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

Okay. We'll go ahead and get started. Welcome to the Tuesday morning of the 2020 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 Therapeutics, and speaking on behalf of the company is CEO, John Crowley. John?

Great. Thank you, Anupam, and good morning, everybody. Thanks for being here. We'll be making forward-looking statements, so I'll reference you to Slide #2. We describe Amicus as a rare company. And this slide will give you an overview of some of the key pieces of the company that we've been building and where we are today and I think, in large measure, why we're so excited about 2020. So again, the cornerstone of our success with Galafold, our precision small medicine for Fabry disease; our world-class biologic now in a Phase III study fully enrolled for Pompe disease; and increasingly, our gene therapy technologies and portfolio now looking at potentially dozens of disorders, again, all focused in the rare diseases. So you see a breadth of technologies, one of the largest portfolios of products in rare diseases in the industry. But importantly, also two, strong cash position. We ended the year with more than $450 million in cash. As well as our employees. We now have Amicus employees in 27 countries. One of the key advantages, I think, in what we've been building at Amicus are the team -- is the team that we have. We describe our team as you have to be a passionate entrepreneur. And there's 2 parts to that. That's the passion, the mission, the extraordinary patient focus; and the entrepreneur to work the hours, to work in a world often filled with uncertainty in biotechnology in the rare diseases. I think it's one that's given us a great competitive advantage as we build out this company and this team. Also, a rare opportunity today. Three key pillars of value at Amicus. One, again, is our precision small medicine, Galafold for Fabry disease. We describe that as the cornerstone of our success. We see that as having the opportunity to treat thousands of patients around the world. And also the potential for $1 billion-plus in peak revenue opportunity. The core of our portfolio and our crown jewel remains our advanced biologic for Pompe disease, with breakthrough therapy designation now with a fully enrolled Phase III reading out in the first half of 2021. That is the one single medicine in our portfolio that has the potential for a $1 billion to $2 billion revenue opportunity and we believe has the potential to become the next standard of care for everybody living with Pompe disease. We're also very excited about our gene therapy portfolio, again, having the rights to dozens of programs, 2 now in the clinic, 8 in active preclinical development and that portfolio itself with a potential for $1 billion in peak recurring revenue. And underlying it all, of course, the ability to transform the lives of thousands of patients. So that rare opportunity driven, again, by this rare portfolio with an approved product Galafold as the anchor. And what you see here is we've divided now our portfolio into franchises. Fabry, Pompe, Batten disease, a family that will call next-generation research programs that haven't yet been divided into particular therapeutic franchises, an MPS franchise. And throughout this year, with our rights to up to 50 rare disease programs, including 12 very large rare diseases, 9 of which have yet to be disclosed. I think through this year, you'll see much more data coming from our gene therapy research engine and our partnership with Jim Wilson and UPenn. And I think you'll see an expansion of this portfolio and the potential for an addition of a further franchise. So look for that in 2020. This is what we did last year. We met or exceeded all of our goals. Again, Galafold revenue coming in at $181 million; completed -- actually overenrolled the Pompe study by the end of last year; the data that I'll highlight in Batten disease; proof of concept -- in fact, strong proof of concept in Pompe disease that has now led us to our IND-enabling toxicology studies and a clinical program in Pompe and gene therapy in 2021. And importantly, with our financial exercise in the third quarter last year, the prioritization of programs, the phasing of capital expenditures and with enhanced revenue projections for Galafold, we, again, are reiterating a strong financial position with cash existing now well into 2022. So what are we going to do this year? #1 priority, continue to drive Galafold to more patients living with Fabry disease, with amenable mutations. This will be the second full year of launch in all the major geographies, Japan, Europe, United States. And we will achieve at least $0.25 billion in revenue, and we see a path to potentially $260 million in revenue this year. Secondly, lots of activities around our Pompe program to support the 2021 final BLA filings and MAA. We've completed enrollment of the pivotal study. We'll continue to enroll children in pediatric studies, lots of work with our partners at WuXi Biologics on the manufacturing of that drug in advance of the commercial launch. So much going on, again, for that crown jewel in our portfolio. A lot of work as well as we build out our gene therapy research center and Center of Excellence in Philadelphia. So we'll see more clinical development, manufacturing, and importantly, we will be able, we believe, to define the regulatory pathways and time lines for both clinical programs, the CLN6 and the CLN3 Batten disease programs. We will continue to progress the Pompe gene therapy towards the IND. We expect to complete the IND-enabling toxicology studies. Lots of work going on with our partners at Paragon for the scale-up and manufacture, getting ready for the 2021, beginning of clinical studies. And we also expect to release at least 2 additional IND candidates this year. And we will continue to maintain a strong financial position. So we come back then to the meaning of what we do. Why we do what we do at Amicus? I described in the beginning our team is a group of passionate entrepreneurs. We believe that we have a fierce culture of compassion at Amicus. What I ask everybody in our company to do every day is to think if you had this disease, whichever rare disease it may be, or you were the mom or a dad of a child with that disease, what decision would you make? Where would you invest? Who would you hire? When would you start a program, stop a program? If you think through it with that lens every time, you will make better decisions, you will do it focused on our mission for patients, and we think you will maximize shareholder value and create one of the most successful and enduring companies in all of biotechnology. So we try to live this extraordinary patient focus every day, and we think it gives us a great competitive advantage in all of these rare diseases. So again, with the success across our science, clinical, regulatory and now commercial efforts, we think we really are at that transformational period for Amicus. Again, this year with $0.25 billion plus in revenue from our lead product, late-stage program in Pompe, the portfolio that we've now assembled, together with a strong financial outlook in the company, I think, puts us in a unique position. I think if you look at Amicus' value today, I think it's a tremendous value proposition for where we are and where we hope to go. So let me talk a little bit more about Fabry disease. When we first began developing this small molecule precision medicine for Fabry disease, Fabry was thought to be a very rare, rare disease, thought to affect only males, largely presenting with kidney disease. What we now know is, while that is a portion of the population, the vast majority of the population includes not only classic males, it includes females. The leading cause of death for people now with Fabry disease is recognized to be heart disease. Stroke and CNS events are also a leading cause of death. Patients live with severe irritable bowel syndrome-like effects, severe GI effects and pain. So it's a multi-organ multi-systemic disorder. And again, the way that our medicine works, it is a small molecule chaperone delivered every other day taken by a patient orally, designed to target, bind to and stabilize a patient's own enzyme, increasing the enzyme activity and reducing substrate. So Galafold, the product, again, one of the most successful rare disease launches ever in industry. Last, our revenue guidance, as I stood at this podium, was $160 million to $180 million. Even with about $5 million in FX headwinds, we achieved revenue -- preliminary revenue as we see of about $181 million, the second year in a row that we've exceeded the top end of our revenue guidance. Again, this year, we expect $0.25 billion or north of that in revenue. This continues to be a product expanding its approvals and its global reach. We now have Galafold approved in more than 40 countries around the world. And importantly, this is a precision medicine so that you have to have what's known as an amenable mutation to be suitable for this therapy. We now have identified and updated in the U.S. label, for example, 348 known amenable variants that are suitable for treatment with Galafold. And here, you just see the revenue launch and the ramp quarter-by-quarter throughout last year. You can see, as has been typical in the last 2 years, the second and the fourth quarters being significant periods of growth for us, and again, with north of $180 million in revenue last year. So what's driving this revenue? A couple of key metrics that we follow. One is compliance. What we've seen is that when a patient comes off of the approved standard-of-care enzyme replacement therapy and comes on to Galafold, in more than 90% of the cases, they stay on Galafold. So strong compliance and adherence. Importantly, of people treated with existing enzyme standards of care, we've only penetrated about 30% of the market, which is excellent, but still significant room for us to begin to switch additional patients as more data evolves and as more geographies come online. So from that 30% treated population, you can see steady growth here in the United States. The product just launched in August of 2018. We've seen continued growth and adoption. Now well more than 100 prescribers. Again, in the EU, we see growth in the treatment-naive population, people who have never received enzyme replacement therapy, and growth in other regions of the world. This is the growth trajectory that we see from here to 2023. We see, on average, about a 40% compounded growth rate, getting us to revenue of about $500 million in 2023. But importantly, we are increasingly confident that this will be a $1 billion drug. Couple of activities that we're doing, we're increasing the use of genetic screening. We're also looking in high-risk populations in IBS clinics; in pain clinics; interestingly, in MS, multiple sclerosis clinics. One study in Germany went into a large MS clinic and found that 5% of the patients, in fact, did not have the MS, they actually had Fabry disease. So a lot of work that we're doing. We're working with Invitae and other companies looking at screening of populations, again, all to get us towards that $1 billion in global revenue. So an exciting time for us, an opportunity to transform the lives of many people living with Fabry disease, and again, a very strong IP protection and orphan protection around this product around the world. So that's the cornerstone of our success, Galafold, our precision medicine for Fabry disease. Again, these are sold by Amicus teams around the world. Let me talk now about the center piece of our portfolio, our AT-GAA. Again, Pompe disease is a rare neuromuscular disease affecting patients from infancy all the way through adulthood in various iterations of the disease. In every case, though, it leads to a defect of the same protein, a buildup of the same substrate, glycogen, in the muscles that affects skeletal muscles, breathing muscles, cardiac muscles. A devastating disorder. In children, think of a childhood form of ALS, something very similar. There is an approved standard of care. It's been approved for nearly 14 years here in the United States. Last year, it crossed the $1 billion mark. Our goal was to come up with something meaningfully different. And we did that by differentiating the protein that we made. And this, I think, is the real genius of Hung Do, our Chief Science Officer, our team of glycobiologists, to have created an enzyme that is properly glycosylated, highly phosphorylated to target the receptor necessary for absorption into muscles. We also combined that with a small molecules chaperone, which adds stability when it's infused and we think enhances the potency of the enzyme. It's had incredibly strong results now in more than 3.5 years of Phase II studies, strong enough results that it led to the only breakthrough therapy designation ever granted for any next-generation lysosomal disease product. So with that breakthrough therapy designation, again, we intend to begin a rolling BLA this year. We would expect to have priority review when the BLA is completed for filing in 2021, with the potential for launch as early as the second half of 2021. And importantly, the nature of this product and the results that we've seen in the Phase II are sharply contrasted with any program that has ever been developed in Pompe disease. It's something we're very excited about, and again, I think the fact that we were able to enroll what was the -- is the largest clinical study ever conducted in lysosomal storage disease, overenrolled that study, do it within a year, in fact, we actually had wait list for many patients at a number of our clinical sites around the world, speaks to both the unmet need and the data that we've seen, the science behind this product. It is intended to have the potential to become the next standard of care, again, for everybody living with Pompe disease. This is intended for use in pediatric populations, adult populations, intended for people switching from the approved ERT standard of care, or for people who have never taken ERT. We have alignment with the EMA and the FDA on the outcome and the broad label potential of this drug based on this PROPEL Phase III study. And again, the breakthrough therapy designation was granted on the standard of showing preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. So we continue to be incredibly excited about this. We showed this data here on Slide 23 at our Analyst Day back in October in New York. We showed from the 2 largest studies ever done with the published literature of what's known for people on the approved ERT standard of care, where any improvement seen in the first couple of years tends to lead to a plateau and almost a uniform decline. Here, we show it on 6-minute walk. You see it, though, in multiple measures of the disease, sharply, again, contrasted with what we've seen throughout our Phase II studies. And again, I can't overstate how important it is to take somebody who, for years, had been on an approved enzyme replacement therapy and in most every case, to not only stop the continued decline, the continued path toward weakness, but to actually reverse the course of their disease. If they could walk, most all of our patients in our Phase II could walk further. If they could breathe, they could breathe better. For people in wheelchairs, we had a small cohort of patients, many of those patients hadn't moved their arms in years. They will be able -- they then were able to regain upper body strength and show significant improvement in amenable muscle. So again, you see a lot of reasons why we're excited about this, why we are now deep into this Phase III pivotal study in Pompe disease. We announced last week that we have enrolled -- we targeted 100 patients. We had enough success in manufacturing with our partners at WuXi Biologics that we enrolled 123 patients in the study. That's great. It gets to more patients who we think may benefit, gives more physicians experience with the medicine through the clinical studies that we're doing. But it also even further strengthens the statistical analysis plan. We need to show, we believe, only about a 15-meter delta between the AT-GAA, our drug-treated arm, and the randomization of patients, again, on a 2:1 basis, those randomized to stay on Lumizyme, the approved standard of care. In our Phase IIs, in the switch population, we showed more than a 40-meter improvement at a year. In the treatment-naive patients, we showed more than a 60-meter improvement. So again, we think that we've teed up what we hope to be a very successful study and then a very quick path toward the market. Important focus on biologics manufacturing. Again, we've been working for a number of years with our partners at WuXi Biologics. The current material made at their plant in WuXi City, and WuXi also now constructing a plant just north of Dublin that will provide the commercial supply together with the China site for the launch of the product, importantly, as well, all patients are being treated at PROPEL study with commercial scale material. These just summarize the key takeaways, the Phase III study, the breakthrough therapy designation, the plan to submit and initiate the rolling BLA, the manufacturing PPQ runs that are well underway at WuXi to support the CMC module of the BLA. We're doing everything we can to take as much risk out of this program and to tee it up not only for a successful conclusion through the clinic but teeing it up for what we hope will be very rapid discussions with regulators and a path to a very, very successful launch. Again, the one product in our portfolio with $1 billion to $2 billion in peak revenue potential and exclusivity well into the 2030s. In the last 1.5 years, let me pivot now to what we see as the future growth for Amicus as well, and that's our gene therapy business. This is a natural evolution from what we did with small molecule precision medicine chaperones; what we did with the invention of our biologic, the AT-GAA product in Pompe. What we're now focused on is stabilizing and targeting what we call internally produced enzymes, enzymes expressed through the gene therapy vectors. We licensed a series of programs from Nationwide Children's Hospital in September of 2018 in a disease called Batten disease. There are 14 different subtypes of this disease. It is a pediatric disease. Regardless of the subtype, in every case, the child will die with this disease. There are tremendous amounts of unmet need across all of these diseases. We focus our lead program on CLN6 Batten disease. It's actually one of the most advanced gene therapy programs in development today. We shared this data in the summer of last year. We've now treated 13 patients. And these are the patients for whom we had data out just past a year. These are matched controls to a scale known as a Hamburg scale that we think could be the basis of an approval as a comparator. And here, we actually see the green lines represent patients treated with the gene therapy intrathecally delivered compared to the red lines of the natural history of patients, again, matched for age and baseline Hamburg Scores. Here, again, remarkable results in a number of children, particularly the younger children treated. If you can intervene early enough, we believe that you can stop the progression of this disease. And kids who would normally die before their tenth birthday can have substantially better lives. With that, we now have a franchise in Batten's disease. CLN6 is our lead program. We also have a program in CLN3. We've now treated 4 children with gene therapy. We'll have data in that program in the second half of this year. CLN3 is the largest of the Batten disease programs. It's also believed to be the largest cause -- genetic cause of blindness in children. We have other programs CLN8, CLN1 and others that we're investigating in Batten disease. Again, 2 programs in the clinic, others in preclinical development. The other pillar of the future for Amicus is going to be our partnership with UPenn and the Wilson's gene therapy center and Orphan Disease Center at UPenn. We entered into an initial collaboration in the fall of 2018 around Pompe, Fabry and CDKL5 deficiency. We then substantially expanded that in May of last year. What this does is combine 2 excellent science organizations. We take the Amicus expertise in protein engineering and glycobiology and the focus on engineering the proteins that would be expressed by the gene therapies. We combine that with the Wilson experience and next-generation technologies focused on next-generation vectors, manufacturability, safety, delivery, all the parameters that we're looking at in the years and decades ahead. Again, we now have rights to about 50 of the rare disease programs coming out of UPenn. Those are global exclusive rights to those programs. We've disclosed that it's a majority of the lysosomal storage disorders. It's larger disease like Angelman's and Rett and myotonic dystrophy. And this is why we moved all of our science organization last year and we continue to build out the science function at Amicus in Philadelphia. Again, just examples of what we've been able to do, not just with Pompe, where we have a very exciting gene therapy program, but what we've been able to do in a number of other cases. In every case, with Amicus protein engineering, we can combine it with the gene therapy excellence from the Wilson Lab, we think, to make better gene therapies for patients living with these diseases. From our Wilson program and the UPenn collaboration, our most advanced program is our Pompe gene therapy. Again, along the lines of we have an obligation to obsolete our own technologies. We're very excited about our enzyme replacement therapy, our AT-GAA, to become the next standard of care. But we're also focused on gene therapy, and we expect that to enter the clinic in the first half of 2021. So very exciting work that we're doing in gene therapy. You'll hear a lot more data, a lot more news, disclosure of additional programs throughout this year, updates on our manufacturing success. But let me conclude then with our financial strength. Again, we begin the year with $450 million of cash, 2.5-plus years of runway and cash well into 2022. With that, we're at a major point on our path toward profitability. And again, that's why we think this will be such an exciting year 2020 at Amicus. Thanks for listening.

Yes, we'll go ahead and get started. John, if you want to introduce who's on the stage up here with you, we can get started.

Sure. Good morning, everybody. With me here is Bradley Campbell, our President and Chief Operating Officer; and also, I'm joined by Dr. Hung Do, our Chief Science Officer.

Maybe, I'll just start out the Q&A with the guidance that you gave $250 million, $260 million for Galafold. What are kind of some base case assumptions around achieving that? Where are some upside levers? And if there are any potential risks, what would they be?

Sure. A couple of key drivers. Brad, I'll let you field that one.

Sure, John. Thanks, Anupam. So key drivers for us this year are, first of all, continuing to drive market share. So we announced an update this year. We have a global market share of treated amenable patients of about 30%. Remember, Galafold is indicated for patients with a specific amenable mutation. So that's one key growth driver continuing to drive market share within those regions where we have approved product. The second piece is, also remember that there are about an equal number of diagnosed untreated patients in the market. So not only bringing on switch patients, but also bringing on diagnosed untreated patients. And we're seeing in our more mature markets, whereas at launch, it's more like 80-20, 70-30 kind of rate of switch to naive patients coming on to Galafold. In our more mature markets, it's more like a 50-50 rate. And the last piece is we're still driving market expansion. So you saw at the end of last year and the beginning of this year some additional approvals. So looking at LATAM and other smaller to midsized markets, like Canada and Australia, where we've already launched. Those I think are the primary growth drivers over the next year and really getting to that $500 million peak revenue -- or excuse me, revenue in 2023 on our way to $1 billion in peak. In terms of upside drivers, I think continuing to see newborn screening, high-risk population screening, finding more patients, I think that's really important. Continuing to see that sort of more rapid uptake in the naive population, and particularly in the United States, where that's been a slightly faster opportunity for us. I think those are 2 big upside drivers. I think there are always risks, obviously, in our business. It's a competitive space, but we've been very successful in taking market share from Fabrazyme and Replagal, the 2 other approved products, the enzyme replacement therapies. And so I think, again, you just continue to execute, and I think we've demonstrated the ability to do that.

What new geographies should we be thinking about for 2020 as being potentially layered on to the existing core market?

Well, we will continue to look at Central and Eastern Europe. So we have, of course, Central European approval, but you're still pursuing reimbursement in some of those smaller markets. We did, again, announce approvals in some Latin American and Asia Pacific regions. We're working on reimbursement in those regions. What we've said is that really growth from geography is the countries we recently launched in, the United States, Japan, Australia, as an example. So those are still really in launch phase, so lots of growth still there. Those newer approved markets, Anupam, we think will contribute more in the '21, '22 kind of time frame.

Question from the audience? Go ahead.

Are you guys looking at second-generation small molecules for the Galafold as far as the -- to try to find something that, that could extend maybe the path and life after that runs out?

Sure. Again, we think the molecule Galafold works very well for people with Fabry disease. And again, we've got great intellectual property protection, orphan drug protection in the United States extending well into the 2030s. We think the right area of focus for us for next-generation therapies is going to be in the gene therapy space. What you've seen in the Fabry community is it's really segmented since the launch of Galafold into the amenable and the nonamenable population. We believe that the amenable population for some time would be very well served with Galafold. We think a gene therapy would perhaps be most appropriate first for people with nonamenable mutations given the burden of ERTs, the biodistribution of the ERT products. So we're going to focus on that. We are developing our own next-generation -- I'm sorry, our own Fabry disease gene therapy product, and that's really where our focus is.

Additional questions? Go ahead.

You have plans for the Middle East?

Middle East.

Sure. Plans for the Middle East. Brad, do you want to talk about the expansion of Galafold?

Yes. So there are some markets, actually, where we have compassionate use patients, in particular in Egypt, where we had a clinical trial site, and we haven't gotten to reimbursement and approval there. If we look at sort of Middle East, North Africa, broadly, there is -- there are diagnosed Fabry patients in those regions, and it is an area where we would look to expand into over time. But we don't have a direct presence there now. So we are working with partners. So yes, I would say, in the kind of sort of '22, '23 time frame, that would be an opportunity for us to expand into that region. And in the meantime, if there are patients with a severe medical need, then we do have a compassionate use program that we would actively look to provide patients access through that mechanism.

John, historically, at the presentation at this conference, you've highlighted the WORLD lysosomal storage disease meeting in February as a key place that the company will have a presence. This year, maybe I missed it, but what presentations, and what should we be focused on in that conference? And what kind of presence will you guys be having there?

Brad, do you want to field what we're going to do at WORLD?

Yes. So WORLD for us this year, there -- I don't believe there's any sort of seminal new data on our core programs. We always have an opportunity to do, I would say, supportive updates from our physician collaborators. So there will be, I'm sure, a handful of abstracts, et cetera, presentations across the programs. But we don't have -- for example, Pompe data was last given at World Muscle. So that was the last big update for Pompe. It's a huge opportunity for us from a commercial and medical affairs perspective. We'll do CME Symposia. We'll do our own physician meeting to bring our KOLs together. And so it's a great opportunity to share data, do medical advisory boards, interact with the physicians. It's by far the biggest opportunity for us. So we'll have a -- from a company perspective, from an overall presence perspective, it's one of the most important meetings for us.

We'll also, again, host an analyst and investor dinner as well. And as we've done before, we'll bring in some experts to talk about their experience with our medicines and technologies.

Questions from the audience? On -- in your presentation, John, I think related to PROPEL, you talked about a 15-meter delta for achieving statistical significance. We can try -- power trials, like to get some delta. How did you come to that 15-meter delta, particularly given the population that you're enrolling in PROPEL is a little bit more heterogeneous with naives and switch patients? And what's clinically meaningful in the eyes of...

All right -- yes. Maybe I'll ask Jeff Castelli, who's our Head of Portfolio Development, and who's also done a lot of work on the biostats for that program to comment.

Yes. Sure. Thanks.

Guest speaker coming to the front of the room.

Yes, Anupam, that's a great question. So that 15-meter approximate difference that we would need between AT-GAA and the Lumizyme arms to hit a superior outcome is really based on enrolling the 123 patients, the 2:1 randomization and looking at the variability in 6-minute walk that we observed in the Phase II trial as well as what's been reported in the medical literature. So if you look at estimated standard deviation in the range of 40 meters or so, which is about what we've seen blended across the different groups, that would mean a 15-meter difference would give you that significant outcome in the superiority trial. And in terms of clinical relevance, so what's really nice is in 6-minute walk, which is generally accepted as clinically meaningful is around a 20-meter improvement or difference. So that 15-meter is able to deduct just below what would be considered clinically meaningful. So it's sort of aligned very well with a significant outcome and also, generally mean a clinically meaningful difference as well.

And again, to remind everybody, that's well below what we saw in the Phase II study. So we think we've been very, very conservative here. In the switch population compared to other medicines that have been in development that showed no change or actually a continued decline, for most all patients, we showed a reversal and a gain of strength, improvements in 6-minute walk and multiple other measures of the disease in our switch population at the 1-year time point. So the same as our PROPEL study. We saw about a 40-meter improvement in that cohort. In the cohort that had not previously been treated with enzyme replacement therapy, we saw about a 60-meter improvement. So I think we've been very conservative here as well. And again, lots of other measures of disease and efficacy that we're evaluating in this study.

Questions from the audience? Go ahead.

What would be your strategy for bringing the products into Latin America? Bring your own? Or through third parties?

Right. Again, we just got marketing approvals in Colombia, Argentina and Brazil for Galafold. So it's something that we're focused on today. Maybe Brad, comment on where we are with Galafold and then where we see that going in the future.

Sure. So from a direct presence perspective, our core strategy is to have Amicus employees who are customer-facing. So we want the first conversation with a physician or with a patient, where it's appropriate, to be with an Amicus employee. And in most of major regions around the world, we have a direct presence. Latin America is the only region today where we have primarily a distributor presence. And as I'm sure you're familiar with, that's in large part because of the long process, both to get approved and then go through in Brazil, for example, the traditional review process while you're pursuing central reimbursement. So today, we work with distributors -- through different distributors across Latin America. In the longer term, we would evaluate, as that business grows, as we have additional products come on board, whether or not we would want to take a direct presence there as well, but for now, we do work with distributors.

Additional questions? Maybe I could just ask a competitive question. More broadly speaking, in Pompe disease, how are you thinking about potential competitive ERTs as well as gene therapy relative to what -- your internal programs?

Again, when we began our program at Amicus, we focused on making a novel biologic. We realized the significant shortcomings of the approved standard of care. And we think much of that has to do with the absorption of the enzyme through the mannose 6-phosphate receptor. So we focused on the glycobiology of that. Maybe Hung, I'll ask you to comment on: What did we make? And why do we know it's very, very distinct from what others have attempted?

Sure. Yes, so John, he alluded to the fact that we actually focused on the actual protein in terms of having the proper characteristics that allow it to be targeted and be delivered to lysosomes in affected cells. And so that's where we started. And really, that's been key to how we have developed most ERT programs, but also subsequently from gene therapies. We understand what's actually necessary to target these types of proteins. And what we've done with our particular AT-GAA protein is that we actually developed a production cell line and a manufacturing process that naturally produces the enzyme with the bonafide natural carbohydrate structure that is able to bind and be delivered very efficiently to cells. Whereas, our competitors -- I think that's where we have a distinct advantage. And again, what we've done in regards to gene therapy is we apply that knowledge and capability to designing proteins through the transgene so that the gene that's been used to produce a protein, it always ensures that the protein is well targeted. In that regard, we actually use a slightly different approach. We -- instead of using carbohydrate-based targeting, we use a protein that is known to bind a receptor well and able to deliver it. So in effect, what we've done is made a much more potent protein through this gene therapy. So it ensures that, that protein will be well targeted.

Questions from the audience? Within gene therapy, one of the topics that we always continue to talk about is manufacturing. Can you talk about kind of what manufacturing looks like for the company, both with your internal and external strategies, say, over the next 2 to 4 years, 5 years?

Yes, there are a couple of key pieces to it, Anupam. What we're doing in manufacturing actually builds on our experience with our Pompe enzyme replacement therapy product. So the team that we've built -- we've got about 50 people in technical operations and manufacturing at Amicus. They had focused for the last few years on the design and the scale-up of the AT-GAA product, which is the most complicated biologic, highly glycosylated biologic, ever produced in the industry. We and the team at WuXi, I think, did a very, very good job at scaling that. A lot of those skill sets now translate into the biologic manufacture of gene therapies. Our initial programs were provided material from either Nationwide Children's Hospital. And then again, some manufacturing done at UPenn for some of the IND-enabling studies that were underway. We began last year to secure, number one, all the plasmids that we'll need for all of these programs. So we have plasmids to enable all of these programs as they advance now secured. We also began discussions to secure and reserve capacity at both Brammer Thermo Fisher and at Paragon now acquired by Catalent. Thermo Fisher Brammer is focused on our CLN6, CLN3, manufacture. The tech transfer there is well underway, and we would expect throughout this year into 2021 that they'll provide material for dosing additional patients. And particularly for CLN6, the backbone of what will be the CMC module, we hope of a BLA. So the strategy right now is to lever the experience, capacity capabilities of our key partners. In the meantime, we are focused on securing property for the construction of an Amicus facility. We're deep into the basis of design of that facility. It will be a flexible facility that can incorporate a range of technologies. And we'll have more to say about that throughout this year in terms of final site selection and the team that we're building.

Any final questions?

Can we ask about Sanofi?

We ask broadly the competitive dynamic in Pompe. So...

You can ask Sanofi about their data, I'll let it speak for itself.

All right. Great. Thanks, everyone.

Thank you.

Thank you.