Earnings Call Transcript - FOLD Q3 2020

Operator, Operator

Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics Third Quarter 2020 Financial Results Conference Call and Webcast. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Faughnan, Director of Investor Relations. You may begin.

Andrew Faughnan, Director of Investor Relations

Thank you, Rens. Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics’ third quarter 2020 financial results and corporate highlights. Speaking on today’s call, we have John Crowley, Chairman and Chief Executive Officer; Bradley Campbell, President and Chief Operating Officer; Daphne Quimi, Chief Financial Officer; Dr. Jeff Castelli, Chief Development Officer; and Dr. Mitch Goldman, Senior Vice President of Clinical Research. As referenced on Slide 2, we may make forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, as well as our plans and prospects. Our forward-looking statements should not be regarded as representations by us that any of our plans will be achieved. Any or all of the forward-looking statements made on this call may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. You are cautioned not to place undue reliance on any forward-looking statements, which speak only to the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and we undertake no obligation to revise or update this presentation and conference call to reflect events or circumstances after the date hereof. For a full discussion of such forward-looking statements and the risks and uncertainties that may impact them, we refer you to the Forward-Looking Statements and Risk Factors section of our Annual Report on Form 10-K for the year ended December 31, 2019, and the quarterly report on Form 10-Q for the quarter ended September 30, 2020 to be filed later today with the Securities and Exchange Commission.

John Crowley, Chairman and CEO

Great. Thank you, Andrew, and welcome everyone to our third quarter 2020 results conference call. As we did last quarter, we hope you and your families continue to remain safe and healthy. Our leadership team at Amicus continues to emphasize a range of programs and initiatives to protect and support our global workforce during the ongoing pandemic. While adapting to all of the changes brought about by the global pandemic, for Amicus, 2020 has been a period of excellent growth and execution across all aspects of our business, including science, clinical, regulatory, and as you see in our commercial efforts, as we continue to build one of the next great biotechnology companies, positioned to impact people around the world living with rare diseases. As we did in this morning's press release, I'd like to highlight several key accomplishments. First, Galafold continues its strong launch performance and remains the cornerstone of our success with $67.4 million in third quarter revenue; the Galafold launch continues to exceed expectations. The third quarter revenue represents the performance across all the global business, including new patient starts from both switch and naïve patients throughout the quarter. Second, our key R&D timelines remain on track. We now expect the Phase 3 PROPEL study for AT-GAA in late onset Pompe disease to read out in the first quarter of 2021. Additionally, the rolling BLA submission remains on schedule, and we expect the first submission before the end of this year. Today, we will also be sharing results from the Amicus-sponsored natural history study in Pompe disease. Within our gene therapy pipeline, we continue to advance our lead Batten disease programs for both CLN6 and CLN3, as well as our most advanced preclinical gene therapy programs. Through our major research collaboration with Dr. Jim Wilson and the University of Pennsylvania, we are pleased to announce this morning that a Fabry disease gene therapy clinical candidate has now been selected to move into IND enabling studies. Based on the data that we have seen to date, this program has moved much faster than originally planned for and highlights the capabilities and potential that this collaboration can bring to people living with rare diseases. Third, following our strategic financing in the third quarter, the Amicus cash position is sufficient to achieve self-sustainability without the need for any future diluted financings. Our continued revenue growth, our prudent expense management, and the growth potential for Amicus has allowed us to reach this important milestone, as we continue to realize our vision of delivering groundbreaking, potentially curative new medicines for people living with rare diseases around the world.

Bradley Campbell, President and COO

Thanks, John. Good morning, everyone. As John mentioned, I'll walk you through in more detail our Galafold performance for the quarter. I’ll start on Slide 6, where we review the continued growth of Galafold revenue in the third quarter of 2020. Here, we provide a global snapshot of the Galafold commercial progress. For the third quarter, our total product revenue was $67.4 million, driven by strong patient demand, favorable reimbursement dynamics, and business continuity. Importantly, the global compliance adherence rate continues to exceed 90%. The geographic breakdown of revenue during the quarter was $47.2 million or 70% of the revenue generated outside the United States, and the remaining $20.3 million or 30% coming from within the United States. I'm pleased to announce today the addition of Poland, Iceland, Luxembourg, and Argentina to the growing list of countries around the world with regulatory approvals and now access to reimburse products. As a reminder, before these newest additions, we had approvals in 40 countries and commercial sales in over 30 of those today. This expanding global footprint is essential not just to support the continued expansion of access to Galafold for Fabry patients, but it also lays a very strong foundation which is highly leverageable to support the potential launch of AT-GAA and future products as well. Turning now to Slide 7, as John mentioned, the third quarter was another strong quarter for us. The business continues to be incredibly resilient, and the quarter comes in above the internal expectations for Galafold, with patients added in all of our major markets. In select geographies outside the United States, we did see the COVID pandemic impacting the rate of new patient starts, largely due to disruptions in the interactions between patients and physicians and some bottlenecks in the provision of patient care. Importantly though, our supply chain remains fully intact. Our customers have confidence that they can access Galafold, and our field team has been able to achieve a substantial majority of their pre-COVID touch points, through a combination of in-person, digital, telephonic, and other means of interacting with their physicians. As we close out the year, we will continue to monitor the pandemic's impact and duration, but the good news is today, we’re ten months in, and more confident we will deliver on our guidance and see continued growth into next year. From a true operational performance perspective, sales increased by 35% compared to the same time last year, indicating great growth from quarter 2019 to quarter 2020. And as we mentioned in previous calls, while we do continue to expect strong quarter-to-quarter growth, due to a variety of factors, that growth is typically non-linear. Despite the recent COVID-related headwinds in certain ex-U.S. geographies, we continue to be very confident in our guidance of $250 million to $260 million in full year global sales. At this time, we expect to come in the top half of that range.

Mitch Goldman, Senior Vice President of Clinical Research

Thank you, Brad. Good morning, everyone. Moving on to our R&D updates on Slide 10, I would like to remind everyone of our highly differentiated Pompe therapy AT-GAA and its mechanism of action. AT-GAA is our novel next-generation therapy consisting of ATB200 or cipaglucosidase alfa, an investigational human recombinant GAA enzyme administered into the body through intravenous infusion, designed to target muscle cells throughout the body, combined with AT2221 or Migalastat, an orally administered enzyme stabilizer. The AT2221 is administered shortly before the infusion as the enzyme replacement therapy begins and is intended to bind and stabilize the ATB200 in circulation, allowing more active enzyme to be taken up into cells and delivered to lysosomes. The combination of enzyme replacement therapy and enzyme stabilizer is one major distinction from the standard of care and from any treatment currently in development for Pompe disease. The other distinction, and we believe more impactful advancement is the unique carbohydrate profile of the enzyme itself. Our Chief Science Officer and his team have been working over the past decade to develop this Pompe enzyme replacement therapy that has both improved binding target receptors for efficient uptake into cells, as well as the ability to be processed by those cells in mature form of GAA.

Jeff Castelli, Chief Development Officer

Thank you, Mitch, and good morning, everyone. Moving now to Slide 14. I'll briefly highlight here our industry-leading portfolio of gene therapies for rare diseases. During this time of COVID, we've been able to maintain our critical science and lead programs across the gene therapy portfolio, including CLN6 and CLN3 Batten disease, as well as Pompe and Fabry gene therapy programs at PENN. Last month at the Virtual Child Neurology Society Annual Meeting, we reported positive interim data in our ongoing Phase 1/2 clinical study in CLN6 Batten disease. The data showed a meaningful effect in slowing disease progression after 24 months, compared to Natural History. The data continue to suggest that our gene therapy has the potential to be a treatment option for children living with CLN6 Batten, an ultra-rare debilitating condition that leads to progressive declines in cognitive and motor function and often results in death in early childhood. We continue to advance regulatory discussions to finalize the clinical and regulatory path and expect to provide an update in 2021 for CLN6. We believe the initial CLN6 results also provide important read-through for our clinical study in CLN3 Batten disease, the most common form of childhood neurodegeneration. We plan to report initial data from the ongoing Phase 1/2 study in CLN3 early next year at a medical conference. Additionally, we continue to make great progress on our commercial manufacturing process for both CLN6 and CLN3 programs and remain on track to initiate studies for these programs next year using this commercial material.

Daphne Quimi, Chief Financial Officer

Thank you, Jeff, and good morning, everyone. Our financial overview begins on Slide 20, with our income statement for the quarter ending September 30, 2020. For the third quarter, we achieved Galafold revenue of $67.4 million, which is a 38% increase over the third quarter of 2019. This includes year-over-year operational revenue growth measured at constant currency exchange rates of 35%, further benefited by a positive growth of currency impact of 3%. Cost of goods sold as a percentage of net sales was 12.5% in the third quarter compared to 11.5% for the prior year period. The increase in cost of goods sold as a percentage of revenue was due to sales in select countries achieving the highest royalty rate in this quarter. Total operating expenses were $111.8 million in the third quarter of 2020, reflecting an increase compared to $100.5 million in the third quarter of 2019. On a non-GAAP basis, total operating expenses were $92.4 million in the third quarter of 2020, compared to $89.7 million in the third quarter of 2019. The increase in research and development costs reflected our continued investment to support the gene therapy program pipeline and the PROPEL study, as well as realignment with our strategic priorities. Our investment in research and development includes the impact of the implementation of cost reduction measures, as does the decrease in selling, general and administrative expenses. We define non-GAAP operating expense as research and development and SG&A expenses, excluding share-based compensation, changes in fair value of contingent consideration, and depreciation. The net loss for the third quarter was $64 million or $0.25 per share, compared to a net loss of $61.8 million or $0.24 per share for the prior year period. As of September 30, 2020, we had approximately $260 million shares outstanding.

John Crowley, Chairman and CEO

Great. Thanks, Daphne. So, as you can see, we continue to be relentlessly focused on performance across the business. I am incredibly proud of our team and the resiliency that they've shown, despite the great global pandemic, and all the challenges brought about by it. We have a great global team of passionate entrepreneurs, who have led and will continue to lead us through this. I am confident that as the world emerges from this crisis, Amicus will emerge even stronger. So with that operator, we're happy to take questions.

Operator, Operator

Thank you. [Operator Instructions] Your first question comes from the line of Anupam Rama from JP Morgan. Your line is open.

Anupam Rama, Analyst

Hey, guys. Thanks so much for taking the question.

John Crowley, Chairman and CEO

Sure, Anupam. Good morning.

Anupam Rama, Analyst

Hey, how are you John?

John Crowley, Chairman and CEO

I'm great. Thank you.

Anupam Rama, Analyst

So, just a quick one for me. Thinking about Slide 7 in particular, on Galafold, when you look deeper into the operational growth that you're seeing, how do we think about sort of deeper penetration into the core regions versus, say, new patient ads in some of the newer emerging market regions? Thanks so much.

John Crowley, Chairman and CEO

Yes, sure. Bradley, do you want to provide some more color there to Anupam's question?

Bradley Campbell, President and COO

Yes. Thanks, Anupam. So, it's still a mix. I mean, we have Japan and the U.S., who are still pretty early in their launch cycle. So you're getting really strong switching in those markets, although we are starting to see some naïve patients come on there as well. In Europe, those markets are a little bit further along in their launch curve, so there you're seeing both switch and naïve patients coming out at almost an equal rate, which is what we would expect over the course of the evolution of the launch there. And then maybe a third of the growth is new patients from different geographies. I highlighted a few on the call today. None of those individually are large, particularly large markets, but taken together, they're an important part of the growth story as well. So it is still a mix. I think for the next two to three years, we're going to be very much in that kind of continue to penetrate in the mature markets, continue to push the launch in the big new ones, Japan and U.S., but also bring out as many of the small and mid-sized countries as we can.

Anupam Rama, Analyst

Great. Thanks for taking our question.

Bradley Campbell, President and COO

Thanks, Anupam.

Operator, Operator

Thank you. Your next question comes from the line of Ritu Baral from Cowen. Your line is now open.

Ritu Baral, Analyst

Good morning, guys. Thanks for taking the question. Glad to hear you guys well. I want to focus on…

John Crowley, Chairman and CEO

You too.

Ritu Baral, Analyst

Hi. The new -- sorry that Pompe, POM-002 natural history data. I was wondering to know how much the 002 data contributed to the powering of the PROPEL study, first of all? And second, how do your potential assumptions around powering for PROPEL change or not change, if you think about the placebo arm of the Phase 3 new GAA study that we saw? Just one housekeeping staying on PROPEL. If you could talk about the number of primary endpoint visits you've managed to retain and timing of that?

John Crowley, Chairman and CEO

Good. PROPEL, okay. So, Ritu, we have furiously been taking notes. I think that's only three questions, but that's actually quite good.

Ritu Baral, Analyst

One question.

John Crowley, Chairman and CEO

But in multiple parts. So, yes, we are happy to answer. Let me, before I ask Jeff and Mitch to weigh in again, I'll just emphasize the POM-002 study was originally done as potential for a competitor had there been a window for an early filing. Here, once we completed it, I think it adds to our body of knowledge, adds to the field, but it looks to be entirely consistent with everything that's been known about any benefit for Lumizyme and then the decline over time. So, with that, Jeff, and maybe you want to begin, and then we can ask Mitch to add any comments or colors to it. Did you capture those questions from Ritu, Jeff?

Ritu Baral, Analyst

Sure.

John Crowley, Chairman and CEO

I have him up on video, muted with our video system, so I can see him trying to talk. But then we'll go ahead and Mitch, and I'll be happy to take the questions. So, Mitch, do you want to talk about the first part in terms of powering and what we assumed? I think the takeaway is that the study PROPEL was extremely well powered. And again, based on what we know, we think we need somewhere around 15 or so, 15 to 20 meter delta to show statistical significance on superiority.

Mitch Goldman, Senior Vice President of Clinical Research

Sure. I think it's really largely right, John. I mean, it helped us to have the in-house data sets with the variability that we would see. We used that along with our Phase 2 data to really understand moving against the six-minute walk time point, the variability in the variable outside of the study. So that's how we landed on 100 or so patients with PROPEL study and looking to deliver a 15 to 20 meter improvement in six-minute walk at the end of the study versus the competitor, alglucosidase.

John Crowley, Chairman and CEO

Thank you, Mitch. I think, you know what this does and looking at all, once we saw this, this just gave us further confirmation, there. This study PROPEL was extremely well powered. And again, based on what we know, we think we need somewhere around 15 or so, 15 to 20 meter delta to show statistical significance on superiority. It’s interesting, Ritu, your second part of the question, you referenced the neo data. And while I won’t speak to the neo arm, just their control arm, we did see that they had, I believe it was a 3 meter improvement that one year, so essentially flat to where those patients began. That is worse than we assumed for Lumizyme. Again, that is in a naive patient population. Again, our study is about 70% switch, about 30% naïve. But in respect to the naive patient in our studies, we expected that they would look more like 25 or so meters was our assumption. So if, for whatever reason, the patients randomized to Lumizyme and the control arm of our study in the PROPEL study were to be closer to what we saw in neo, it would just further add to the powering of our study as well. The third part of your question was around assessments lately. We did see some disruptions in the March, April timeframe. By mid to late May, all of the sites were receiving patients; patients were getting not only their infusions but their assessments. Even in the height of the pandemic back in early spring, the vast majority of patients we were seeing were still getting their infusions, and all of their assessments, and we look at the aggregate of the 3,100 assessments and infusions, we're still well more than 97% of those have gone off as planned. So the integrity of the study remains very high. And again, in any study, of course, you plan for missed infusions and missed assessments. Actually, even with the pandemic, we're in a better place than we assumed we would be without a pandemic. And I think that's a real testament to the effort of the team here.

Ritu Baral, Analyst

Great. And are you guys making any adjustments for an increase in pandemic-related logistics, as cases are rising right now and before?

John Crowley, Chairman and CEO

We follow every patient every week. We've got a master tracker of every set of activities for every patient. And again, the vast majority of patients now have completed that PROPEL study. We of course remain blinded to all of that, but virtually all patients have completed. Last patient out is scheduled in December.

An Unidentified Analyst, Analyst

Hey there, this is Julie dialing in for Joe. Thanks for taking our question. My question is on AT-GAA. Could you just remind us if there are any key steps remaining to complete your rolling BLA submission once you have your Phase 3 data?

John Crowley, Chairman and CEO

Sure. We will have completed and submitted by the end of this quarter, the first module, the preclinical module; all of those activities have been completed. So, that will begin the rolling BLA process, Julie. We are nearly complete with all of the PPQ activities. We've completed the manufacturing parts of it, both upstream and downstream. So, some final last work and time on the stability studies and of course, all the final reports necessary for that CMC module. And we're already drafting the clinical module. Once we have the PROPEL data, we would expect to update the clinical module with all of that important data. So no, there are no barriers left for us other than receiving the PROPEL data.

Salveen Richter, Analyst

Good morning, thanks for taking my question. So, really two around the gene therapy portfolio. One around your Fabry candidate that's moving forward, and how you see it differentiated versus competitors out there? And we've had a few others discuss their target or the protein as well as construct an approach here. And then on the Battens program, what do we need to understand regulatory-wise in order to move forward or expand into a pivotal stage?

John Crowley, Chairman and CEO

Great. Thanks, Salveen. Hung, maybe you can speak to the science work that went into our Fabry gene therapy and the differentiation, what was unique about the protein and the tech that you took, and then we can come to Salveen's Battens question in a moment.

Hung Do, Chief Science Officer

Sure. Thanks, John. Hi, Salveen. To your question about how we develop our approach for the Fabry gene therapy, it actually is quite differentiated between us and how everyone else is approaching that. First and foremost, I should stress the importance of that protein being expressed as a dimer of two identical subunits. It's imperative that that dimer stays together and intact for it to be functional. With that in mind, what we've been able to do is to engineer the transgene so it produces a protein that maintains that dimer formation, and it maintains its activity. That's important, as we were showing you that it remains active while being expressed and secreted into the blood prior to its targeting to various tissues. This is a huge advantage that we've seen, where we have been able to increase the activity and potency of that protein. So, when it targets, it will be much more potent and effective for clearing substrates. So again, as far as we know, this is the only gene therapy approach that may offer a more potent enzyme through the transgene.

John Crowley, Chairman and CEO

And then Salveen, I'll just comment briefly to your questions around regulatory. Again, this year we've spent an enormous amount of time and effort focused on the CMC and the technical operations parts of these programs. We have successfully completed the tech transfer from Nationwide Children's to Thermo Fisher Brammer. They are now producing at commercial, what we believe will be the commercial scale and quality. A lot of work has gone into the analytical development, the tightening of the potency assay, and all the related analytics. In terms of regulatory interactions, a good part of our regulatory interactions are to make sure that the key regulatory bodies are comfortable with all of the technical operations and CMC components of both CLN6 and CLN3. On the clinical side, we’re going to dose additional patients in both of those diseases with the commercial scale and quality material from Thermo Fisher. Right now, we're going to work with the regulators to figure out what is the right amount of time for additional follow-up for these patients. For CLN6, in particular, what is the amount of time, and what is the number of patients as well? For CLN3, we've only dosed four patients with the nationwide material. To Jeff's point earlier, we'll be able to provide a first look at that clinical data in the early part of 2021. So we’re moving as fast as we possibly can in those programs and in other programs, neurologic Batten programs which continue through our preclinical pipeline.

Mohit Bansal, Analyst

Hey there, this is Keith on for Mohit. Thanks for taking the questions, and congratulations on the quarter. So, we're just looking at expectations for gene therapy in general, they seem to have moved away from the cure and more towards a very long-term therapeutic. It’s obviously very early, but looking at the CLN6 data, the probability of no decline seems to be pushed out rather than avoid it entirely. How are you thinking about the mid and long-term expectations for this therapy? And then what would be the bar there for efficacy over time?

John Crowley, Chairman and CEO

Yes, candidly we continue to have very high expectations. These patents for these programs, as you know, they're really just awful devastating diseases. It seems that the earlier that you treat children in their disease progression, the better the outcome will be. Right now, it's unclear whether you can ever reverse neurodegeneration, it doesn't seem that you can based on today's tools and technologies. It's really important to identify these children as soon as possible after birth and to administer gene therapy, but we remain optimistic that for children without significant brain damage, with the properly targeted and safe gene therapy, that you can have a profound difference in fundamentally changing their quality of life. Will it be a cure for some of the younger children or something more along the lines of curative therapy? We still think potentially so, but there is still much to be seen over time. Mitch, Jeff, if you guys want to add color?

Jeff Castelli, Chief Development Officer

Hey John, this is Jeff. Can you hear me?

John Crowley, Chairman and CEO

You’re back. Yes, you paid your phone bill. Good.

Jeff Castelli, Chief Development Officer

Yes. My apologies for getting disconnected at the wrong time before. One thing I will comment on, as John mentioned, we think it's the baseline severity that can impact whether kids treated with these neurological gene therapies can remain largely normal, live a pretty normal life, or if they're impacted already and there's other damage that's done, there still can be some progression that's not really due to the underlying genetic factor that you're addressing with the gene therapy. So, we think that that's a big factor here. In terms of durability of gene therapies, we know that's an issue with some of the liver directed gene therapies and some of the blood disorders, for example. With CNS delivery, we really do expect that these gene therapies should be durable. There's really not a lot of data suggesting that there's any sort of turning off of expressing cells or turnover, so we are really hopeful that durability at least for CNS directed gene therapies could be quite good.

Mike Ulz, Analyst

Hey guys thanks for taking the question.

John Crowley, Chairman and CEO

Hi Mike, good morning.

Mike Ulz, Analyst

Good morning. Just a quick follow-up on the PROPEL study. John, you mentioned closing the last patient in December, can you talk a little bit about the timeframe to turn that dataset around and provide the topline results? And I'm just curious if you see any unique challenges created by COVID and if that could potentially extend the timeline there? Thanks.

John Crowley, Chairman and CEO

Thanks, Mike. Yes again, we've tightened the timeline. We always said it would be first half of 2021. Now that we're just on the cusp of the last patient out, we're confident that we'll be able to report the data out in the first quarter. That patient will receive the last infusion assessment as part of the protocol in December. Shortly thereafter, into early 2021, we’ll lock the database and go through all of our protocols that we have in place and standard operating procedures for our clinical operations, clinical research teams, to go through all of the data once we're confident that the integrity of the data and the database is scrubbed. We don't foresee anything with respect to COVID that would delay that, but we'll have to see as we get into. That's why I think we gave ourselves some cushion by narrowing it to Q1. But we’re also very confident that in the 12 weeks or so in Q1 that that should be ample time, even if there are some challenges at some sites in the final data assembly. So, I think we'll be in a really good place to report that out in Q1. By Q2, we expect to file the BLA in the United States and complete that submission.

Evan Wang, Analyst

Hi. Thanks for taking the question. I had a question on gene therapy CMC broadly. We've seen some difficulty with its communication or regard to the guidelines with FDA, with comparability, especially between clinical grade to commercial grade. Has there been any change with respect to regulatory agency requirements regarding CMC? Or is it some sort of growing pain for the gene therapy industry? If this impacts work towards building out in-house capabilities compared to utilizing the CMO? Thanks.

John Crowley, Chairman and CEO

Yes. Evan, I'll just state broadly, I think if Amicus is going to become one of the world's leading gene therapy companies, we've also got to be one of the world's leading gene therapy companies in process science. In many respects in gene therapy, the process is the product. We have been just hyper-focused on it. I think Amicus is uniquely suited to succeed here, based on all the experience we have with AT-GAA. That is among the most complicated glycosylated biologics ever produced. For that Pompe enzyme therapy program, we have successfully scaled it, produced it at commercial scale. With our partners at WuXi Biologics, we have a really sophisticated and experienced team in technical operations, quality, regulatory CMC, and we're applying all of that excellence together with our partners at Thermo Fisher Brammer in these lead Batten programs but also with other CMOs, with Jim Wilson and his UPenn team. A lot of work on the CMC and the analytics and manufacturing side. I think it will be a great strategic advantage for Amicus. The part of your question about the regulatory environment without question, in the last 12 to 18 months the regulatory framework at the FDA has continued to evolve. There have been much strengthened and tightened standards around the analytical components, CMC requirements, manufacturing requirements for gene therapy. I think it's a good thing, I think it was necessary, I think it's important for patient safety, but also important so that we understand exactly what we're providing patients so we can assess efficacy. Gene therapy is fundamentally different, with AAVs in particular; most patients are going to, based on today's technologies, only get one chance. And we’ve got one shot as innovators and drug developers to get it right for patients. That's why we are just hyper-focused and a lot of focus attention on a lot of our resources into the CMC side. We are busy at work designing a world-class state-of-the-art clinical manufacturing gene therapy facility. We're also in the early stages of thinking through a larger commercial-scale facility as well. We would expect in very early 2021, that we'll be able to describe a lot of that more fully. A lot of work behind the scenes on CMC for all of our programs, really, including investigating next-generation technologies and working to develop and invent what I think will be some of the key technologies in gene therapy manufacturing ahead. We really want to be, and we need to be at the forefront of gene therapy manufacturing.

Kristin Gorski, Analyst

Hi, everyone. Thanks for taking my questions, and congrats on the great progress you've made over the last quarter. So, I wanted to ask on Fabry disease, how are you looking at the trends of identifying more amenable mutations on the label in the U.S. and Europe? And then for your gene therapy program, could you remind us what you would view as the key differentiators and advantages to Amicus versus some of your peers, including your understanding of the market, of course, through Galafold? I know in the past that you've discussed in detail the importance of a really safe approach here, as well as targeting higher transduction to the heart and other key organs.

Bradley Campbell, President and COO

Sure, yes. So, I think there are really two pieces to that. One of them, Kristin, as I'm sure you saw last quarter, we did announce that we expanded the European label to include all of the potential mutations in the GLA gene. We went from 350 or so mutations in the European label to 1,384 mutations. We were able to do that from the great internal science team that we have and the creative approach that the Europeans took with the ability to update that label just with the preclinical assay determining amenability. In the United States, that process is a little bit different. There, we actually have to have a patient who has been diagnosed with a new mutation in order to update the label. You see that the number is growing in the United States, but it's growing in ones and twos as we find patients with those mutations. So, that's one piece of the puzzle. The second piece is identifying new Fabry patients. There, we're doing a ton of work. We've talked before about some of the interesting data looking at an underdiagnosed Fabry disease in MS clinics. We're going through some investigator initiated studies to look more closely at that. We've also looked at PENN and GI clinics. We're doing some really exciting things around both artificial intelligence, looking to improve the diagnostics. We hope maybe in the first part of next year, we can talk a little bit more about some of the exciting findings there. Lastly, we’ve talked about work we've done with a company called NBK; they help promote the use of diagnostic genetic testing. We’ve partnered with them to include Fabry in the panel, particularly amenable Fabry mutations. And finally, for every Fabry patient you find, because it's an X-linked disease, you typically find four to five family members with undiagnosed Fabry as well. There’s a tremendous amount of work going on there. I think everybody in the field is really focused on that. That’s why you continue to see significant increases in diagnosis for Fabry, identifying more patients with amenable mutations.

John Crowley, Chairman and CEO

Great. Thank you, Bradley.

Operator, Operator

Thank you. At this time I would like to turn the conference back to Mr. John Crowley, Chairman and CEO, for closing remarks.

John Crowley, Chairman and CEO

Great. Thank you, operator. Thank you, everybody, for listening. Have a great day.

Operator, Operator

Ladies and gentlemen, this concludes today’s conference call. Thank you and have a great day.