Well, at least he got eaten. Yeah. All right. Good afternoon, and thank you for joining us at Guggenheim's inaugural healthcare innovations conference. I am Debjit Chattopadhyay, one of the therapeutic analysts here. Joining me today on stage are Simon Harford, CFO, and Sébastien Martel, Chief Business Officer of Amicus. Thank you so much for your time, both of you. Pleasure. Maybe we can start with a very quick introduction of a classic rare disease company. Yeah. I mean, obviously, as a rare disease company, we're in a slightly unique position because we have two products that we're commercializing currently, both in terms of Galafold for Fabry disease, which, as we guided to last week, we're anticipating sort of 16%-18% growth in 2024, which, for a product that has been on the market for sort of seven or eight years at this point in time, is pretty remarkable growth. And we continue to see the market for Fabry disease expand from the roughly sort of $2 billion-$3 billion mark by the end of the decade. I think in terms of the second product, Pombiliti+ Opfolda, we were in a position whereby we had been guiding previously for this year to $62 million-$67 million. We actually came out and raised that guidance for the full year to $69-$71, so we had an extremely strong Q3, and so as we look at the future, we're seeing really strong growth. Total revenue growth this year is likely to be in the 30%-32% range. You then combine that with the fact that we've said, from a point of view of sort of operating expenses, we're lowering those, which means that our guidance of full-year non-GAAP profitability is dropping straight to the bottom line. That's a pretty powerful story from our perspective, so it's a profitable small-mid-size biotech. Not everyone's doing that, and as we think about the future, it's about reinvesting those funds back, both in the top line, obviously, as our key priority, but also in terms of thinking about the future and business development opportunities. I'll stop there, but that's kind of where we are at the moment. Got it. So another interesting tailwind, at least, which happened very recently, is obviously the Galafold IP resolution with Teva. 2037 was a better outcome than most had expected. Mm-hmm. Do you think the one holdout right now, you would push for the same 2037, or you could settle for 2036 or something like that? So look, we settled with Teva for January of 2037. I think most sell-side analysts assumed there would be a generic somewhere in the 2030, 2031 range. Our secondary composition of matter patents sort of run in the 2038, 2039 time frame. So 2037, to take uncertainty for investors out of the stock as it relates to Galafold, made a lot of sense to us. And we're really pleased with the outcome. And we think that it confirms the strength of our patent portfolio. I think in terms of the follow-on sort of contenders, Aurobindo and Lupin stayed. Aurobindo, there is technically a trial next summer. We plan to make sure that our... Scratch it for the webcast. Is that OK? I think that's good. Yeah. We We will defend our patent portfolio. We're not going to comment on it. All I can say is Aurobindo will have to decide. Do they want to spend the legal fees, or do they want to move on and settle? We'll see where they come out. Got it. So let's turn to the Pombiliti launch. While it was a strong quarter, the raised guidance, there was a little bit of disappointment in terms of the new patient adds. And maybe sort of help us understand that dynamic a little bit. And how do you think that's going to play out when you start thinking about 2025? Yeah, absolutely. So look, we're very pleased with the way the POMOP launch has been going on. As we speak, we're now into five different markets: the U.S., the U.K., Germany, Spain, Austria. And we just got recently pricing and reimbursement in the Czech Republic. If you look at the way we started off the year, we gave guidance of $62 million-$67 million. We actually performed slightly better than expected in Q2. And again, the Q3 sales were slightly ahead of our expectations. So we raised the guidance now to $69 million-$71 million, let's say roughly $70 million for the sake of it. If you go back a few years when we were just launching Galafold, we did not even reach that level of sales in the first full year. We had initially $5 million with Galafold and then $37 million in year two. We're, again, going to deliver around $70 million this year for POMOP. When it comes to the dynamics, we see in the European markets a strong switch because, let's face it, the single biggest opportunity for us is to switch Myozyme and Nexviazyme patients onto POMOP. We're seeing switches in the same relative market share that these two products have, meaning in Europe, we see a lot more switches from Myozyme because that's still the lion's share of the Pompe business in Europe. We do also see switches from Nexviazyme for markets where Nexviazyme has been a little longer. In the U.S., because we were two years after Nexviazyme switch, we're actually seeing the majority of switches coming from Nexviazyme because the dynamic here is roughly 60% Nexviazyme patients versus 40% Myozyme or Lumizyme patients. So, happy with the performance to date, happy that we were able to deliver better than what we had guided for earlier this year. As you look to next year, there are a number of important growth drivers for us. So one, and quite important, is that overall, the Pompe market continues to be a healthy, growing market. We think that by the end of the year, this will be close to $1.5 billion. It's growing in the mid-teens. We saw that when we launched in the Fabry market. We had two established players, Sanofi and Takeda. And yet today, we have a product that will generate over $450 million in the Fabry space. We saw that our entry into Fabry helped sustain the overall Fabry growth rate. So we would expect the Pompe market to continue to grow. We're projecting that market to reach $2 billion by the end of the decade. So overall market growth will play an important role in our continued expansion here. Second, as you look to Europe, we expect to continue to grow our share. I'll talk to you about the U.K. market situation. This is the market where we've been the longest. We've actually been on the market for three and a half years in the U.K. As a result of our early access program, we got access through EAMS a couple of years before we launched. So as we speak, we've actually been in the U.K. for three and a half years. And we're now the leading product. We have 35% share in LOPD patients in the U.K. We would hope that that becomes a bit of a benchmark for us to reiterate that in other markets where we launch. We have, I would say, eight ongoing pricing and reimbursement negotiations, which we would hope to see coming to fruition in the six to nine months. So there's a number of additional European markets and Japan, Japan being more of a Q4 launch next year that will contribute to additional growth. And then in the U.S., as you look to accelerating the number of switches, the feedback from physicians, actually even prior to launch, was that they would want to see patients on a drug for one plus to two years before considering switching a patient. And so as we entered this year, we estimate that there was about 10% of Nexviazyme patients who had been getting to that two-year time point. As we get into 2025, we anticipate that there will be more like 40% of patients who would have been on already two years of therapy. And so our expectation is that we'll continue to increase the number of switches also from the U.S. market next year. So again, threefold drivers here for our POMOP product next year. When you think about the prescription habits or patients who need to switch, do all patients need to switch, or it's more like 30%-40% of the patients who need to switch? And when the patients start to plateau, do physicians keep them on their existing therapy for another 12-18 months before they finally make that switch? Or the moment they start to plateau, they start talking about the switch? And And whenever that next visit is, the switch happens. Yeah. Unfortunately, I don't think that any of the ERTs represent a cure for the disease. And so while they've been extremely useful at slowing down the disease, the disease continues its damage in some way. And over time, you will have patients starting to decline. We've seen that from Myozyme historically. We've seen longer-term data on Nexviazyme as well. And it looks like the two-year time point is when you start seeing a growing proportion of patients declining. We usually say that by the time we launched, there was about 25% of patients that are decliners. The bulk of the market, maybe 50%, are stable, qoute on quote. And so there's a lot of debate going on about what stability is. How do you assess patients on a regular basis? Is it more the usual clinical endpoints, six-minute walk test, FVC, or is there more actually that should be considered? We're having these discussions also with key opinion leaders, through advisory board, through symposia, and various exchanges we have. And then you've got 25% of patients who are still doing pretty well on therapy. Those are unlikely to be switchers. For now, most of the switchers we've had are coming from that decliners pot. But again, of the 50% stable, remember, our label says patients not improving on other ERTs. So in some way, those are potentially eligible. And this is where, as people get confidence in POMOP, as they use it more, we would anticipate to see also a fair share of those so-called stable to consider a therapy that could allow them to improve. Got it. So of the 40% or so patients in the U.S. who would have been on Nexviazyme for two plus years in 2025, how much more evangelizing or educational campaign do you need to do at the physician level to make that switch happen? I think that that's an ongoing engagement plan that we have through various means. Part of it comes from the communication around case studies. We regularly have at World Muscle Society or even company-sponsored symposium physicians coming to present their own experience in prescribing Pombiliti+ Opfolda. And those case studies are quite impactful. When you look at the data, comes the two-year point. There's probably up to 40%-50% of patients who would start to see signs of decline. So again, in our own projections and ambition, is to see a growing number of switchers from the US as of next year. So based on when Pombiliti was not Pombiliti when Nexviazyme was available in the United States, summer of 2025 will be the fourth year, right? So do you think there's going to be a big bolus on the back end of the year and not so much in the first half of the year? Tough for me to guide you here on a half-year basis. I think we look at it on an annual basis. We simply see a growing proportion of patients that would be eligible to POMOP switches next year, throughout the year, I would say. Got it. OK, so from an organizational perspective, do you think you are pretty close to the right size you need? Yeah, I do. And that's been part of what I was talking about in the intro in terms of profitability, et cetera. We built the infrastructure essentially across the globe to support the launch of Galafold. And really, we're using that infrastructure now, whether it's on the front line with sort of sales force or whether it's more internally through regulatory, through support functions to operate in those markets. So that's built. So as we think about the future from this point forward, it's really I'm not going to say there won't be some nominal increases in the headcount to support that growing business. But it's going to be nowhere near what it was needed in terms of ramp for Galafold initially because we're essentially there at this point in time. Got it. How many countries does Amicus have a footprint in currently? Something like 40, I think, which gives you an idea. And that's part of the benefit that we have, particularly as we think about potentially in-licensing commercial assets that we can use in infrastructure that most companies of our size don't want to have to build, particularly outside of the United States. To that very question then, during your conference call, you sort of laid out therapeutic areas of interest. How does that align with whether field forces? And how late- stage an asset are you looking at? Does it have to be post-Phase 3? Yeah. Yeah, so look, our number one focus is now on growing Galafold. And you've seen this year that we've been growing at 18% year- to- date, which is actually slightly higher than the growth rate we delivered last year. And with the long runway that you described through the IP settlement, I think we've got a lot of value to be created again through Galafold. We're very much focused on continuing to expand POMOP in the markets where we're already launched and preparing for a successful launch in additional markets, as I said, up to eight new countries in the next six to nine months. And then besides that, we think that we can leverage the infrastructure we've built from a regulatory clinical development capability, but also commercial and medical platforms that we've built to further expand the revenue growth story and the profitability growth story. We'll be looking for more of a string of pearls approach, adding a number of quotes on quote incremental assets, if you want, to the story. We're looking for programs that would be close to commercialization. Something that is undergoing regulatory review or something that has just launched in the U.S. from a company that doesn't have the bandwidth to do ex-US launches. Some of these regional in-licensing opportunities for fairly large global opportunities where ex-US alone would still represent a sizable opportunity for us. Obviously, we'll be looking at global rights as well. I think Bradley said on the call, in the next 12- 24 months, so there's not an immediate need for us to do things given, again, the very strong growth profile that we have with the existing therapies. In 24 months and beyond, we would want to continue to build the pipeline. Our P&L will also allow us to invest in clinical development on our own dime and therefore rebuild a Phase 3 pipeline with more mature products from a development standpoint than super early stage assets. And I would just add to your question about therapeutic area. As long as we stay in rare disease, if it's a different therapeutic area, we might need to add some sales force, obviously. But again, it's rare disease. That's not a large expense. And most of the regulatory and support staff is more therapeutic agnostic, so to speak, from an infrastructure perspective. So a lot of things have gone right, right? I mean, you've got the IP result. You've got two medicines, both growing. But it's also been a very frustrating environment for the investors. The stock hasn't done anything. So what are you hearing from your current investors? And what can you do to sort of address this big delta that you're seeing between progress within the company but not being reflected in the value of the company? I think what people want to see is they want to see in the core business increasing profitability, which, let's be honest, is primarily driven through revenue growth because that will then allow us to fund the sort of what I call phase two of the Amicus story since Bradley's been CEO, which is to then build, as Sébastien has just described, the future. But I think they want us to get to that. I think we've done, if you go back to when Bradley became CEO two years ago, we've done exactly what he said he was setting out to do, which was to accelerate sales with the launch of Pombiliti +Opfolda, which is happening, while at the same time recognizing that we need to become a profitable organization given the core structure we have today. I think as we think about the future, honestly, I think people are waiting to see what exactly is that future that Sébastien's just been talking about, and that is the intent going forward. As it relates to stock price, what I can say to you is over the last couple of years, we've been pretty committed to not diluting shareholders for the core business. Obviously, if we do something from a business development perspective, that's a separate discussion, but we've been pretty strict in that, and I feel pretty good about that, and it's actually quite extraordinary how much we've gone from loss to profit, albeit on a non-GAAP basis at this stage. Eventually, we will get to a GAAP basis, so we're committed to that journey. We're committed to building the business for the future. Got it. And this may not be the right venue, but Sangamo just got an interesting regulatory update on the Fabry side of things with the gene therapy. Is that a concern? I know it's still out there, probably another year and a half before it can become commercial. But any concerns on cannibalization, et cetera? No, I think we look at the Fabry market as a healthy, growing market. If you look at Sanofi, Takeda, and our own reported results, all in all, you're talking about a 9%-10% growth rate right now, a market that is over $2 billion, growing to $3 billion by the end of the decade. We don't see anything in the late-stage development having a significant impact on the overall market growth rate. I think it's tough to comment precisely on how Sangamo will come to market and how this will be perceived by physicians and patients. We've seen in some areas, take hemophilia, for example, that the commercial success has been a bit of a struggle. In some way, that might be tied to the severity of the disease that you're talking about. Clearly, gene therapy in the space of, let's say, SMA or DMD have had greater commercial success than with diseases like hemophilia. I would say that I wouldn't compare Fabry disease to DMD or SMA, let's put it this way. Awesome. I think we just ran the clock out. Thank you so much. Pleasure. Simon, thank you. Thank you. I appreciate it, Sébastien. Thank you, Debjit.