Good morning, ladies and gentlemen, and welcome to the Amicus First Quarter 2019 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. [Operator Instructions] As a reminder this call is being recorded.

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

Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics' first quarter 2019 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; and Daphne Quimi, Chief Financial Officer.

Also joining for Q&A are Dr. Jay Barth, Chief Medical Officer, Dr. Hung Do, Chief Science Officer, and Dr. Jeff Castelli, Chief Portfolio Officer and Head of Gene Therapy.

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 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 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, 2018 filed with the Securities and Exchange Commission and its quarterly report on Form 10-Q for the quarter ended March 31, 2019 to be filed tomorrow.

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

John?.

Great. Thank you, Sara, and welcome everyone to our first quarter 2019 results conference call. I am very pleased today to be on this call from our international headquarters in Marlow here in the United Kingdom just outside of London.

We opened this new office earlier this year and it’s the heart of our business operations outside of the United States and with now over 25% of our 600 employees working outside the United States, it’s a great reflection of the increasingly global nature of everything that we do.

I’ll begin by noting that this year is an important execution year for the global Galafold launch.

The launch trends that we are driving will not only deliver immediate results throughout this year, but the very strong trajectory for Galafold is setting the basis for this precision medicine’s success in getting to as many patients as quickly as possible we hope for years to come.

This is of course also an important year for the advancement of our expanded pipeline in Pompe and multiple other rare diseases and we are very pleased with where we are today in terms of our goals and priorities for the year as highlighted here on Slide 3.

As you can see, we have five key strategic priorities in 2019 and we are well on track to achieving or exceeding all of them. First, Galafold, our precision medicine for Fabry and now one of the most successful rare disease drug launches ever. As previously announced, we expect to nearly double annual revenue again in 2019.

At the end of the first quarter, more than 800 people living with Fabry disease with a medical GLA variance also referred to as genetic mutation were taking this oral precision medicine as their only treatment for Fabry.

In the first quarter, we saw the largest number of net new patients added globally since the launch more than 150 net new Galafold patients. We saw higher than anticipated prescriptions around the world, in the EU, Japan, and in the United States as we saw continued global compliance and adherence rates exceeding 90%.

With the strength of our global launch in Galafold including the continued very strong momentum in the very early stages of our U.S. and Japan launches, and with our continued growth in our earlier launch geographies, we are highly confident in our full year 2019 guidance range of $160 million to $180 million.

Second, Pompe and our AT-GAA program continues to be incredibly important for Amicus. In addition to receiving Breakthrough Therapy Designation or BTD in the first quarter, we’ve seen tremendous momentum in clinical study enrollment across this program. We completed enrollments of the fourth and final cohort in our Phase 1/2 clinical study.

In the pivotal PROPEL study we now have 24 active sites throughout the world well on track to complete enrollment again by the end of this year. Additionally, later this year, we look forward to further Phase 1/2 data from cohort – 4 and the public disclosure of the natural history data of Pompe patients on currently approved ERT standard of care.

Third, within our leading rare disease gene therapy portfolio of 14 programs, we expect very important data in the third quarter. Here we anticipate additional two-year data and about half of the 12 patients in the CLN6 batten disease clinical study.

In addition, our second clinical-stage gene therapy program, the ongoing CLN3 batten disease study has quickly enrolled full low-dose cohort a total of three patients who all continue to participate with no serious adverse events to-date following a single one-time administration of the gene therapy.

Our fourth goal is to achieve pre-clinical proof-of-concept for our Fabry and Pompe gene therapy programs. The first set of positive data for our pre-clinical Pompe gene therapy program was presented as many of you saw last week at the American Society of Gene and Cell Therapy Meeting in Washington D.C.

We are excited at the amount of research now well underway in collaboration with Dr. Jim Wilson and his remarkable team of scientists at UPenn. They are working together closely with the Amicus research and gene therapy team in our new Global Research and Gene Therapy Center of Excellence in Philadelphia.

The focus now in this collaboration is in Fabry, Pompe and CDKL5 deficiency disorder or CDD. Our goal is to present these data at medical meetings and in peer-reviewed publications throughout this year. Finally, but a continued importance we will always maintain a strong financial position.

Our cash runway is sufficient to fund our operating plans at least until mid-2021 advancing us several years closer toward our 2023 vision to treat 5,000 patients and achieve $1 billion plus in global revenue which will be on par with today’s leading global rare disease biotech companies.

So, with that overview, let me go ahead and hand the call over to Bradley Campbell, our President and Chief Operating Officer to highlight the details behind the very successful Galafold launch. Brad, I’ll turn it to you back in New Jersey..

Great. Thanks, John. Good morning everyone. Let me begin on Slide 5 with a snapshot of the continued Galafold launch through March 31.

First as John mentioned, we were very pleased with the strong adoption of Galafold in the first quarter and the continued strong launch trajectory and we remain very confident that this strength will continue throughout the remainder of 2019 and beyond.

Our first quarter revenue was $34 million, a year-over-year increase of approximately 104% from the first quarter of 2018. And during the quarter we continue to see exceptionally strong momentum in new markets including the U.S.

and Japan, as well as in our more mature markets and as a reminder, we have pricing reimbursement secured in 24 countries around the world. Moving on to Slide 6, I will talk a little bit more about the global launch metrics that we follow.

As John mentioned in his opening remarks, following a very strong first quarter with our highest number of net new patient adds and positive momentum across all of our key commercial metrics. We now have more than 800 patients on Galafold globally. Let me add a little bit more color here.

First, compliance and adherence to this oral precision medicine dose and dose regimen continues to exceed 90% globally. This a remarkable adherence rate for an oral treatment regimen or any regimen for that matter.

We estimate our global market share for Galafold is approximately 18% of all treated amenable patients around the world which captures both more mature markets as well as our new launch markets.

And it’s worth noting that we are starting to see equal growth contribution from ERT-Switch and previously untreated patients within the EU 5 and the more mature markets.

And again this trend is right on target with our strategy for higher initial adoption of Switch patients at launch followed by increasing market growth from previously untreated patients. In the United States, we saw a significant increase in patients on Galafold from a growing and very wide subscriber base.

As of April 30, more than 200 prescriptions have been written by more than 90 prescribers since launch. And thanks for the very strong work by our team and the dedicated employees in our Amicus assist hub. We’ve obtained broad reimbursement coverage and are experiencing shorter and shorter time for prescription to patients receiving drug.

In Japan, we are ahead of forecast on patient numbers in Q1 with a slightly expanded commercial team and finally across all markets, we’ve maintained a balanced mix of male and female patients, classic and late-onset patients with both Switch and previously untreated patients who have amenable mutations.

Turning now to Slide 7, let me comment on the quarterly trends seen in 2018 throughout the year to help provide more color on 2019. First quarter 2019 was in line with management expectations and so far, second quarter is ahead of expectations.

And consistent with Galafold adoption trends and ordering patterns in previous years, we expect that quarter-over-quarter revenue growth will not be linear, so that we will see higher growth in second quarter and fourth quarter this year. Turning now to our guidance on Slide 8.

With the strength in the commercial metrics I just described, we remain highly confident in our current guidance range of $160 million to $180 million for this year.

Although as Daphne will highlight in a moment, with the majority of our sales continuing to come from outside the United States in 2019, and with expected modest foreign exchange headwinds, we believe our reportable revenue to come within the middle of this $160 million to $180 million guidance range.

Importantly, by the end of this year, we expect that more than 1,000 people living with Fabry will be taking Galafold as their only treatment for Fabry disease. This will be a fantastic achievement that could represent a meaningful impact on how Fabry disease is treated around the world.

And finally, while on the topic of patient numbers for modeling purposes, I’d like to remind everyone that in line with our year-end guidance range, we’ve factored in a build-up over the course of the year to that 1,000 patient number that also includes our global average gross to net discount of around 15% to 20% and the 90% adherence rate.

Finally on Slide 9, we continue to believe that Fabry maybe one of the most under and misdiagnosed human genetic disorders in the world.

The global Fabry market was $1.4 billion last year and with continued growth expected in the Fabry population, particularly through the increased use of newborn screening and other diagnostic initiatives, as well as reach an extension of our Galafold IT that covers a treatment method through 2038.

We’ve been more confident in a $500 million potential Galafold sales by 2023 and an addressable market of over $1 billion in 2028 with the potential to impact thousands of people living with Fabry disease who are amenable to this novel precision medicine.

So with that, let me turn the call back to John to discuss our AT-GAA program in Pompe in more detail as well as our gene therapy portfolio.

John?.

Great, thanks, Bradley. So, here on Slide 11, if you could look to our Pompe program, I’d like to take a moment to highlight the tremendous execution of our Amicus teams around the world in enrolling this study within our AT-GAA clinical program.

In the Phase 1/2 study, we are now fully enrolled in all four cohorts including the fourth and final cohort. Given the enrollment momentum and the availability of global sites now participating in this pivotal PROPEL study, we closed enrollment of our Phase 1/2 study after six patients in order to focus on enrollment into PROPEL.

As a reminder, this fourth cohort is very similar to the FOLD’s first cohort in the Phase 1/2 study having switched from ERT standard of care. Cohort – 4 had been on standard of care for a minimum of seven years where cohort -1 was on for two to six years.

And now that this cohort – 4 is fully enrolled, we anticipate the first dataset from these cohort – 4 patients on track for later this year. In the Pivotal PROPEL study, as shown in the schematic on this slide, 24 sites are currently recruiting and we plan to initiate up to 90 sites globally.

Enrollment is going very well, attracting both ERT Switch and Naïve patients. But we are on track to fully enroll the target number of 100 patients by year-end. On Slide 12, I’d also like to remind everybody that we were granted Breakthrough Therapy Designation or BTD by the USFDA in the first quarter for AT-GAA in late-onset Pompe disease.

This is the first second-generation therapy, as well as the first therapy for Pompe disease to receive this important designation with several key features as outlined on this slide.

This BTD, together with our results and the ongoing Phase 1/2 study and the ongoing PROPEL Pivotal study, support our strategy to advance AT-GAA as quickly as possible with the potential to become the new standard of care for people living with Pompe disease.

Even with this BTD though, we will remind you that our base case remains that the Pivotal PROPEL study will be the basis to support full approval of AT-GAA. Moving to Slide 13, I’ll highlight here the key accomplishments year-to-date in this important Pompe program and reiterated number of objectives for our AT-GAA program.

Since the beginning of the year, we presented Phase 1/2 data out to 24 months at the World Symposium in Orlando with a granted BTD, we fully enrolled cohort – 4 and we have made significant progress with our pivotal study enrollment.

For the remainder of this year, we will continue to concentrate on PROPEL study enrollments, additional Phase 1/2 and natural history data, supportive studies including the initiation of our pediatric study, as well as the advancements of agreed upon CMC requirements from the very important related manufacturing work with our partners at WuXi Biologics.

And while we will engage with regulators frequently, and even more so now with the BTD, we will not be providing any color or expectations on any pending or future regulatory interactions until after they have occurred and only if they materially impact our assumptions from the base case.

Let me just say, that we really could not be more excited about AT-GAA, as well as our preclinical Pompe gene therapy program to build that could be the largest and most valuable franchise in the industry with the potential to offer solutions to all patients living with Pompe disease globally. Moving on now to Slide 15 on Gene Therapy.

I’ll highlight here our leading portfolio and the lysosomal disorders which strongly positions us to become the consolidator of some of the greatest gene therapy technologies, products, and minds including currently Dr. Jim Wilson at UPenn and Dr. Brian Kaspar formerly at Nationwide Children's Hospital.

Through our partnership with Nationwide Children, we have ten programs in the neurologic lysosomal disorders, two of which are in the clinic. That’s an addition to a very strong collaboration with Dr. Jim Wilson at Eupenn that focuses on Fabry, Pompe and CDKL5 deficiency disorder.

That’s where our team in Philadelphia now works across the street in close collaboration with Dr. Wilson’s team to advance these programs as quickly as possible and of course, we were very excited and encouraged by the data that we presented from Dr.

Wilson’s labs and our Amicus team at the conference – the Gene Therapy Conference in Washington last week. Continuing to Slide 16, this year is very important across the gene therapy programs at Amicus and the R&D engine for future growth. Let me highlight here a few of the key milestones already achieved.

First, we delivered our first set of preclinical results. Again, a very compelling dataset for our Pompe gene therapy which I will highlight in a moment. We expect more pre-clinical data in Pompe as well as pre-clinical data in Fabry and other ongoing programs throughout the remainder of this year.

Next, we have fully enrolled the low-dose cohort in our CLN3 batten study with a total of three patients and we expect the high dose cohort to commence in the coming months.

And we remain on track to report additional two-year data in our CLN6 batten disease study, which we previously said was mid-year and which we have now narrowed to the 3Q timeframe when we expect to have two year follow-up from approximately half the patients enrolled in this study.

The first announcement we expect to be a top-line corporate announcement with more details to follow later in the year. Again, our goal is to change the course of the fatal, childhood disease compared to the natural history.

As has been seen in other neurodegenerative diseases, we believe treating orally will be important to maximize the benefits in this patient – these patients that are very much looking forward sharing the state event in the third quarter.

Turning to Slide 17, I’ll remind everyone of our initial pre-clinical data for our Pompe gene therapy and refer you to additional data in our conference call transcript or the replay of that call from last week.

These data for our Pompe pre-clinical gene therapy show compelling preliminary data that the Amicus technology to design construct, but enhanced protein targeting maybe a significant platform for multiple lysosomal disorders.

Specifically, our engineered hGAA builds upon our experienced use to successfully develop AT-GAA designed for optimal expression, secretion and targeting which enables efficient cross-correction in target tissues.

And the pre-clinical results show that our Amicus engineered hGAA is optimized for uptake into target tissues and gets to the right cellular compartments, especially in the central nervous system. As shown on this slide, this is robust glycogen reduction in CNS.

Here in the spinal cord that was observed only with our engineered hGAA and not with the naturally – or the natural unmodified hGAA. Additional preclinical studies are already underway to build from these initial results to look at various doses and routes of administration.

This program is advancing ahead of schedule and we anticipate selection of a clinical candidate with 2019 to move into IND-enabling studies. From the context of our broader gene therapy portfolio, we plan to leverage this platform across our gene transfer programs to become a literature in treating and possibly curing rare metabolic disorders.

To summarize on Slide 19, we look all of the expected upcoming milestones for 2019 anticipated across our portfolio. Let me now go ahead and turn the call over to Daphne Quimi who will cover our first quarter 2019 financial results. Daphne, please..

Thank you, John, and good morning, everyone. Our financial overview begins on Slide 21 with our income statement for the three-month period ending March 31, 2019. For the first quarter of 2019, we achieved Galafold revenue of $34 million, which is a 104% increase over the first quarter of 2018.

At a constant currency exchange rate from the first quarter of 2018, 2019 first quarter operational revenue would have been $35.8 million. This implies operational revenue growth measured at a constant currency exchange rate of 114.9%, offset by negative currency impact of 11% or $1.8 million.

While the impact this quarter is relatively modest, we are introducing this measure as the majority of our revenue this quarter is generated outside of the United States. Cost of goods sold includes manufacturing cost, as well as royalties associated with the sales of our products.

Cost of goods sold as a percentage of net sales was 11.9% in the first quarter ended March 31, 2019, as compared to 15.7% for the prior year period. Cost of goods sold as a percent of revenue is favorable as the U.S. Galafold revenue is subject to lower royalties.

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 as we evolve into one of the leading global rare disease biotech companies.

During the first quarter of 2019, we recorded $64.6 million in R&D expense, compared to $40.8 million for the prior year period. This increase was attributed to investments in our AT-GAA Pompe clinical programs in addition to the clinical and preclinical gene therapy programs that we added to the pipeline in the second half of last year.

Total selling, general and administrative expense for the first quarter of 2019was $44.3 million as compared to $27.4 million for the prior first quarter period. The increase represents the expanded geographic scope of the ongoing Galafold commercial launch, including launch activities in Japan and the United States.

Net loss for the first quarter of 2019 was $120.3 million or $0.56 per share, compared to a net loss of $49.9 million or $0.28 per share for the prior first quarter period. And as of March 31, 2019, we had approximately 230.2 million shares outstanding. Moving on to slide 22, a few comments about our current cash position and 2019 financial guidance.

Cash, cash equivalents and marketable securities totaled $438.2 million at March 31, 2019, compared to $504.2 million on December 31, 2018. 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 net cash generated from 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 anticipated net cash generated from Galafold revenue, we have sufficient capital to fund ongoing operations into at least mid-2021.

As we have noted in the past, potential future business development collaborations, pipeline expansion and investment in manufacturing capabilities may impact our future capital requirements. This summarizes our key financials for the first quarter of 2019. Additional details can be found in our quarterly report on Form 10-Q.

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

Great. Thanks, Daphne. So it’s been a very successful first quarter here at Amicus and we look forward to continuing to provide updates on the progress throughout this year much needed to come. As a reminder, I’ll conclude on this slide that we are well on our way to achieving our 2023 vision to treat 5,000 patients.

So, with that, operator, we will hand the call over for questions and answers. Thank you. .

[Operator Instructions] Your first response is from Ritu Baral of Cowen. Please go ahead. .

Good morning guys. Thanks for taking the question. I just wanted to dig down a little further on the disparity between the revenue growth and the incredible patient – growth in patient starts that you saw in the quarter.

Daphne, you mentioned the $1.8 million in currency impacts, were there any other factors seasonality trend setters, et cetera, that we should be keeping in mind for this quarter and for Q1 going forward? And then, I have a follow-up..

Sure. Ritu, good morning. Thanks for the question. Yes, so, again, this was an extraordinary first quarter in advancing the Galafold launch. It will not only contribute to achieving the range this year but also lays a great foundation for building this product in the years ahead. I am going to turn it over to Brad.

Brad, maybe just reinforce those key trends and then specific to Ritu’s question, maybe just remind everybody of the time to put people on drug, the time for reimbursement and then, Daphne, of course if you can comment more on the foreign exchange headwinds that we experienced in the first quarter. So, Brad, I will turn it to you. .

Yes, sure. Thanks, Ritu for the question. I think, as we’ve said on the call, this is a great quarter and just as you highlighted the best number of new patient starts this quarter more than 200 PRFs at the end of April in the U.S. across that broad subscriber base continuing to see great adherence rates around the world.

But really, I think if you think about the quarter-to-quarter growth, it’s in line with what we saw last year and what we expect to see this year. So, of course not all of those 150 patients are starting on day one. They come in over the course of the quarter.

We’ve seen last year, stronger growth in 2Q and 4Q and we would anticipate that again this year. And it’s from everything we’ve seen, the business is going great and we are looking forward to continuing to execute. And we did provide a little color that already this quarter is ahead of our expectations. So, nothing unusual there.

The only other thing I will comment on is the reimbursement piece which is that, we continue to see strong coverage around the United States. We’ve actually started to decrease that time from PRF to shipment. But you do still have patients in the Q from a U.S.

perspective who have a patient referrals want who is still going through the reimbursement process. And as a reminder that our target last year was 60 days and now we’ve actually brought that down below 60 days. So, we continue to make progress there. .

Hey, Daphne, do you want to comment on anything with the foreign exchange?.

Sure. Just to say that, the majority of our revenue is still outside of the United States and currency does play a factor, especially as currency compared to last year to this year and for the balance of this year, we do think that it will be a stronger dollar, but we don’t – we are not forecasting exchange rates.

We are just basing that comment on currency exchange rates as of today. .

Got it. So nothing….

Ritu, maybe I’ll….

Go ahead, John. .

No, nothing at all beyond that. .

Okay..

I’ll just highlight to pricing, I think that’s important. We were very, very thoughtful I think in how we brought Galafold to market and where we priced it around the world. And we see no pricing pressures on Galafold. We continue to see pricing 100% at the same levels at which we launched in Europe.

And we continue to see very strong acceptance from payers in the United States. So, certainly, nothing to do with any challenges on pricing. Actually, I think we are going to get placed on the pricing with Galafold. .

Got it. Okay, that was very helpful. And then, actually my next question is on the Pompe program. As we look at cohort – 4, John, you mentioned that the cohort – 4 patients have been therapies ERT for seven years versus from two years.

With cohort -1 are there any demographics baseline differences between cohort - 4 and cohort -1 that we should keep in mind as first clinical data emerges and is it likely that this is going to be one of the datasets that you could potentially have it rolled later this year?.

Sure. I’ll let Jay Barth, our Chief Medical Officer comment in a moment.

In addition to these patients having been on Lumizyme much longer than any patients we’ve seen from an ambulatory Switch study before the one thing that we did differently as well is these patients also had to have a well documented historical baseline before they came into the study, not just a single baseline on study entry.

In terms of demographics, Jay of these half-a-dozen or so patients, could you comment on that?.

Yes, we haven’t – hi, Ritu. We haven’t shared that specifically. We will and when we share the data as a whole, but generally similar.

It was cohorted more of an extension of cohort – 1 other than the fact that they have been on treatment for a longer period of time with ERT prior to coming to the study, we want to expand to a broader population the purpose is cohort – 4 and we look forward to sharing it later in the year we haven’t said it’s actually when. But we will. .

Biologically speaking, is there any reason for a patient that’s been on ERT longer to respond differently to your ERT?.

No, there isn’t. In fact, I will just remind you in other cohort – 2 is already has been in the study.

We’ve discussed 21 months data and shared that non-ambulatory ERT experienced patients have been on treatment for an average of nine years prior to coming on to AT-GAA and they have shown good responses in the measures we’ve assessed for body strength for example, but clearly the capability of responding even after a longer time on ERT. .

Got it. Very helpful..

Thanks, Jay. And, Ritu, just to, yes the last part, obviously any patient studied would be an important part of our regulatory submission one day. So, this will be a piece of the puzzle, but again the basis for approval we continue to believe will be the Pivotal PROPEL study. Certainly it’s important information, Ritu. Sure, thank you..

Thanks for taking the questions. .

Thank you. Next response is from the line of Anupam Rama with JPMorgan. Please go ahead. .

Hey guys. Congrats on the progress and thanks for taking the question. Just a quick one from me on the CLN6 lead out mid-year.

Just help us think through the level of details we will be getting on the various – on the endpoints, specifically beyond Hamburg or would we get a breakdown of the different components of Hamburg in the top-line release versus saving it for a medical conference a little bit later? Thanks so much. .

Sure. First of all, Anupam, congratulations to you on the birth of your child. That’s just beautiful. I’ll thank special time. I’ll ask Jay and Jeff Castelli is here as well to comment on the data release that we will see in Q3.

Again, we expect the top-line results to be shared in mid-year in Q3 and we expect much more detailed information at a scientific congress later in the year.

I think that’s – do you guys have anything to add in Cranberry?.

At a high level, that’s what we have said and we look forward to sharing that in 3Q. It will be focused on the patients who completed the two-year time point and you point out that the Hamburg, that’s certainly going to continue to be the primary efficacy assessment that we are going to be sharing data on. .

I’ll just add on upon, we put back into the top of the list for these targets for up in gene therapy. Remember, when we started, looking at the whole universe of rare diseases, we then selected about a 100 diseases and a few months later, we narrowed it to 15.

CLN6 and several other sub-types of batten we are really at the top of that list, because we felt that, a gene therapy could substantially impact the disease. They were very few people if any in some of these sub-types working in the disease.

And I’ve met a number of these children and families over the last two decades and it’s just a devastating disorder. You have to remember this – and I know, you know, it’s a disease that is 100% fatal in children. Nobody have survived at childhood in this disease. And CLN6 is a really aggressive form of a disease.

And just have described it before it kills children, it robs them of the ability to speak, to walk and to think. We know that we can’t reverse neurologic damage that’s already done.

But we hope that our gene therapy could fundamentally and really meaningfully change the course of the disease in children as compared to the natural history of this just awful disease.

So we shared the data when we brought these programs into Amicus last October and the data that we have seen in the first two children that we shared at that time really gives us hope to believe that we may really have the potential here to change the fundamental course of this disease. So, really excited to share the data in mid-year in Q3..

Great. Thanks so much for taking my question. .

Thanks, Anupam..

Thank you. Next response is from Schwartz Joseph from Leerink. Please go ahead..

Hi, good morning. Thanks for taking our questions. This is – dialing in for Joe. So, thanks for all the updates and congrats on the all the progress. I have just two quick ones – questions, one on the CLN program and one on the cash guidance update. So, John, at the ASGCT last week, I was surprised by a presentation on a CLN5 study using the sheep model.

And in this group study, they basically show that an intracerebral ventricular delivery of their CLN5 gene therapy improve the motor and the functional aspects, but the sheep still lost vision over time. And I know vision loss is a progressive symptom for a CLN patient.

So, just wondering, can you provide some context around what you saw in the preclinical setting and you did nationwide or under your hands were ovine model study? The second question is on the cash guidance for Daphne, just looking at the reported OpEx and a continued expectation of OpEx increase over the year, can you maybe put some more granularity around how we can get to that $300 million cash balance by year end? Thanks.

.

Sure. Let me ask Jeff Castelli to address what we are doing in CLN6. The research that’s been done and specifically the broad biodistribution that we’ve seen and how we’ve thought about the eye part of that. And then we will have Daphne comment further..

Sure. So as a reminder, we reported data on CLN6, CLN3 and CLN8 pre-clinically. There are no available larger animal model to us for those diseases. We have looked in the mice. We have seen robust expression of the target CLN protein in the retina. So we are encouraged by that.

We are following visiting the clinical trials and we will put that data out when it’s available. But we are encouraged that we’ve seen the expression in the eyes and hope to have an impact on that type of a disease. Most importantly, we really hope to improve survival, motor function language as well. But we will continue to look at vision as we can.

A good point on CLN5 we are aware of that model and we hope to look at some more models like that in our future CLN programs where we can learn more about the disease. .

Great. And I think you know, on the second part, I will turn it Daphne in a moment, Digon but I think really underlying that is the confidence we have in the continued revenue growth from Galafold to offset some of the spending in the company and then of course the judicious management of expenses both on the research and the SG&A side.

Daphne, do you comment further?.

Sure. The only I would comment on is, our spending in the first quarter is in line with our expectation in our forecast. And there were certain discrete cash-only items that occurred in the first quarter that will be more fully discussed in our 10-Q that we will release tomorrow. .

Yes, I think because of that Digon, yes, I think you can’t take the cash spend. I would not take the cash spend in Q1 and just extend that out throughout the year. .

Got it. Thanks very much guys. .

Sure, of course..

Thank you. The next response is from Tazeen Ahmad of Bank of America. .

Hi, good morning. Thanks for taking my question. Maybe, this is a question for Brad. I am afraid that U.S. with regards to Galafold’s pricing.

Can you comment on any contracting you have done? I know it’s early in the launch and perhaps you could talk about any kind of discounting at least directionally, any discussions around that that you have to had to get this start covered?.

Yes..

Yes, Brad, go ahead please..

Sure. Thanks, Tazeen for the question and we’ve talked about this before. So in the U.S., we do not do any contracting with private payers. The only discount that we give are the mandatory discounts to government payers, Medicaid, Medicare, Tricare et cetera.

So, the other piece to keep in mind is that percentage of the population that is – that goes through the government channels. And I think we’ve sort of given broad guidance that historically in Fabry, that’s kind of around a third of the population. Although, it remains to be seen how much of – how many of those patients will have amenable mutations.

But we effectively charge the price for Galafold in the U.S. and the patients that are government patients have the mandatory discounts afforded to them. .

So, is one-third of your revenue coming from government payers? Or is it something else?.

We haven’t been so specific about that. I would say, by the time we get to steady state, that should be a reasonable expectation. We have said that so far we have had government patients be reimbursed. So we’ve seen for us broad coverage both in the private payer universe as well as the government payer universe.

So, we feel very comfortable about the receptivity in the coverage from payers.

And then the other thing which I think is another – kind of another way of looking at this is, we continue to shrink that time from prescription or PRF to shipment which I think clearly shows that that we are getting on plans as all the payers and we are getting patients through the reimbursement process at a higher – faster and faster rate which is fantastic.

.

And in early stages of the launch if you have to talk about what’s the rate-limiting factor right now.

What would it be?.

I think it’s going, if anything better than expectation. So we are out there in front of all the docs. I think, one of the questions is, are you going to be able to get a broad adoption among prescribers. We had a nice start in the U.S. with clinical trial sites. But we now have over 90 prescribing physicians.

The way we think about it, there is about 50 top KOLs in the U.S. and about 250 total prescribers. So, that’s a great penetration in less than a year of launch. So that’s really strong. Payer coverage is always a question mark. But again, we feel very good about that.

So, I think it’s really continued to execute as we have and the numbers bear out that we are having great adoption and hopefully that reflects a great experience by patients’ physicians. .

Okay. And then, maybe one question….

One just comment, Tazeen, I think, you know….

Yes..

And maybe just to add that, I’ve been in Europe for about a week travelling to many of our offices, here with our country team and what I saw there is continued remarkable enthusiasm from physicians, patients and what struck me in all my business reviews was, how much more opportunity exists.

We really just are in the growth curve – in the early days of the growth curve of getting Galafold to patients. And that’s what merely gives me confidence that this is going to get to thousands of patients and ultimately be a $500 million to $1 billion opportunity. There are just so many people continuing to be diagnosed with Fabry disease.

More and more people choosing Galafold as their therapy for Fabry. But they are switching or having been diagnosed for some time coming on. So, I think, much, much more room to go. .

Okay. Thanks, John. And maybe just one quick question on Pompe. Sorry, so, you mentioned about the natural history study of the - coming in later this year.

Is that going to be something then you would present at a medical conference or would you talk about it for example on an earnings call?.

Unclear yet. I think as we get closer to it and get into the second half of the year we will think about what the right forum is. Certainly, it would be presented at a medical conference. I think it will be a very important piece of contribution to the field, whether it’s presented first and any top-line announcement and we are not quite sure yet.

But once we share it publicly, we will talk more..

Okay. Thank you. .

Thank you. Your next response is from Mike Ulz from Baird. Please go ahead. .

Hey guys. Thanks for taking the questions. Maybe just a follow-up on the Pompe program and the natural history study.

Can you just give us a sense of what datapoints you’ve planned to share? And then, how we should be thinking about that data in terms of what’s the key endpoint, what would be the format of the data? Would it be for example, six minute walk tests over a certain period? Any color there would be helpful. Thanks. .

I am sorry, Mike, that’s for the natural history study?.

Yes..

Yes, the natural history.

Jay, maybe you want to field that please?.

Yes. We have collected the data and we will be analyzing it across a range of endpoints. Certainly a six minute walk test to the key endpoints. And we will be focused on that. But we will – have been gathering whatever available data are there are for these patients who have been on ERT treatment for whatever period of time they’ve been on it.

And we look forward to sharing that data later in the year. .

Got it. Thanks. .

Thank you. Your next response is from the line of Mohit Bansal with Citigroup. .

Great. Thanks for taking my question. Maybe if I could delve deeper into this 200 referrals you have talked about. I remember you reminded – you talked about roughly 20% of them at the last timepoint with naïve versus switchovers.

Can you please update that metric for us? And the related question is that, what’s so big to as we get incremental uptick in those naïve patients in the U.S.? Thanks. .

Yes, this is in the 200 prescriptions we’ve seen across those 90 prescribers in the United States.

Brad, I’ll let you comment on the split that we are seeing ERT treated switch versus naïve and how we are continuing to see substantial opportunity to help ERT treatment naïve patients in particular?.

Yes, thanks for the question. So, we do continue to see, I think a similar rate of uptick in naïve patients in the United States and the color we’ve given there is that’s slightly faster than most of our markets outside of the United States.

I think there are structural elements that we talked about before that allow us to – I think drive awareness in the patient population as well as in the physician population.

I think certainly, you can infer that that with the high adherence rate that we are seeing over 90% adherence rate with the broad prescriber base, and with that trend that you can infer that patients and physicians seem to be having a positive experience with the products which is great and we hope to continue to follow that over time.

We do globally though, see the diagnosed untreated population as a very important growth segment for us and that’s been our strategy all along which is start with the Switch patients who are more in the system every other week for their infusion. So there is sort of available systems.

But anticipated market growth in the diagnosed untreated patients and we are starting to see that which is great. .

Very helpful. And then, if maybe I can switch back – switch on the manufacturing part of gene therapy, given that it’s important and you are in a unique position where you have cash to invest in that plan.

How you are thinking about the manufacturing, so that, at this point, so that, going forward, you don’t have to make much changes as you get to the market?.

No, it’s an incredibly important part of what we focus on. I mean, everybody in gene therapy does. I think at Amicus, we really, really are uniquely positioned to be a manufacturing leader in gene therapy.

And again, we have in the last five years, solved for designed and executed on making the world’s most complicated glycosylated protein with AT-GAA, AT-B200 or Pompe enzyme. We’ve done that with our partners at WuXi. We’ve scaled it successfully, multiple times, now produced it at the 1000 liter point which is our commercial scale.

So, when I look at that, of our 600 people, we have about a 100 people at Amicus in manufacturing, technical operations and quality focused on biologics manufacture.

So our strategy with gene therapy is to work on relationships with the very best of the contract manufacturers and we expect in the months ahead to be able to announce who those partners and the scope and scale of those collaborations which would be quite significant.

In addition, we think we could translate our Amicus success in the biologics business now to the biologic gene therapies. And we absolutely expect to have into build our own manufacturing capacity and capabilities at Amicus. We will have more on that to say in the months and quarters ahead.

But I think you will see by the end of this year, we not only have one of the very best pipeline and scientific capabilities in gene therapy, we also increasingly will have one of the greatest capabilities to manufacture. So, it’s something we are hyper, hyper focused on. .

Got it. Very helpful. Thank you. .

Thank you..

Thank you. Your next response is from Whitney Ijem of Guggenheim. Please go ahead..

Hey guys. Thanks for taking the question. Just curious on CLN6, I am wondering if you can remind us what you’ve said around next steps once we get the data.

Is your plan to sort of wait for the full 12 patients worth of data before taking any steps in terms of regulatory discussions or anything like that? Or you are thinking about the evolution of this program on that front this year?.

Yes, we’ve not said anything about kind of a regulatory path forward. Let’s get the data out, maybe year end, Q3, Whitney. And once we see that - hopefully, strength in that data, we will be able to talk more about a path forward.

But we are planning everything internally to move that program including manufacturing, planning, and regulatory planning to move that to patients as absolutely quickly as possible. So, we will have more to say on that in the second half of the year. .

Great. Thanks. .

Sure..

And the next response is from Elemer Piros of Cantor. Please go ahead..

Yes, good morning. John, may I please ask whether it’s safe to assume that the 150 plus patient adds here in the first quarter. The majority of those may have come from the U.S. .

That’s actually not correct, Elemer. I’ll let Brad comment on it. But just at a high concept, we continue to see really strong growth in new patient prescription in Europe, in Japan and in the United States, all at or above our target numbers for the quarter.

Brad, do you want to add some more color?.

No, I think that’s exactly right, John, while the U.S. is a large and growing contributor to that number, still majority of our patients come from outside the United States. Over time, if you look at the markets, the Fabry market broadly, I think the U.S. is about a third of global sales.

So, I think that’s a good metric to think about in this sort of steady state. But right now, U.S. is still growing and again the majority is from outside the U.S. .

So, the 200 new PRFs during the quarter, would that change this ratio in the second and third quarter you think?.

Yes, sorry, let us be clear there. So that 200 PRF number is actually since launch. So that’s 200 patient referrals by them since the launch of last year. So that maybe part of the question there. .

Yes. Thank you for clarifying. Thank you very much. .

Yes, and that’s also, sorry one of the thing, that’s also through April 30. So, it’s a slightly apples-to-oranges comparison..

Thank you. .

But we thought important to share that continued strong trend, we began the year with little over 650 patients on Galafold. We ended the quarter at the end of March with more than 800 patients. So, a remarkable growth in product adoption. .

Yes, thank you. .

Thank you, Elemer..

Your next response is from Yun Zhong of Janney. Please go ahead. .

Hi. Thank you for taking the questions. So, the first question is on the diagnosed untreated patient and then, the burden of IV infusion is a major reason for patients to postpone treatment initiation.

And is there anything that’s preventing the uptake in diagnose to untreated patients, should these even faster than the pace that you are seeing currently? Anything besides patient identification, payer coverage?.

Bradley go ahead, please..

Yes, I think there is really two different dynamics going on there outside of the United States. As we have said before, it’s very restrictive in terms of how you can educate or interact with patients.

You really have to go through physicians and because diagnosed untreated patients aren’t necessarily seeing their physicians very frequently, maybe once or twice a year only. I think it takes more time to get to those patient segments. We are seeing increased growth there and now that we’ve been on the market for up to three years in some countries.

And that’s why I think it was important to provide the color on the call today that the rate of growth in those more mature markets is starting to be roughly equal this year in terms of continuing to switch patients, but also driving adoption in those diagnosed untreated patients. In the U.S.

if you cut the answer a little bit, earlier, the dynamic is slightly different. There is an ability to educate patients directly. And so, there is perhaps a chance to interact with them more frequently than you can versus having to go through the physician. And I think there is an opportunity to that and drive a faster adoption rate.

We also of course, I think, in part because of the longer timeline to get it approved here in the United States, there perhaps was more awareness built up in that segment which could drive faster adoption as well. .

Okay.

And on the patient diagnosis, and I think you said in the prepared remarks that, Fabry is well known to be difficult to diagnose and is the company doing anything to help patient diagnosis to so that the diagnosis can be faster and more accurate?.

Yes, we are doing a lot on diagnosis and finding people living with Fabry.

Bradley, please?.

Sure. So, as you might imagine, this has been something that some of the other folks in the lysosomal disorder space have been working on across all diseases, I think you could safely say that most lysosomal disorders are under diagnosed and misdiagnosed.

Fabry, as you look at the newborn screening reports and the other more recent population screening, you can see in fact it could be the most under diagnosed of the lysosomal disorders. We are looking at pilot programs, everything from screening populations and masses and IDS and other kinds of potentially high risk populations for misdiagnosis.

We are looking at other ways to drive newborn screening here in the United States than elsewhere. So, I think you will see over the coming months and years that we begin to take a real leadership role in that effort which I think is important for everybody to really starting appropriately diagnose this disease. .

Okay. Last question.

You mentioned a pediatric study in Pompe disease and are you able to provide any additional details, if not, and when do you think you will be able to provide that information?.

Yes, Jay, please?.

We haven’t discussed it in too much detail. But we do look forward to sharing more information in future communication. .

Great. Thank you. .

Yes, it’s such an important priority for us and for others in the field to be able to get this medicine to children as well. In my travels in Europe over the last week, I’ve had a chance to meet with a number of people living with Pompe and their families of all ages. And there remains really significant interest in the potential for a new therapy.

And that’s obviously something that we are just absolutely hyper focused on. .

Great. Thank you for the answers. .

Thank you. .

Thank you. Your next response is from the line of Salveen Richter of Goldman Sachs. .

Yes, hi. Thank you for taking our questions. It is Maryana Breitman for Salveen. Congrats on the progress you’ve made. I had a quick question on CLN patient identification, especially for CLN3.

I was just wondering if how you guys thinking about patient identification given how quick are those – the clinical pipeline seems to be going forward? And I had a follow-up..

Yes, incredibly important to find these kids as quickly as we can. We are working with all the world’s experts and leading centers in CLN6. So, where there are patients existing today, as new patients are referred to these centers, we have a really open almost day-to-day dialogue with those centers.

In addition, over the mid-term to long-term, it’s just going to be, Maryana, so vitally important that we find these kids as soon as we can. You can’t reverse neurodegenerative damage.

So to get these kids as soon as we can to put them on a gene therapy for what we believe could be a cure, it’s just – I mean, it’s going to be an enormous responsibility and obligation for us, the community and more broadly society for these disorders, particularly diseases of neurodegeneration.

So, Jeff do you have anything else to add any particular efforts, but I think that’s really our focus today working with the world’s leading experts and the top centers. .

Yes. .

Got it. And I had a quick….

Yes please..

I had a quick question on the Pompe gene therapy. I just was wondering, how you are thinking about the vectors, because, that will be a very important part of the – of the inclusion.

And what are you thinking about you need to be thinking like how you basically like thinking about choosing the vector both in delivered to the tissues and then B, diluted immunogenic?.

Sure. Very important part and actually a highlight as we came into the gene therapy field, why we chose to partner with Brian Kaspar Nationwide Children, Kathrin Meyer and their team, but also why we chose to partner with Jim Wilson and the UPenn team.

And why earlier this year we moved all of Amicus Science to Philadelphia and why we are building out a 75,000 square foot state-of-the-art Gene Therapy and Global Research Center of Excellence in Philadelphia.

It’s because, we believe, we bring the expertise in protein engineering, in understanding disease biology, pathophysiology , pharmacology and the ability to develop these medicines.

We are combining that with Jim Wilson and his more than 250 scientists in the gene therapy in orphan disease center where Jim is bringing the expertise in gene therapy and 30 years of experience and we are leveraging that as we just did in Pompe. But also Fabry if you detail five disorders as well.

And it’s been an extraordinarily positive seven months. Hung is on the phone here as well.

Maybe Hung and we can conclude I think then that’s the end of the questions in the queue, maybe Hung a good place to conclude, why we are so excited about our potential with Pompe gene therapy, but even more broadly our potential to be successful in gene therapy science?.

Sure. Thanks, John. As before I making my comment already, what we bring to table is clearly our understanding of the disease and our true ability with regards to engineering the protein. So that’s better targeted. Specifically, to vision must be sort of captive proteins.

The expectation is that, when introduce into the body, the body will mount and may response to any AV capsulate. So I think that’s something that we recognized very clearly. But it’s something the way we really will surgeon like Dr. Wilson’s expertise to help us deal with that issue.

But to be clear, I think that the expectation is that where the AV will induce any real good response. So I don’t know of any AV vector to-date that’s actually able to get around that problem.

Jeff, do you have anything to add to that?.

No. .

That’s very helpful. I have a quick follow-up. At the meeting then, the 1934 Gene and Cell Society Meeting, there was some presentation that showed that a very high AV that the concentrations can cause oncologics diseases.

What are you thinking about that, like how do you think about going forward especially given that in kids, you have to be basically thinking about the sort of risk benefits?.

Absolutely. And again, it’s important to remember in gene therapy, if you are somebody living with Pompe or ultimately any of these, you have one chance likely in your life to get a gene therapy that would better the most complete effective and safe approach. Safety is something that we design from day one into what we build.

It’s obviously, top of mind for Jim and his team and UPenn and it is for Hung, Jeff and our team, as well. So, we spend a lot of time thinking about the importance of designing that’s to be as safe as possible. It’s one the great advantages of working with Jim Wilson and the technologies he has developed and continues to develop.

Again, he is – that could we use the proprietary UPenn vector for Pompe and what we developed.

So, for us, that continues to be incredibly important to focus on safety as, well and we think that with a better targeted enzymes, coming out of the gene therapy expression, it will give you potentially more ability to deliver the product at a lower dose and of course that could be the greatest way to manage the safety profile going forward.

And it’s why the targeting of thee proteins understanding, engineering and characterizing that is just vitally important to what we do and one of the great advantages that we bring. So, I think it’s really going to be an advantage for Amicus going forward to solve that important problem. .

Got it. Very helpful..

Maryana, thank you very much..

Thanks a lot. Thank you. .

Okay. Great.

Operator, any other questions?.

I am showing no further questions in the queue at this time. I would like to turn the call back to John Crowley, Chairman and CEO..

Great. So, everybody thank you for listening to the call this morning. It was great to do it from here in the United Kingdom. And great to spend a week-and-a-half or so visiting our teams throughout here in Europe. It was a great first quarter of execution and much more ahead in the year to follow. And much more news to share.

So, thank you everybody for listening. Have a great day. .

Ladies and gentlemen, this concludes today's conference. Thank you for participation and have a wonderful day. You may now disconnect..