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

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 talk a little bit about that.

Yes. Thank you, Ellie. Thanks to the UBS team for having us. We're happy to be here. Yes, we just had third quarter earnings yesterday. Very excited to give an update on the launch of Pombiliti and 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 I'm 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 3 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 see naive patients in Europe. So really exciting early days. Happy to talk more about that. Also a lot to talk about in terms of Galafold and our drive towards profitability. So ask away, Ellie.

Where do you want to start?

Maybe just a quick overview here. First, Amicus is our mission at Amicus is to develop transformative medicines for people living with [ rare ] diseases. Really, 3 key value drivers today we see. The first is our product Galafold, which is for Fabry disease and people with amenable mutations. We actually just reported yesterday for 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% to 18%. That 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, but that also is up to $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 R&D, needing to have capital to actually now turn in the corner to profitability and funding things moving forward.

Exciting. Well, maybe just on profitability. For -- 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 decreases in OpEx, how should we think about this as a business going forward?

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 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 the 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 have -- are able to fund those pipeline programs. So as you can hear from what I'm saying is we are really focused on growing top line, managing expenses, turning towards profitability.

Absolutely. And Pompe and Pombiliti and Opfolda will definitely be a key part of that, right? If your expenses are flat, then that essentially will go down to profits.

Yes, exactly.

So let's talk about the launch. 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? And then we can talk about competition from there.

Yes. So just a quick background, Pompe. 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, that, that is -- 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 5 years growing to about $1.8 billion, $1.9 billion in that time frame. In longer term, we see, as I mentioned, the opportunity for Pombiliti and Opfolda, we believe that we can obtain a dominant share of that market and ultimately work towards a $1 billion opportunity.

And maybe with respect to competition in the Pompe space, how do you think that you're differentiated from Nexviazyme?

Yes. So really, fundamentally, the mechanism of action, we believe for Pombiliti and 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're the only program to study the real-world population of experienced patients and naive patients. And there, we -- 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.

And I guess from a marketing perspective, how do you ensure that physicians are aware of this difference?

Yes. Well, it's really our marketing team going out and engaging with those centers. So 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 is 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.

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. Maybe starting with not improving on ERT and what that means in terms of the indication statement.

Yes. 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 III 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 in 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%, those 25% of the patients who might not be -- who are improving today, 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. Discussions we've had about how physicians and patients are going to interpret not improving, it really seems like it's going to be more of a holistic assessment. 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 the patient things like FVC and 6-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 up stairs? So it's really going to 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?

Makes sense. And maybe starting with like in the U.S., so it's 3Q? I mean you mentioned, I think, like 2/3 had prescription referral forms already. Tell us a little bit more about that and what you saw with the conversion from the clinical trial patients.

Yes. 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 all 100 of those over from trial or access onto commercial therapy. About 20 of those are in Germany have been transitioned, 45 or so 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 PRF for most of those patients. We're still -- PRFs are 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 products. So it's about a 60-day on average process to do that. And that's why we said we're on track in the U.S. But from a revenue perspective, we did just report out $2.8 million in revenue for the quarter. As a reminder that's really just U.K. 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 building Opfolda and again, that's really going to be driven from U.K., Europe. There'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 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 3 geographies. We've seen patients switch from Nexviazyme, from Lumizyme. We 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.

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?

Yes, $40 million to $50 million, depending on just for the 100-or-so transition patients. It depends prices higher in the U.S., a little bit lower in Europe on average. We had said that 100 would translate to $40 million to $50 million run rate.

That's helpful. And maybe curious about some of these dynamics you're seeing outside of the conversion to paying but with new starts. What's the mix of switches versus naive, maybe just in Europe, maybe if not in the U.S.?

Yes, 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 will be very interesting as we get further into launch to kind of look at sort of the timing of those switches, how long patients have 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. And interestingly, we've heard a number of cases where patients have proactively reached out to the 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.

I mean we started with saying that almost the majority of patients -- vast majority, like 75% or so are not improving on their current ERT. How do we think about the patient motivation, how involved the patients are in their care?

Yes. I think we've seen over the years in rare diseases, in particular, 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. I just alluded to some of those anecdotal reports we're hearing of patients actually proactively advocating -- especially here in the U.S. that patient voice and experience in kind of word of mouth, we think, is going to be a big driver, ultimately, of the treatment decision of which treatment they go on to.

Do you think it's the patients that are on Nexviazyme that are going to be the first to switch because they're the ones that are motivated in seeking new treatments? Or is it the patients that are on Lumizyme and really are waiting for 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. Some of those patients, we know that had stayed on Lumizyme have been -- we've heard that they have been waiting for Pombiliti approval. We expect that a good number of the patients that switched early on to Nexviazyme were really maybe progressing a lot on their current treatments. So it'll be interesting to see now that they've been on for a year or 2 in the U.S., how those patients are doing. So it's still early, but I think we expect to see a good mix of switches from both products.

And I know you've mentioned sort of reimbursement in Germany and the U.K., but maybe we can talk about the rest of Europe and how to think about the timing there. [Audio Gap] I guess what are you hearing in terms of like requests as you begin kind of the -- in the U.S., also the insurance process.

Yes. I mean so far in terms of payers, all those discussions, everything seems to be going really well. We feel that 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 their interactions they've had. So we're very excited about where we are, looking forward to getting further into the launch. And 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. And we did expect a lot, like I said, we are even better than we had projected, but about what we expected because we're very positive going into the launch.

Yes, 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. What's a reasonable way to think about how this could change over time?

Yes. So I said there was 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 a lot of the infantile patients who go into treatment right away, but now physicians are starting to follow those young LOPD patients, that typically wouldn't be treated until 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've already been hearing cases that those kids are being put on treatment earlier. So really interesting dynamic there of potential growth, especially in the U.S. But we just feel that 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 the genetic panel, and then it starts making that diagnostic process much easier. We've also had a few cases now, and it seems to be growing 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're not actually a carrier. You actually have Pompe disease. We've heard of numerous cases with that already recently in the U.S. as well. So just we expect a lot of continued growth in that Pompe market long term. 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 [ Rosella ] 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.

Interesting. And yes, when can we expect data from these studies?

Kind of on a rolling basis, again, that 12- to 17-year-old population, the data will be available sooner. Some of those studies like the IOPD study is still early in the enrollment stage and 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 end points and are presenting that, 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 the key part of the story will be differentiated mechanism of action, the benefit we're seeing across end points and then the long-term durability. So that's really our evidence generation focus moving forward. But getting into those kids where it's not as much of the market opportunity. Market opportunity is 80%, 90% the adults, but huge unmet need and an important part from our mission for delivering this medicine for us to fulfill.

Absolutely, makes sense. And I'm not going to ask if you're going to give guidance for Pompe, but maybe just...

You can ask.

Maybe just what metrics can we expect as we continue to get updates like anything in terms of patient numbers? Like how should we think about that?

Yes. I think as you just saw here for the third quarter, 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 it's just challenging given some of the unknowns around exactly when you'll get reimbursement in different countries in Europe, 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 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 or in the ballpark of where they're going.

And there's a lot of debate among investors about the competition 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?

Yes. So just as a little bit of a background, in the U.S., 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 and Nexviazyme market. It's still early to say 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 going to 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 and Opfolda then that's a real opportunity to have that conversation as well. But it's still early days, and we'll give more color as we learn from the launch.

How should we think about how centralized or decentralized the treatment of Pompe is both in the U.S. and in Europe?

Yes. So it really depends by country. So as I mentioned, we had about 75 sites globally that we're involved 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, have seen firsthand how their patients have done. Within the first 30 days, our team went out, engaged that kind of second tier of core treaters. So in terms of kind of education about the data, we feel really good foundation starting to get there. In the U.K., it's like 6 centers treat the vast majority of patients, and they all had experience. So that's a really great example where it's 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. And then if you look at 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 look globally, it's about 1/3 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 of those Pompe centers.

I mean it seems a lot of the physicians have already been involved in clinical trials. How do you think about awareness, particularly of your clinical data?

Yes. I think it's good with those sites that participated in our studies. We have -- as we've been waiting on the approval over the last year, as you well know, as we are waiting for the inspection, we do know that the other companies that have been out there and speaking to physicians and telling them about the data from their perspective. So 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 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 that's what we're -- it's what we do best and we're looking forward to it.

Thinking longer term, and I know this is all very hypothetical, how do we think about duration of treatment, particularly for those 2 next-generation ERTs in the market? If you start on one, whether it's yours or Sanofi's, at some point, you progress, then you switch to the other, maybe improve for a bit and then unfortunately, it eventually progress. Do you switch back, I guess, from a mechanistic perspective, like how do you see this playing out?

Yes, it's a great question, and it will be interesting to see. Certainly, there will be patients that would probably have been on Lumizyme, switch to one of the other ones, maybe not feel like they're doing well and switch to the other. And I think some of those patients at that point might say, okay, I'm on this final treatment. I've tried all 3, I'm going to stay on it. I think there could be some mindset now that we have 3 options, which is a great thing to have, that people might have tried all 3 and be like, you know what, I actually was doing best on this other product that actually had stopped it on. So very interesting to see those dynamics. What we do feel is 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 based on the data we've seen. So -- but it will be very interesting to see how those dynamics play out. And in the U.S., there's already more than half of the patients have been on Lumizyme and have now been on Nexviazyme for a good period of time. So it'd be very interesting to see how those patients kind of treat switching versus ones that might have just been newly diagnosed or been on the Nexviazyme only.

Absolutely. Pivoting to Galafold, so tell us about the recent growth drivers. You recently raised your guidance and -- both in the near term as well as longer term, what brings you to the $1 billion in the next 5 years?

Yes. So with Galafold, initially, our guidance for the year is 12% to 17% at constant currency. We then had raised that to 14% to 18% and then we just recently raised that to 16% to 18%. We -- as I mentioned, we had $101 million in third quarter, that was 19% growth. So we've been really pleased with just the overall growth we've seen with Galafold this year, and it's really been driven by gross 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 the -- where we're currently launched, we have about 60% market share of treated amenable patients. And we've seen in countries where we've been the longest, we can get that to 85%, 90%. So we continue to get good switching in the markets where we currently are. We also continue to expand our geographic footprint, probably about 15% to 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, just done a submission in New Zealand. So there still are some of those countries that could have meaningful impact of revenue that we're just getting launched into. And then really what's driving things broader is just this continued diagnosis of patients. Some of those patients being very symptomatic and you need to go into treatment right away, some maybe being not quite to the point of treatment going into the diagnosed untreated bucket. And then we're seeing diagnosed untreated patients come on to 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 X-linked dominant disease. So when you find one baby in Missouri through the newborn screening program, you can find 3 to 5 family members that also have Fabry that could live anywhere in the country. So really, with 4 companies now also doing diagnostic initiatives, we can start to really make some progress towards finding all of those patients that are out there. And 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. 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 patients. So all of that potential growth in the future, we think, is going to be highly enriched for [ amenable ] patients for Galafold to now become the standard of care in most countries.

Absolutely. It seems like a lot of factors at play driving the growth maybe over the next 5 years to get to this $1 billion. What are the some of the assumptions that are baked in, maybe just starting from a geographic perspective, what's the mix in that $1 billion?

Yes. I don't know specifically how much of that $1 billion would come from whatever geographies exactly. But I think we're going to continue to see that transition from -- of the 60% share today, as I mentioned, to an 85%, 90% share, we're 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 5 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 intellectual property well into the 2030s, we really view this as a potential $1 billion opportunity longer term. Maybe 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.

Well, it's certainly a growing revenue base. Tell us more about the IP.

Yes. So -- and I'll talk both about Galafold and Pombiliti and Opfolda. So 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, 38 of those patents have an expiration in 2038 or beyond, and 10 of those are a 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 and 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. And I think as you see with ERTs, even after patent exploration, 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 it would be for a small molecule.

And I guess, with Galafold being a small molecule, I mean I think you've had a 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?

Yes. I mean really, the strategy has just been to patent around the innovation that, that medicine brings. As 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 patent the different unique aspects that we have around the medicine. And we'll see exactly where that ends up in terms of runway, but we feel very confident going into the -- well into the 2030s.

Understood. Maybe turning to the pipeline.

Near and dear to my heart. Chief Development Officer, love the pipeline.

I'm so sorry for not bringing it up sooner. Tell us about some of your work in gene therapy.

Yes. So I mean we're still very bullish on genetic medicines. I think the delivery of RNA and DNA is going to 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. In 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 very exciting proof-of-concept data we 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 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 add 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 the 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 share it.

That's very interesting. How do you prioritize that relative to gene therapy?

It's really just based on the data. We're going to 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, we can manage to 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 the non-amenable part of the Fabry market is one where 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 effect of durable gene therapy could be a great offering there, would fit perfectly with Amicus. But we want to 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 in the pipeline long term.

And given turning the corner on profitability, thinking longer term, how should we think about the potential for business development? When you think about further growth, do you see it coming from internal R&D or perhaps external?

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 and 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 going to be bringing things forward from our early pipeline and what looks most promising for sure, in particular, something to offer the non-amenable Fabry patients. And then business development, it will be part of that long-term picture. 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 reasonably 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 that we would have as we bring forward our preclinical assets in the clinic. There still could be an opportunity to leverage our really world-class clinical team and regulatory team as well.

Absolutely. What are you most excited about in the pipeline?

In the pipeline, I think at this point, I'd say I'm excited about all 3 of the pipeline programs. I think -- as I mentioned, there really is a need for the non-amenable Fabry patients to have 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 3 programs at this point look promising, and we'll hopefully be able to bring forward whichever one merits it based on the data. And then obviously, not pipeline anymore, but Pombiliti and Opfolda is still just launching, still lots to do in terms of generating data, educating physicians on that data. So again, we'll see that still as a pipeline program in some way.

Understood. Can you tell us a bit more about this at least the science behind the next-generation Galafold?

Yes. It's really just looking to see if with Galafold fermentable mutations, they basically result in an enzyme that is stuck 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 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 enzymes 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. And also, is the opportunity possibly to improve upon Galafold substrate reduction in amenable patients. So that's a pretty high bar already, but that's something that we're also going to explore with the molecules.

Absolutely. And 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. 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 if you look today where our stock price sits, we feel that there is very limited downside given that base, and there's a lot of upside. And it's 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 -- it's a great value proposition for the company.

We're excited to track the launch next year. Thank you so much for joining us. And yes, thanks for everyone in the room.