Hello, good afternoon, everyone. I'm Ellie Merle, one of the biotech analysts here at UBS. Thank you so much for joining us here at the UBS Biopharma Conference in Miami. Very happy to have Amicus Therapeutics here with us today for a fireside chat. Joining us from Amicus is Jeff Castelli, Chief Development Officer. Thanks so much for making the trip to Miami. Maybe just to kick it off, you guys reported earnings yesterday, including first sales in Pompe. So, tell us a little bit about that.
Yeah. Thank you, Ellie. And first, thanks to the UBS team for having us. We're happy to be here. Yeah, we just had third quarter earnings yesterday. Very excited to give an update on the launch of Pombiliti Opfolda in Pompe. As a reminder, we just recently received approval in July in Europe, in August in the U.K., and here at the end of September in the U.S. and are really excited by early days of launch. We said that we're well on track to convert all of our clinical trial access patients in those three lead countries by the end of this year. We said we had about 60 patients already currently transitioned over. We've been seeing new patients come on, both from the existing products, Lumizyme, as well as from Nexviazyme, and we've seen naive patients in Europe.
Really exciting early days. Happy to talk more about that. Also, lots to talk about in terms of Galafold and our drive toward profitability. So,-
Mm-hmm.
Well, ask away, Ellie.
All right, great. Where do you want to start?
Maybe just a quick overview?
Sure.
Okay. So, you know, first, Amicus is... Our mission at Amicus is to develop transformative medicines for people living with rare diseases. Really, three key value drivers today we see: the first is our product, Galafold, which is for Fabry disease in people with amenable mutations. We actually just reported yesterday, the first time, $101 million in third quarter revenue. It's the first time we've gone over $100 million in a given quarter, so, really great runway on that product. We actually were able to raise guidance based on that for the full year to 16%-18%. It was a 19% growth in the quarter over last year. And really excited about the runway there and what we're seeing, and happy to talk more about Galafold.
And we think ultimately with the runway, that that has a potential to reach up to $1 billion in market potential. In terms of, we've already started to talk about Pombiliti and Opfolda and how the launch is doing there. Really excited there as well with how the launch is, what we know about that market, that that also is up to a $1 billion potential. And then in terms of our financial strength, we finished the quarter at $280 million.
Probably more importantly, we actually reiterated that we're on track for fourth quarter non-GAAP profitability, where we're really looking to leverage everything we've built with Galafold and really now add to the top line with acceleration with the launch of the Pompe product, continue to manage OpEx, and really start to go down the path towards cash flow positivity, funding our own operations. So, exciting time for the company, really transforming from that sort of, you know, R&D, needing to have capital, to actually now turning the corner to profitability and funding things moving forward.
Mm-hmm. Yeah, exciting. Well, maybe just on profitability. To remain profitable going forward, particularly thinking on the OpEx side, what's baked in from a Pompe perspective? And do you expect OpEx to remain completely flat? Any growth, any, you know, decreases in OpEx? How should we think about this as a business going forward?
Yeah. So, really moving forward, we expect to see OpEx remain pretty flat, maybe a little bit of growth here and there. And what we're really doing is continuing to fund everything with Galafold and Pombiliti and Opfolda in terms of additional studies, extension studies, investing in manufacturing to make sure that we're really solid there. So, there's still amount of R&D investment there. And then in terms of, you know, looking at the pipeline, we continue to look at the pipeline as investing what we're able to on that drive towards profitability. So, we're really optimizing our leads there. We have early Fabry and Pompe gene therapies. We have a next-gen chaperone program, and we're really trying to optimize those products before really starting to invest fully to bring them towards the clinic.
But we will do that over these next coming months and years as we are able to fund those pipeline programs. But as you can hear from what I'm saying, we are really, you know, really focused on growing top line, managing expenses, turning towards profitability.
Mm-hmm. Absolutely. And Pompe and Pombiliti Opfolda will definitely be a key part of that, right. If your expenses are flat, then that essentially will go down to profits.
Yeah, exactly.
So, let's talk about the launch.
Yeah.
Okay, maybe before I go into the specifics from the quarter, just high-level, how should we think about the size of the Pompe market opportunity as a whole?
Mm-hmm.
Then we can talk about competition from there.
Yeah. So, just quick background, Pompe, you know, it's a lysosomal storage disease, leads to the accumulation of glycogen in the lysosome, and that causes muscular dystrophy. Patients generally have really severe muscle weakness over time. There's about 4,000 patients today diagnosed with Pompe. We know from newborn screening studies, which now most states in the U.S. do newborn screening for Pompe, there's more people living today with Pompe that are not diagnosed than actually the 4,000 diagnosed. And we continue to see a lot of additional patients being diagnosed. So, we see the current $1.2 billion market today, over the next five years, growing to about $1.8-$1.9 billion in that time frame. And longer term, we see, as I mentioned, the opportunity for Pombiliti + Opfolda.
We believe that we can obtain a dominant share of that market and ultimately work towards a $1 billion opportunity.
Mm-hmm. And maybe with respect to competition in the Pompe space, how do you think that you're differentiated from Nexviazyme?
Yeah, so, really fundamentally, the mechanism of action we believe for Pombiliti Opfolda is very differentiated. We knew that there was a deficiency with the first-generation enzyme replacement therapy, that it did not have optimal uptake into muscles. So, we really worked on making sure that Pombiliti had the right glycans for uptake into muscle. Importantly, we did that in a way that maintained the ability for that enzyme to be processed to the more active form after uptake, which we believe is differentiated and very important in terms of getting optimal enzyme activity. We also add in the stabilizer as well, so in terms of the mechanism of action, that is differentiated. That is a key part of what we are out there and trying to educate physicians about. We also have a very differentiated data set.
We are the only program to study the real-world population of experienced patients and naive patients. And, you know, in terms of going out there, it's really the mechanism, the data set we have, and more and more some of the long-term data that we're seeing from our ongoing extension studies and the durability that we're seeing.
Mm-hmm. I guess from a marketing perspective, how do you ensure that physicians are aware of this difference?
Yeah, well, it's really our marketing team going out and engaging with those centers. So, you know, we had 75 centers worldwide that had participated in trials and access programs. Within the first 30 days of launch in each country, our team has gone out and engaged all of the core centers in Pompe, in those countries. And then obviously there's continued medical education at conferences, advisory boards, and we continue to generate evidence. So, it's sort of a field engagement, continue to engage and tell the story of the data at conferences and continue to add to that data with our trials.
Mm-hmm, absolutely. And let's speak a little bit about the label. So, at least in the U.S., you have a bit of a different label than Nexviazyme. I'm maybe starting with the, you know, not improving on ERT and, you know, what that means in terms of the indication statement.
Yeah. So, outside of the U.S., we have a broad label, adults living with Pompe disease or late-onset Pompe disease. In the U.S., the label says it's for patients not improving on their current enzyme replacement therapy. As a step back, as a reminder, our phase 3 study was a superiority study for standard of care, and where we had the most compelling data set there was in the large set of ERT experienced patients. So, as we were in negotiations on the label, we actually advocated to use that not improving language in the label. Pragmatically speaking, if a person or a patient is doing well on their current product, they're probably unlikely or shouldn't switch anyway. And we know that as we've talked to physicians, probably 75% of the people currently in the U.S. are not improving on their current ERT based on those conversations.
So, it's really an opportunity to go in and engage and really talk about the data and how there is a possibility for improvement in those types of patients across different parameters. And in terms of that 75%, 25%, you know, those 25% of patients who might not be, who are improving today and might not be eligible necessarily over time, it's likely that they might become eligible as they continue on treatment and plateau or start to decline. The discussions we've had about how physicians and patients are gonna interpret not improving, it really seems like it's gonna be more of a holistic assessment. You know, it's driven by some of the measures that were in the trials and that they actually do assess when they kind of work up a patient, things like FVC and six-minute walk.
But it's really a lot more of the other parameters about how a patient is doing, how have they been feeling from fatigue? Have they been able to climb upstairs? So, it's really gonna be a conversation between the physician and the patient, kind of in a more holistic assessment of are they actually improving or are they worsening or stable on their ERT today?
Mm-hmm. Makes sense. And, maybe starting with, you know, like in the U.S., so, with 3Q, I mean, you mentioned, I think, like, two-thirds had prescription referral forms already.
Mm-hmm.
You know, tell us a little bit more about that and what you saw with the conversion from the clinical trial patients.
Yeah. So, even a step back beyond the U.S., as a reminder, we had about 200 patients at the time of approvals on trial or access. About 100 of those were in our 3 initial launch countries, the U.S., the U.K., and Germany. And we've said that within, by the end of this year, our goal is to transition 100 of those over from trial or access onto commercial therapy. About 20 of those are in Germany, have been transitioned. 45-ish of those are in the U.K., and we're well on the way towards transitioning most of those. And in the U.S., there's about 40 adults. Had PRFs for most of those patients were still PRFs or planned for the rest.
And actually, once we get the patient referral form or PRF, we do have to kind of interact with each of the different insurance companies and then get to finally getting the patient onto commercial product. So, it's about a 60-day on average process to do that, and that's why we've said we're, we're on track in the US. But from a, you know, revenue perspective, we did just report out $2.8 million in revenue for the quarter. As a reminder, that's really just UK and Germany at this point, and it's partial parts of the quarter for each patient. For the full year, while we're not providing full revenue guidance, we have said we would expect about $10 million in revenue this year from Pombiliti Opfolda, and again, that's really gonna be driven from UK, Europe.
It'll be patients in the U.S. will have transitioned, but they still will have just started to take their commercial infusions. Where we really see the opportunity is from a getting patients onto treatment and the run rate by the end of the year. So, the 100 conversion patients, we continue to now add new patients across all three geographies. We've seen patients switch from Nexviazyme, from Lumizyme. We'd have new naive patients in Europe. So, it's really getting that run rate of patients on by the end of the year to really set us up for a great revenue performance next year.
Mm-hmm. Absolutely. And so, at the very least, with the clinical trial and expanded access patients, I mean, rough math, that's like a run rate of $50 million annually going into next year?
Yeah, $40 million-$50 million, depending on, you know, just for the 100 or so,-
Mm-hmm.
Transition patients. It depends. Price is, you know, higher in the U.S., a little bit lower in Europe. On average, we know, we had said that 100 would translate to $40 million-$50 million run rate.
Mm-hmm. Got it. That's, that's helpful. And maybe, you know, curious about some of these dynamics you're seeing, you know, outside of the, you know, conversion to paying, but with new starts. What's the mix of switches versus, you know, naive, maybe just in Europe, since naive's not in the U.S.?
Yeah, it's still early days, so, we're not getting too granular yet other than saying we're seeing multiple patients in each of the categories. What we are excited by is seeing that we really are seeing switches from both of the other products. It'll be very interesting as we get further into launch to kind of look at sort of the timing of those switches, how long patients had been on treatment before switching. But what we are able to say is really positive engagement so far. What we are hearing from physicians and the patient experience is that things are going well. They're very pleased with the engagement from Amicus.
Interestingly, we've heard a number of cases where patients have proactively reached out to their physicians, and physicians have proactively reached out to our sales reps, which is very atypical to see that we're getting sort of that inbound level of kind of interest coming in.
Mm-hmm. I mean, we started with saying that almost the majority of patients, or vast majority, is like 75% or so, are not improving on their current ERT.
Mm-hmm.
How do we think about the patient motivation? How involved the patients are in their care?
Yeah, I think we've seen over the years in rare diseases, in particular, you know, with availability of medical information online from Dr. Google, but also more importantly for rare disease patients, their interactions with their patient communities. They have a really significant voice in the treatment decision. You know, I just alluded to some of those anecdotal reports-
Mm-hmm.
We're hearing of patients actually proactively advocating. You know, especially here in the U.S., that patient voice and experience and kind of word of mouth, we think is gonna be a big driver, ultimately, of the treatment decision of which treatment they go on to.
Mm-hmm. Do you think it's the patients that are on Nexviazyme that are gonna be the first to switch because they're the ones that are motivated and seeking new treatments? Or is it the patients that are on Lumizyme and, you know, really are waiting for, you know, a new next-generation treatment?
I think, as we've seen in the early days, it's likely to be a mix of both, Ellie. You know, some of those patients we know that had stayed on Lumizyme had been... We'd heard that they had been waiting for Pombiliti and Opfolda approval. You know, we expect that a good number of the patients that switched early on to Nexviazyme were really maybe progressing a lot on their current treatment. So, it'll be interesting to see, now that they've been on for a year or two in the U.S., how those patients are doing. So, it's still early, but I think we expect to see, you know, a good mix of switches from both products.
Mm-hmm. And I know you've mentioned sort of reimbursement in Germany and the UK, but maybe we can talk about the rest of Europe and how to think about the timing there.
Yeah. So, as I mentioned, we got the approval in July in Europe, and typically, you get free pricing in Germany, and that's your initial launch country, and Austria references Germany. So, we're ongoing in our reimbursement discussions in Germany and expect to have that kind of in the middle of next year, but that should sort of be seamless. We—I did mention in the U.K., which is not technically part of Europe anymore-
I'm sorry.
But we did have a very positive appraisal from NICE, where we actually got a positive assessment prior to getting approved, which we believe is the only case we've so far found where that's actually happened. And that assessment said that Pombiliti and Opfolda were cost-effective compared to both of the other products. So, you know, leveraging that assessment from NICE throughout the rest of Europe is, you know, obviously something that we're very excited to do. We're leveraging, and we do expect throughout next year that we'll see kind of a rolling approval in terms of reimbursements throughout all the major European countries.
As a reminder of the 200 patients that we had on treatment, kind of going into approvals, in addition to the 100 or so, in the three markets, we had about 40 more in those European countries, so those will be additional transfers next year.
I mean, are these a meaningful contributor to revenues in 2024? How should we think about the later in the year coming on, middle of the year?
Yeah, I mean, I think for next year, it's a much different proposition in terms of this year. It's, you know, very, you know, end of the year, few months. But next year, with the run rate going in, kind of the rolling approvals, those should contribute more significantly to revenue than we're kind of seeing from some of the transitions this year. Obviously, if it's a country that does take longer and it's like in the third or fourth quarter, it might not contribute as much. But really, for next year, it's the continue on the transitions or complete the transitions, you know, in the case of the first three countries. But then it's really putting new patients onto product across whichever countries we're launched in.
Mm-hmm. Can you speak to initial interest of demand? I mean, we talked about the conversion, but I mean, like, I guess, what are you hearing in terms of, like, requests and as you begin kind of the, you know, in the U.S., also the, you know, the insurance process?
Yeah. I mean, so far, in terms of payers, all those discussions, everything seems to be going really well. We feel that we're, we're on track or ahead of schedule in terms of conversions. I mentioned some of the incoming inquiries and interest coming in from patients and ultimately even from some of the physicians. I mean, all the conversations we've had, people seem very pleased with the interactions they've had. So, we're very excited about where we are, you know, looking forward to getting further into the launch. And, and, you know, I think we can start to give more and more color about that kind of experience and the rate of those transitions from different segment groups as we get here throughout the end of the year. But things are going really well so far.
Anything surprising?
... Nothing really surprising per se. I think, really, so far, it's about what we expected.
Mm-hmm. Well, we're excited-
And we did expect a lot. So, I said, we are. It's even better than we had projected, but about what we expected-
Mm-hmm.
because we're very positive going into the launch.
Yeah, absolutely. Going back to just thinking about the overall size of the patient population, I mean, you mentioned there's a large portion of Pompe patients that are not diagnosed.
Mm-hmm.
What's a reasonable, like, way to think about how this could change over time?
Yeah. So, I said there's about 4,000 patients today. What's great about Pompe, as I mentioned, in the U.S., nearly every state does newborn screening. What we're seeing is, you know, a lot of the infantile patients will go on a treatment right away, but now physicians are starting to follow those young LOPD patients that typically wouldn't be treated till they're 30 or 40. And what they're starting to see is they're showing signs and symptoms as young as 3, 4 years of age. So, we are even hearing cases that those kids are being put on treatment earlier. So, a really interesting dynamic there of potential growth, especially in the U.S. But we just still know Pompe is very underdiagnosed. There's more people still that haven't been diagnosed.
They tend to get stuck kind of with, in a muscular dystrophy clinic, with limb girdle muscle weakness, or just they have elevated CK of unknown reason. And I think what we're seeing now with all rare diseases is with the access to low-cost genetic testing, that we're just starting to see quickly physicians saying, "I'm not sure what this person has. Let's just get them a genetic panel," and then it, it starts making that diagnostic process much easier. We've also had a few cases now, and it seems to be growing, that as people go, to get some genetic testing, if they want to have children, that they're actually now being diagnosed and said, "Oh, you know, you're not actually a carrier. You actually have Pompe disease." We've heard of numerous cases of that already recently in the U.S. as well.
Mm-hmm.
We expect a lot of continued growth in that Pompe market long term.
Mm-hmm. Makes sense.
And importantly, as I mentioned earlier, on the adolescent side, we are excited to get into the pediatric market. We do have an ongoing trial in LOPD patients, an ongoing trial in IOPD patients, the ZIP and Rossella study. And we are looking for label expansions there. Probably the earliest expansion we'll see in pediatrics would be the 12- to 17-year-old LOPD patients, and that could be as early as 2025. And we think that's a really important segment because that would be the one where we start to see maybe some of that earlier treatment for those kids that were diagnosed through screening.
Mm-hmm. Interesting. And, yeah, when can we expect data from these studies?
Kind of on a rolling basis. Again, that 12- to 17-year-old population-
Mm-hmm.
The data will be available sooner. Some of those studies, like the IOPD study, you know, it's still early in the enrollment stage, so it will take some time. I think what we'll see more, in the near term in terms of new data, we continue to look at, the PROPEL data across different endpoints and are presenting that. But importantly, the extension studies that we have, we're continuing to show some of the long-term effects that we've seen. So, we're continuing to put out publications, and a key part of the story will be differentiated mechanism of action, the benefit we're seeing across endpoints, and then the long-term durability. So, that's really our evidence generation focus moving forward.
Mm-hmm.
But getting into those kids where it's not as much of the market opportunity. Market opportunity is, you know, 80%-90% the adults, but huge on that need and an important part, you know, from our mission for delivering this medicine for us to fulfill.
Mm-hmm. It absolutely makes sense. And I'm not gonna ask if you're gonna give guidance for Pompe, but maybe just-
You can ask.
I can ask.
I'm gonna ask Simon. No.
I'm getting the eyes right now. Maybe just what metrics can we expect, as, you know, we continue to get updates? Like, anything in terms of patient numbers-
Yeah.
Like, how should we think about that?
Yeah. I think as you just saw here for the third quarter, you know, I think we can even get more specific as we talk about patient numbers from different segments, from different geographies. We can talk about patient referral forms, which are a leading indicator, and I think that will be initially some of the kind of metrics we're able to provide. I think where we can give some high-level revenue guidance, like we did for the full year this year, we will. But, you know, it, it's just challenging given some of the unknowns around exactly when you'll get reimbursement in different countries in Europe. You know, exactly what the rate of new patient adds in a given segment will be. We feel like we need to get a few quarters under our belt before we can give guidance that we're comfortable, you know, giving.
But we will certainly do everything we can to provide the street and folks with enough information to have a sense of kind of how things are going and the ballpark of where they're going.
Mm-hmm. There's a lot of debate amongst investors about competition and, and how to think about market share. I know it's early, but maybe can you speak to some of the initial learnings, particularly from the U.K. and the first couple of months in Germany, in terms of thinking about market share relative to Nexviazyme?
Yeah. So, just as a little bit of a background, you know, in the US, Nexviazyme share was about 50-55%. In Europe, it's about 25%. So, in Europe, where we're launching, it's a little bit more of a contemporaneous, sort of head-to-head, whereas in the U.S., it's really kind of broken up into the Lumizyme market, the Nexviazyme market. It's still early to say, you know, too many insights we're hearing, other than it's clear that we are able to get patients looking to switch from both products, naive patients in Europe.
So, I don't want to get too much into kind of speculation about how we're gonna do in one group or the other, but we feel really good, as I mentioned, about sort of the value proposition around the mechanism, around the data, and think we have a good proposition, both for Lumizyme patients that haven't switched yet, that might not have switched because they were perceived as stable and trying to really show the data that there is an opportunity for improvement in those patients. And then in Nexviazyme patients, if they switched and they're not doing as well as what it looked like patients did when they switched to Pombiliti Opfolda, then that's a real opportunity to have that conversation as well.
Mm-hmm.
But it's still early days, and we'll give more color as we learn from the launch.
Mm-hmm. How should we think about how centralized or decentralized the treatment of Pompe is, both in the U.S. and in Europe?
Yeah. So, it really depends by country. So, as I mentioned, we had about 75 sites globally that were involved in treatment in clinical trials or access. And importantly, a lot of those were kind of the key opinion leader centers. So, they have-- While they might not treat all the patients, they have influence over a lot of the other physicians. So, we have a great kind of foundation of physicians that have experience with the product, who've seen firsthand how their patients have done. Within the first 30 days, our team went out and engaged that kind of second tier of core treaters. So, in terms of kind of education about the data, we feel, you know, really good foundation starting to get there.
You know, in the U.K., it's like six centers treat the vast majority of patients, and they all had experience. So, that's a really great example where sort of you have a big runway. In the U.S., it's a little bit more dispersed. It's probably about 40 or 50 centers that sort of treat 75% of the patients. And we do have experience with most of those centers, I would say, already, and have reached out to the others.
Mm-hmm.
And then as you look other countries, Germany, it's a little more dispersed, kind of like the U.S., Japan, similarly. What we have said is, what's great is we can really leverage our current team that's out there for Galafold and Fabry. And as we've looked globally, it's about a third of the physicians are actually the same physicians we already are talking to for Fabry. 50% of the centers are the same kind of academic centers, and then approximately 80% of the cities are the same. So, we're really able to leverage the current team and sort of what they're already doing for Fabry, which is helping us sort of reach out to all those Pompe centers.
Mm-hmm. And, I mean, it seems a lot of the physicians have already been involved in clinical trials. How do you think about, you know, awareness, particularly of, of your clinical data?
Yeah, you know, I think it's good with those sites that participated in our studies. You know, as we've been waiting on the approval over the last year, as you well know, as we were waiting for the inspection. You know, we do know that, you know, the other companies have been out there and speaking to physicians and telling them about the data from their perspective. So, you know, it is a great opportunity for us now to get out there, have those discussions, educate on the data. So, I'd say it's a good foundation of knowledge, but certainly now it's, you know, our job to go out there and educate physicians appropriately about the data and what we think is a great treatment opportunity or option for their patients.
So, it's a good foundation, but certainly work to do, and it's what we do best, and we're looking forward to it.
Mm-hmm. Thinking longer term, and I know this is all very hypothetical, how do we think about duration of treatment, particularly? So, there's two next-generation ERTs on the market. If you start on one, whether it's yours or Sanofi's, at some point, you progress-
Yeah.
then you switch to the other. Maybe improve for a bit, and then, unfortunately, eventually progress. Do you switch back? I guess from a mechanistic perspective-
Yeah.
like, how do you see this playing out?
Yeah, it's a great question, and it'll be interesting to see. You know, certainly there will be patients that would probably, you know, have been on Lumizyme, switch to one of the other ones, maybe not feel like they're doing well, and switch to the other. I think some of those patients at that point might say: "Okay, I'm on this final treatment. I've tried all three. I'm going to stay on it." I think there could be some mindset now that we have three options, which is a great thing to have, that people might have tried all three and be like: "You know what? I actually was doing best on this other product that I actually had stopped in on." Very interesting to see those dynamics.
What we do feel is, you know, we have a lot of confidence in Pombiliti and Opfolda and what we believe the experience that patients will have, and we do think long term, that the majority of patients, we hope, will end up on our product, you know, based on the data we've seen. So, but it'll be very interesting to see how those dynamics play out, you know. And in the U.S., there's already more than half the patients have been on Lumizyme and have now been on Nexviazyme for a good period of time. So, it'll be very interesting to see how those patients kind of treat switching versus ones that might have just been newly diagnosed or been on Lumizyme only.
Mm-hmm. Absolutely.
Yeah.
Pivoting to Galafold.
Yes.
So, tell us about the recent growth drivers. You recently raised your guidance, and, you know, both in the near term as well as longer term-
Yeah
... what brings you to the $1 billion in the next 5 years?
Yeah. So, with Galafold, you know, initially, our guidance for the year was 12%-17% at constant currency. We then had raised that to 14%-18%, and then we just recently raised that to 16%-18%. Uh, we as I mentioned, we had $101 million in the third quarter. That was 19% growth. So, we've been really pleased with just the overall growth we've seen in with Galafold this year, and it's really been driven by growth and net new patients. It's not driven by pricing. And what's really exciting is we're seeing that growth come from lots of different places. One is just on continuing to switch patients. If you look at where we're currently launched, we have about 60% market share of treated amenable patients.
We've seen in countries where we've been the longest, we can get that to 85%-90%. We continue to get good at switching in the markets where we currently are. We also continue to expand our geographic footprint. Probably about 15%-20% of the global opportunity is still in countries we haven't yet launched into. We have recently just got reimbursement in Taiwan, and we are in negotiations on Turkey, and just done a submission in New Zealand. There still are some of those countries that could have meaningful, you know, impact of revenue that we're just getting launched into. Then really what's driving things broader is just this continued diagnosis of patients. Some of those patients being very symptomatic and needing to go on a treatment right away.
Some maybe being not quite to the point of treatment, going into the diagnosed untreated bucket. Then we're seeing diagnosed, untreated patients, you know, come onto treatment as well. So, it's really been great to just see. We know Fabry is probably one of the most, if not the most, underdiagnosed rare genetic diseases. Lots of levers on how you can diagnose those patients. It's an X-linked dominant disease, so when you find one baby in Missouri through the newborn screening program, you can find three to five family members that also have Fabry that could live anywhere in the country. So, really you know, with four companies now also doing diagnostic initiatives, we can start to really make some progress towards finding all of those patients that are out there.
One of the nice things from a Galafold perspective is, we believe that a lot of the people and families that have not been diagnosed yet with Fabry have late-onset Fabry disease. You know, it's not the typical signs, and that's why they haven't been diagnosed yet as a family, and those late-onset Fabry patients typically have amenable mutations. So, all of that potential growth in the future, we think, is going to be highly enriched for amenable patients, where Galafold has now become the standard of care in most countries.
Mm-hmm. Absolutely. It seems like a lot of factors at play driving the growth. Maybe over the next five years to get to this $1 billion, what are some of the assumptions that are baked in, maybe just starting from a geographic perspective? What's the mix in that $1 billion?
Yeah. You know, I don't know specifically how much of that billion would come from whatever geographies exactly, but I, I think we're going to continue to see, you know, that transition from... Of the 60% share today, as I mentioned, to 85%-90% share where we are. The geographic expansion plays a part of that, but really, it's the underlying diagnosis and growth. Today, it's about a $1.9 billion Fabry total opportunity. In the next five years, we see that growing towards $3 billion and $1 billion of that being the sort of amenable opportunity. And with our runway, we see in terms of, you know, intellectual property well into the 2030s, we really view this as a potential billion-dollar opportunity longer term.
I think the biggest driver there is probably the underlying just growth in the market, but also continuing to get market share as well as geographic expansion.
Mm-hmm. Well, it's certainly a growing revenue base. Tell us more about the IP.
Yeah. So, I'll talk both about Galafold and Pombiliti Opfolda. So, you know, both products are very innovative, and part of that is why we've been able to build such a really strong intellectual property estate around them. So, with Galafold, we have 54 Orange Book-listed patents. Thirty-eight of those patents have an expiration in 2038 or beyond, and ten of those are composition of matter around the mutant enzyme and small molecule complex. So, we feel really good about that patent estate for Galafold going into the 2030s. If you look at Pombiliti Opfolda, obviously just launching, you don't typically think too much about the runway there, but we have patents that go into the late 2030s currently, potentially an opportunity to expand that.
I think as you see with ERTs, you know, even after patent expiration, you typically see that those products continue to have a runway until something comes along and displaces them. There's not really that sort of generic threat for an ERT, the same as there would be for a small molecule.
Mm-hmm. Mm-hmm. And I guess with Galafold being a small molecule, I mean, I think you've had an intentional patent strategy, and I think there's certainly been a lot more IP that's been filed over the last few years. Tell us about that strategy with respect to Galafold and maybe what the puts and takes are in terms of the key pieces of IP.
Yeah, I mean, really, the strategy has just been to patent around the innovation that medicine brings. There's the unique dosing that we had to kind of discover about how to use a molecule that actually inhibits, but in a way to ultimately chaperone. Very unique IP around the amenable mutations in the label, and importantly, all the amenable mutations are part of the label, and a generic needs to copy the label, so, all of the IP around the amenability is a key part of it. And then, as I mentioned, sort of the composition of matter of other unique aspects. So, the strategy we've had is really just to patent the different unique aspects that we have around the medicine.
You know, we'll see exactly where that ends up in terms of runway, but we feel very confident going into the 2030s.
Mm-hmm. Understood. Maybe turning to the pipeline, tell—
Near and dear to my heart, Chief Development Officer loves the pipeline. Thank you.
I'm so sorry for not bringing it up sooner. Tell us about some of your work in gene therapy.
Yeah. So, I mean, we're still very bullish on genetic medicines. You know, I think the delivery of RNA and DNA is gonna be one of the ways that we can kind of transform treating rare genetic diseases. That being said, I think as a field, we've seen some of the challenges that AAV gene therapies have encountered. As Amicus looked to really get into gene therapy, where we started was around our expertise, which was we've learned how to kind of deliver enzymes to different cellular compartments, deliver them optimally to cells, keep them stable in circulation, and it's really that protein engineering that we've used in Fabry and Pompe to develop kind of engineered transgenes that, in essence, are just more potent than the wild-type transgene.
And that way, no matter what you're able to kind of deliver through your gene therapy, you're able to have the most efficacious product possible. So, we have a really exciting proof of concept data we've put out there with our gene therapies. Where we are in terms of our focus on turning the corner on profitability, we really end with some of the challenges on AAV. We've really been focused on optimizing the delivery, kind of the manufacturing around those, and look to start to really move them forward towards the clinic, where we need to invest a little bit more dollars, you know, here in the coming years. I think we've said probably not to expect any of those, either of those to make it in the clinic for the next couple of years.
But super excited about the potential there, and we have seen a lot of the other gene therapy programs kind of stop or run into challenges. So, we think it's important to really get something that could be transformative long term, in those areas. But investing in Fabry and Pompe, we think adds value for Amicus, for shareholders, for patients. Because of that, we also are looking at a next-generation Galafold. So, we are looking to come up with a molecule that can expand the list of amenable mutations. We know that there are some people out there that have a mutation that can benefit from Galafold; it just doesn't quite reach the amenability criteria, and we think that we might be able to discover some molecules that could kind of expand that list of amenable mutations.
Again, earlier stage, and probably no significant updates externally for a year or so. But as we get sort of a lead molecule and we're able to kind of show some of that data, we certainly will share it.
Yeah, that's very interesting. How do you prioritize that relative to gene therapy?
You know, it's really just based on the data. We're gonna let the data drive things. It's a great position to have, that you have multiple programs, and then as you look to what you can afford to move forward, you can pick the best of those, or if they all look good, you find a way to fund them all, if we can manage to, you know, get the funding. But I think what is most important from our strategy, it's really focused on Fabry and Pompe, bring value. I think that the non-amenable part of the Fabry market is one we would love to be able to bring a product to that group. It's a significant percent of the Fabry market. We think a next-generation effective, durable gene therapy could be a great offering there and would fit perfectly with Amicus.
But we wanna make sure we bring those pipeline programs forward in a way that fits with our strategy to turn the corner on profitability and fund our own operations and pipeline long term.
Mm-hmm. And given turning the corner on profitability, thinking longer term, how should we think about the potential for business development? When you think about, you know, further growth, do you see it coming from internal R&D or perhaps external?
You know, I think it's a mix of both. I think certainly here in the next 12 months, we are laser-focused on growing Galafold and really executing on the Pombiliti Opfolda launch, and that's how we're prioritizing resources. Certainly business development, I think as you look long term, as we have those dollars coming in, and we can figure out how to invest in the future, part of that is gonna be bringing things forward from our early pipeline of what looks most promising for sure, and in particular, something to offer the non-amenable Fabry patients. And then business development will be part of that long-term picture.
You know, it's a real opportunity for us to leverage our commercial international commercial team and look at something that could be sort of a ex U.S. opportunity that might be, you know, reasonably, you know, affordable for us to bring in, something that could add to both top and bottom line, and then ultimately also looking to fill some of the gap in the clinical pipeline, you know, that we would have as we bring forward our preclinical assets in the clinic. There still could be an opportunity to leverage our, you know, really world-class clinical team and regulatory team as well.
Mm-hmm. Absolutely. What are you most excited about in the pipeline?
In the pipeline, I think it's—at this point, I'd say I'm excited about all three of the pipeline programs. I think the... As I mentioned, there really is a need for the non-amenable Fabry patients to have-
Mm-hmm
Something to potentially get away from those every other week infusions. So, I think from an unmet need and a market opportunity, that's kind of an additional market that would be the one that's most exciting for Amicus. But all three programs at this point look promising and, you know, we'll hopefully be able to bring forward whichever one merits it based on the data.
Mm-hmm.
And then, you know, obviously, it's not pipeline anymore, but, you know, Pombiliti Opfolda is still just launching. Still, lots to do in terms of generating data, educating physicians on that data, so, I almost view that still as a pipeline program in some way.
Mm-hmm. Understood. Can you tell us a bit more about this, at least the science behind the next generation Galafold?
Yeah, it's really just looking to see if, you know, with Galafold, amenable mutations, you know, they basically result in an enzyme that is stuck in the enzyme, in the ER and can't get to the lysosome, but still catalytically active. Galafold is actually an inhibitor, so, it binds to the active site and then gets the, that endogenous enzyme over to the lysosome. So, we're looking for a molecule that can maybe even better at sort of stabilizing and trafficking enzyme to the lysosome but inhibit less possibly. And that ultimately could make it so, like, if there's a non-amenable mutation that might see a 2% increase in activity with Galafold, if we can kind of do better trafficking, less inhibition, that might go up to 10%, and now it becomes an amenable mutation.
It also is the opportunity possibly to improve upon Galafold substrate reduction in amenable patients, so that's a pretty high bar already.
Mm-hmm
... but that's something that we're also gonna explore with the molecules.
Mm-hmm. Absolutely. Maybe just to round it out, what do you think is most underappreciated about your story?
I think what's most underappreciated is the opportunity for really executing on the Pombiliti Opfolda launch. You know, what we've built so far with Galafold, we were already on the path towards becoming non-GAAP profitable on that alone, and just the amount that we can leverage that infrastructure, leverage those relationships that we already have and the footprint we have, and really now grow that top line. I think as you look today, where our stock price sits, you know, we feel that there's very limited downside given that base, and there's a lot of upsides, and its all-around execution, and that's something that we've shown that we can do with Galafold.
So, we feel that there should be a pretty good confidence people should have that we can execute on the Pompe launch, and I think based on that, we feel that there's a, it's a great value proposition for the company.
Well, we're excited to track the launch next year.
We are too, Ellie.
Thank you so much for joining us.
Thank you.
Yeah, thanks for everyone in the room.