenue perspective? Are we talking about in 10 years or in five years, you know, just kind of ballpark, when do we, when should we expect those tailwinds to actually kick in? I mean, I think the tailwinds have been kicked in. If you look, as Simon said, I think we've seen more new patient starts in Fabry in the last few years than we've seen historically ever since early launch for Galafold at least. I think that's what's driving the current growth. You know, what we're seeing is not any growth in price. It's not that much market expansion, although there still is some. What we're seeing is mature markets where we already have 85-90% share of amenable patients. We're just seeing a lot of new diagnosis and new patients going on treatment. I think we're seeing it. I think that's what's going to continue to see that growth. You know, you see sometimes people put models together and after three or four years they put sort of 1% or 2% growth with population. Like there is just a lot of continued potential for Fabry. I think we're seeing it now. I think it'll continue to fuel that growth for the foreseeable future. I think that's very interesting because, you know, when you look at your guidance, you know, I think 10%-15% year-over-year growth, so kind of in the low teens. And then when you look at consensus numbers moving forward, it's actually a pretty steep deceleration over time. If you're telling me that with all these education and tailwinds and things like that, is there a scenario where Galafold actually accelerates from some of these efforts, right? Do you guys have any comments on that in terms of... All I would say is, you know, we believe in taking these things a little bit step by step. Yeah. But now that we're into the third year of that strong patient growth, obviously our comfort level with the sustainability of that growth continues to build, no question. The only point I'd say is it is always off of a bigger base of patients. So while we're adding more patients sort of each year than the next, as a percentage, it's gone down a little bit. And I think that's what you've seen with the Galafold growth has gone down in that mean level. But it's actually from a just sheer number of new patients being diagnosed, going on to treatment, it's actually been growing the last few years. Yeah. I mean, I think even outside of these different initiatives, just the fact that there's still additional room for penetration, just that on its own can contribute to that year over year increase in net patient adds, right? And I totally understand that like from a percentage basis, it would naturally decline. Once some of these initiatives kick in, why wouldn't that, like why shouldn't we be talking about a low teens growth rate over the next three to five years, right? And then with the, you know, with the generic settlement and visibility into 2037, like why shouldn't we think about Amicus as a Galafold business rather than I think the narrative out there right now is more around POMBILITI OPFOLDA. Yeah. I think you have a very valid point. I also think obviously, you know, as the CFO, we are investing in some of these initiatives. One wants to see the value of that being created. I think we all believe with the programs on AI and the algorithms with UPenn, et cetera, that those are great opportunities to expand and diagnose at faster rates. We all know that as an X-linked disorder, you know, there will be other family patients out there as well. You know, I think your question is a totally valid one. That is what we are striving for. Obviously, we will take it step by step as we progress. Can you give an update on the AI initiative with UPenn? Yeah. This is a collaboration we initially had with a company, OM1, that basically uses AI and medical records. We created a kind of diagnostic fingerprint of medical records for Fabry. We were doing a pilot project with UPenn where we've screened over 500,000 of their medical records of their patients at Penn and ordered them from 1 to 500,000 in terms of risk for Fabry based on the algorithm. Penn is in the process of engaging with those top 100 at risk and then moving on now actually to the second 100 at risk and seeing if they're willing and able to come in and get worked up for Fabry and tested. We're in that patient engagement, getting screened, getting tested. We'll have more to report out here probably in the second half of the year on how that's going. Assuming that we can show proof of concept, this is a way to effectively find Fabry patients. We would look to potentially do additional pilots at multiple healthcare systems in the U.S. and then importantly, I think ex-U.S. In the U.S., as I mentioned, we already have newborn screening that is seeding a lot of index patients with families that could be all around the U.S. I think that's a really strong core already. Things like the medical records can add to that. For me, it really would be exciting to do outside of the U.S. We do have some similar projects in the U.K. and in Canada starting to look at sort of medical records and how to use those to diagnose patients. Okay. Okay. Sounds good. Now that we are in June of Q2, I'm just curious, you know, what sort of incremental color you can give around Galafold and maybe remind us Q1 and some of the seasonal ordering pattern things that happened that may have shifted in Q2. Just remind us of some of those dynamics now to think about Q2 Galafold revenue. Yeah. So in terms of Galafold, as you know, we guided to 10%-15% growth for the full year, which is consistent with what we've been saying since the beginning of the year. And that's really on the back of the strong patient growth we were just talking about. I think in terms of sort of quarterly dynamics, yes, there were a couple of things. One was this U.K. rebate called VPAG that was higher than anticipated. That will continue during the year, but at least we're now aware of what the rate is. But bottom line is we didn't change our annual guidance. Typically, we tend to have in absolute dollar revenue, the smallest quarter is Q1 due to reinsurance, those type of things. What I can say to you is, you know, we have the guidance we have and we feel fairly good about where we are. Okay. Let's talk about Pompe and, you know, POMBILITI OPFOLDA. Can you remind us what happened in Q1 and, you know, some of the underlying patient trends? And I know you guys also talked about April or, you know, was it April or May? April. April being a very strong month in terms of patient adds, particularly in the U.S. I'm just curious if you saw that trend continue in May. In terms of Q1, we did adjust our guidance to 50%-65% growth for the full year, which is roughly $105 million-$115 million. Why did we do that? We did that because, frankly, while we are seeing good prescriptions that you referenced in April and May, the same thing, if you do not catch the patients right up front in revenue terms, then they push further out. That is what created the sort of the revision. It was primarily due to two things: patients in the U.S. and, secondly, patients in a couple of key markets, primarily the Netherlands and Italy, where we have got pricing and reimbursement, but we had to go through like regional formularies in Italy. You know, the patients in the Netherlands are part of a tender and there is only one center. It's going to take time to get them all fully onto drug. That was the major reason. We are, you know, April was, as you referenced, a very good month and we continue to see positive trends. Okay. What are your thoughts on, or do you have any updated thoughts on the whole NEXVIAZYME switching? You know, now that we're a couple of years into the launch, do you have, you know, because before you guys mentioned one or two years, like I just wonder if there's any kind of updated metrics based off of like real-world experience in terms of the switches. Yeah. I think a lot of that is coming from the U.S. where Sanofi launched NEXVIAZYME basically a year and a half right before we launched and they managed to switch a significant part of the U.S. market. I think what we've come to understand is it really is more about two years where physicians and patients have enough time, enough meetings with their physician, which turns out to be more annually than twice a year. We're just not seeing a lot of switching before two years. It's not that surprising necessarily. We do know that as patients switch from Lumizyme to NEXVIAZYME, they do generally start to do better. We are seeing that a significant% of those patients, especially after two years, look like they are now looking to potentially switch. Good dynamics for us on that front. We continue to sort of learn as we go along in terms of that journey. We continue to hear really positive feedback from patients, from physicians on the experience with POM OP. We remain very bullish on long term. We believe in the product. We believe that this will ultimately deliver differentiated mechanism efficacy. We do think that eventually we'll have majority market share. It's just sort of the pace at which that happens, in particular in countries where they've recently switched to a new drug and sort of they need to go through that journey with that new drug before they're necessarily immediately looking to switch to something else. From a numbers perspective also, you know, last year as we entered the year, maybe 10%-15% of patients in the U.S. had been on NEXVIAZYME two years or longer. As we exited last year, that was like 30% or 40%. Now this year, started the year at 30%-40%, we'll end it around 60%-70% in two years. It is just a much bigger pool of patients that had been on NEXVIAZYME long enough to kind of have a sense how they're doing and potentially be looking then to switch to another option. Outside of time on NEXVIAZYME, are there any other kind of barriers or considerations that doctors are thinking through that would prevent them from switching somebody onto POM OP? No. I mean, it's interesting as you speak to the physicians and patients, there's barriers you didn't necessarily expect, like just things like, oh, they need to come into the office for a few infusions if they're on home infusions. Oftentimes they might have to switch nurses that are doing the infusions. Sometimes that could be a barrier. There is the fasting for two hours during the infusion because of the OP stabilizer or once every two weeks. All very minor things you would think compared to potentially getting on a drug that could actually treat your disease in a different way. Those are, in essence, what we've learned is there needs to be sort of a compelling initiative from the patient or physician to want to switch. It's not just going to naturally happen without sort of a reason. That reason can often be the patient's not doing well or they didn't get the benefit they hoped to get when they had switched. I think it's, that's been a learning, but there's no specific barrier. The reimbursement initially I think was challenging for some of the trial patients. There still is this mindset that like the reimbursement could somehow be challenging. We're seeing, you know, reimbursement is not an issue from the payers. I think it's just combating some of that mindset of like, oh, we need to go through this switch and it's really not that hard to switch. I think we've heard great outputs of what's happened when those patients have switched. Okay. We have five minutes left. Let's talk a little bit about FSGS. Can you remind us some of the details of the transactions and just the thought process and rationale behind the Dimerix asset? Yeah. On a big picture level, and then Jeff can talk about the details, but in terms of business development, we had said that one of the things we wanted to do was to do step by step business development as we became more profitable to build sustainability and expand the portfolio for the long term. I think in the case of Dimerix, it really fit the bill both from a point of view of being totally on strategy to assuming the drug is successful in phase three, leveraging the infrastructure that we already have built in the U.S.. You combine that then with the fact that we did not need to finance the upfront costs of doing this. Basically we paid $30 million to, is like a call option to flip the card on the phase three data that if successful, you know, we believe has blockbuster potential in the US alone. The remaining sort of milestones in cash flow, assuming the drug is successful, which we would then be happy to be paying out on, will match much better with our sort of cash flows going forward. It really felt like almost perfect's too strong a word, but a very good opportunity for us that fit exactly what we were trying to achieve as it relates to FSGS. Yeah. I mean, I would just add we're super excited to be partnered with Dimerix, you know, FSGS. There's no approved treatments. There are 40,000 plus patients in the U.S. suffering with FSGS, 5,000 new each year. We think it's a very differentiated mechanism of action that really targets this monocyte macrophage driven inflammation that seems to be a significant driver of the kidney damage in a good set of the patients. We were very excited by the phase two data that we saw. That's a really well-powered phase three study. They just got clarity from FDA, or we got clarity that proteinuria can serve as the primary endpoint. A really well-powered study. As Simon said, we thought it was a perfect fit for us. You know, we have kidney experience and interactions with nephrologists through Fabry. We can leverage sort of our understanding and knowledge about the endpoints, our interactions with the physicians and kind of build that base to go into FSGS. Super excited now to be engaged with that community as well. We think it's a perfect fit for us. We would love to also have something for our ex-U.S. team as well. We'll certainly keep looking for similar opportunities. It checked every box I think we could hope for. Right. So maybe talk a little bit more about some of those other opportunities now that you have done this deal with Dimerix. What's next? Should we look for something similar, but OUS, meaning more clinical stage, you know, like late stage but clinical, or should we think about commercial? That That would be immediately accretive. My comment would be business development always has an element of opportunity attached to it. You have to be a little bit cognizant of that as to exactly what you do in what order. Suffice it, however, to say the framework within which we're sort of working is commercial asset that would continue to leverage our infrastructure, whether frankly outside of the U.S. only or on a more global basis, depending on circumstances. In the rare disease space, it does not always have to be something that's got an identical sort of sales force or overlaps with the sales force, because in rare disease that tends to be the less expensive piece. Where we can at least leverage the infrastructure on regulatory, on, you know, internal stuff, yeah, could be again late stage depending on circumstances. Nothing that is going to what I would describe as overextend the balance sheet. We're trying to be quite thoughtful about that. You know, we've just, you know, the ink is just drying on this deal. We will proceed from here as we see suitable. That is the sort of direction of travel. Okay. Back on the FSGS, remind us, you know, I know it's $30 million up front, but remind us of the developmental milestones that may need to be paid out. Yeah. There are about $75 million worth of milestones to be paid to the point of approval. Then beyond that, there are sales milestones and there are sort of primarily royalties on sales in the sort of the low teens to, I think, low twenties roughly. Okay. Good. Which we would be happy to pay out if the drug is successful. Yes. Great. Thank you guys so much for hanging out with us. Really excited about the outlook moving forward and all the different catalysts actually that we see in the second half this year. Good luck and have a great day. Thank you. Thank you.