Amicus Therapeutics Inc (FOLD) 2015 Q2 法說會逐字稿

Good day ladies and gentlemen and welcome to the Amicus Second Quarter Results Conference Call and Webcast. (Operator Instructions) As a reminder, this conference call is being recorded. I would now like to introduce your host for today's conference, Sara Pellegrino, Director of Investor Relations. Please begin.

Good evening and thank you for joining our conference call to discuss Amicus Therapeutics second quarter 2015 corporate highlights, program updates, and financial results. Present on today's call we have John Crowley, Chairman and Chief Executive Officer, Chip Baird, Chief Financial Officer, Bradley Campbell, President and Chief Operating Officer, Dr. Jay Barth, Chief Medical Officer, and Dr. Hung Do, our Chief Science Officer.

The slide deck to accompany this call is also available on our corporate website at www.amicusrx.com in the investors section.

As a reminder, this conference call contains forward-looking statements about our future expectations regarding our business, operations, and financial conditions including, but not limited to preclinical and clinical development, cash runway, regulatory timelines, the potential success of our product candidates, and amenable patient populations. Actual results could differ materially from those projected in Amicus' forward-looking statements due to numerous known and unknown risks and uncertainties including the risk factors described in our annual report on Form 10K for the year ended December 31, 2014, which is available from the SEC and on our website.

All forward-looking statements are qualified in their entirety by this cautionary statement and Amicus undertakes no obligation to revise or update this conference call to reflect events or circumstances after the date hereof.

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

Great. Thank you, Sara, and good evening everybody. It's a pleasure to be here joined by our executive team. Certainly a pleasure to host this conference call coming off what was our most significant and most value-creating quarter in Amicus history.

For those of you who are able to access the document that we've put up online, we have some slides to reference as well, and I'll just begin by noting some of the key achievements and program highlights from a business perspective in the last quarter. This is on slide four if you're looking at the deck.

Really four things -- many, many good things happened at Amicus in the second quarter, four we think were particularly transformational. First, of course we had the name accepted, our trade name and announced for Galafold, migalastat hydrochloride, now known as Galafold, our Precision Medicine, personalized medicine for Fabry disease monotherapy.

As you know, we submitted the MAA to Europe under accelerated assessment. It was also validated by the European regulatory authorities. We are also pleased to announce on this call that the FDA has accepted our pre-meeting, NDA meeting request, and that's now been scheduled for later in the third quarter. The briefing document for that's now complete and Jay Barth, our Chief Medical Officer, will go into some more detail about that in the call. We think that's a great advancement here very recently for the program.

And we continue to make great advancement across the global regulatory processes in other geographies as well and some terrific new additions to the Amicus commercial team. I'll highlight some of those and Brad Campbell will speak to some of those as well. So tremendous progress for Galafold and Fabry disease.

Secondly, our Pompe program now very, very close to the clinic. Our next-generation enzyme replacement therapy regimen for Pompe disease. We're pleased to announce on this call that we have now completed the first campaign, GMP manufacturing production run. It was very, very successful. We'll take you through some of the details both from a material quantity standpoint as well as for the quality, the very high quality of the material, and that's now completed its manufacturing including all the purification steps. So we're very pleased that that went well. Our second campaign is underway, but the first material for patients is already ready for the clinic as well as the IND-enabling studies that Dr. Hung Do, our Chief Science Officer, will comment on those through the call. And we are also going to describe for you here today our clinical strategy as we move forward in Pompe disease. Dr. Barth, Jay, will take us through that as well.

The third area to highlight from our second quarter and now as we sit here today is that we are very well capitalized to continue to build on our vision of creating one of the world's great new biotechnology companies focused in the rare diseases. Chip of course will take us through the financial performance in the second quarter including the $258.8 million follow-on public offering that we offered at $13.25 a share back in early June that leaves us with a very, very strong cash position.

And finally the fourth point that I'll highlight here as part of our success in the last quarter has been building an absolute world-class international commercial leadership team. The key elements of that leadership team are in place and eagerly preparing for the hopeful launch of Galafold, and again, Brad will take us through more of that.

With that as my introduction, again if you have the slides you can flip forward to slide number six. I'll turn the call over now to Jay Barth, our Chief Medical Officer, and Jay, I'll ask you to speak to the global regulatory strategy for Galafold.

Thanks, John. Things in our regulatory strategy have really been proceeding very well, getting us closer to bringing Galafold to patients. Starting with the US, the FDA, as John mentioned, has accepted our request for the pre-NDA meeting which is scheduled, and the briefing document is finalized. It will be submitted shortly to the FDA.

An important goal of the pre-NDA meeting is the discussion of the Phase 4 component of our program. And the proposed plan includes a study of GI symptoms in Fabry patients as well as supportive data from the registry that we're planning post-marketing.

On the European side, the MAA is under review under Accelerated Assessment which of course shortens the timelines. The review times go from 210 to 150 days, and therefore we are expecting the CHMP opinion by the end of the year. And that's proceeding well.

Finally in the rest of the world we have started the process of starting the rest of the world regulatory activities following on the MAA and the NDA submissions. So on all fronts we are moving forward with our regulatory strategy as planned, and I'll now turn it over to Brad to discuss the Fabry market.

Great. Thanks, Jay. Good evening everybody. So as we know, on slide seven, the enzyme replacement therapy market for the treatment of Fabry disease is a large market. It's over $1 billion in sales in 2014. That's based on products that are priced at about $275,000 to $300,000 per patient per year. And we continue to see robust growth in that market fueled primarily by an increase in diagnosis rates that continues to be shown in the United States, Western Europe, and the rest of the world, and bringing new patients on therapy.

If you look to slide eight, this really shows how we look at the Galafold commercial opportunity. You have the schematic on the right that we've looked at before which shows our three key patient segments. The patients in the center there, the blue segment, who are the ERT-treated market. That's $1 billion in sales which we think represents about 4,000 to 5,000 patients. And then the next outer ring, which represents the diagnosed but untreated population, which is another significant population about as large as the treated patient market today. And then finally the outer ring, which represents what we think is a significant under-diagnosed population or undiagnosed population, which I'll talk through in a minute.

But importantly we have studied both switch and naive patients who represent a cross-section of phenotypes throughout these patient segments, both males and females, and you have a range of genotype from classic to late-onset. So we think the data package that we studied with Galafold over the course of its development support the application across these patient segments.

Moving on to slide nine. As you'll recall, there have been a number of newborn screening studies over the course of the last decade, beginning in Italy and moving through various geographies in Asia, in Europe, and in the United States which continue to show that rather than the historic published incidence of 1 in 40,000 to 1 in 50,000 live births with a GLA mutation, these studies continue to show a significantly higher portion of patients with GLA mutations, looking like 1 in 1,000 to 1 in 4,000, so almost tenfold greater than the historic published incidence.

And even if you are to look at those what we call index patients who were discovered through those high-risk screening populations or newborn screening populations, you may not choose to treat that patient and you'd choose to follow them through their disease course. But certainly based on the fact that this is an X-linked disease, we've shown through the literature that that brings another 3 to 5 additional patients through that family screening opportunity. And what these (inaudible) reports have shown is that a high proportion of those patients have amenable mutations ranging from 75% to even 100%. So as that market grows, as we find additional patients through newborn screening and other screening populations, we expect those to have a significant portion of amenable mutations.

Moving on to slide ten, importantly as we have generated all this data over the course of 2014, we were able to go back out to the market with an updated target product profile, interact with our key stakeholders, with physicians, with patients, with payors, and present that target product profile to get their receptivity to what the new value package that we're bringing with Galafold would represent. And I think in each of those key patient segments that we've talked about in diagnosed and treated patients who would have to switch off of their current standard of care, in diagnosed untreated patients, and in new patients, physicians clearly show that in a large majority of the patients across those segments, 65% to 75% based on our current target product profile, they would look to switch their patients or put their patients onto Galafold. So very clearly a high and positive response to the value that we think we can bring to the market with Galafold as an oral therapeutic for Fabry patients.

In a similar vein, on slide eleven, we go through some of the payor feedback. And here too I think very important recognition by the payors who said both based on the clinical trial data, so the data that we showed through [ON1] and [ON2] studies, and also through the improvement in the route of administration, reducing that burden of treatment going from every-other-week infusions with enzyme replacement therapy to an every-other-day small molecule pill with Galafold, payors very clearly said that if you were to model a parity pricing, again that $275,000 to $300,000 per patient per year, very strong support for reimbursement for Galafold. So very good feedback from both payors and physicians in terms of the target product profile and the value package that we would bring with Galafold.

So very encouraging feedback from the market. And importantly too, on slide 12, as John mentioned, we continue to be impressed with the level of quality, experience, and patient-centric focus of our key commercial hires. We now have leaders in place in all of our key functional areas internationally as well as our key regions who will be able to lead the launch of Galafold successfully, and this of course builds upon the strong history that we've established with a very broad global footprint in terms of our clinical trial activities but also a strong history of patient advocacy, medical outreach, et cetera.

So very strong momentum leading into the second half of this year, a very strong team in place, and great feedback from the market so far. So with that I will turn it over to John to walk us through the Pompe program.

Great. Thank you, Brad. Thanks for the great overview, both to Jay and to Brad. And hopefully you sense not only the great confidence we have in the regulatory strategy and where we are in the process, both in Europe and the United States, and also looking to rest of world. But the more and more we've reached out to physicians, to patient groups, the more we've looked at much of the work done to understand how many people are living with this very devastating disease, Fabry disease, the more we are convinced that this is indeed one of the largest human genetic disorders in the world today and one for which we're very excited to have our product, Galafold, with the potential to offer significant potential ways to treat this disease that may be potentially differentiated from existing therapies but also to use that as the cornerstone for a broad Fabry franchise where we are also of course building our own proprietary next-generation enzyme replacement product.

We're not going to talk about that in this call. I would expect in the months to come we'll have much more to say about the success we've had scientifically and from some early manufacturing in our next-generation ERT. But again, with Galafold and the Fabry, the opportunity to help people with Fabry is something we're very, very excited about here at Amicus.

Let me now go ahead and shift to our Pompe program. This is one, as you know, for several years has been in development here at Amicus. Really accelerated in the fall of 2013 with the acquisition of Callidus Biopharma, and Hung Do, now our Chief Science Officer, is the founder of that company helping to lead that effort.

I'll remind you on slide 14 from a disease overview standpoint, this is a devastating lysosomal storage disease, Pompe disease. While there is an existing improved enzyme replacement product, we still think that this is a devastating disease, even for patients on ERT today. Our goal here, as with all of our programs, is to either be first in class or best in class.

Let me describe for you a little bit more and you can reference again on slide 15, what's the problem that we're trying to solve for here? So we think there are three significant deficiencies in the current enzyme therapy. The first is activity and stability, the second relates to tolerability and immunogenicity, and the third relates to uptake and targeting.

Those first two we address with the addition of our CHART platform technology, which is the chaperone-advanced replacement therapy, a specific small molecule designed to bind to and stabilize our proprietary enzyme replacement therapy. We think that has shown in pre-clinical models and in some early human proof of concept studies with an existing ERT the potential to address both of these problems.

We also know through our own design of the proprietary cell line that we use, our base enzyme therapy, ATB200, we think we have shown dramatic improvement in pre-clinical models in uptake and targeting with our uniquely engineered GAA cell line that has optimized levels of mannose-6-phosphate and very importantly what we believe to be very appropriate levels of glycosylation and the right sugar structures in carbohydrates.

This was our belief when we acquired Callidus a year and a half ago. Much of the work for the last 6 or 7 quarters has focused on taking this base enzyme together with the addition of the small molecule chaperone and developing a drug rapidly for patients that would, we believe, have the potential to become best in class. To do that we've worked with our partners at WuXi in China at designing this cell line, and if you look on the next slide, on slide 16, you can see much of the key activities over the last year and a half, really culminating in the second quarter of this year as we have now completed the GMP run.

But you know, I can't emphasize enough how much of our teams' effort in technical operations and in science has focused on ensuring that we not only design the right cell line and drug regiment but that we're able to scale it efficiently and effectively and to have a drug product that we think is very highly differentiated.

So with that we've completed of course the master cell banking in 2013. Throughout 2014 we scaled from the 5 liter scale all the way up to the clinical production scale which is 250 liters. Our first GMP batch again was just completed in the second quarter of this year, and we're very, very happy. It continued to have very high levels of mannose-6-phosphate, continued to have the right and proper glycosylation. It's also a very high yielding cell line. So we think in every way we achieve manufacturing success.

So the material for our first clinical studies is now complete and ready for patients. We now have additional GMP manufacturing runs underway for further long-term clinical supply, and we're now also working on finalizing the very last parts of the IND-enabling toxicology studies that are nearing completion here.

Let me -- Hung, if I could turn it to you and if you can just comment on some of the [cross] studies and the good news that we've had there and the progress. And then if you can just comment a little bit more on slide 17, we also show some additional data on pre-clinical proof of concept which gives us further reason to be excited by this program.

Sure. Thank you, John. Hello everyone. Yes, so let me just speak a little bit to what we have learned so far on our IND-enabling toxicity studies. We are nearly complete with these studies. We actually have tested our molecule ATB200 alone as well as ATB200 that has been co-administered with our chaperone AT2221.

To date we have seen no overt toxicities with any of the trials that have been performed, and I think we are in the final stages of testing. We are doing the final pathology test right now with (inaudible) reports pending. And those are expected by Q4 of this year.

So so far, so good. Everything looks very good with the tox?

Everything looks fine. We have not seen any signs of any issues at this point.

Great. Excellent. So continue to have a clear path to the clinic.

That's right.

Very good.

And importantly I think that one thing that we have learned from our pre-clinical studies is that we actually have now a much better understanding of the dose that we want to go into the clinic for our chaperone. There was a lot of work to determine this particular dose. We actually have now selected our final dose for our enzyme as well as for our small molecule chaperone enhancer, and that provides the utmost stabilization of the enzyme in blood, as John alluded to earlier, as well as for improved uptake and activity in the tissues.

And one thing I just want to remind everyone why we are so excited about this particular approach is that if you look on slide number 17, one thing that we have come to find is that our enzyme is significantly better targeted and provides much better effect for accumulated glycogen in the muscle tissues. As shown in this figure, the glycogen clearance of our enzyme with the chaperone is significantly better than the current standard of care. It reduces the glycogen levels not nearly to wild type but certainly close.

But more I guess encouraging from our standpoint is that it also appears to have a robust effect in terms of improving the muscle physiology as shown in the lower panels. What is shown in the LAMP1 staining slides is that LAMP1 is a protein component of these vesicles which are known to accumulate in Pompe disease. The fact that our enzyme product is able to clear these particular accumulated vesicles to nearly wild type levels is certainly very encouraging. And we think that we can replicate this combination of enzyme with chaperone in the clinic to maximize the effect.

And with that, let me turn it over to our -- back to Jay to given an overview of our clinical strategy.

Yeah, this will be really important this evening. This will be the first time that we are discussing our Pompe clinical development plan and strategy. I think you'll find it's something that we've worked on throughout this year. We've vetted with patients, with our patient advisory board. We've vetted in sessions with key opinion leaders around the world. We believe it's a smart and very rapid path into and through the clinic with what we believe to be a very differentiated product. So Jay, I'll let you describe it more fully.

The clinical development plan begins -- the first study as an observational study where we will collect longitudinal data in patients on the current standard of care ERT. That study will be starting in the next few weeks. The next study which will start by year-end, is a Phase 1/2 study of the next-generation ERT, ATB200 plus chaperone in both naive and ERT-switch patients. And we expect to have data from that study in 2016. And then third, in the middle of 2016 we'll be starting our Phase 3 pivotal study which will be of ERT-switch patients.

Now we'll be meeting with US and European regulators in the coming months to discuss this plan with them and we will be able to provide additional details after we have those interactions. But I'm happy to be able to share with you at a high level the overview of the plan that we think is both robust and streamlined to get us through to regulatory submissions.

Great. We're happy to discuss this further in the Q&A as well, but it's a program we're very excited about. It's been vetted with some very, very experienced and smart people, and we think this could offer a great benefit for people living with Pompe. So it's something we're very excited about, something that will generate some very important data for us and certainly a very fast path then by mid next year into the Phase 3 study for Pompe. So more to follow on that.

Chip, let me turn it to you for the 2Q '15 financial results and guidance.

Great. Thanks, John. Good evening everyone. I'll start today's financial discussion with a few comments on our current cash position and financial guidance beginning on slide 20. Amicus continues to maintain a very strong balance sheet. At June 30 of this year we had $361 million of cash and cash equivalents compared to $169 million at the end of last year.

The balance sheet was significantly strengthened during the second quarter with an oversubscribed follow-on financing raising $258 million in gross proceeds. We expect this cash position and current -- including the proceeds from the offering to fund our operating plan into 2017.

Turning our second quarter 2015 financial results on slide 21, I'll be referencing tables one and two in the press release we issued earlier today and additional details will be found on our Form 10Q which will be filed later this evening.

Total operating expenses for the second quarter 2015 increased to $26.9 million compared to $14.7 million for the second quarter of 2014. The year-over-year increase was primarily due to increases in pre-clinical and clinical development costs on the Fabry monotherapy program and the Pompe ERT program, as well as investment in prelaunch activities for Galafold.

A net loss attributable to common stock holders in the second holder was $27.1 million or $0.27 per share compared to a net loss of $14.6 million or $0.22 per share in the second quarter of 2014. The [water] net loss is primarily attributed to an increase in operating expenses and as of June 30, 2015, we had approximately 118 million shares outstanding.

I'll also note that during the second quarter we paid off the outstanding balance of our term loan and currently have no debt on the balance sheet. As a reminder, in December 2013 we did a debt financing in which we drew $15 million of aggregate principle amount with an 8.5% interest rate. From January 2014 till now we have been making interest-only payments, and in June we paid off the outstanding balance.

This summarizes our key financials for the second quarter as well as our updated full-year 2015 guidance. More information on our financials will be available in the 10Q which will be online later this evening. I'm happy to address questions during the Q&A, but for now I'll turn it back to John.

Great. Thank you, Chip. So I'll just finish up on the last slide here that talks about all of the milestones ahead of us. Certainly a great first half of the year for Amicus and we hope an equally great and perhaps greater second half of the year. A lot of work ahead of us still.

If you look at the Fabry franchise, the first two milestones for Galafold. Again, we have [announced] accepted by the FDA a pre-NDA meeting request, and that meeting will occur later in 3Q. We then immediately hope to be able to file our NDA based on that meeting, and specifically with an agreement on the Phase 4 plan. Much of the work on that NDA submission is ongoing now. So important milestones ahead for Galafold.

But also too, we continue to invest significant resources in developing our own proprietary next-generation enzyme replacement therapy co-formulated with our own proprietary chaperone. To advance that program in the second half of this year, in the coming months we will initiate a Phase 2 co-administration study of chaperone plus existing enzyme therapies for further proof of concept, also important to facilitate our own Fabry next-generation ERT, a clinical program as well. And that cell line continues its development and early manufacturing, and we'll have more to say about that and some specific data to share through the second half of this year.

Again, on the right-hand of that slide then focusing on some of the key milestones ahead. Quite a few of them for our Pompe program. As you can see, a lot of activity in Pompe, a lot of excitement now that we have what we believe to be this very high quality and highly differentiated product ready to enter into patients. Continued discussions with regulatory officials, as Jay indicated, in the third quarter.

We will here in the next month or two begin first patient in, in the Pompe observational study. We will, in addition to the pre-IND and MHRA meetings in the third quarter, we will also then have final completion of the IND-enabling tox studies very early in the fourth quarter. And in the fourth quarter we will begin our Phase 1/2 study in people, both ERT experienced and naive patients in Pompe disease, again leading into what we hope will be a rapid transition to a Phase 3 program in 2016.

So a lot of work still ahead of us. The mood at Amicus continues to be very, very positive. We continue to welcome extraordinarily capable and passionate new leaders to the Company, both here and with our significant European operations led by our Senior Vice President of International, David Allsop. And all of this continues to build toward our mission and our vision of building one of the next great biotechnology companies in this industry focused on the rare diseases.

And to that end, we're very excited now to have a program ready for commercial launch we hope with Galafold as that part of the pipeline advances. We're very excited that by the end of this year we'll have another clinical candidate in patients with our Pompe program. We also continue to invest and work diligently in research and development science, continues to be a very strong core competence together with clinical research here at Amicus, and we will continue to advance our pipeline and we'll have much more to say about that in the second half of this year in research and development and as science increases with our pre-clinical programs, again looking to develop products for devastating rare diseases where we can be first in class or best in class.

And with that we also continue to be very, very active on the business development front, looking at products, programs, and technologies that will enhance our existing programs or add to our pipeline to help us fulfill this vision.

With that, operator, we're happy to take any questions.

Thank you. (Operator Instructions) And our first question comes from Ritu Baral with Cowen. Please go ahead.

Hi guys. Thanks for taking the question. First question I have is on Galafold in Europe. Have you -- can you give us a little more color on the depth and breadth of your payor work in Europe? I know you have a quote from the UK, but have you had preliminary conversations with different companies on how they view the benefit of the data package produced?

And also have there been any changes in Fabrazyme or Replagal pricing or access recently in Europe, potentially in anticipation of a Galafold launch?

To your first question, it has two parts, Ritu. We'll let Brad take both of those.

Yes. So thanks, Ritu, for the question. So from a market research perspective, what we showed you there was I think a snapshot of the work that we had done with over 20 different payors through the major markets in Europe, rest of the world, and the United States. So that was a high-level snapshot. That was reflective of those conversations.

I won't speak to the formal conversations that will happen with regulatory authorities and reimbursement authorities around the potential approval of the product, but I think rest assured that the feedback we've gotten from payors through that market research process was very supportive based on the target product profile that we showed them from the data package we generated over the course of last year.

And I think too the acknowledgment that it was both the data that they saw but also I think the value that bringing in [an oral] small molecule into that space would be perceived well from that group as well.

The second part of your question, remind me, was?

If there have been any changes?

Changes. So from what we understand there has not been price taking in enzyme replacement therapy in Europe, in the major European markets. There was a couple of years ago some look at a number of the enzyme replacement therapies in terms of whether or not they were bringing the value that their prices were commanding. But at this point from our perspective there hasn't been any major change in terms of reimbursement for enzyme replacement therapies.

One of the areas, Ritu, that we've done quite a bit of diligence on is understanding the pricing of enzyme replacement therapy around the world. And of course there's distinctions by geography and certainly given that enzyme therapy is priced on a milligram per kilogram basis, differences in patients. And I think we have a very clear view of the dynamics of pricing on enzyme therapy in the Fabry market space and maybe, Brad, if you just want to comment about where we see enzyme therapy priced today?

Yeah. From our understanding from the research we have done, and again it's -- this is a global average. It's of course a weight-based product, and as John's mentioned, there are differences by geography, but in general that average looks like it's around $275,000 to $300,000 per patient per year. And from what we understand, there's not much difference between Fabrazyme and Replagal, so you could consider that a global average price.

Bit it hasn't gotten easier for patients to get the enzyme in what might otherwise be restricted access across Europe? I'm just wondering about competitive dynamics in advance of a potential launch.

I don't know if we've seen any changes in the reimbursement dynamics in anticipation of Galafold. I will say that one of the advantages that we have, of course there is competition, that's always going to be a challenge, but one of the advantages that we have over other new product launches is that we don't have to go out and convince payors that Fabry disease is a life-threatening progressive disease that it's worthy of [improving] a treatment and a treatment that would command an orphan pricing level. So that reimbursement very clearly exists, those payors very clearly acknowledge the unmet medical need in the Fabry space, and the regulators frankly based on granting us Accelerated Assessment clearly acknowledge that that unmet need still exists. So we don't have to build that reimbursement environment which I think gives us an advantage over other new products coming into this space.

Got it. Last question, just turning to slide 18 where you outlined the proposed Pompe clinical development plan. What data will you get out of the Phase 1/2 before the start of the pivotal that will help inform the pivotal? I mean obviously you're not going to be completely done. What do you need -- what information do you need out of the Phase 1/2 to best design the pivotal?

Yeah. I'll let Jay answer that question primarily. I can tell you, Ritu, in working with the doctors and thinking about again this notion of a smart and rapid path into and through the clinic, what we heard was the doctors want to see safety. They want to understand the pharmacokinetics of the next-generation enzyme therapy. That primarily will inform the ability to switch patients, and they'd like to see that in both naive and ERT-experienced patients. So that'll be important data to gather. Jay, I'll let you comment further.

The safety data is critical of course. And it's hard to be more specific yet until we have the regulatory interactions, but clearly things like the endpoints that we study in the Phase 1/2 study will inform us further on the Phase 3 study and the inclusion of both the naive and the ERT-switch patients in particular, that is the switch patients, will give us data that will help us in the Phase 3 study in the switch patients.

At this point I think the plans that we're going to submit to the regulators I think will be well received by them, and we're very eager to have those meetings. We'll be able to provide more details after we have those meetings on specifics.

Got it. Thanks for taking the questions.

The next questioner is Anupam Rama from JPMorgan. Please proceed.

Hey guys. Congrats on all the progress and thanks so much for taking the question. I just had a quick question on slide ten. When you talk to physicians and KOLs, maybe could you provide a little bit more color on what are the drivers of switching from ERT to migalastat? Is it the oral convenience that's driving it, the LVMI data, the GI data, or is it the totality of the data?

And then conversely, what is the strategy for those physicians that are sort of on the left side of this slide in terms of the strategy of trying to convince them to become early adopters ahead of the launch? Thanks.

Yeah. Thank you, Anupam. Great questions and I'll let Brad provide the answers.

Yes, so great questions, Anupam. I think a couple of things. Without question, the totality of the data weighs in our favor. You know one of the upsides of having such a long development program is you have almost 8 or 9 years now of experience with Galafold in Fabry patients, and over that period of time we've seen a consistent safety profile. We've seen very strong evidence both in naive and in switch patients for substrate reduction, for stabilization of kidney function, for impact on left ventricular mass. Of course it all depends on what label you end up getting in those markets, but at least the totality of that data package which goes into the target product profile was very well received by physicians. There's no question that that is a very important part of the value proposition.

That being said, we were also I think very pleased and not surprised to understand that there is value ascribed as well to this being an oral therapeutic into an injectable and infused market where again patients are getting infusions every other week of their life. One day out of their life every other week to dedicate to their Fabry infusion. So that's a very important part of the value proposition as well.

From a how do you move patients from left to right on this -- or excuse me, how do you move physicians from left to right on this graph, I think part of it is certainly experience. And so as more patients get -- as more physicians get experience they will be more comfortable in looking to their peers and moving across to the other side of that market.

I think that there will also of course be significant efforts working with key opinion leaders to help us to continue to work through congresses, we'll work through publications, et cetera, just to get the information out there so I think it's a broad gestalt of activities that we'll be doing now as appropriate and then of course once we get our labels that we'll be able to promote on specifically to those labels. So lots of activities to help move that from left to right and I think a great data package to support that.

Yeah. I have to say, Anupam, starting with this as our baseline, and this data is already several months dated as well so it doesn't incorporate a lot of the work we've been doing in the last handful of months, but this is a great baseline to start from, even in all these three different segmentations of the patient population.

So to Brad's point, to the ones on the left, I think it's more work, more conversations. They're doctors who did not have experience in the clinic generally with the drug, so we're already beginning those conversations. And this is as much about science education as it is about medical and clinical practice given the very unique mechanism of action of this drug that's very, very differentiated from enzyme replacement therapy but also differentiated from any other drug in development today in Fabry.

Great. Thanks so much for taking our question.

And the next questioner is Joseph Schwartz with Leerink Partners. Please proceed.

Great. Thanks so much. I was wondering first of all on your pre-NDA meeting, how do you expect the focus of that meeting to differ, if at all, from previous interactions you've had with the FDA, like the Type C meeting? And how much of the NDA is actually already in the works at Amicus? And do you think that you might communicate with the street if the outcome of the -- how the outcome of the FDA meeting, the pre-NDA meeting might differ from your expectations? It seems like you're doing a great job anticipating what the FDA would like you to focus on. I'm just wondering about your communication strategy afterwards given you've got a second half of '15 guidance for NDA filing. I'm just wondering if that might be refined further after you've actually sat down with the FDA again.

Sure. Great. Yeah, I think I heard three questions there, Joe, so I'll ask Jay to address them, the first on the FDA meeting coming up, the pre-NDA meeting, the nature of it. Second, how much we have done on the NDA submission itself, the percent progress if you will. And third, the communication strategy. So Jay, maybe if you'll take those first two and then we'll take the third?

Yeah. The pre-NDA meeting is really going to be based on requests that we got at the Type C meeting and the discussion. So it's a follow-on with regard to the content of the NDA, the under Subpart H, and specifically it's going to be forward focused on the proposed design for the Phase 4 commitment, confirmatory studies that are a necessary of Subpart H. So we're picking up where we left off at the Type C meeting and providing more details to the FDA with regard to our plan, which and they had requested a GI study, what that study would look like as well as additional supportive data that we'd be able to provide out of the registry.

And we are quite far along in the NDA. I can't give a specific percentage, but from the moment that the MAA went in we turned around and started converting that as it were to an NDA. So we're very much on track for a submission this year following the pre-NDA meeting.

Great. That's super helpful. Thanks. And then maybe one on Pompe. Is this your final scale for production of ATB200? And then I actually wanted to followup with that with some questions on your trial design.

Yes, of course, Joe. Yes. So this is the scale sufficient to going to the clinic. This will be our clinical scale. We do anticipate moving from 250 liters to 1,000 liters at some point in the next year for the last of our clinical supply and also importantly our early commercial supply. We want to make that transition for patients. We think those drugs will be the same, but we want to do that in the final stages of the clinic. Importantly we have that material to move forward.

Technically just to let you know, it's 1,000 liter working volume, 2,000 liter bioreactor technically.

Okay. That's helpful and it's encouraging you're doing that sooner rather than later. Can you give us any more details on the Pompe observational study in terms of the size and what data you're going to focus on gathering? And then also maybe the doses, endpoints, and size of the Phase 1/2 study and when we might be able to see data reported from that trial?

Jay, maybe why don't you take the observational study part first, please?

Sure. The observational study, we'll be looking at multiple outcome measures of the type that have been studied in Pompe as I said on standard of care. We're coming out with the sample size shortly when the study is initiated, but it's certainly something that is doable and going to be recruited in a relatively short time. And we will gain important longitudinal data once we follow that patient for a period of time that will inform us for the remainder of the program. And let me turn it over for the Phase 1/2?

Yes, Phase 1/2. Yeah, and again I think we can, having not yet vetted this fully with the regulators, probably want to not release all that. So just the general thinking on the Phase 1/2, Jay, the purpose and general study design.

Yes. We will -- I mean in any Phase 1/2 study in this realm, safety is the first step that you're looking at. We don't anticipate any safety issues whatsoever based on what's known pre-clinically and with ERTs, but of course it's a necessary step. And we will cover a range of doses, and those doses increase as you monitor safety towards an anticipated end-dose of 20 milligram per kilogram for the enzyme.

And then these patients will be studied for a period of time for safety, for pharmacokinetics, as well as activity of the drug, informing us even further in this population as I had mentioned before for the Phase 3 study that is planned to start by middle of next year.

Okay. Great. Thank you for taking my questions.

And the next question is from David Lebowitz with Janney Capital. Please go ahead.

Thank you very much for taking my question, and it's great to see the progress. Would you be able to I guess explain why the Phase 3 in Pompe is examining the drug in switch patients whereas the Phase 1/2 is looking at naive and ERT switch?

Sure. I think there are different learnings from those two different populations. Jay, I'll let you comment a little further.

We feel that the naive patients will be studied adequately in the Phase 1/2 study, that we will gain as much data as is needed on both safety and activity of the drug in that population, and therefore there won't be a need to study naive patients further in the Phase 3 study, whereas as it's designed now, to get complete information on the ERT-switch patient, the ERT-experienced patients, would require that additional Phase 3 study. So in the program as a whole, we're going to be studying both populations adequately. It's just divided up between the two studies in that way.

So I think if you look forward, David, I think it's important for labeling purposes for this drug that we have appropriately studies naive patients and to do that sooner rather than later makes sense we believe.

Secondly, also in the immunology of this disease, as you know the current enzyme therapy, significant issues around tolerability, immunogenicity, all patients are known to zero-convert and develop antibodies. We're particularly interested in studying patients who have never seen enzyme replacement therapy to see what the tolerability and immune response would be with this new regimen that we've developed.

Thank you for that. Would you be able to provide an update on the migalastat ERT co-admin trial as well as the next-gen ERT in Fabry?

Sure. So the next-gen ERT again is our own proprietary enzyme therapy that we're making again also with WuXi now that we're developing the cell lines here and together with our partners at WuXi, co-formulated with migalastat. That continues its science progress and work both here at Amicus and having been transferred now to WuXi, at WuXi as well and some of the early stages of manufacturing.

We'll have more of an updated on that in the months to come but that continues to be a very exciting and very fast moving program for us.

In terms of the co-administration study, again remember there the intent is to replicate what we did in a single-dose study with both Fabrazyme and Replagal with the oral co-administration of our chaperone given every other week with the every-other-week infusion just prior to the infusion. Again, the belief being and the early data in the clinic showing that you can extend the half-life, increase the tissue uptake, and in pre-clinical studies not only increase uptake into key target organs of disease but show much better substrate reduction.

So we're going to, having done that a couple of years ago with single-dose studies, we're going to do that with multiple-dose studies. We don't believe that the right path and the best path for patients is going to be to extend that for a full drug development program. We think this Phase 2 will be very important in understanding the long-term safety and efficacy of combining chaperone and ERT. We also think it will provide very important information that will facilitate our path into and through the clinic for the co-formulated next-generation ERT that we develop.

Thank you very much for taking my question.

And I am showing no further questions in the queue. I would like to turn the conference back to Mr. John Crowley for any final remarks.

Great. Thank you, operator. I think that's all we have. It was an excellent call, an excellent quarter, and we look forward to continued good news ahead. Thank you so much. Take care.

Thank you all for joining us today. This does conclude the conference and you may all disconnect. Everyone have a wonderful day.