Amicus Therapeutics, Inc. (FOLD) Earnings Call Transcript & Summary

Hi. Welcome, everyone, to the JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, [ Priyanka Grover ], [ Malcolm Kuno ], [ Rati Pinhe ]. Our next presenting company is Amicus Therapeutics. And presenting on behalf of the company, we have CEO, Bradley Campbell. Brad?

Thank you. So first of all, thanks very much to JPMorgan for inviting us here. It's always great to see folks in person. Great way to kick off the year. Thanks a lot to Anupam. All the hard work you guys have done over the years, really appreciate it. Thanks to the team as well. So I will be making certain forward-looking statements today, so I'll refer you to our safe harbor statement. I'll let you read that in detail at your leisure. Just as a reminder, Amicus Therapeutics, we are a company dedicated to developing transformative medicines for people living with rare diseases and our vision is to become one of the leading rare disease companies in the biotech space. And I think this year, in particular, in the backdrop of what is -- clearly continues to be a tumultuous market, I think we represent a fairly unique story in biotech. So what do we mean by that? So first and foremost, we delivered over $0.5 billion in global revenue from 2 commercial products. That was a 32% annual growth rate at constant exchange rates. Of course, we have our core product, Galafold, which is the first small molecule chaperone for the treatment of Fabry disease. On top of significant growth last year, we look to do 10% to 15% and growth year-on-year in 2025, again at constant exchange rates. We also launched our first 2 component therapy for Pompe disease, Pombiliti + Opfolda. And that product, we look to do 65% to 85% in growth at constant exchange rates in 2025. All that helped us get to full year non-GAAP profitability last year. It's on the back of a very leverageable global commercial and clinical infrastructure. And for the first time, we are stating that we project to surpass $1 billion in global revenue by the year 2028. So I'm proud to say that we delivered on all of our key strategic priorities in 2024. Of course, I already mentioned the great growth for Galafold. We delivered 18% growth in the end year-on-year in 2024. Had multiple successful Pombiliti + Opfolda launches around the world, and we'll talk a lot about the exciting launches we have coming up and how we see that product continue to grow. We continue to advance our scientific and medical leadership in Pompe and Fabry. And in particular, we will look to expand labels in Pompe disease in the years to come. And again, that was on the back of achieving non-GAAP profitability last year. And let me just double-click on a few things that we think are worth highlighting for folks. First and foremost, despite the fact this is a product that's been in the market for 7 years now, Galafold grew at the largest rate of new patient demand since the first years of launch. So really robust growth there. Really exciting news on the IP front last year. We settled with Teva so that they are not allowed to enter the market until 2037 in the United States. So that provides a significant runway to continue to grow that product, and I'll talk more about the implications of that long-term runway. Galafold now is the fastest-growing treatment in the Fabry disease space. Again, I talked about the successful launch of Pombiliti + Opfolda, we'll talk a lot more about that in a few slides. We're getting great early feedback from physicians and patients as they continue to build their body of evidence using that treatment. And again, strong financial discipline, in particular, to judicious use of our expenses and our OpEx, leading that way to that transforming the company to a profitable company going forward. So what do we hope to do this year? Again, we'll do 17% to 24% in combined revenue between the 2 products. That will be double-digit revenue growth for Galafold again at 10% to 15%; significant growth for Pombiliti + Opfolda, 65% to 85%; continue to advance our studies to broaden our labels in Pompe, in particular. And again, we hope to turn GAAP net income positive in the second half of this year. So let's dive a little bit into the Galafold franchise. Just as a reminder, Fabry disease, a serious, progressive genetic disease that's caused by a deficiency in the lysosomal enzyme, alpha-galactosidase alpha. It leads to significant accumulation of a substrate GL-3, which then leads to progressive organ damage, primarily kidney, heart, CNS. Patients leave with significant pain, challenges with headaches, GI distress, et cetera. If left untreated Fabry disease typically is fatal. I'll talk a lot more about the prevalence and epidemiology. But for a minute, let's just look at the Fabry market and its evolution over time. When we launch this product earlier this decade -- excuse me, last decade, it was a little over $1 billion in sales. By 2017, it had passed $0.25 billion sales. By 2024, it was over $2 billion in sales and it's projected to grow to $3 billion in sales by the end of the year. A few important points that I'll highlight on the right-hand side of this slide. So first and foremost, we believe that by the time this market gets to $3 billion, well over 1/3 of patients will have an amenable mutation to the chaperone, so over $1 billion of revenue opportunity in the market. And importantly, again, Galafold continues to be the largest growing product within the Fabry treatment space today. So what does that look like from a patient perspective? And I think this tells an even more compelling story. Again, when we launched this medicine back in 2016, we had done market research leading into the launch that showed us that about 10,000 people around the world were diagnosed with Fabry disease. About 5,000 of them were treated, and that represented that $1 billion market. It's about a $200,000 on average therapy per year around the world. And there were about 5,000 diagnosed but untreated patients. So significant market both treated and untreated patients. Fast forward to 2024, the treated market alone has more than doubled. There are now 12,000 patients around the world living with Fabry disease who are on one form of treatment. But there are 6,000 patients who are now diagnosed untreated. So the treated market has more than doubled and the diagnosed untreated market is actually larger than it was 10 years ago. So significant underlying growth primarily driven by diagnosis, and I'm going to come back to that in a minute. So how has Galafold performed within that overall market. So as I mentioned, we've now delivered over $458 million in global sales in 2024. So significant revenue last year alone, expect to grow 10% to 15%. That represents a 60% market share of treated amenable patients. That's important because despite the fact that a lot of our growth is going to come from diagnosed untreated patients or naive patients, and we're going to explore that in more detail, we still have a significant amount of patients still to switch over to Galafold. The total number of patients at the end of last year was roughly 2,730 patients, and I'll talk more about the split between switch and naive patients in a minute. But as I said, we think 35% to 50% of the patients living with Fabry today have amendable mutation. And we're now present in over 40 countries around the world. So this shows a nice picture of how we've grown over time. You can see, in particular, I think, a resurgence in growth coming out of COVID. But what's really driven that growth. So first and foremost, as I said, there's a mix of 60% switch, 40% naive patients -- excuse me, other way around, 60% naive, 40% switch patients. So part of our job is to continue to drive penetration into both of those patients. There will be a little bit of market expansion. There are some countries, Turkey is probably the largest one, remaining where we have approval, but not yet reimbursement. We're relatively newly reimbursed in some of the Latin American countries, Southeast Asia, there's some opportunity in the Gulf states as well. So there's some opportunity to continue to expand from a geographic perspective. We will continue to drive over 90% adherence and compliance to this medicine, pretty unique for an oral small molecule, and we've seen that since the beginning of launch. So when patients start on Galafold, they tend to stay on Galafold. And one thing, for those of you who are into modeling, you'll look in the back in the appendix of our posted slides, and you'll see a nice layout of the quarter-on-quarter distribution of sales, we continue to expect nonlinear distribution of sales, and I would encourage you to take a look at those numbers as you think about how to model out the rest of this year. But one question we're really starting to ask ourselves, in particular because we've demonstrated that Galafold is standard of care for people living with amenable patients is how big could this population really be? How big is the unmet need remaining in the Fabry space today? And I'll point you to the slide, so just really quickly to orient you to the way it's laid out. That center circle, the burgundy color is the treated patients. Again, that's the 12,000 patients today. There's another 6,000, that green band of diagnosed untreated. But if you look at the published literature, if you look at newborn screening studies, high-risk population studies, it's reported over and over again that Fabry disease is likely 10x more prevalent than what is diagnosed today. There could be 100,000 Fabry patients around the world today, living with Fabry, who have an incorrect diagnosis. Think of how much good a small molecule like Galafold could do for those patients. And that's part of the journey we're on. And what are we doing to help solve that issue? Two different studies highlighted here on this slide. The first is on the left-hand side of the slide, a company called OM1, which is a machine learning AI diagnostic company helped us develop a Fabry footprint, looking at medical records to help try to decide where the undiagnosed Fabry patients live with a machine learning algorithm. We've now applied that to the Penn Medicine system and screened over 0.5 million -- or excuse me, all-comers patient records and found 100 people who have a high suspicion of having undiagnosed Fabry. Our physician collaborator there is now following up with those patients. And if you just think for a minute, let's just say 20% of those people actually had Fabry disease. 20 patients, relatively large number for a rare disease. An important part of Fabry is that typically, when you find 1 diagnosed family member, 3 to 5 additional family members actually have the disease because it's an X-linked disease. Suddenly, that 20 could become 60 or even 100 patients. Let's say half of them came on to Galafold over the course of this year. That in and of itself would almost equal the naive patient growth in the United States for this year. So this one pilot study could find as many patients as we were able to put on drug in the United States in 1 year. We're already deployed to be able to put that against multiple other health care systems. And then you can imagine how much good you could do if you could just offer patients an appropriate diagnosis and then let them choose what therapy they want to go on. The NHS pilot program was kind of the other side of that coin. So instead of looking at it from an underdiagnosis perspective, we ask ourselves in the NHS system, which, of course, is a closed system, it's a single payer system. We asked ourselves what were the demographics of the Fabry patients who are diagnosed. And this is -- I guess it shouldn't surprise us anymore these days, but if you want to think about a health inequity, 90% of the Fabry patients diagnosed in the U.K. today are white. And 85% of them came from the highest socioeconomic deciles. Fabry disease is not a rich white person's disease, but that tells you very clearly in a system with free health care, like the United Kingdom, super well meaning, highly, highly educated physicians who know Fabry really well, that's the proportion of inequity that's going on in that country. You can imagine applying the same kind of machine learning algorithms to go find the real diagnosed patients or the patients that should be diagnosed in that country. So 2, I think, very important ways of thinking about the disease. And so what does that mean for us, for our business? If you think about all that unmet need that's out there, if you think about how well we've established Galafold as standard of care, if you think about now 12 years of IP exclusivity, 12 more years from today, if you think about the market growth that I talked about, to me, this says we can get to well past $1 billion in product sales for Galafold by the end of its life cycle. So really exciting, I think, evolution of this franchise and very excited to see some of the outcomes of those initiatives that I talked about. So switching gears, Pombiliti + Opfolda. Again, taking a step back, looking at Pompe disease, also a serious progressive disease, also a lysosomal storage disorder, in this case, caused by deficiency in the lysosomal enzyme acid alpha-glucosidase. Pompe disease typically leads to significant deterioration in the smooth and skeletal muscles. If left untreated, patients typically end up in a wheelchair, on a ventilator, feeding through a G tube or J tube and typically pass away from Pompe if they're not treated. So a similarly serious progressive disease. Kind of a similar story here as well. Significant growth over time in the Pompe market, if you look at a revenue perspective in 2017, a little over $800 million in revenue. Fast forward to 2024, about $5 billion in global revenue, and then looking at the end of the decade, $2 billion in revenue. In the case of Pompe disease, our label is for inside the United States, patients on enzyme replacement therapy, who can switch to Pombiliti + Opfolda upfold adults with LPD and outside the United States, all patients who are adult LPD patients. So really eligible for the vast majority of the market that I showed you there. Pombiliti + Opfolda is a 2-component therapy. It's a next-generation enzyme replacement therapy combined with a small molecule enzyme stabilizer called Opfolda. It's the only -- we're the only company to have studied the vast majority of our Phase III patients who were switched patients or experienced patients. They were on standard of care when they came in the study. And we're the only product to have shown in a controlled part of the study, a significant benefit on both 6-minute walk and forced vital capacity when patients switch from standard of care. So a very differentiated clinical benefit. In our first full year of launch, we delivered $70.3 million in global sales, so really strong start there off of a base of 11 and change in 2023. One of the questions we've gotten quite a bit is what's the geographic mix of revenue. If you look at the average over the course of last year, it was about 57% outside of the U.S., 43% inside the U.S. that's about the global average for all Pompe sales today. If you look at our run rate coming out of the fourth quarter, it was about 50-50. That number will move around a little bit over the course of the year. The U.S. is the biggest market with the highest price point, but we're launching in a bunch of countries, which I'm going to talk about in a minute here. So eventually, that will net out probably around that kind of 56%, 44% split. Importantly, we're very keen on tracking the number of patients we're bringing on to drug. A couple of numbers to orient you to here. First and foremost, at the end of this year -- last year, sorry, 2024, we had 220 patients who were treated or scheduled for treatment, 209 of them actually had been treated by the end of the year. And importantly, in Q4, so Q4 discretely, we added 25 new patients who were scheduled to be treated or treated on drug. All the clinical trial patients have been converted at this point. And importantly, too, one of the markers we've looked at over the course of the year was bringing down the time to insurance. We've now optimized that to less than 30 days, and that's where we had hoped to get to for steady state for launch. And another point that we've made is that we pull proportionately from the market share of the competitive products. So in the markets where Nexviazyme is the largest share like the U.S., most of our switch patients come from there. In Europe, it tends to be more Lumizyme and naive patients. So just a couple of more pieces to go through with Pompe and then I'll wrap up and we can get into Q&A. So geographic expansion is going to be a big part of the story for 2025. We have 10 markets that we're hoping to get reimbursement in over the course of the year and launch. We already have 4 of them that we've locked in at the end of last year and the first part of this year. Those patients will come on to commercial drug over the first part of the year. And then there are 6 more markets we hope to get reimbursement and launch in. That total group represents 600 to 650 new late-onset patients who could be eligible for it to come on Pombiliti + Opfolda. So a huge new cadence of launch that will contribute to the growth over the course of the year. And then also 3 new approvals we're seeking, Australia, Canada, Japan, and Japan is one of the markets we can get to reimbursement in this year. As I mentioned earlier, though, we are looking to expand our label in Pompe, in particular, into pediatric patients. It's a smaller portion of the opportunity. But I think over time, you'll see treatment move earlier and earlier in the disease course. These are progressive diseases. And as we find younger patients through newborn screening and other measures, I think it will be important to have Pombiliti + Opfolda as an offer for a treatment for those patients. We have 2 ongoing clinical studies, our ZIP study, which is our infantile onset Pompe disease study, our Rosella study, which is our late onset pediatric Pompe disease study. Both of those, we think, could lead to label expansion over the next couple of years. And then we do have an ongoing registry where I think we'll have significant and interesting data over the course of the years. And speaking of data, in addition to continuing to look more closely and more deeply in our Phase III in extension studies, which continues to be an important part of the conversation we have with physicians, I think a really important opportunity this year is to start to look at real-world evidence. So you're starting to see a number of case studies that are presented to physicians at congresses over time, looking at patients in their hands that have switched to Pombiliti + Opfolda. I think you'll see more and more of that looking at Nexviazyme in patients who switch to Pombiliti + Opfolda. And then importantly, we're starting to see large enough cohorts of patients where physicians are actually comparing among therapies, and we hope to able to see some of those publications come out over time as well. So I think that real world evidence supporting the use of this product, this therapy will be really important going forward. Really quick on the growth drivers for Pombiliti + Opfolda to get to that 65% to 85% guidance range, of course, getting new patients on drug. One important part of that, that I haven't talked about is the proportion of Nexviazyme patients who are coming to that kind of 2-year switch point, I think that Anupam might ask me a question there, so I'll save fire on my answer to that question. But that will be an important segment for us going forward. Increasing the breadth and depth of prescribing physicians will also be important to continue to see that expand. I mentioned the launch countries, the real-world evidence. One other piece that we've seen, and I think we'll continue to see is, again, just like Galafold, well over 90% compliance adherence to this product. So really when patients come on Pombiliti + Opfolda, they tend to stay on it. And remember, we've had patients now for upwards of 10 years from our Phase II studies that are still on therapy. So a really important part of the stickiness of those programs. So again, just to wrap up, I really do believe that we're a unique story in biotech today. We talked about each of these key drivers of value. And I think at the end of the day, the more patients' lives that we can touch with an Amicus medicine, the more sales we can drive. The more sales we can drive, the more we can put back into research, building the business over time and create value for patients and for shareholders. With that, I thank you very much, and I will turn it over to Anupam for Q&A and ask some of the team to come up and join us.

Do you want to just introduce who's up here?

Sure. We have Sebastian Martel, who is our Chief Business Officer; we have Dr. Jeff Castelli, who's our Chief Development Officer; and we have Simon Harford, who is our Chief Financial Officer.

I just want to remind folks that there are kind of 3 ways to ask a question, right? So you can e-mail me. You can do the old school way, raise your hand, I'll call on you or you can send the question to the portal. So I'll start out. Brad, you gave today like a new update on the $1 billion plus of revenues expected by 2028. That was a new data point. Like how do you think about the components of that in terms of Galafold versus Pombiliti + Opfolda?

Yes. Great question. So yes, we are committing now to surpassing $1 billion in global sales by 2028. If you just look at the growth rates of those 2 products, we still think that Galafold will be the majority, the slight majority of sales at that point. I do think over the next 5 or 7 years, you could see Pompe pass Galafold or catch up to Galafold in terms of proportionate global sales. But at that point, it should still be slightly more Galafold than Pombiliti + Opfolda.

Got it. Maybe a couple of questions on Pombiliti + Opfolda. Can you speak to a little bit about the time periods of assessment for considering a switch from Nexviazyme to Pombiliti + Opfolda particularly here in the U.S., right? And then what portion of patients in the U.S. or EU have reached this type of time point?

Sure. Yes, I'll let Dr. Castelli take that question, if you don't mind.

Yes. So patients are monitored typically by their Pompe treating physician every 6 months or so -- or every 6 months, so twice a year. What we've seen when -- there's even some treatment guidance that suggest you should wait at least a year after a patient switches treatments in Pompe to assess how that treatment is -- how the patients doing. What we're seeing in the U.S. is usually after initiating Nexviazyme, either a naive patient or a switch patient, we see that they follow those patients for about 1.5 years before they would start to look to transition to a different treatment, mostly looking to see as a patient progressing or not. And then what we know in the U.S. last year, as we entered the year, it was only about 10% of patients in the U.S. had been on Nexviazyme 2 years. As we entered this year, 2025, that's more than 40% of U.S. Pompe patients on treatment have been on Nexviazyme for more than 2 years. So we think there's a much bigger pool of patients that are in that range where they will start to look for other treatment options if they're not doing well.

And I think, Anupam, that phenomenon probably also exists in Europe. Although as I mentioned earlier, because the vast majority of patients are still on Lumizyme, we tend to take patients from Lumizyme at a higher rate than Nexviazyme. The only other thing I would add there is one of the parts about 2 new products within a short time period in the context of a legacy product that's been on the market for well more than a decade is physicians really haven't had to ask themselves before like how are my patients doing? When should I think about switching? So a big part of the work that Jeff and his team are doing and, frankly, the whole Pompe community is going through is really saying at a more, I would say, granular level, what are the things that we should be following when we want to think about making a switch. I think over time, based on the data we've seen, based on the experience we've seen, I think we'd want to see physicians looking to switch patients sooner. But I think part of it is educating them on exactly what to look for.

Questions from the audience? Brad, you talked a little bit about initiatives for improving diagnosis in Fabry. You talked about the AI initiatives. Can you ask -- can you maybe give us a sense of when we might see some pull-through from some of these initiatives, number one. Number two, are there any other initiatives ongoing globally that we should be aware of?

Yes. It's funny, we've always known that there was an opportunity to look for more patients. I think part of it is when you're the newcomer, finding new patients oftentimes ends up them going on a different therapy. And so part of it is establishing Galafold as what we think is the standard of care for patients with amenable mutations. So we haven't really invested as much in those programs. Clearly, the OM1 program that we talked about, I think, Jeff, we should start to see -- hopefully, see some results from that in the first half of this year. So that could be really exciting. And as I said, we're kind of poised to then deploy that into some other systems in the United States at any rate. The NHS product program is ongoing as well. So that's over the course of the year. A couple of other places where we've been successful, though, we talked about newborn screening. You would think now that that's kind of standard of care. Genzyme has been talking about it forever, Takeda, I'm sure it does as well. Now Sanofi, sorry. But the reality is, in a number of countries, they kind of moved away from that. So we've used that very successfully in a number of countries in Europe. And then we have looked over time, we've talked a little bit about MS. There seems to be some overlap in undiagnosed Fabry disease within the MS population, idiopathic pain, cardiovascular. So I think there are some other places, but part of it was really sort of the advent of low-cost genetic testing and now some of these Fabry algorithms that I think will let us accelerate that process. So to me, this really could be a meaningful change this year, next year and the foreseeable future.

And how are you thinking about sort of for Galafold core market growth versus, say, some of the emerging market growth?

Yes. Sebastian, maybe hit where we saw the most growth and where there are some still pockets of geographic expansion?