Good afternoon. Welcome to the Jefferies London Healthcare Conference. My name is Dennis Ting, biotech analyst here. I have the wonderful pleasure of having the CEO of Amicus Therapeutics, Bradley Campbell, here with us. Welcome.
Thank you.
Before we kind of get into it, maybe just familiarize everybody with Amicus as a company and some of the tremendous progress you guys have made this year.
Great. First of all, thank you, Dennis. Thanks to your team here at Jefferies for inviting us to the conference. It's been a great schedule. Good to see people, a little colder than I expected, but maybe my fault for not checking the weather. Amicus Therapeutics, we are a company that is focused on developing transformative therapies for people living with rare diseases. We have a great foundation in our first product that was approved for a disease called Fabry disease. That's a product called Galafold. It's now been on the market for almost 10 years in Europe and almost eight years in the United States. What's remarkable, and this is a core foundation of who we are and the great progress we've made, is we're still doing double-digit growth in Galafold for Fabry. In fact, we're growing at 10%-15% this year.
We'll do over $500 million in revenue for the first time this year, which is really exciting. We can talk a lot about how we see that product continuing to evolve over time. We have a second therapy, which is actually a two-component therapy called Pombiliti and Opfolda. We sometimes shorten that to POMOP, which is approved for Pompe disease. That has more recently launched over the last couple of years. We have some interesting dynamics coming into the launch of that product. What's really exciting is now we've had, I think, two great quarters, and we continue to see an acceleration of revenue there. Great line of sight to that continuing to grow significantly for us. This year we'll do 50%-65% in revenue growth from Pombiliti to Opfolda. That's in the backdrop of an evolution of the company.
We had a big investment in R&D for a period of time. When I took over as CEO three years ago, we had a goal of getting to profitability. Actually, for the first time, we're GAAP profitable this quarter, which is great, the third quarter. We continue to see that evolving over time as well. Earlier this year, we announced our first foray into a rare disease called FSGS. We licensed a product from a company called Dimerix, which is based in Australia. It's a late-phase III development. We have U.S. commercial rights for that product. Eagerly anticipating that evolving over time as well. Really core financial foundation, really strong growth now with another asset in the portfolio. Eager to talk more about it with you today.
Yeah, for sure. Why don't we start off with Galafold? It seems like the market is much bigger than you originally anticipated. M aybe talk about some of the drivers there and how you're thinking about 2026 plus and whether it's 2032 or 2037, whenever it expires. Just talk about the growth trajectory over the next five, 10 years.
Yeah. Fabry disease is, Pompe as well, belongs to a family called lysosomal storage disorders. Fabry is an X-linked disease, so it passes down from a mutation in the X- chromosome, one of them, if you're a carrier of the disease. When we first launched into the Fabry space, which again was over 10 years ago, we estimated it to be, as did the whole world, sort of a one in 50,000 live birth incidence, which would translate to what was diagnosed at the time, which is about 10,000 patients worldwide diagnosed with Fabry. Half of them were on treatment, and at that time it was enzyme replacement therapy. There were two that were approved at the time. Half of them were diagnosed but untreated.
We knew that there was that diagnosed untreated pool that we could launch into and also switch patients in the treated part of the equation . What's fascinating is we just started to see this when we were launching. There were a number of newborn screening studies that predicted Fabry could be more like one in 5,000 or even more like one in 3,000 live birth incidents, so significantly bigger than what we had anticipated. What we've seen over time since then is that now the treated population has more than doubled. In less than 10 years, there are now 12,000, we estimate, patients on therapy globally. It's a $2.4 billion market. It was a $1 billion market back then. Interestingly, the diagnosed untreated market has also grown from 5,000 now to 6,000 patients.
Now, of course, many of the original 5,000 are now treated, but we're finding so many more patients. Why is that? First, there is a growing recognition that Fabry affects both males and females, even though it's an X-linked disease. That's one piece of it. More than that, I think, is really the availability of low-cost genetic testing, whereby if you have a suspicion, in particular in nephrology or cardiology, of a genetic disease, they can order a test. It's less than a couple hundred bucks globally. Fabry is on those screening panels. Interestingly, and this maybe was an insight that came from our lunch today and a couple other conversations, there are a number of companies, of course, looking for these genetic diseases in the rare cardiac space and the rare nephrology space. It's not just us. I think all of us probably benefit from that kind of patient-hunting approach.
Going forward, I think you're going to continue to see that dynamic. We think artificial intelligence is going to play a role, an increasing role. There are a number of companies developing better tools there. We think we'll penetrate into that 6,000 diagnosed untreated, but we think there's probably a 10%-15% inherent growth rate in the patient market, which will translate to long-term growth. To your point, we think it's 2037, highly confident that that's the case, and we can talk more about that. We think this market continues to grow well through that period.
Okay. F or Galafold specifically, how do you think about the growth profile of that business over the next several years? Because it's been growing double digits. I think, maybe correct me if I'm wrong, maybe consensus has you guys at high single digits next year. How can we maintain that double-digit growth? What sort of initiatives do you have in 2026 and after?
Yeah. I do think there's still an opportunity to grow in that range. Of course, we're not giving formal guidance yet for next year. What drives you up and down the chain? More than anything, I think it is better patient finding. One of the things we've talked about as an example, which has already led to tangible patient finding, is we did a research project really with NHS in England here in England, broadly in the U.K., and looked at the diagnosed population of Fabry patients. Now, what you should know about the U.K., it's a very concentrated market for Fabry and Pompe, very knowledgeable KOLs. At some point, they get tired of genetic disease companies like us telling them that maybe there's more undiagnosed patients out there.
Effectively they said, "Look, there's nobody left. Stop bothering us." We said, "Let's just look then at the demographics of your patients." This was published, by the way, multiple times. NHS has used us as a poster child for some of these collaborations. We looked at the demographics and we found that 80% of the patients with Fabry in the U.K. were in the top three socioeconomic deciles, so the richest three deciles, and 90% were white. Fabry is not a rich white person's disease.
We used that then to prompt the physicians to look more closely into the population. They found very quickly, actually, two families with undiagnosed Fabry in the Pakistani community, which of course is a pretty large minority community in the U.K., which probably has an inequity of care. Almost immediately we found, again, two families. When I say families, when you find one undiagnosed Fabry patient, you typically find three to five family members who have undiagnosed Fabry. One case study, we're doing more in that place. I think OM, sorry, AI, and we're partnering with a company, OM1, will also be a driver of finding more patients over time.
Sure. There is still kind of a lag between identifying them and actually putting them on treatment. What does that process look like? Maybe touch upon the Penn collaboration and outreach that is happening right now.
It's a great point. There's two pieces there. One is you think about that diagnosed untreated pool, which there are 6,000 of them. Like many of these progressive diseases, there is a growing appreciation for the rate of progression in the disease and therefore finding better tools for understanding what that progression looks like. There are a number of investigator-initiated studies that we're focused on, as are I'm sure many people in the space, saying you should probably treat earlier if you have an effective intervention, a nd we think Galafold could be that intervention. You have seen, as an example, some treatment guidelines change and get more permissive. In some cases, Australia being one of them, where actually we got moved to first-line therapy. There are opportunities to do that.
The second piece to your point, OM1, which is the project I alluded to earlier, which is using AI in the Penn medical system as an example. Interestingly, what we found was because you're using a diagnostic algorithm to screen all of their patients and finding ones that you suspect of Fabry, I've used this a little colloquially, but the callback rate when some random doctor calls you and says, "Hey, you might have a genetic test, y ou want to come in and figure that out," if you weren't already talking to that doctor, has been lower than we'd hoped. We are working more on both widening the net, so contacting more patients, but also figuring out how to make that a less invasive process. I'm sure we'll make traction there.
We did, though, look at the demographics. Just to say, "Hey, should there be undiagnosed Pompe patients in the Penn medical system?" Found again, 90% of them were white, and the majority of them were in higher socioeconomic deciles. You know they're there. We just need to maybe figure out smarter ways to get in touch with them.
Got it. Maybe one last question on Galafold before we switch over to Pompe. Sanofi is going to report phase III data for their SRT, probably in early 2026. Can you just help us frame that readout for Amicus and Galafold specifically and why you may not be worried?
Yeah. You have to be very careful. It's somebody else's product. Don't want to comment too much. What I will say, though, it's a very different mechanism. It's an oral product, but it's a very different mechanism. SRT stands for substrate reduction therapy, which actually doesn't reduce existing substrate. It works by interrupting a biological pathway of synthesizing that substrate or making that substrate. It actually prevents the creation of new substrate. What does that mean? That means if you're probably an existing Fabry patient, if you haven't been treated before, you need to take something first to debulk or to chew up the existing substrate. Today, that option is ERT or Galafold. ERT is an infused product. We're an oral product.
From our market research, as we think about how that could work, if it does indeed get approved, of course, we'll wait to see what the data says. If you're already on a product like Galafold, which is oral, and you have a chance to switch to another product that's oral, I don't see a world where the data or the product profile would support that. We have seen in the case of Galafold, if you're on an ERT, you might want to switch to an oral product. There might be some utility to that. From our perspective, switching from a chaperone oral product to a substrate reduction therapy, I think that's a low likelihood outcome.
Sure. Perfect. POMOP. So it's been on the market for several years. There's been some twists and turns along the way, but certainly the outlook this year, at least going to 2026, looks a lot better. Can you just remind us of the progress there and just how you're thinking about 2026?
Yeah. I think on an absolute basis, if you take a step back, I think this product has done really well. We're going to generate over $100 million in sales this year, 50%-65% growth, great opportunity to continue to grow, IP well into the end of the next decade. We feel really good about the direction of travel. That being said, and in particular, we kind of had two regions. We have the European region with some ins and outs there, and then we have the U.S. region. What I would say, and you and I have talked about this, I've talked to a lot of investors about this, we didn't fully appreciate the sequencing of the launch in the U.S. in particular, where you had a second-generation product by our competitor come out while the FDA, unfortunately, was delayed in their inspection. Our launch date was delayed.
We did not fully appreciate the sort of stickiness of that first switch product because it was the first time, frankly, patients and physicians had a choice. What we have clearly heard, and actually a number of you and your peers have done calls with physicians that I think bear this out, is that once a patient switches, what we are hearing very definitively is that they want about two years before they consider switching again. For us now, though, we are getting into a point where last year only about 1/3 of the Pompe patients who had switched to the second product had been on for two years. Now it is more like 2/3 of those patients. The patients that are eligible, we think, to switch to Pombiliti Opfolda is much larger.
I think that's bearing out in our quarterly numbers where we've shared that in the first nine months of this year, we've doubled the numbers of patients who've switched from Nexviazyme, the second-generation product, than we had at the end of last year. You're already increasing the rate by definition . The other piece is we've seen an acceleration, and we've said that the U.S., as an example, saw the two best quarters. Second quarter was the largest ever commercial quarter. Now, third quarter was the largest ever commercial quarter, so you can see momentum building. We feel like we have a really good handle, and we're seeing the kinds of acceleration we want to see in the United States. Likewise, outside the U.S., we've continued to see great progress.
We have some real bright spots in the U.K. where we're now the leading market share product from our estimation. We've seen some real-world evidence actually come out of that cohort, which is very supportive of the product in the real-world setting. We see the Netherlands, which with a significant cohort of patients that will now switch by mandate 70% of the patients at that one site, which is about 70 patients. We are making great progress in a number of our other European launches. It was a little bit of a tale of two cities, but we do feel like now, number one, we're growing at a robust rate, which we're demonstrating with execution. Number two, we have some predictability on what that's going to look like.
Okay. Can I ask a little bit more detail around some of your comments on the U.S. and the new patient switches? Part of your hypothesis was that, okay, maybe patients have to wait two years before switching or three years before switching. In the U.S. and some of the momentum you've been seeing in Q2 and Q3 and some of those switches, has that hypothesis, is that hypothesis consistent with what you are seeing in real time?
Yeah, it exactly is. I think there are two camps there. One is you have what we call kind of hand raisers, so patients that come forward and say, "Hey, look, I feel like I've tried this long enough and I want to switch." The other thing is that you have physicians who are saying, "Yeah, look, you've been on for two years or maybe you've been on for three years. I'm not as happy with your progress and let's switch." We do generally know the dynamics. What we know is that they've been on, majority of them have been on for two to three years. We know that the vast majority are switching from Nexviazyme versus Lumizyme. Those things corroborate.
The other color that we've given is we know we have more prescribers in the U.S., so we're broadening the prescription base. We also know that there are more people who have repeat prescriptions. We're seeing some really important KOLs who had switched all of their patients to Nexviazyme originally upon its launch are now starting to prescribe for the first time as well. There's kind of anecdotal stuff. There are specific facts and figures. There are KPIs, but all of that points to that sort of dynamic playing out.
Okay. It sounds like, at least in the U.S., things are accelerating. They're trending in the right direction. They're going to likely exit the year with momentum into 2026. The reason I bring that up is because I feel like the overall feedback from investors over the last 6-12 months is that consensus in 2026 for POMOP was too high. Now it's come down to, I think, $175. It seems a lot more doable, I suppose, as you think about 2026. W ithout giving guidance or anything like that, of course, just talk about the confidence that you have in the exit rate from Q4 into 2026.
Right. I will be very careful not to give forward-looking guidance right now. You said it and I did not, but I think your logic holds true as it relates to the direction of travel. We have seen momentum. We were pretty specific about the exit on Q4, which we said in our Q3 call. Q4 will be a growth quarter for us again for Pompe, Opfolda, and Galafold for that matter. I actually feel like consensus is right in line with where we think the quarter is going to end up. That should give you kind of a direction of travel, which then the trend line suggests that next year looks reasonable. Of course, we need to see what this quarter looks like, what the real exit rate is, and we will be more specific. I think the community understands where we're headed, and we are executing against that in a very positive way.
Okay. Perfect. If we can shift over to the pipeline, the FSGS program that you enlicense. Tell us about the rationale behind doing that deal and the timing of that deal and just how to think about some of the regulatory updates over the next few quarters.
Yeah. Thank you to you and your team for doing research there. I do not think people are really focused on that right now in a broad sense. Investors, I think they have been more focused on, can we execute? We have had two nice quarters of that. We are excited to start to hear more emphasis and more folks digging in on the DMX-200 program. DMX-200 is an asset for FSGS, which is a rare and often fatal kidney disease. It is a devastating disease, one that we did not know very well before. However, remember, Fabry has a heavy kidney component to it. We are already in front of a lot of the cardiologists. We know a lot of the endpoints actually, proteinuria and glomerular filtration rate, are very relevant endpoints for Fabry disease as well.
Rare kidney was in our list of synergistic rare diseases that we were looking at. We also wanted something that was relatively de-risked and late stage and something that we could have more back-end success-based economics because we do not have as much firepower as some other folks do. Just so happens, our Chief Business Officer is in the room here, I have been giving him credit for this all day, Sebastian. We happened upon this company who had a, like many U.S. companies, would never give up the U.S., but these guys see themselves as a development company, super smart company. They had already out-licensed Europe and then Japan. They were looking to license their U.S. business to an existing established rare disease company. I think we fit perfectly within that. It fits strategically from an economic perspective. The bet we placed was great.
We don't pay anything until we flip over the phase three data card. That all worked really well. We think it's a billion-dollar-plus opportunity. Great opportunity here in the United States. From a regulatory perspective, leading into the license of DMX-200 this year, Dimerix, who is the originator company, had had a regulatory interaction where the FDA, based on the Parasol data, which is that KOL-driven nephrology cohort with some industry and some regulatory involvement as well, looked at and helped determine that proteinuria was an appropriate endpoint that reasonably predicted clinical outcomes. The FDA, in a meeting with Dimerix, agreed that proteinuria could serve as the primary endpoint of the ongoing phase III study. That's what we had coming in. That was great news for us. We really liked that outcome.
The study right now has, and I should say specifically, they said two-year proteinuria data could serve as the basis of approval with support of GFR data. The handful of regulatory things in our future are this. First, we have a peer in the space, Travere, who, of course, is going in front of the FDA in January for their PDUFA date for a totally different mechanism, but for FSGS. That will be really interesting to see what the FDA shares with them and their outcomes. We're eagerly watching that. Likewise, we're planning to go in front of the FDA sometime in the first half to talk to them about what does the full two-year endpoint look like. It's proteinuria, but is it changed from baseline or is it responder analysis, etc.? We'll have that conversation.
They did say that they are open. The FDA said they were open to an accelerated path. I'm going to be very careful to set the expectations. The baseline for us is the straightforward approval path, which is great. We will explore that avenue and we will come out and share with investors and analysts what we believe that looks like. Either way, I think you have a nice set of milestones culminating in some sort of interim analysis next year, which will make sure that we're well-powered for whatever endpoint that we're looking at.
Okay. In your base case of two-year proteinuria, when do you think the top line would be then?
We are on track for enrollment by the end of this year. I think the last estimate was we were over 90%. That was a few weeks ago. That is moving really well. What does that mean? Plus two years on the primary. You are probably talking realistically beginning of 2028.
Okay. If there were some sort of alignment on one-year proteinuria, and by the way, the confirmatory trial or the confirmatory endpoint has to be.
At two years on.
At two years, something that you would have to agree with as well.
Exactly. Yeah.
That's good.
You're looking at maybe a year upside there, a year, year and a half upside.
Okay . Perfect. What gave you the conviction from a data perspective to think that, "Oh, this is super interesting"?
Yeah. Of course, we did diligence. They had run a number of phase II studies that showed, we thought, really impressive data. We shared that in diligence, we saw patient-level data there. We haven't disclosed what that looks like, but that gave us further confidence as part of our diligence. We loved the FDA's feedback on proteinuria. We thought that was very compelling. It really did, because originally I think it was a GFR study, but really we thought de-risked the outcome on the primary measure of proteinuria. Of course, we looked at safety and preclinical and all those other things. We thought very highly of their scientists and their team. It's a small company, but we think they do great work and they've done great work.
Of course, you also have the fact that two other parties licensed two other regions. They went through a similar diligence analysis. That gives you some conviction that multiple independent parties have done diligence, come to the same conclusion that it's highly likely to succeed. The economics were such that we could afford from our own balance sheet to place the bet. Now we get to turn over the card. If it's successful, everybody wins. If it's not, then it was something we did without having to go back to investors and ask for help.
Okay. Maybe in the last few seconds, just talk about your cash position and just how you're thinking about BD and this Dimerix deal is something that we should be thinking about going forward.
Yeah. C ash, we had over $260 million, a little bit on the balance sheet. We actually were GAAP profitable. So we made a little bit of money, which is good. We are committed to staying on that road to profitability, full-year profitability. Look out for more commentary there. From a BD perspective, yeah, I think the emphasis is on late-stage de-risked assets where there's some value asymmetry. It could be a regional deal, etc. It could be a commercial deal or anything in the Fabry, Pompe space that follows a similar kind of trajectory. Our intent is to continue the financial discipline that we've had over the last three years and really more than anything focus on revenue growth.
Perfect. Thank you so much, Bradley. Looking forward to a great 2026.
I am too.
Thank you.
Thanks.