Amicus Therapeutics Inc

NASDAQ:FOLD

Earnings Call Transcript 2018-Q4

[Operator]

Good day, ladies and gentlemen, and welcome to Amicus Therapeutics Full-year 2018 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. Instructions will follow at that time. [Operator Instructions]. As a reminder, this conference call is being recorded.

I would now like to turn the conference over to your host, Sara Pellegrino, Vice President of Investor Relations and Corporate Communications. You may begin.

[Sara Pellegrino]

Thanks, Nicole. Good morning and thank you for joining our conference call to discuss Amicus Therapeutics' full-year 2018 financial results and 2019 corporate highlights.

Speaking on today's call, we have John Crowley, Chairman and Chief Executive Officer; Bradley Campbell, President and Chief Operating Officer; and Daphne Quimi, Chief Financial Officer. Dr. Jay Barth, Chief Medical Officer, is also here, and Dr. Hung Do, Chief Science Officer, and Jeff Castelli, Chief Portfolio Officer and Head of Gene Therapy are participating from Philadelphia and available to participate in the Q&A session.

On this call, as referenced on slide two, 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 representation 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 the cautionary statement and we undertake no obligation to revise or update this presentation or conference call to reflect events or circumstances after the date hereof.

For a full discussion of such forward-looking statements and risks and uncertainties that may impact them, we refer you to the forward-looking statements on slide two of our full-year 2018 results slide deck as well as the forward-looking statements and risk factors section of our annual report on Form 10-K for the year ended December 31, 2018, to be filed later today with the Securities and Exchange Commission.

At this time, it is my pleasure to turn the call over to John Crowley, Chairman and Chief Executive Officer of Amicus. John?

[John Crowley, Chairman and Chief Executive Officer]

Great. Thank you, Sara. Good morning and welcome everyone to our full-year 2018 results conference call. This is the third year we are holding our full-year results on the last day of February on Global Rare Disease Day, a true reflection of our dual mission of making a positive and meaningful impact for people living with rare diseases, as well as our important mission to drive shareholder value for all Amicus shareholders.

The theme of this year's Global Rare Disease Day is bridging health and social care. And that's a very relevant one for Amicus, focusing on bridging the gaps and the coordination between medical, social and support services in order to tackle the challenges that people living with rare diseases and their families around the world face every day.

Indeed, Amicus strives every day to bridge these gaps through the commercialization and development of our portfolio of medicines for rare metabolic disorders, as well as our strength in patient advocacy, our corporate citizenship and our other support services.

And beyond just the medicines we develop and deliver, our Healing Beyond Disease initiative brings team Amicus into the rare disease communities to help bridge these gaps in very unique and extraordinary ways.

Hopefully, throughout the course of this call today, as you listen to our full-year 2018 results and recent corporate updates, you'll understand even more deeply how Amicus contributes to this year's rare disease theme and to the rare disease communities every day, and how we are committed to our mission to build one of the great and enduring companies in all of biotechnology.

As we shift into our financial results and outlook, I'd like to draw your attention to slide four to note the highlights that I first outlined in early January.

The first is the extraordinary success we have had with the launch of our precision medicine Galafold for Fabry disease. At the end of last year, more than 650 people living with Fabry disease with amenable GLA variants, also referred to as genetic mutations, were taking this precision medicine as their only treatment for Fabry disease.

As Brad will detail in a moment, with the strength of our global launch, including the continued very strong momentum in the early stages of our US launch and our continued launch in Japan and other geographies, we're highly confident in our full-year 2019 guidance range.

Indeed, based on the continued exceptionally strong trends that we're seeing globally for Galafold in the first two months of this year, we believe that the potential for achieving this range significantly exceeds any downside risks.

We are also even more confident now with our pathway to drive Galafold sales toward $500 million by 2023 and to $1 billion plus addressable Galafold market in 2028, with the potential to positively impact thousands of people living with Fabry disease who are amenable to this novel precision medicine.

The second pillar is AT-GAA for Pompe disease, our novel biologic combined with a pharmacological chaperone. In February, at the WORLD Symposium in Orlando, we presented Phase I/II data out to 24 months in persons living with Pompe disease, some of whom were confined to wheelchairs, some still with the ability to walk and the group who had previously been on treatment and others new to treatment.

The effect of AT-GAA continues to impress and to be persistent and durable. The vast majority of patients in this study receiving AT-GAA have improved in their muscle strength and muscle function.

And earlier this week, as I will highlight later on the call, we announced that the US FDA granted breakthrough therapy designation, or BTD, for AT-GAA in late onset Pompe disease, a significant accomplishment for team Amicus and the patients, physicians and collaborators who have worked with us to advance AT-GAA to be the next potential standard of care as quickly as possible, again, with a potential $1 billion to $2 billion peak sales opportunity.

Our third pillar is our gene therapy portfolio of 14 gene therapy programs, two of which are clinical stage programs, which we acquired during the second half of last year through two strategic transactions with Nationwide Children's Hospital and doctors Brian Kaspar and Kathrin Meyer and also through a major research collaboration with Dr. Jim Wilson's team at the Orphan Disease Center at the University of Pennsylvania.

And now, with the announcement this week of our new Global Research and Gene Therapy Center of Excellence located in Philadelphia, adjacent to UPenn, we further advance our commitment to world-class science through gene therapies that will make a meaningful difference in the lives of people living with these life-threatening conditions and that have the potential to one day lead to cures.

And again, we see our gene therapy programs at Amicus potentially leading to more than $1 billion in peak recurring annual revenue.

Our fourth pillar continues to be our financial strength. We have always been stewards of our balance sheet and ensuring we are properly funded, while we're judicious in investing appropriately in the right programs and technologies.

We began 2019 with more than $500 million cash on hand. Our runway is sufficient to fund our operational plan at least until mid-2021, advancing us several years closer toward our 2023 vision to treat 5,000 patients with Amicus medicines and to achieve $1 billion plus in global revenue, which would be on par with today's leading global rare disease biotech companies.

Turning to slide five, as I highlighted in our press release this morning, we have five key strategic priorities for this year, 2019, and we are well on track to achieving or exceeding all of them.

First strategic priority, for Galafold, our precision medicine for Fabry. Again, we expect to nearly double annual revenue in 2019. Again, based on what we're seeing thus far into the first quarter of this year, we're highly confident in achieving our full-year guidance.

Second, Pompe continues to be incredibly important for Amicus. And with the recent BTD, there is a lot of momentum right now for this program and an enormous amount of activity here at Amicus.

We also expect this year to complete enrollment in the pivotal study, which we're calling the PROPEL study, as well as provide additional Phase I/II data from cohort 4, and the public scope disclosure of the natural history of Pompe patients on currently approved ERT standard of care.

Third, we now have two gene therapy programs in the clinic in two different types of Batten disease. We expect very important data in the middle of this year in the CLN6 Batten program in additional patients at two years following a one-time administration of our gene therapy.

We also expect to complete enrollment of the ongoing CLN3 Batten disease clinical study. The initial child with CLM3 Batten disease in that study continues to participate with no serious adverse events to-date, following a single one-time administration of the gene therapy at the end of last year.

Our fourth goal is to achieve preclinical proof-of-concept for our Fabry and Pompe gene therapy programs, likely at science meetings and in peer-reviewed publications.

A lot of work is now well underway in collaboration with Dr. Wilson and his scientists at UPenn, together with our Research and Gene Therapy team in Philadelphia.

And five, again, we will always maintain a strong financial position here at Amicus.

So, with that as the overview, let me now hand the call over to Bradley Campbell, our President and Chief Operating Officer, to highlight the Galafold launch. Brad?

[Bradley Campbell, President and Chief Operating Officer]

Thanks, John. Good morning, everyone. Let me begin on slide seven with a snapshot of the Galafold launch through December 31.

First, as John mentioned, we're very pleased with the strong adoption for Galafold in 2018, including new countries such as Japan, the United States and Canada. And we remain very confident that this strength will continue in 2019 during our first full year of launch in these major markets and also as we enter new markets around the world.

Our full-year revenue in 2018 was $91.2 million, which is a year-over-year increase of approximately 147% from fiscal year 2017. And as we move through our first quarter, we continue to see exceptionally strong momentum in new markets, including the United States and Japan, as well as in our more mature markets.

Let me provide a little qualitative color in the different regions around the world. We do continue to see growth across the EU 5, and Europe more broadly. And in more mature markets such as Germany and the UK, we see an increasing proportion of previously untreated patients come on to Galafold. This is right in line with our strategy for initial adoption in switch patients followed by uptake in previously untreated patients.

In the United States, we continue to see significant increase in patients on Galafold from a continuing, growing and very wide prescriber base. We've got a balanced mix of male and female patients, with both switch and previously untreated patients who have amenable variants.

We have obtained broad reimbursement coverage and continue to make great progress with payers, experiencing shorter and shorter times toward moving from prescription to patients receiving drug.

And finally, across all markets, we continue to see an exceptionally high rate of compliance and adherence to this oral treatment option.

Turning now to our guidance on slide 8, now that we're about two-thirds through this first quarter and with the strength in the commercial metrics I just described, we are highly confident in our guidance range of $160 million to $180 million for this year. And by the end of the year, we expect that more than 1,000 people living with Fabry will be taking Galafold as their only treatment for Fabry disease.

This would be a fantastic achievement for Amicus and will represent a meaningful impact on how Fabry disease is treated around the world.

On slide nine, we continue to believe that Fabry may be one of the most under and misdiagnosed human genetic disorders in the world, with continued growth expected in the Fabry population through newborn screening and other diagnostic initiatives.

We believe we can get to, as John mentioned, $500 million in potential sales by 2023, with a $1 billion plus addressable market opportunity in 2028.

With that, let me hand the call back to John to provide an update on our pipeline programs.

[John Crowley, Chairman and Chief Executive Officer]

Great. Thanks, Brad. I'm on slide 11. And as we look to our Pompe program, I'd just like to take a moment to highlight the importance of the breakthrough therapy designation recently granted to AT-GAA in late onset Pompe disease.

Here on this slide, I'll highlight what BTD is, the basis for AT-GAA receiving BTD and the specific features that BTD provides.

First, by definition, to receive a breakthrough therapy designation, there must be preliminary clinical evidence indicating that the drug may demonstrate substantial improvement on a clinically-significant endpoint over available therapies. And in the case of Pompe disease, we believe significant unmet need remains despite an approved therapy.

For AT-GAA, the BTD is based on clinical efficacy results from the ongoing Phase I/II clinical study, including improvements in six-minute walk distance in late onset Pompe patients in comparison to natural history of treated patients.

And now, with this BTD for AT-GAA, it will facilitate multi-disciplinary, comprehensive discussions of the AT-GAA development program with the FDA, including planned clinical trials and plans for expediting manufacturing development strategy.

We're also eligible for all fast-track features, including the potential for a rolling BLA and priority review.

This BTD, together with our results from the ongoing Phase I/II study and the ongoing PROPEL pivotal study, support our strategy to advance AT-GAA as quickly as possible with a potential to become the new standard of care for people living with Pompe disease.

In addition to the more frequent and intense dialog with the FDA on this program and also all of the initiatives that may advance this medicine to Pompe patients as quickly as possible with this BTD, we also believe that the BTD represents an important acknowledgment of the great unmet need that exists for patients with Pompe disease, despite an approved ERT. And also, the significance of the data that we have shown to-date as compared to the natural history of people on the ERT standard of care.

The baseline remains that the pivotal PROPEL study will be the basis to support full approval of AT-GAA. We remain laser-focused on enrolling the PROPEL study and doing what we need to do to further build out our body of data for AT-GAA.

Based on regulatory feedback from both the FDA and the European Medicines Agency, we expect that the AT-GAA development plan, including a planned pediatric study, will support a broad indication for ERT switch and treatment-naïve Pompe patients in adults, as well as in children.

Moving to slide 12, let me reiterate here a number of objectives for our Pompe program, the AT-GAA program. We've already made great strides in just the first few months of the year with our data presentations at the WORLD Symposium in Orlando, in addition to the announcement of the breakthrough therapy designation.

For the remainder of this year, we will concentrate on the PROPEL study enrollment, on the additional Phase I/II and natural history data, on supportive studies, including our open-label pediatric study initiation, as well as the advancement of our agreed-upon CMC requirements and the continued important related manufacturing work for AT-GAA with our partners at WuXi Biologics.

And while we engage with regulators frequently throughout this process, and now even more so with the breakthrough therapy designation, we will not provide any color or expectations on any pending or future regulatory interactions until after they've occurred and only if they materially impact our assumptions from the base case.

So, moving now to gene therapy on slide 14, let me highlight here that we now have a leading portfolio in the lysosomal storage disorders, or LSDs, including 14 gene therapy programs. This strongly positions Amicus to become the consolidator of some of the greatest gene therapy technologies, products and minds in the field, including Dr. Jim Wilson at UPenn and Dr. Brian Kaspar from Nationwide Children's Hospital.

Through our partnership with Nationwide, we have 10 programs in the neurologic LSDs, two of which are now in the clinic.

Indeed, on Rare Disease Day, we can reflect on all of the diseases for which there are no available treatments and think about the new programs in our pipeline and the potential to offer hope to people who, in too many cases, particularly children living with these diseases, believe that they no longer have hope.

Up to 10,000 children that we estimate are living with a rare neurologic LSD that may be addressable to the Amicus portfolio. That's in addition to our strong collaboration with Dr. Jim Wilson at Penn that focuses on Fabry, Pompe, CDKL5 deficiency disorder, or CDD, where our team in Philadelphia now work across the street and in close collaboration with Dr. Wilson's team to advance these programs as quickly as possible.

As outlined on the next slide, number 15, 2019 is a very important year of execution for us in gene therapy across these programs and this R&D engine for future growth.

By the end of the year, in terms of data, we anticipate having additional two-year data in our CLN6 Batten disease study, as well as proof-of-concept for our Fabry and Pompe gene therapy programs.

On slide 16, here you'll find a rendering of the new Amicus Global Research and Gene Therapy Center of Excellence. It's located in uCity Square, overlooking the UPenn campus in Philadelphia.

This, as many of you know, is a burgeoning hub for medical breakthroughs. The establishment of this center for Amicus is an important next step in the evolution of our science, research and gene therapy capabilities, which greatly advances our commitment to world-class science that makes a meaningful difference in the lives of people living with rare metabolic diseases.

The new facility in Philadelphia is being led by Dr. Jeff Castelli, our Chief Portfolio Officer and the newly appointed Head of Gene Therapy, as well as our Chief Science Officer, Dr. Hung Do. Together Jeff and Hung will serve at the headquarters for the global Amicus Science organization and the gene therapy leadership team.

We are honored to be a part of the exciting Philadelphia research community and we look forward to fostering collaborations to significantly contribute to our role in advancing further medical innovation.

Slide 18, to summarize, here we list all of our upcoming milestones for 2019 that we anticipate across our portfolio. These are also highlighted in this morning's press release and are all on track with several already achieved.

At Amicus, we have key organizational strength as well that provide us with a strategic advantage to build the next great leading global biotechnology company in rare diseases. And, again, this fits with the notion that we are building one of the great and enduring companies in biotechnology.

Over the next several quarters in 2019, on these calls, I plan to highlight different teams at Amicus that are driving us toward our vision, beginning with our commercial organization on this call.

In future quarters, I plan to highlight our technical operations and quality organizations, our global clinical development and regulatory affairs teams, and our science and research teams and, of course, throughout our patient advocacy focus.

So, with that, turning to slide 20, let me first emphasize that we're a global organization with a presence now in all four major regions around the world, including a presence in 27 countries, with a direct presence in 20 of them, and Amicus offices in 11 countries around the world.

The reach and breadth of our footprint is remarkable when you think that just a few short years ago, in 2015, Amicus in total had fewer than 200 employees operating out of our one location here in New Jersey.

Then we took the decision to commercialize Galafold on our own and have now built an organization of more than 600 total global employees, including more than 150 Amicus employees who support the Galafold business around the world.

And with the strength of our clinical development and patient advocacy and medical affairs team, we have now laid, we believe, the groundwork for developing and delivering a global rare disease portfolio that will create even more value with each additional product we can deliver globally for people living with rare diseases.

The second aspect I'd like to highlight on slide 21 is the tremendous team of entrepreneurs that brings the utmost passion for patients and for our mission to bring great new medicines to people living with rare diseases.

Among these individuals, there is extensive experience from leading organizations within the orphan disease space and from biotechnology more broadly, who have built very successful multi-product franchises around these diseases, with significant unmet need.

This diversity created an optimal combination that not only prepared us to launch Galafold, but have now established Amicus within the LSD field and position us for our longer-term success and move us toward our greater vision.

Third, as we see here on slide 22, is part of our success that is truly the result of the qualities of Galafold in our efforts to drive the science. Again, Galafold is a truly differentiated product.

As the first oral treatment option for Fabry patients with amenable variants or mutations, and the unique website where physicians can determine whether the patients' mutations are eligible for treatment with Galafold, the team worked tirelessly to educate physicians about this new treatment approach and to drive the science behind Fabry disease.

In addition, we're building further data through our followME registry, post-marketing and investigator-initiated studies and publications.

Again, the credibility and relationships this team has built within the Fabry and lysosomal storage disease space through these efforts will support our future programs and we think will continue to be a strategic advantage for Amicus and a very differentiating feature for our company.

And finally, slide 23, we have a corporate responsibility and a broad commitment to market access, which has been the key to our success based on our core value that our medicines must be fairly priced and broadly accessible.

For Galafold, this means we have generally priced at parity to ERT within each market, which then saves the system the cost associated with the infusions. We believe this has translated into a meaningful value proposition for reimbursement authorities and that it has led to rapid access and reimbursement for Galafold in markets around the world.

In the United States, we introduced the Amicus promise. And in that PROMISE, we pledged that we would never raise the price of our medicines – Galafold in this case – above consumer inflation annually, which again has been very well received by payers.

And we are supporting patients throughout their Galafold journey through our in-house Amicus Assist patient services group, including various financial assistance mechanisms for qualifying persons to help ensure broad access to Galafold.

We have also made a commitment, an AMICUS pledge, to reinvest a portion of our revenue from Galafold back into the Fabry disease community, specifically to Fabry research and development until there is a cure for this disease. This pledge is already underway through our Fabry gene therapy program with UPenn, which we initiated last year.

So together, just to summarize, and I'll turn it over to Daphne just in a moment, I think that all of these efforts and initiatives highlight our broad commercial organization and our capabilities that are a key part of our success with Galafold and also laid the foundation for our future growth. And I think it also reflects the essence of what we're building here at Amicus.

So, with that, and thank you for indulging me in just highlighting a very important organizational strength of Amicus. Let me now pass the call over to Daphne to discuss the financials for the full year. Daphne?

[Daphne Quimi, Chief Financial Officer]

Thank you, John. And good morning, everyone. Our financial overview begins on slide 25 with our income statement for the 12-month period ending December 31, 2018.

For the full-year 2018, we recorded Galafold revenue of $91.2 million, a 147% increase over 2017.

Cost of goods sold includes manufacturing costs as well as royalties associated with sales of our product. Cost of goods sold as a percentage of net sales was 15.8% for the full year ended December 31, 2018 as compared to 16.9% for the prior full-year period.

We continue to make significant investments in R&D and manufacturing, with the ongoing pivotal study and commercial scale-up in our Pompe program, as well as the expansion of our gene therapy portfolio and capabilities.

During the full year of 2018, we recorded $270.9 million in R&D expense, which, as a reminder, includes the upfront payment of $100 million for the Celenex asset acquisition. This compares to $149.3 million for the prior full-year period.

Total selling, general and administrative expense for the full year of 2018 was $127.2 million as compared to $88.7 million for the prior full-year period. The increase represents the expanded geographic scope of the ongoing Galafold commercial launch, including initial launch activities in Japan and the United States.

Net loss for the full-year 2018 was $349 million or $1.88 per share compared to a net loss of $284 million or $1.85 per share for the prior full-year period.

At December 31, 2018, we had approximately 189.4 million shares outstanding.

Moving onto slide 26, a few comments about our current cash position and 2019 financial guidance. Cash, cash equivalents and marketable securities totaled $504.2 million on December 31, 2018 compared to $358.6 million at December 31, 2017.

In addition, net cash spent was $196.3 million for the full year of 2018, which was below full-year 2018 net cash spend guidance of $200 million to $225 million.

Looking at the remainder of 2019, we are reaffirming our full-year Galafold revenue guidance of $160 million to $180 million. Taking into account our anticipated investments as well as anticipated Galafold revenue, we expect to have approximately $300 million in cash on the balance sheet at the end of 2019. This projected year-end cash balance reflects all ongoing investments in our operations, including Pompe manufacturing scale-up, as well as facilities, including our new Global Research and Gene Therapy Center of Excellence in Philadelphia.

With our current cash position and the continued revenue from sales of Galafold, we have sufficient capital to fund ongoing operations into at least mid-2021.

As we have noted in the past, potential business development collaborations, pipeline expansion and investment in manufacturing capabilities could impact our future capital requirements.

This summarizes our key financials for full-year 2018. Additional details can be found in our annual report on Form 10-K, which will be filed later today.

I'm happy to address any questions during the Q&A. But, for now, I will turn it back to John.

[John Crowley, Chairman and Chief Executive Officer]

Thanks, Daphne. Great job. After exceeding our objectives in 2018, we started this year with great momentum. And I am tremendously proud of the hard work from all of the Amicus employees around the world that advance our mission every day. And I look forward to providing updates to our investors on our progress we're making throughout this year.

As you can see on this slide, we are well on our way to achieving our 2023 vision to treat 5,000 patients.

With that, I'll hand the call over to the operator for any questions. Thank you.

[Operator]

Thank you. [Operator Instructions]. And our first question comes from Anupam Rama from JPMorgan. Your line is now open.

[John Crowley, Chairman and Chief Executive Officer]

Anupam, we don't hear you.

[Anupam Rama, JPMorgan]

Sorry. Hello. Can you hear me?

[John Crowley, Chairman and Chief Executive Officer]

Hi. We can hear you now. Yes.

[Anupam Rama, JPMorgan]

Sorry. Sorry about that.

[John Crowley, Chairman and Chief Executive Officer]

That's okay.

[Anupam Rama, JPMorgan]

Thanks for taking the questions. Just thinking about the mid-year CLN6 update, can you remind us of the size and scope of the data we will be getting? Kind of in your mind, what's a win scenario for this data update? Thanks so much.

[John Crowley, Chairman and Chief Executive Officer]

I'll comment, then ask Jay Barth or Jeff Castelli to add any color. Again, we have a dozen patients who have received the gene therapy in this CLN6 Batten program they received from Nationwide. We expect to have data out to two years in about half of these patients by the middle of this year. And we think that's a very important point. That's a point where there is clear separation from the natural history.

If you remember, we had shown data out to two years in the first two patients treated. One patient who looked – was quite older when she received it and she looked to have generally stabilized on the Hamburg scale. And then the other patient, who is her younger sister, who received it when she was quite young, I think she was about two-and-a-half old or so, she actually completely stabilized over that couple-of-year period. We think that data is incredibly exciting. And it is part of what gives us great hope that this gene therapy has the potential to really change the trajectory of the disease.

So I think, by the middle of the year, we'd hope to see, certainly, in the younger children, a similarly profound response and, hopefully, some measure of durability. We are also working with some of the key investigators in the world to assemble the natural history data there. And we would hope in the second half of this year to be able to have that natural history data to compare to what we're seeing in this study.

Jay, Jeff anything to add?

[Jay Barth, Chief Medical Officer]

Thank you. It's Jay. Described it extremely well. The two-year time point, which is what we have said, is really a meaningful time point. We only had that on the two patients that we discussed initially, but more to come. Approximately six by mid-year. And that's where you can really determine an effect of that, as John was describing, is one of stabilization. It's a terribly progressive disease, leading to disability. And compared to the natural history, we are looking for patients retaining abilities, motor function, language function and so on. And that's what we're looking to see in mid-year for about six patients.

[Jeff Castelli, Chief Portfolio Officer and Head of Gene Therapy]

Yeah, Just to be clear, Anupam, we want to see striking results, so that when we look at the data, when we see the evaluations on the patients, when we look at videos internally at least, it is night and day from what you would expect from a course of this just awful, awful disease.

This is a disease where kids, usually by five, six years old, can't walk. It robs them of the ability to perform many motor functions, the ability to think. And life expectancy is usually, in CLN6, Jay, out to 9, 10 years of age. It's that just devastating disease and a disease that only really manifests in children because no one ever lives into adulthood. So, we really want to see something pretty profound here.

[Anupam Rama, JPMorgan]

Awesome. Thanks for taking the question, guys.

[Jeff Castelli, Chief Portfolio Officer and Head of Gene Therapy]

Great. Thank you, Anupam.

[Operator]

Thank you. And our next question comes from Tazeen Ahmad from Bank of America. Your line is now open.

[Tazeen Ahmad, Bank of America]

Hi. Good morning, guys. Thanks for taking my questions. Just wanted to ask you, John, I think in your prepared remarks, you talked about what you think the opportunity could be over time for Galafold. And I think you had said about $500 million or so by 2023. Just wanted to get some more color on how your team is coming to that number and assumptions you might be making about? For example, what percentage of that would be US versus ex-US patients and how would that ramp, if you're able to provide color, compared to the ramp that ERT has had over the last several years? Thanks.

[John Crowley, Chairman and Chief Executive Officer]

Sure. I'm going to turn most of that over to Brad. Only to say that, what we've seen in the international markets is part of what gives us confidence in putting that financial goal out there earlier this year, the $500 million by 2023 and the potential by 2028 for a Galafold addressable market of $1 billion. This year, 2019, is going to be really important, Tazeen, because it's the first full year of launch in the United States, Japan and all the major markets of Europe. I think this year will really establish firmly what that launch curve is over the next several years.

So maybe, Brad, you want to describe what we've got to increasing confidence in that?

[Bradley Campbell, President and Chief Operating Officer]

Yeah. Thanks, Tazeen, for the questions. What I think would be most helpful is to first highlight what we see as the big growth drivers over the next few years, which I think gets you to the 2023 time point, and share a little bit of the sort of distribution of those patients. And then, I can talk a little bit about the long-term market growth we see, the $1 billion plus market opportunity over the next decade.

So, just from a growth drivers perspective, and I think we've talked about this before, the major growth drivers over the next couple of years – this year, of course, continuing to see launch progress in the US and Japan, which are the two largest single markets from a Fabry perspective, but also expect to see continued growth in our major European markets, both in terms of market share, but also, as I mentioned on the call, a higher rate of diagnosed untreated patients coming on board. And then, there are a collective of kind of mid-size markets, the Australias, Canadas, Central European markets of the world that are also launched and will be collectively a significant driver of growth

And then, really, the big regions that are untapped for us right now are Latin America and countries like Turkey, et cetera, where we have some name-patient sales opportunities, but really haven't seen a major launch there. And so, we see 2020 and 2021 as expansion into those regions. So, lots of just really big fundamental growth drivers for the business out over the next few years.

As it relates to distribution of business, essentially, the US is 25% to 27% of the global business today. Europe is 35-plus-percent. And then, rest of world is the remainder, although Japan is, I think, 12% or 15% of the global ERT business. So, that's generally how the market is placed today. I don't know if we would anticipate much of a difference in that, perhaps a slightly higher distribution in the US at peak. But I think, for now, for the future, I think those growth drivers is where I would focus.

And then, in the long term, we said before – and we're not the only ones saying it – Fabry is clearly a significantly under-diagnosed and misdiagnosed disease. We see a greater contribution of newborn screening, which drives both diagnosis growth, but also clearly there has been a significant growth in just enzyme replacement therapy sales over the last decade and continuing forward.

If you look out to towards sort of 2028 or so, we estimate our total amenable patient population – so those are patients that are in kind of our global commercial footprint with an amenable mutation – of between, call it, 4,500 patients to 6,700 patients. And that's how you could get to that billion dollar market opportunity.

So, hopefully, that gives you a flavor of how we see the market progressing over time and our opportunities within that market.

[Tazeen Ahmad, Bank of America]

Okay. Great. Thanks, Brad.

[John Crowley, Chairman and Chief Executive Officer]

Thanks, Tazeen.

[Operator]

Thank you. And our next question comes from Irina Margine from Cowen. Your line is now open.

[Irina Margine, Cowen and Company]

Hi, guys. Good morning. And thank you for taking my questions. I was wondering, just to follow up on the previous question, maybe if you could comment on the magnitude of update you are seeing with Galafold among naïve patients in the US? And how that might differ from dynamic in the EU? Is willingness to treat in anyway difference between the different geographies? Thank you.

[Bradley Campbell, President and Chief Operating Officer]

Yes, it's a great question and one that we're following very closely. Remember, and as I highlighted on the call, our strategy in the US and in Europe has been focus on the switch patients first. They are the patients who are already in the system, getting a treatment for Fabry disease, are already receiving reimbursement. And so, we've focused on switch first and that's where we see the fastest uptick.

And in Europe, we saw an initially relatively slow uptick in diagnosed untreated patients. But as we get to higher maturity, as we get to higher market shares of switch patients, we are seeing an increased growth in diagnosed untreated patients coming on to Galafold, and that's right in line with our strategy.

The way the United States is slightly different there is – and it's still early days. So, we continue to watch this. But whereas most markets have an equal number of diagnosed untreated patients as patients who are diagnosed and treated, it does look like, in the US, that number of diagnosed untreated patients may be larger. So, it may be a larger pool of patients. But you also, I think, have a slightly higher awareness in the patient population, here in the United States than perhaps you did in Europe. And in the early days, we are seeing a slightly faster uptake in the diagnosed untreated patients. Now, we still see the majority of patients coming on Galafold in the US are switch patients, but the rate is perhaps slightly higher in the diagnosed untreated. So, that's a dynamic we'll continue to watch. And again, it's right on our launch strategy. So more to come in the quarters ahead.

[Irina Margine, Cowen and Company]

Great. Thank you so much. And my second question relates to the retrospective natural history data that's coming later in the year. Could you guys give us some color in terms of the type of detail that we should expect and what are the key measures and perhaps the length of follow-up in that data set? Thank you so much.

[John Crowley, Chairman and Chief Executive Officer]

Right. So, just to be clear, you probably meant the natural history data that we've collected for Pompe disease, right?

[Irina Margine, Cowen and Company]

Yes, yes.

[John Crowley, Chairman and Chief Executive Officer]

Yeah. Jay, maybe just speak to the parameters of what we're looking at.

[Jay Barth, Chief Medical Officer]

Yeah. We're looking, clearly, at the key endpoints of importance, the ones that we have measured in the Phase II study, focusing a lot on the six-minute walk test. It's the primary endpoint. And it's also the primary endpoint that we're carrying forward into our PROPEL study. So, clearly, that data is going to be critical, but we're looking at all available natural history data in treated patients.

[Irina Margine, Cowen and Company]

Thanks so much, guys.

[John Crowley, Chairman and Chief Executive Officer]

Thank you.

[Operator]

Thank you. And our next question comes from Mike Ulz from Baird. Your line is now open.

[Michael Ulz, Robert W. Baird & Co.]

Hey, guys. Thanks for taking the question. Maybe just another one for Brad here. You provided some nice color on the trends you are seeing with the Galafold launch in US and Europe. Maybe you can just make a few comments on what you're seeing in Japan and maybe how that compares to US and Europe? Thanks.

[Bradley Campbell, President and Chief Operating Officer]

Yeah, sure. Japan is going really well. The last update we gave is that we had double-digit patients on drug in Japan and that was the last update from last year. And we'll continue to put patients on drug there.

From a market dynamics perspective, it's slightly different in the sense that more – a far greater percentage of diagnosed patients are treated in Japan. So, it's primarily a switch opportunity. And again, that's right in our strategy. We have a very motivated team, very experienced team. We had a fantastic launch meeting last year with all the top KOLs who attended. And as you might remember, Galafold came out of technology from Japan. And so, I think there's a lot of reasons why Japan will continue to be an important market for us.

[Michael Ulz, Robert W. Baird & Co.]

Great, thank you.

[John Crowley, Chairman and Chief Executive Officer]

Thank you, Mike.

[Operator]

Thank you. And our next question comes from Mohit Bansal from Citi. Your line is now open.

[Mohit Bansal, Citigroup]

Great. Thanks for taking my question. And a very good morning. And also, congrats on all the progress. Maybe if I may ask one question regarding the patient count. I've noticed that you usually provide the snapshot of patient count. And it is not – like, you don't have patient counts in this. Just wondering if this is going to be the case going forward or you're going to provide quarterly update. I'm asking because then my fancy monthly bill would be less useful. Thank you.

[John Crowley, Chairman and Chief Executive Officer]

Sure, Mohit. Let me get the slides here. We're just showing annual. So, we did indicate – we ended the year with just over 650 patients on Galafold. And we're expecting to end this year, 2019, with just over 1,000 patients. We don't expect – now that we've got such better handle on the financials here, and I think that's a more important metric, we're going to be providing the financial results every quarter. And other important trends like the number of prescribers, the breadth of the prescription base, patient referral forms in the US. I think those are important metrics. The challenge is getting a lot of granularity on actual patient numbers quarter-to-quarter is increasingly difficult. But we feel very confident that we can get it within a range on an annual basis. Is that helpful?

[Mohit Bansal, Citigroup]

Yeah. That helps. And then, if I may ask, on the manufacturing plant, now that you are actually building up your own gene therapy hub in Philadelphia, could you please help me understand how you are thinking about manufacturing now, when you start all those clinical trials and then eventually commercial? Just if you can give me some kind of framework how you're thinking about it? Thank you.

[John Crowley, Chairman and Chief Executive Officer]

Great question. I think, for our gene therapy, we're going forward. A lot of it, of course, will be anchored with Jay Barth and his group in clinical operations, research, regulatory affairs, medical affairs.

But two parts we wanted to substantially invest in at Amicus to grow our capabilities in gene therapy. Part one is what we announced this week, and that's our Global Research and Gene Therapy Center of Excellence. That's where the science and the research are going to occur in Philadelphia. And as you saw, it's going to be a 75,000 square foot state-of-the-art facility. The top three floors of our brand new research tower, it just opened a couple of months ago. Right on Market Street in Philadelphia, right across from UPenn, adjacent to Dr. Wilson's labs. That will be a very, very important global research center for Amicus.

We also expect to open, this year, a global manufacturing and technology operations and innovation center. We're currently finalizing our evaluation of locations for that center and we expect that to have all of our late process development for gene therapy manufacturing and our own gene therapy manufacturing capacity and capabilities.

And this actually, I think, is one of the great strategic advantages for Amicus coming into the gene therapy space in such a strong way here. We have about 100 people at Amicus, of our 600 people, in technical operations and in quality. Much of that team has been developing our Pompe AT-GAA program, as you know, one of the world's most complicated glycosylated biologics. A lot of that biologic experience, we believe, can serve as a foundation for our move into gene therapy manufacturing. So, we think that could be an incredibly important asset and strategic driver for Amicus.

In addition to that, we're now finalizing our agreements with some of the leading contract manufacturers. So, again, to remind you, we're moving from the academic manufacturer for the Batten programs and the lysosomal disorder neurologic programs from the Academic Center at Nationwide Children's Hospital into these leading contract manufacturing organizations. And in parallel, we're building our own Amicus capabilities and capacity in manufacturing.

[Mohit Bansal, Citigroup]

Very helpful. Thank you very much.

[John Crowley, Chairman and Chief Executive Officer]

Thank you, Mohit. Have a great day.

Operator

Thank you. And our next question comes from Whitney Ijem from Guggenheim. Your line is now open.

[Whitney Ijem, Guggenheim Securities]

Hi. Good morning. First, I just wanted to follow up on CLN6. For the mid-year update, just to clarify, will we get data out to two years only or will we get additional follow-up for the patients that have it beyond two years?

[John Crowley, Chairman and Chief Executive Officer]

We'll provide the data that's available at that time. So, it's at least two years for about six patients.

[Whitney Ijem, Guggenheim Securities]

Okay, got it. And then, are there specific medical meetings that we should have on our radar for that update mid-year?

[John Crowley, Chairman and Chief Executive Officer]

I think in – give us a couple of months, Whitney. We're outlining that now. I think in our May earnings call, the Q1 earnings call, we could provide some more guidance around that.

[Whitney Ijem, Guggenheim Securities]

Okay. And then, just last quick one, back on Galafold and kind of longer-term market opportunity, I think you had a slide in one of your decks earlier this year talking about, I guess, the rate of misdiagnosis in different categories based on screening studies. And two that were of particular note were MS and IBS. So, is FOLD sort of – or is Amicus doing any sort of active outreach or screening in those settings to find patients?

[John Crowley, Chairman and Chief Executive Officer]

Yeah, very much. Brad?

[Bradley Campbell, President and Chief Operating Officer]

Yeah. We actually kicked off a pretty comprehensive initiative this year focusing on a whole host of areas within the Fabry disease space, looking at ways that we can support the community in improving and enhancing both diagnosis, but also of course addressing misdiagnosis. And so, for example, we do have a number of investigator-initiated studies that I'm looking at, some of those high-risk populations. MS is one that's come to our attention. As you said, we've shared some of that, pain clinics, IBS, et cetera. And so, yes, we are supporting that this year and a number of other initiatives as well. And as we hopefully drive that science and get results from those studies, we'll certainly share that with the community.

[Whitney Ijem, Guggenheim Securities]

Great, thanks.

[John Crowley, Chairman and Chief Executive Officer]

Thanks, Whitney.

[Operator]

Thank you. And our next question comes from Kristen Kluska from Cantor Fitzgerald. Your line is now open.

[Kristen Kluska, Cantor Fitzgerald]

Good morning. And thanks for taking my question. Of the 200 employees you've communicated could work at the Global Research and Gene Therapy Center in Philadelphia, could you break down how many of these employees could be split across different departments? And of the 200 people, how many do you anticipate would be new hires?

[John Crowley, Chairman and Chief Executive Officer]

Sure. The one part of Amicus that has maintained a pretty steady state over the last four years of our growth has been our science organization. And that's largely because a lot of the early work that they had done on Galafold and then AT-GAA was transitioning to later-stage development. A lot of that work was supportive of that. But, now, with our move into gene therapy, Kristen, we really want to invest in science. And science has always been at the core of Amicus. So, we have right now about 35 people in our Core Science and Research Organization. A substantial number of those – the majority of those have relocated already to Philadelphia into the temporary lab space in that building at 36/75 Market Street. So, the vast majority of that over the next couple of years will be new hires. And again, that's already budgeted for and that's in our financial runway as well.

In terms of the breakout, expect, of those 200 people at our Global Research and Gene Therapy Center of Excellence, the vast majority of those will be scientists. We also expect to have some members of our technical operations team in Philadelphia working primarily on the early stage process development, getting that science ready for manufacturer and, ultimately, then hand off either to a CMO or to our later stage process development in our own Amicus manufacturing team.

And then, we'll also have small numbers of people under Jeff Castelli at the Global Center and also throughout our organization with some dual reporting that we'll have – who will be focused on clinical, regulatory, patient advocacy, some of the other business functions as well. So, we did not want to set up a standalone business unit. We think it needs to be fully integrated as part of team Amicus. But we set up this Center of Excellence model.

And I think you'll see that at Amicus. Again, we have our international headquarters and international center of excellence. We just opened that couple of weeks ago actually in Marlow in the United Kingdom, just outside London. So, we now have our Philadelphia facility for research. And I would expect, in the months ahead, that we'll see an announcement of that Amicus Center of Excellence for Gene Therapy Manufacturing.

[Whitney Ijem, Guggenheim Securities]

Great. Thank you, John.

[John Crowley, Chairman and Chief Executive Officer]

Thanks, Kristen. Have a good day.

[Operator]

Thank you. And our next question comes from Salveen Richter from Goldman Sachs. Your line is now open.

[Unidentified Analyst]

Yes. Hi. Thanks for taking the questions. [indiscernible] for Salveen. Congrats on all the progress. Very encouraging. I had a couple of questions. One of them, for the AT-GAA program, what is the CMC requirements that are still sort of in process of being completed for the Phase III and what is the work that you basically expect to do there in the next couple of years?

[John Crowley, Chairman and Chief Executive Officer]

Yes, I'll let Brad to handle the manufacturing question.

[Bradley Campbell, President and Chief Operating Officer]

Sure. As we've mentioned before, I think the most important thing we've done over the last few years is that successful scale up to the 1,000-liter scale. Now, having being -- having manufactured at GMP scale, that material has been released to the clinic. We've shown and demonstrated comparability to the 250-liter scale. So, that was a decision we took years ago that we needed to make sure that by the time we started the Phase III study that we had the commercial scale available and we've done that successfully.

From a regulatory perspective, as you might imagine, there are number of pieces, but really the biggest one is the PPQ runs or process performance qualification runs. And as we've said before, those will be part of any submission and will be part of the discussions that we have with regulators over time. We haven't given specifics about when exactly we'll start and complete those runs, but, rest assured, we'll be well prepared for them.

[Unidentified Analyst]

Got it. Thank you. Very helpful. And another question I had, I actually was wondering about the data that was presented at Muscle for the – in general, for the forced vital capacity predicted volume. I was wondering why is it going down for the ERT switch population. If you could give some color of how you're thinking about it? Thank you.

[John Crowley, Chairman and Chief Executive Officer]

Yeah, I'll turn it to Jay. It's actually not coming down. We actually saw a nice trend back toward baseline with the 24-month data, which was very encouraging. Jay, I'll let you comment.

[Jay Barth, Chief Medical Officer]

I think that's exactly right. What we showed and what we've said is for the ERT switch population. Again, these are patients who have been on the standard of care for an average of five years prior to switching. So, they – and patients who've been on treatment that long, generally, are declining in the various functions that you measure. Pretty far along in their disease. And we were able to show stabilization. This is now two-year data. There is some variability, of course. There is going to be a difference between month 12 and 18 and 24. But, now, we have a firm grasp of the data two years and it really is stable. And that's probably about as good as you can get for these patients, who would have been declining otherwise. Stabilizing.

And along with that, we showed in the naïve patients, who have not been treated before, a quite robust increase in their FEC and their pulmonary function tests. And I really think that shows the ability of AT-GAA to have a pretty profound effect on their function. And we saw that also in the motor function. Of course, the six-minute walk increasing in both groups. So, I think all the results are pretty much as we expected and as good as they could be for these different populations.

[Unidentified Analyst]

Got it. Thank you. Very helpful. Would the ERT-naïve basically data will be a better comparison with the natural history? Is that the thinking?

[Jay Barth, Chief Medical Officer]

It depends which – natural history could be in untreated patients. And then, of course, naïve patients you compared to those. We also use or refer – the term natural history to refer to patients who have been on treatment. And the natural history that we are talking about later in this year are primarily in treated patients, patients who are treated with standard of care, you can also on historical controls. And we'll be mainly comparing our ERT experience, ambulatory patients to the natural history data.

[Unidentified Analyst]

Got it. Thank you.

[Operator]

Thank you. And I'm not showing any further questions at this time. I would now like to turn the call back to John Crowley, Chairman and CEO, for any further remarks.

[John Crowley, Chairman and Chief Executive Officer]

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

[Operator]

Ladies and gentlemen, thank you for your participation in today's conference. This concludes today's program. You may all disconnect. Everyone have a great day.