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

Welcome, everyone, to the 39th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by Tessa Romero and Matt Bannon from the team. Our next presenting company is Amicus and presenting on behalf of the company, we have, CEO, John Crowley. Before I turn it over to John, [Operator Instructions] With that, I'll pass it over to you, John.

Great. Good morning, Anupam. Good morning, everybody. Thank you, JPMorgan, for hosting. I will mention that I'll be making forward-looking statements, and we'll refer you to our forward-looking statements section on Slide 2. Let me begin though on Slide 3, and this is really the foundation of Amicus. Again, what we've been striving to achieve over the last several years and now looking out to the future is to build a great biotechnology company. And this slide on 3 here really shows you the foundation for that. Again, we finally believe that we have the people, the programs, the technologies and the financial capital to achieve our vision to become one of the world's leading global rare disease companies in biotechnology. And if you think here, we're really poised for success based on the cornerstone of our success being Galafold, our small molecule precision medicine. The crown jewel of our portfolio, continuing to be very excited about AT-GAA for Pompe disease that we believe has the potential to become the next standard of care in Pompe disease. We're excited about the future with our pipeline, particularly our pipeline for gene therapies, the largest rare disease pipeline for gene therapy products. And again, all of that against a strong financial background. But we've got to build the foundation for the company. And to do that, we need to have an incredibly strong culture and focused on our people who will deliver on the mission. So on Slide 4, I just want to make sure to highlight, this has been incredibly important for myself, for Brad Campbell, the Amicus Board of Directors and everybody at Amicus, and that's diversity, equity and inclusion. So pretty bold challenges that we've put out to the team, and that is beginning in 2021, 50% of all hiring slates will include diverse candidates, 50% of all director and above hires will be diverse, and 1/3 of all other hires will be diverse. That's just in 2021. Looking out to 2023, we'll maintain global gender diversity of 50% or greater and increase our U.S. diversity to 40% while maintaining pay parity. This will be an incredibly important part of strengthening the culture at Amicus and enabling us to deliver on our mission for patients. If you look on Slide 5, this is our passion for making a difference. The Latin phrase that you see there, Per Ardua Ad Astra, from adversity to the stars. You look at the faces of these patients, faces that remind us every day of why we do what we do. Turning to Slide 6 now with those great foundations for Amicus. We look forward to a future poised for significant value creation. You think about the product that we have, Galafold; the product to come with AT-GAA, strong revenue drivers that will build shareholder wealth that will enable us to invest in this great pipeline to deliver novel medicines for people living with rare diseases. And again, we currently will continue to maintain our strong financial position. We now have a cash position sufficient to achieve profitability, self-sustainability without the need for any future equity-dilutive financing. Slide 7 talks a little bit about our rare portfolio. Again, the approved product, Galafold, approved now in dozens of countries around the world, including all major geographies, all major markets. But we really think about this now in terms of our franchise opportunities. So in Fabry disease, we have our precision medicine, Galafold, but we also now have named a candidate for a gene therapy. We announced this back in November. So we also have built into the Amicus value statement that we wrote 15 years ago, that we have a duty to obsolete our own medicines and our own technologies. So while we're excited to continue to deliver Galafold around the world, we're also excited about the potential to make new medicines for people living with Fabry and very excited about the potential for gene therapy. Similar approach for Pompe disease. We are on the cusp of data. Nobody at Amicus has seen any of the PROPEL results yet. We're still going through all the quality checks. But that data will come to us, and we're eagerly awaiting it in the first quarter for AT-GAA. I'll talk more about that deeper in the presentation. But with that, our science team is also busy at work developing a novel Pompe gene therapy. And again, you can see the similar approach for other gene therapies in our Batten franchise, our next-generation research programs. And again, I'll highlight our strong and continued collaboration with Dr. Jim Wilson and the University of Pennsylvania rare disease and gene therapy center. So a great portfolio for the years ahead. Turning to Slide 8. 2020 was a great year for Amicus. We achieved all of our key strategic priorities. On Slide 9, you can see that we're actually poised for what could be an even more profound year for shareholders and for patients in 2021. So let me just highlight here a couple of the objectives for this year for Team Amicus. First, we're going to continue to drive growth for Galafold. Even against all the headwinds as we entered 2021 due to COVID, we see double-digit Galafold growth in even the most conservative scenarios. We're -- at this conference, we're coming out with a baseline revenue of $300-plus million. We think that's on all conservative assumptions we'll be able to achieve for Galafold. And in the February earnings call, we'll be able to provide a broader range on guidance and be able to set what we think will be the top end of guidance as well. So continue to drive Galafold to patients. Secondly, of course, we're going to report the PROPEL data here shortly, together with all the regulatory filings in the United States, Europe and other major geographies necessary to advance that program. Third, broadly across our gene therapy portfolio, there's so much work going on at Amicus in our scientific labs, with our manufacturing partners, continuing to advance our lead Batten programs while also preparing over the coming years to enter the clinic in Fabry, in Pompe and a number of other rare diseases. Our fourth strategic priority this year, I firmly believe that if we are going to be one of the world's leading companies in gene therapies -- rare disease gene therapies that we also need to be one of the world's experts in manufacturing of these gene therapies. If you look at what we did for AT-GAA, we manufactured what is one of the world's most complex glycosylated proteins, delivered it to the clinic, now poised to deliver it to the market. We're taking that expertise in complex biologic manufacturing and we're transitioning that now to gene therapy. So taking our expertise, our capabilities, working with our partners at Thermo Fisher (Brammer), but also now beginning this year, construction of our own 30,000 square foot gene therapy manufacturing facility to be followed by larger-scale facilities for commercial supply. And again, all of that against a very, very strong balance sheet and continued judicious management of our profit and loss statements and our financial flows. So let me talk a little bit about Galafold here. Galafold, off to a great start. Last year was a very successful year for Galafold. We announced our global revenue exceeding the top end of our guidance yet again for more than $261 million in Galafold revenue. We'll provide the final audited numbers in February. But again, despite all the headwinds of COVID, being able to effectively transform our business model to make sure that all patients in need of Galafold were able to get Galafold as their prescription in 2020. We think it sets us up for a great 2021 to continue to deliver Galafold. Turning to Slide 12, again, just to give you a little bit of the historical success. And what you can see is strong and continued growth for Galafold. Q4 revenue coming in at about $70 million, again, for fiscal year 2020 total revenue of about $261 million. Slide 13 is important, and I wanted to share this to really show all the different ways in which we were able to achieve success in bringing Galafold to patients. First of all, now more than 1,400 Fabry patients with amenable variants are taking Galafold as the standard-of-care medicine for the treatment of their Fabry disease. Back in March and April, we understood that the world had changed in the delivery of medicines and that we wanted to be at the forefront of that. So we effectively transformed our business model, so that we can continue to reach physicians to share medical information and what we now have is a hybrid model, a mix of virtual and in-person, that will allow us to achieve a majority of our pre-COVID call volume. We continue to move patients from standard of care enzyme replacement therapy to Galafold as their standard of care. We're now just at about 49%, we estimate, of global market share of treated amenable patients. We continue to expand the geographies for patients for access to Galafold. And likewise, we continue to see a nice mix, about 60% of all new Galafold prescriptions are switch patients, but an increasing proportion of new patients to Galafold are newly treated patients, about 40% or so. Slide 14 just graphically shows what we've been able to do to add a new way of delivery for our medicines, a new way of communicating with physicians formally, informally being able to share that important medical data, ways in which we train our sales forces; again, ways in which we've effectively transformed our entire business model. So again, on Slide 15, to highlight the outlook for 2021. 2020 execution across the board in overachieving our goals for Galafold lays a solid foundation for 2021. We continue to see strong demand for Galafold. We continue to see also incredibly strong compliance, still more than 90% of all patients prescribed Galafold continue to take that medicine long term. In 2021, we continue to project double-digit revenue growth for Galafold, with new patient starts to be consistent -- at least consistent with what we saw in 2020. If you move forward, while we do have headwinds to manage and we do see increased lag times between patient identification and the Galafold prescription, we do see a building queue of potential Galafold patients, and we think that bodes well for getting the medicine to as many people in need and continuing to grow the franchise. Importantly, for 2021, that continues to lay the foundation, if you look on Slide 16, for our near-term goal in 2023 of achieving $500 million, $0.5 billion in Galafold revenue. And increasingly, we're working on achieving a goal of peak sales of $1 billion plus. That would transform many lives of people living with Fabry disease. It would deliver on our mission for patients and would also deliver on our mission for shareholders. If you look on Slide 17, you'll see all the different ways that we're doing it, while Fabry continues to be recognized as one of the world's most prevalent rare diseases, increasingly recognized to be undiagnosed, underdiagnosed and misdiagnosed. We're also working very hard to proactively find more people living with Fabry. And again, important to remember that Fabry is an X-linked disease. So when you do identify a new patient, whether it be a newborn or an adolescent or an adult, you can screen the entire family. And on average, you will find 3 to 5 other family members affected with Fabry. Many efforts that we have here in addition to continuing to push newborn screening in the United States and beyond. We're looking at screening of high-risk populations. We're looking at screening of populations such as the multiple sclerosis population that increasingly seem to present with symptoms that are being diagnosed as MS, but in fact are Fabry disease. We're using AI technology to find new patients. So we continue to see the size of the patient population living with Fabry grow and Galafold continuing to be an important and meaningful part of that population. So we're really excited about the potential to find many new patients in the years ahead and to grow this to a $1 billion franchise. I'll also note, and you saw in our press release yesterday that we now have 24 issued patents for Galafold, including 13 as of just yesterday, listed in the Orange Book, 13 patents going out to 2038. I'll move next to AT-GAA, the crown jewel of our portfolio and what we believe is the medicine that has the potential to be the new standard of care for people living with Pompe disease. Pompe, again, a severe neuromuscular disease affecting patients from infancy to adulthood. And you see on Slide 19 here representations of the devastating effects of Pompe disease. On Slide 20, to remind everybody what our medicine is, we have created through our science and glycobiology teams a novel enzyme replacement therapy that is properly glycosylated and highly phosphorylated, designed to optimize targeting of the protein to be absorbed into all muscles of patients: skeletal muscles, respiratory muscles, cardiac muscles, diaphragm -- into the diaphragm as well. It's also combined with a small molecule chaperone, while much of the benefit, we believe, is conferred by this new enzyme replacement therapy that we've developed. We do believe that the addition of the chaperone enhances activity, keeps the enzyme wall in blood, in proper conformational state, and we also think has the potential to improve the tolerability of the enzyme as well. So a very novel invention, again with composition of matter protection going out into the late 2030s. We wanted to have a medicine that had the potential to transform people's lives. You saw we've done years of Phase II studies. We've tested this in patients who had been on enzyme therapy and switched. We tested the medicine and people who had never been on an enzyme therapy. We tested this in Pompe patients who could walk. We tested this in Pompe patients who were wheelchair-bound, Pompe patients on ventilators. And what struck us and the experts across these years of Phase I and II studies was the magnitude of response, the consistency of response across all patient groups and the durability of response going out years. On Slide 21, again, just a snapshot of those years of work, importantly focused on the 6-minute walk endpoint as well as forced vital capacity, an important secondary endpoint for us. And just to highlight, Cohort 1, about 10 patients, who had switched from enzyme replacement therapy standard of care to AT-GAA, and what we showed at 1 year was a mean improvement in 6-minute walk of 42.2 meters. If you look at the 5 patients in Cohort 3, all 5 significantly improved with a mean improvement of 63 meters. We learned a lot from this study, and it helped inform our Phase III study. And on Slide 22, you can see that Phase III PROPEL study, a study that began enrolling patients in 2018, fully enrolled by the end of 2019. And just a month ago, the last patient last visit was completed with data now expected in the first quarter. Again, the teams are going through the quality checks, querying any of the 59 sites to ensure high-quality data. Importantly, even with the headwinds of COVID, we were able to execute this study, so that more than 97% of all the infusions were administered in the appropriate window and 97% of all the key assessments were conducted in the appropriate window. So we've conducted, I think, a great experiment to test this medicine, and we have high confidence in AT-GAA and look forward to the data ahead. I'll go ahead -- and just to remind everybody, on slide 23, some of the key takeaways here. A lot of activities around our Pompe program. While a lot of focus right now is on the collection of the final data and the dissemination of that data in the weeks ahead for the PROPEL study, we also continue to enroll patients in the adolescent study. We do have an expanded access program for infantile Pompe patients. We'll expand that to a broader population -- infantile population here later in the year. We are looking forward to finalizing the BLA submission. Again, we have begun a rolling BLA submission in late 2020. We'll complete that submission in the second quarter of this year. We'll soon follow that with an MAA filing in the second half of the year. And again, we think this has the potential to transform many lives for people living with Pompe disease. I'll -- just in the final couple of minutes, let me highlight some of the work that we're doing on the Amicus gene therapy pipeline. Slide 25 is important, and this really captures the breadth of what we've been building for the last 2 years at Amicus. And again, we've not only assembled the largest portfolio of rare disease programs in gene therapy in the entire industry, we've also built significant capabilities. We've built our gene therapy center of excellence in Philadelphia. We have leading collaborations, including with Jim Wilson, the University of Penn. We have 9 active programs, including 2 clinical programs. Importantly, now more than 50 rare diseases, including 12 very large rare diseases, only 3 of which that we've disclosed. And we have a dedicated team of 70 bench scientists focused exclusively on developing next-generation therapies for rare diseases with gene therapies. Slide 26, again, just to highlight -- reiterate the data that we shared in October around our lead gene therapy program, that's for CLN6 Batten disease, a devastating and fatal brain disease in children. And you can see the difference here. We have slowed -- meaningfully slowed the disease progression now out to 2 years in all -- in the 8 patients who -- for whom we had data out to 2 years. Again, the key -- on Slide 27, you'll see the key to our approach with gene therapy is combining the Amicus expertise in glycobiology, in protein engineering together with the expertise at the University of Pennsylvania and Jim Wilson's lab on the design of gene therapy vector technologies. We're also announcing at the conference here, on Slide 28, our program in CLN1 Batten disease, building on our commitment to patients. Again, another just devastating disease in patients. We've seen great success in preclinical studies. And this is a program that we intend now to take forward toward the clinic. Also highlighting some of the work that we're doing in some of the larger non-lysosomal rare diseases. Here's Angelman syndrome. It's a brain disease in children. And again, another great example of combining the Amicus expertise in protein engineering together with the expertise that Jim Wilson's lab at UPenn in vector technologies. Slide 30, just to highlight, these are the architect's renderings we've now completed. The -- all the design specification works. On the upper left here, you'll see that's actually going to be the lobby of about a 30,000 square foot gene therapy Phase I/II manufacturing facility. We've also now acquired land to build a much larger 75,000 square foot, and you see the architect's renderings of that facility below, again, believing that if we're going to be one of the world's leading companies in gene therapies, we also need to be among the world's experts in gene therapy manufacturing, and we're well on the way to doing that. I'll finish with a financial summary on Slide 33. Again, Galafold revenue very strong in 2020, laying a great foundation for 2021 revenue of $261 million, again, exceeding our guidance issued. Also for now for the third year in a row, we will maintain flat operating expenses of $410 million to $420 million. Again, we're able to do that because on the G&A side, we can lever the global infrastructure that we've built to deliver Galafold for the launch of Pompe disease. And likewise, on the R&D side, as we shift the significant cost of the AT-GAA development to our gene therapy portfolio, we can invest in 5 to 10 complete gene therapy programs for what it has cost us to invest and develop AT-GAA. So again, strong judicious management of our expenses at Amicus and our cash position, continuing to be sufficient to achieve self-sustainability. And I'll end now on Slide 35 by just reminding everybody that the cornerstone of our success remains in Galafold, our precision medicine for people with Fabry disease amenable variants. The crown jewel of our portfolio is AT-GAA for Pompe disease that continues to advance toward approval and launch. The future of Amicus will also rest in the development of our gene therapy portfolio. Again, all of that with a terrific team, a wonderful culture and a very strong cash position. So with that, Anupam, I think we're going to bring the rest of the team back on and happy to take any of your questions.

Yes. And John, if you want to quickly introduce the broader team, we can get started with the Q&A. [Operator Instructions]

Yes. So we have Bradley Campbell, our President and Chief Operating Officer; Jeff Castelli, our Chief Development Officer. We have Hung Do, our Chief Science Officer; and Daphne Quimi, our Chief Financial Officer.

And John, maybe we'll start out with PROPEL and the data coming up. One of the questions that we continue to get is how do you think about the COMET results for neoGAA reported in the summer? How do you think about that data set relative to what we might see in PROPEL?

Yes. Again, I'll let that data stand for itself. The one thing I will comment on, what was surprising to see was the control arm there, Lumizyme performing so poorly, frankly, at a year, showing -- I believe it was a 3-meter improvement on the 6-minute walk test. So that was surprising. We have different assumptions. We have an assumption that Lumizyme will do better in our control arm. Again, important difference though, to remind everybody, the COMET study was for treatment-naive people. This was not a switch population. This was for people who had never received any enzyme therapy before. So the improvements that you saw were against the background of no treatment whatsoever. The PROPEL study, very intentionally, is designed, and we enrolled 75% of the 123 patients are switch patients, people coming from the standard of care, a significant majority of patients in the developed world living and diagnosed with Pompe disease are treated with enzyme therapy today. So we think very important that we have studied that population and 25% will be treatment-naive as well.

One of the comments that we receive is, well, in the COMET data, so basically, the Lumizyme patients were able to switch to neoGAA, and those patients saw a 20-meter benefit, right? But how do we think about that given that, that was after a year, and the patients that you guys will be enrolling as your "switch population" have most likely, correct me if I'm wrong, been on therapy much longer and potentially in more of a decline phase of the disease. Is that how we should be thinking about it?

I think that's fair. If you talk to the experts, if you look at the literature, it's very clear that Lumizyme does have a benefit for patients. Typically plateaus at about 2 years. So in that second 12-month period, you're still going to see room for improvement generally for those patients. Also too, I'll highlight that was uncontrolled. If you look at our uncontrolled Phase II, we showed a 42-plus meter improvement. So Jeff, I'll let you comment further on anything else relative to what we've seen and how to keep that in the context of what we are doing with the PROPEL study.

Yes. Anupam, just as you said, really at 1-year switch data in the COMET study and the patients have been on the Lumizyme arm, they still are in that sort of respond to treatment stage in the first 2 years. And remember, they only had a 2-meter improvement. So for whatever reason, they sort of underperformed at [indiscernible]. So I think you would expect to see some continued improvement in those patients regardless of treatment. But again, there's no comparator arm for those switch patients, even though we don't really define switch the same way in our study. It's at least 2 years on treatment and as long as possible. And in our Phase I/II, the average time on Lumizyme have been 5 years previously, and we expect to see something similar in PROPEL. So very different patients in terms of ours will be on that, very consistent decline stage, whereas the switch patients from COMET are still in the [indiscernible] kind of improvement stage.

We've got some questions in the portal here. The first is, do you expect durability of clinical benefit to AT-GAA to differ between naive and switch patients? Why might durability be different between the 2 populations for AT-GAA?

Jeff, I'll let you comment. Hung, you have great experience here, feel free to add any thoughts as well.

Yes. I'll go first, Anupam. I don't think we expect durability to be that different between naive and switch patients. We -- from the data from our Phase I/II, we saw improvements in both groups of patients that kind of increased out to 1 or 2 years, and then they seem to maintain those improvements. So far, we don't see any evidence that durability would be different. I don't know, Hung, if biologically, you might expect to see some difference, but I don't think so.

Yes. I don't think we really know enough to say there should be any difference in terms of durability. But I will say that I think it probably does depend on when the initiation of treatment began in regards to how much damage existed prior to initiating the treatment. I think that probably is a greater factor in terms of durability.

We've got another question in the e-mail portal here. Regarding the 50-plus lysosomal disease gene therapy programs or enzymes produced by a therapy, how many reach the brain for neurodegenerative diseases?

Yes, quite a few. I think, Jeff, would probably more -- a little more than half of our portfolio is geared toward neurodegenerative disorders. And that's very intentional. When we laid -- we actually started about 3 years ago with about 1,000 rare diseases, Anupam, and we narrowed that down to about 100 that we felt gene therapy would be an appropriate approach or Amicus can bring technologies to bear. And also, we looked at the competitive environment, but we looked at the unmet need. So some of these -- like -- or that was our decision to be involved with Batten's disease, knowing just how significant and how severe these diseases. Looking at a disease like CLN3 Batten disease is not only the largest of the 14 Batten disorders. It's also the most prevalent fatal brain disease in children -- genetic brain disease in children. So we work in these diseases partly because they are hard.

Maybe I'll pass it over to Tessa to ask a quick gene therapy question. Tess?

Yes, sure. Actually, John, you teed me up for my question perfectly. So I think we're going to see some initial Phase I/II CLN3 data this quarter. Maybe can you walk us through what you would view as kind of a win scenario in that initial data set?

Yes. Jeff, do you want to comment? Go ahead.

Yes. Tessa, so yes, this quarter, we're going to be presenting the first data on post-follow-up on gene transfer for those 4 children that were treated with CLN3 gene therapy. The data will be about a year of follow-up. It will be focused on the Unified Batten Disease Rating Scale physical domain on data, which is really the most established efficacy measure in those juvenile Batten patients. We will -- there is a good body of natural history data actually in CLN3 with that scale. So we'll be able to show what the natural history data has shown in terms of the progressive decline of these kids are worsening. And to see after 1 year, which is a relatively early look, but we're hopeful to see some signs of stabilization in those first 4 kids. But with that size of a sample size, it will be more qualitative in nature to try to see if we're seeing some evidence of stabilization.

And maybe I'll ask a question on Galafold real quick. The slide that you showed, John, highlighted a 42% sort of operational [indiscernible] wondering how that breaks out in terms of trends in the U.S. versus OUS? And how we should be thinking about those geographical dynamics into 2021?

I think, Anupam, you were referencing the estimated 49% global market share of the treated amenable patients. So Bradley, I'll let you comment on Galafold, please.

Yes. Sure, Anupam, thanks for the question. So yes, Galafold did a great job last year. We did a great job with Galafold even in the context of a very dynamic external environment that we've all been facing with. As you mentioned, the 49% share of treated amenable patients, I think that's a great testament to how well we've done so far. And in our markets where we've been [indiscernible] the longest in Western Europe, in particular, those shares look more like 80-plus percent. So we're doing a great job in driving the use of Galafold in those patient populations. And that's right on strategy where we focus on switch patients first. But we've always said over time, we would start to see an evolution from switch to diagnosed untreated. And so, again, if you look at those European markets, this year, it was more like a 50-50 rate of new patient starts, where about half of them were switch patients and half of them were naive patients. In the United States, where we're -- and Japan is another good example, large market, but we've only been in the market for a couple of years. There, we're still building share of treated amenable patients. But we are growing the market, too. And so you get that balance of 60-40. So for us, the upside is -- the upshot is, excuse me, you still have about half of the treated market globally to penetrate into, so lots of room to continue to switch patients. But you have a significant amount of market growth already. And we think that in the sort of medium and then long term, those dynamics will switch. So actually, you'll see a greater proportion of new patients coming on who are naive to treatment.

And maybe a final question here. John, you talked about the CLN1 program in Batten's disease. Maybe you could give us a little bit more color on why CLN1 first because I think beyond CLN1, 3 and 6, I think you have 8 as well. There are 13 total Batten disease sort of subtypes. So why CLN1 first? And how should we be thinking about the broader Batten's disease program?

Sure. Anupam, I'll speak from a patient standpoint. I'll ask Hung to speak to scientifically the rationale here. Again, same as all the Batten diseases, devastating brain disease in children. And from a patient population standpoint, one of the larger of the Batten disorders. We estimate about 2,000 to 3,000 patients in the developed world. And again, there's also a very strong scientific rationale for what we're doing here. And this is also a great example of employing the Amicus technologies together with UPenn's. And Hung, can you describe what we've been doing with our team and Jim's?

Sure. And as John alluded to, I think, one of the things that why we recognize CLN1 as a great target is that in contrast to CLN6 and 3 and 8, those particular proteins are embedded within the membrane. And so for the most part, you're limited to the number of the cells that were transduced for that gene therapy. While it was seen in 1, 2 and others, those are soluble proteins, where we actually feel we can apply some of our experience and expertise for protein engineering to make those -- that produce therapeutic proteins from gene therapies much more potent. So for CLN1 specifically, what we've actually done is to engineer that particular construct, so that's better expressed and secreted. So that on cells that are transduced for gene therapy, they produce those proteins, secrete them out, so that there's opportunity for that protein to be absorbed into cells that were not transduced. So therefore, cross-correcting neighboring cells. We actually added a protein motif onto CLN1, makes them much more amenable to be taken out under those conditions. So again, we feel like this is an opportunity for us to apply a lot of our learnings from other programs. and then make that particular gene therapy much more effective in that sense.

Great. Okay. I want to thank the Amicus team for a really productive session. Actually, we have 1 more e-mail question. Let me just get that in. Can you remind us what is known about why patients don't continue to benefit on ERTs beyond 2 years? Is it a dosing issue? And if so, can higher doses be used with current drugs and -- or are they becoming less effective with time?

It depends on the disease and it depends on the ERT. As Hung indicated, it depends on where in the course of the disease you initiate treatment. So there's a lot of variable factors here. I think if you look specifically in Pompe disease with the approved standard of care, you see in -- if you talk to the experts, you see a peak of effectiveness that seems to be out at about 2 years. Hung, do you want to comment on biologically why that may be?

Yes. I think there are a couple of factors that could impact how effective that treatment is, Anupam. One is that, ultimately, with GAA, that protein is supplemented for Pompe disease. Patients typically make antibodies, some of which could be neutralizing and some certainly could affect how well that particular protein therapy is actually taking up into cells. The other piece there is, I think, with the disease progression is that ERT able to keep up with that particular disease progression. We believe, in the case of the current standard of care, it's not able to keep up. And therefore, that's why patients tend to decline over time. And so I think those are major factors that impact how well patients do on ERT.

And so our goal within the technology of enzyme replacement therapy to make what could be an optimal enzyme replacement therapy, but it's still an ERT. It's one of the reasons why we've invested so heavily in gene therapies. And I'm sure, down the road, in other technologies, until we finally have a cure for Pompe and these other diseases as well. We're very much looking forward to unblinding and looking at the data in PROPEL. And hopefully, that will be the foundation of our success for the regulatory filings, the commercial launch and that becoming the next standard of care. And then in the meantime, we're going to advance our gene therapy and someday, hopefully, that will obsolete ERT. But for now and I think for the foreseeable future, ERT will be standard of care.

Good. All right. Thank you, Amicus.

Thank you, Anupam. We'll talk to you later tonight.

Okay.

Thank you. Have a good day.

Thanks, Tessa.