Amicus Therapeutics Inc (FOLD) 2016 Q3 法說會逐字稿

Good day ladies and gentlemen, and welcome to the Amicus Therapeutics third-quarter 2016 financial results conference call and webcast. (operator instructions).

I would now like to turn the call over to Sara Pellegrino, Senior Director of Investor Relations. Please go ahead.

Good morning. Thank you for joining us our conference call to discuss Amicus Therapeutics' third-quarter 2016 financial results, corporate highlights and program update. Speaking on today's call we have John Crowley, Chairman and Chief Executive Officer; Bradley Campbell, President and Chief Operating Officer; and Chip Baird, Chief Financial Officer. Dr. Jay Barth, Chief Medical Officer; Dr. Hung Do, our chief science officer; and Dipal Doshi, our Chief Business Officer and General Manager of Scioderm, are also here and available to participate in the Q&A session.

On this call, 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 a 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 statement, which speaks only as of the date hereof. Also, all forward-looking statements are qualified in their entirety by the cautionary statements, 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 on Slide 2 in this presentation of our third-quarter results slide deck, the forward-looking statements and risk factor sections of our annual report on Form 10-K for the year ended December 31, 2015 and our quarterly report on Form 10-Q to be filed later today with the Securities and Exchange Commission.

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

Great. Thank you, Sara, and good morning, everybody. I'm pleased to welcome everybody to this call and will begin with an update on the significant progress that we've made during the third quarter across our five key strategic priorities. And for this, I'll go ahead and ask you to please reference Slide number 3 in our back if you are following along on the web.

So first let me begin with the Galafold international launch, which, as you will see, while very early in the product launch, is going exceptionally well. Today is a milestone for Amicus in our evolution to a commercial stage company as we are here for the first time recording full-quarter launch details as well as our first ever quarter with revenue from product sales. Brad will go into much more detail, but I just want to say up front that I really am extremely pleased with the commercial progress in bringing this new medicine to Fabry patients who have not had a new treatment option in more than 13 years and where we know there is still such unmet medical need.

We're pleased to report that we have now 50 patients with minimal mutations on reimbursed Galafold as of the end of October, which is more than double the number we reported on our last call as of July 31. The vast majority of these patients are in Germany, and most are switching from the approved ERT products.

Germany is the only EU country currently where Galafold is commercially available, which of course is typical of an early product launch as Germany is often the first launch country for new medicines approved by the European Medicines Agency, or EMA. And Germany tends, as we know, to be an important indicator for subsequent launch countries. This is a very important country for Amicus and for our first product launch.

So, recently, I had the chance to visit a number of Fabry treatment centers in Germany, and I can tell you, from meeting at those centers, knowing that we have a great leadership team at Amicus in Germany, and I believe they are very effectively communicating the strength of the label and our data package to physicians and that they are doing so in a manner consistent with our high business ethics here at Amicus. There is tremendous enthusiasm about this precision medicine approach and the KOLs' initial experience of treating Fabry's patients with amenable mutations with Galafold seems to be very positive.

I'll note that Germany is also very important because it is the third largest Fabry market in the world, and I think it's also particularly important as well as the bellwether for the Galafold launch in that, prior to the EMA approval that we had in late May of this year, we had no clinical sites nor any patients in Germany at approval at the end of May. So the German launch really was from Ground Zero. So early days but very encouraging. And again, Brad will provide more detail shortly.

Our second priority is to pursue additional regulatory submissions for migalastat. Here we continue to work with regulators in key geographies. We remain on track to provide a US regulatory update in the fourth quarter, and we are targeting a Japanese new drug application in the first half of 2017.

Our third priority is to successfully execute our important clinical studies in Pompe disease and in epidermolysis bullosa, or EB. Here, we are eagerly anticipating initial interim data from our Pompe clinical study by year end 2016. We are also targeting top line data from our Phase III EB study in the first half of 2017.

We also have strengthened the balance sheet, our fourth key strategic priority, in the third quarter and since the beginning of the year to support both our commercial launch as well as the advancement of our pipeline.

And finally, our fifth strategic priority is to build out our biologics capabilities and capacity in our overall pipeline. As part of this strategy, we acquired a new preclinical program for CDKL5 deficiency, a devastating neurologic rare disease, earlier this year and we expect to focus on our current programs for the remainder of 2016.

So, with a commercial launch underway, two programs in the clinic, and a biologics platform for future growth, we are executing our vision to become a leading global biotechnology company focused on making a significant impact in the lives of patients living with rare, devastating diseases.

So, with that introduction, let me go ahead and turn the call now over to Brad who will take us through more details on Galafold. Brad joins us from our international headquarters in London. Brad, go ahead please.

Thanks very much, John, and good morning everybody.

I'll begin on Slide 5 with the same launch metrics that we provided last quarter, and all of these are as of October 31.

First, as John mentioned, we did have over 50 patients on reimbursed Galafold again at the end of October. These include both naive and ERT-switch patients. The majority are being treated on a commercial basis in Germany with the remainder treated throughout expanded access programs, or EAPs.

And as John mentioned, Germany is a very important benchmark for the rest of the launch and we're seeing some very early indicators of success there. To begin, the vast majority are switch patients, and we now estimate that 20% of the eligible switch patients in Germany are now on Galafold, so great early uptake in that market.

As a reminder, all of these patients and their physicians are newly experienced because we did not have any clinical sites in Germany during the development program. And although still early days, our data show that none of these patients have discontinued or switched back to enzyme replacement therapy after starting on Galafold.

Again, while we think that reporting these indicators in Germany provides a sense of our initial launch success, I would note that we do not expect to provide this country level of granularity going forward.

Turning to the rest of the international rollout, we have launched in a total of three countries on a commercial basis and through EAPs, and we've recently secured reimbursement in two additional countries where launch is forthcoming. And finally, we now have 15 countries with active pricing and reimbursement discussions underway, so great progress across the European and international markets.

Turning to Slide 6, I'll comment a little bit further on the EU market, which of course is an important region that represents 34% of the global Fabry market in 2015, a significant portion of which comes from the EU 3. With Germany, as we said before, it's the third largest Fabry market in the world with approximately 1,000 diagnosed patients roughly, half of whom are not currently permitted, so significant growth opportunity there. In France, patients continue to access reimbursed Galafold through our Cohort ATU while we navigate the country's pricing and reimbursement process.

And importantly, in the UK, we are in the midst of pricing reimbursement discussions under the highly specialized technology, or HST, process. And in October, NICE issued their draft recommendation to commission or approve Galafold for patients 16 years and older with a diagnosis of Fabry disease who have an amenable mutation. We're very pleased with this draft recommendation within the evaluation and complication document, and we continue to collaborate with NICE towards the publication of the final evaluation determination that will support reimbursement and launch in England and Wales.

Turning now to our global regulatory strategy for migalastat, which is on Slide 7, I'll begin with an update on approvals and submissions throughout these territories. The EU approval of course opens up our ability to access more than 70% of the global regulatory market in EU member states as well as countries that allow EAPs or accept submissions on the basis of EU approval.

One important update from the CHMP in Europe -- they have now agreed to add 44 new amenable mutations for the EU label, which is now being updated to include a total of 313 amenable mutations. We think this is an important validation for our precision medicine approach as well as our broad dynamic European label where we have formal mechanisms to request updates as new mutations are discovered.

In Switzerland, the therapeutic product authority Swissmedic has now approved Galafold with the same indication as our broad EU label covering all amenable mutations referenced in the EU label. We've now successfully completed six additional regulatory submissions with more to come. And over the remainder of the year, we would expect additional EAPs to come online in both Europe as well as other international territories. And finally, we are on track for targeting the first half of 2017 for a submission in Japan. And as John mentioned in his introduction, we do remain on track as well to provide a US regulatory update by the end of this year.

So, in summary, we believe the momentum for the Galafold launch, our regulatory process, the strength of our data package on our European label, the unmet need remaining in the Fabry base space and, importantly, the quality of our international organization and the relationships they are building in the field, represent tremendous momentum in the launch.

Of course, we remain committed to the broader Fabry community and we have a big vision to help all of the Fabry patients. Not only will we continue our endeavor to seek regulatory approvals for Galafold for Fabry patients with amenable mutations, but for those patients with non-amenable mutations, we are designing a novel proprietary Fabry ERT that incorporates an intravenous form of migalastat in the formulation. We're actively working behind the scenes on this preclinical program so that, in the years ahead, we can offer a solution to all Fabry patients driven entirely by their genotype.

And with that, I'll now turn the call back over to John to provide an update on our clinical pipeline. John?

Great. Thank you, Brad, for all of those updates.

Turning now to Slide 9, let me talk a little bit about the three major challenges again in Pompe and what we're trying to achieve here. So, the first challenge is activity and stability. The second relates to tolerability and immunogenicity. And here we are looking to address both of these challenges with our novel treatment paradigm consisting of our proprietary enzyme replacement therapy designated as ATB200, along with the addition of our chaperone, AT2221, a specific small molecule designed to bind to and stabilize the ERT ATB200.

The third major challenge with the current ERT relates to uptake and targeting. And to solve for this, what we've done is our ERT ATB200 has been designed with optimized levels of mannose-6 phosphate and what we believe to be very important levels of glycosylation and the right sugar structures in these carbohydrates.

So, today, I will describe more details about our clinical study and what we are expecting to see shortly with our initial data readout by the end of this year.

Slide 10 describes the Pompe data cascade. So, here, I'll highlight our ongoing clinical study designated as ATB200-02. This is an 18 -week open label safety and PK study with an optional long-term extension setting that is designed to establish important proof of concept and to differentiate our proprietary ERT product ATB200 coadministered in a fixed dose regimen with our chaperone, AT2221. All patients in Cohort 1 are ambulatory ERT-switch patients. And during the third quarter, the Data Safety Monitoring Board reviewed the safety data from Cohort 1 and cleared us to again involvement in Cohort 2 consisting of nonambulatory Pompe switch patients as well as our Cohort 3 with Pompe patients who have never before receive ERT, or ERT naive patients. So, I am pleased to report that we are currently treating patients in all three cohorts of this study.

So what is the data sequence among these cohorts? Let me just walk you through that.

In the fourth quarter, we are on track to report interim data in the first four ambulatory ERT-switch patients in Cohort 1. And then in the first half of 2017, we expect to include additional important readouts. These include additional 18-week data and extension data from Cohort 1. These data will also include 18-week data and extension data in Cohorts 2 and 3. Beyond that, we'll continue to generate long-term data and functional measures in the ongoing extension study. We believe that, given the complexity of this disease, that the totality of the data from this study will be available by mid next year to inform both the dose selection and the design of our next clinical study.

So Slide 11, we talk a little bit about what we call our scorecard here. So now that I've reviewed the study design and the major inflection points in this study, let's turn to Slide 11, where we've outlined the multiple ways which we think we may achieve success here.

So, first, very importantly in Pompe is safety. Our initial question is can we safely switch patients immediately from Lumizyme onto our drug? We are very encouraged by the safety profile this far, especially following our positive Safety Monitoring Board review the summer.

The next question is can these patients tolerate our treatment regimen with limited infusion associated reactions? This would be a very positive indicator that our product is distinct, because more than 25% of patients on Lumizyme have been reported to have infusion associated reactions, so it's something we'll the monitoring with our drug regimen very closely.

With respect to PK, we want to answer the question can we demonstrate a differentiated PK profile within an optimal range? This is also extremely important because, in our preclinical studies, even at lower exposures, ATB200 demonstrated significantly greater glycogen reduction than equivalent doses of Lumizyme.

Also looking at the immune profile of our drug will be very important. As a reminder, 100% of patients on Lumizyme develop antibodies, as has been reported, and antibody titers can impact treatment outcomes.

In the switch patients who already have antibodies to Lumizyme, we want to answer the question, do they antibodies increase or remain the same in this initial look on ATB200 and AT2221? And later on in Cohort 3 with the naive patients, we want to be able to answer the question to know what is the onset and level of antibody formation in patients who have never been exposed to ERT.

And finally, we're also looking at a series of exploratory biomarkers and the indirect read-through on targeted uptake as well as immunogenicity. We expect to have all data from this study by mid-2017, and we're also continuing to do preclinical studies in Pompe. And we'll also have more to share in the coming year on some very important findings from this preclinical work.

We are actively working to get into a pivotal study as soon as possible. And in the meantime, we're scaling up manufacturing right now to the 1,000 liter scale so that we can run our next study with the commercial scale of ATB200 plus chaperone, which we believe will be very important.

On Slide 13, let me discuss briefly our EB program before I hand the call over to Chip to take us through our financial results. So let me review here the Phase III study, which we designated SD-101 for EB. And again, this is on Slide 13.

We've seen significant momentum in the enrollment in this study and the data is on track to report in the first half of next year, 2017.

During the third quarter of this year, we submitted our statistical analysis plan, or SAP, to the FDA for finalization. This SAP is based on written feedback from the dermatology division at FDA in which the Agency agreed to elevate the important endpoint of time to wound closure as a co-primary endpoint together with our previously specified primary endpoint of proportion of patients with target wound closure.

So, in terms of progress with this study, there continues to be a high level of interest from the EB community. We are seeing a very strong uptick in enrollment now with a total of 28 sites active in the United States, Europe, and Australia. We continue to see 100% conversion of patients from the primary treatment period to the extension study. We believe also that our strict entry criteria as well as the overall study design now increases our likelihood of success for this study and we look forward to advancing to completion into topline data. So with that, Chip, let me go ahead and turn it over to you for the financial overview.

Great. Thanks, John, and good morning, everyone. I'll start today's discussion with our financial results on Slide number 15, beginning with our third-quarter revenue. And this is a notable milestone. It's the first time we are reporting product sales in the Company's history and reflective of our transition to a commercial stage company.

Total product revenue in the third quarter of 2016 was $2.1 million and as of September 30, we have made the transition to recognizing revenue on an accrual basis and expect to continue as additional countries come off.

Moving down the P,&L total R&D expenses for the third quarter of 2016 increased to $32.5 million as compared to $21 million for the third quarter of 2015. The increase here is primarily due to one-time expense associated with the MiaMed asset purchase as well as investment in our Phase III EB clinical development which was not part of Amicus at this time last year.

Total selling, general, and administrative expense for the third quarter of 2016 was $17.5 million as compared to $15.4 million in the third quarter of last year. The increase was primarily due to investment in pre-commercialization and commercialization activities related to the Galafold launch.

Net loss was $46.7 million, or $0.33 per share, in the third quarter of 2016 compared to a net loss of $37.8 million, or $0.32 per share, for the third quarter of 2015. The wider loss is attributed to an increase in total operating expenses. And as of September 30, 2016, we have 142.3 million shares outstanding.

Moving on to Slide 16, a few comments on our current caste position and our overall 2016 financial guidance. Cash, cash equivalents, and marketable securities totaled $212.4 million at September 30, 2016. As previously disclosed, we raised an additional $39.3 million in net proceeds through the ATM equity appliance facility during third quarter. As a reminder, we have raised the full $100 million registered under the ATM facility.

Through continued careful management of our expenses, we expect to remain within original 2016 net cash spend guidance of achieving between $135 million and $155 million. And our current cash position, including proceeds from the ATM and additional debt earlier in the year, is projected to fund operations into late 2017 through several important inflection points that John outlined previously in the call.

This summarizes our key financials for the third quarter of 2016. And additional details will we found on our Form 10-Q, which will be filed later today. I'm also happy to address any questions during the Q&A but, for now, we'll turn it back to John.

Great. Thanks, Chip. And I'll just go ahead and conclude before we turn it over to Q&A on Slide 18, again with just a brief snapshot of our key value drivers and upcoming milestones related to our three lead programs. Lots of momentum, as you've heard here. Obviously, very excited with the launch of Galafold in the very early days, particularly in Germany, the addition of these 44 new mutations to our label, the positive draft recommendation from NICE on first review, which is quite unusual. So in many ways, I think it was a very, very strong quarter for us. And again, all three of our lead programs in Fabry, EB, and Pompe represent a commercial opportunity of between $500 million and $1 billion in sales.

As a reminder, we fully own all of the rights to all of our products and technologies platforms. And while there has been significant amounts of interest in all of our programs from a partnering and licensing perspective, either for full program and/or certain territories, and while this could provide a source of financing, we will do so in the future only if any partnerships would provide a better, faster, and more cost effective way to advance our medicines and to deliver them to patients.

I continue to believe that we have one of the strongest portfolios in the field of rare devastating diseases and that we are on track to achieve a very bold vision to become a leading global biotechnology company and to provide medicines that have the potential to positively impact people's lives.

So, operator, with that, we're happy to take questions.

(operator instructions). Ritu Baral, Cowen and Company.

Hi, guys. Thanks for taking the question. I did want to ask about the US discussions. Is the structure of the discussion as you previously guided with the type B meeting around now, or has it moved to an iterative sort of structure and discussion? I have one follow-up.

Ritu, we're not going to comment on ongoing discussions and regulatory discussions with migalastat here in the United States. We'll only confirm that we will provide an update by the end of this quarter.

Got it, which is why I have my follow-up. Okay. So I'll ask a real question about Europe then. Can you go into the profile of the patients that you are seeing in Germany, the profile the switch patient versus the profile of the naive patients that you've seen so far? Maybe not in Germany. And also what's your approximate pan-European price you are seeing at this point?

So, two questions, one kind of the general nature or profile of the patients, these first 50 commercial patients, that we're seeing, and second you asked a question -- it tailed off there at the end -- about pricing?

Yes, the pan-European price that you are seeing right now?

Brad, if I can, I'll ask you to comment on both of those for Ritu.

Sure. Thanks, John. Ritu, I think the first point for Germany in particular is we will reiterate what we made on the call previously, which was that these are all patients and physicians who have had no previous experience with Galafold as we didn't have any clinical sites there. So, clearly, I think that reflects an interest on the part of physicians and patients to explore Galafold as a new treatment option.

From a profile perspective, other than being in line with our label, of course, I'll say that I think it's in line with where we thought these patients would be, which is at the mix of patients who perhaps have been dissatisfied on current ERT, patients who have been looking for a treatment option but for whatever reason weren't willing to start an enzyme replacement therapy for the naive patients. It's males and females. So I think it's reflective really of the broad label that we received from the EMA, and we would expect that to continue in other markets as well.

On your second question around pricing, I'll say that our pricing strategy remains in line with our previously stated strategy, which is that this is the first precision medicine approved for Fabry. It's the first new therapy in over a decade. And we have chosen our strategy to price roughly at parity with enzyme replacement therapy on a country-by-country basis. And we think that reflects the value that Galafold can bring to patients and also can give some savings back to the healthcare system by avoiding the infusion associated costs. And so far, that pricing strategy I think has been quite successful. And just as a reminder, the global average price, list price, for ERT is roughly between $200,000 and $300,000 a year, although of course that varies country by country.

On the profile, are you seeing any trends in classic versus non-classic mutations?

No, again, I think it's reflective of the patients. Remember, we studied both of those populations in our clinical studies and they're reflected in the label. Really, physicians and patients are asking do I have an amenable mutation? And if so and if they are interested in trying Galafold, then they do. So it's not -- hasn't been skewed so far to one part of the population or another.

Great. Thanks.

Ritu, I'll just add to that, having been in the field last month for a couple of days in Germany and visiting a number of these key treatment centers. There were a number of skeptics prior to launch and we were priced conservative with our internal metrics in this very competitive market in Germany.

In terms of patients switching -- in fact people told us you'll never get people off of ERT to come on this product -- and to see in the first full quarter that we already have 20% market share in Germany of amenable patients, treated amenable patients, is pretty extraordinary. And I think, again, goes to the data, the quality of our leadership team. And I can tell you physicians in Germany are extremely experienced and quite sophisticated and quite rigorous in their review of data and the care of their patients. So again, a very important market for us to see in the early days such significant uptake I think hopefully bodes well for the product.

Anupam Rama, JPMorgan.

Hi. This is [Yuka] on the call for Anupam. Thanks for taking our questions. Of the 15 countries where you have reimbursement negotiations ongoing, how many do you expect will conclude in 2017? And also, what additional metrics on the launch trajectory do you think you will need, given the country by country rollout, before you are able to provide revenue guidance?

Brad, maybe do you want to comment, to the extent we can, on what we may see by the end of 2016? And then maybe, Chip, if you want to handle the question on what metrics do new we need to see before we start providing revenue guidance?

Sure. So, in terms, of when specifically we expect countries to come on board or how many, we've refrained from giving that level of specificity. But again, I'll draw you to the metric we showed on the call, which is we have recently secured two additional reimbursements, and so we would expect to be launching in those markets here relatively soon. And we would expect to continue to see countries coming on board through the end of this year and through next year as well.

So, I can't give more specifics than that but, again, I think you'll see that rolling launch continue as we continue to secure reimbursement in those markets or secure expanded access where those vehicles exist.

Hi, this is Chip. Just to comment on guidance going forward and the kind of metrics we're providing, we feel, in these early days of launch, that patient metric in terms of number of patients on at the end of a given month near the earnings call is the most meaningful metric in these early days of launch as we move through that rolling launch period. As we have greater insight and clarity around when these additional countries will come off, we will in time provide revenue guidance. We've not set the dates of that guidance. But as we move to revenue guidance and as revenue becomes a more meaningful and telling measure of a trajectory to launch, we will migrate from more patient focused metrics to metrics focused on the revenue.

Joseph Schwartz, Leerink Partners.

Thanks very much. So, I was just wondering if, since you mentioned that most of the patients who are going onto Galafold in the EU are switching from the current ERT products, I was wondering if you can talk about whether you have any initiatives to penetrate the proportion of the market which is not currently treated? And then do you have any insights on how many of those patients are actually accessible in terms of them being identified and seen by physicians and otherwise active in the community?

Joe, I'll just comment and then ask Brad to add a little more color. Absolutely, the drug, as you know, is labeled for patients 16 and older, both ERT naive and ERT treated. This is absolutely in line with our expectations, although the magnitude is perhaps greater of the patients switching because these are the people by nature who are coming in very frequently to the physician site. The naive patients tend to come into the key treatment centers a couple of times a year, so we knew that that would be a longer cycle to began to penetrate those 500 or so patients in Germany who are diagnosed with Fabry but not treated. So absolutely the discussions with our commercial team and our medical affairs team are both with respect to ERT treated and naive, and we expect over time to see more and more of those naive patients.

Brad, maybe you can comment, within that pool of naive patients, who we believe -- the characteristics of patients who we believe would be suitable for treatment today?

Sure. So, Joe, there is a natural pent-up demand in some cases where those naive patients that want to go on treatment but for one reason or another have not, and that could be access. It could be the burden of caring for multiple family members who are on treatment themselves, as this is typically a familial disease. It could be that they are earlier in their disease progression and haven't yet progressed to a point where they may meet the treatment criteria in their particular market. Or it could be just as John said, that they're in a longer cycle in terms of seeing their thought leader or the physician who would make the ultimate treatment decision. So, there are a number of dynamics going on but, as John said, we fully expected that. And in the short term, the low hanging-fruit is the patients who are on ERT who are in the system much more actively, and in the longer term or I should say perhaps the medium term and then the longer term, those patients who are diagnosed and untreated.

And the only other thing I guess I would remind you of is the expanded access programs that are existing today are really second-line therapies. So, really, Germany is the only place where we have an ability to treat both naive and switch patients. And so we would expect that, as more countries come on board more fully, as we penetrate into the ERT market, we will also penetrate into the diagnosed untreated market as well.

Tazeen Ahmad, Bank of America.

Good morning. Thanks for taking my questions. Maybe a couple for Brad. We were happy to see that NICE, as you mentioned, included your drug and draft guidance. But how does it work in conversion from draft to final? How long does that take? And in that period, would you be able to have any advantage in getting additional traction in the UK? And in that process, do you also have to have any meetings or submit additional data for that draft to become final?

And then secondly, with regards to your addition of new amenable mutations, how does that process work? Was that information that you had in-hand when you had originally filed for your approval in Europe? And if not, how do you go about submitting the request for additional mutations? And is that a quick turnaround from the time that you request it to the time it's agreed upon? Thanks.

Thank you, Tazeen. Brad, if you've got both of those, I'll like you handle both, beginning with Tazeen's question on NICE and the conversion from draft to final.

Yes, so two great questions. For the NICE process, it is ongoing, so we don't want to comment too much on that process other than to say that we're pleased with how it's gone so far and we're collaborating fully with that process.

What we can share is that the next step in the process is the public hearing, which is scheduled for November 22. And typically, they would issue their final evaluation document shortly thereafter. And so we would expect that process to conclude sometime at the end of this year or very early next year, so we're on track there and pleased with that process so far.

As it relates to the process of mutation, it's a great question and I think, again, it reflects how supportive and forward-thinking the Europeans have been in terms of the way that they've embraced the notion of precision medicine. Remember, we did I think provide some color that the initial label, which included 269 mutations, that actually included a number of mutations that were characterized between the study and then getting the final approval. And so we had already had an example of where they were essentially supporting the notion that it was the assay that determined amenability and once amenability was determined, it could be entered into the label.

Now we've seen 44 mutations who were not part of the discussion during the negotiation for the label but have been characterized in the meantime since we've gotten our approval. And so the process there will be you go through the typical regulatory submission to expand the label in Europe. Once they agree to that, which they've now recently done, then we update the website, and it's a very seamless process. So now when a physician goes to look up one of these new mutations, it will be listed as amenable and on-label and then therefore they can prescribe.

On a go-forward basis, that's generally how we'll handle this. So if we characterize a new mutation, and historically it's been something like 5% or so new mutations are characterized each year either if a physician identifies one or we identify one ourselves, we'll characterized it in the assay, determine its amenability, and then submit it probably in some sort of batch form to the Europeans. They will approve it, and it shows up on the website. So it actually is a pretty easy process and one that we think is really reflective of this whole concept of precision medicine.

Tazeen, did that answer your question, or both of your questions?

Roy Buchanan, Janney.

Thanks for taking my question. I just had one on John's comment towards the end of the call to make sure I'm clear about the partnering. Is it -- are you guys going to plan to only finance in the future through partnering?

No, we'll look at a range of finance options again with whatever we think is in shareholders' interest to minimize any future dilution. I just wanted to make the point that, obviously, with a commercial product now with significant potential in the rare diseases and a very robust pipeline, we've had a number of parties reach out to us with ideas and proposals for potentials for partnering either whole geographies or entire programs. We are nowhere near doing a deal necessarily, but I just wanted to let people know going forward potentially we would consider that, so the bar is going to be very, very high.

Mike Ulz, Robert W. Baird.

Hi, guys. Thanks for taking the question. Just on the Pompe program, you are expecting sort of proof of principle data by mid next year. Is the current plans there to go forward into larger Phase II or is it to go directly into a Phase III?

And then secondly, with filing in Japan targeted for the first half of next year, can you maybe comment on the next steps there to meet that goal? Thanks.

Sure. So, to remind everybody, with Pompe, we will see the initial data here in the next month or so, by the end of this year. Again, those are the first four patients in Cohort 1, and that will contain data that we think will help establish very important early proof of principle. But the proof of principle we've always believed in this complex disease is going to come across all three of these cohorts and across a series of data releases from Q4 of this year culminating in about mid-2017. So that's what to expect on a range of outcomes.

With respect to the next study, we've not yet met with regulators to discuss what the next study is. Our hope is that the data may provide the strength to allow us to come to a pivotal study. That is yet to be determined.

With respect to Japan, I'll just comment that we are right now visibly, our regulatory teams and consultants, are preparing the Japanese NDA and that remains on track to be filed in the first half of this year.

Again, if you remember, in the middle of this year, the Japanese regulatory authority indicated that we did not have to do any further clinical studies in Japan or anywhere and that we may move forward now with the filing of the Japanese NDA, which, again, accelerated our time line by about three years to approval in Japan.

(operator instructions). Salveen Richter, Goldman Sachs.

Hi. This is actually Tom on for Salveen. Thanks for taking my question. I just had a follow-up on the Pompe program. So, in the interim readout in the next month or so, as you mentioned, could you just go into a little more detail on what's in the biomarkers MITR? And then since this is -- these first four patients are all Lumizyme switch, would we see comparison to baseline on Lumizyme in those patients? Thanks.

Yes. So, with respect to the biomarkers, there are a number of traditional biomarkers that we are going to be looking at here. Again, very early in terms of the number of patients. You would be looking at things like Hex-4 in the year-end. There are PK/CPK measures in muscle surrogates for potential improvements in muscle strength.

Again, in very early studies and in a handful of patients. These are exploratory and we're not sure what to see. I'll remind everybody that we have not seen any of this data other than the safety data that was reported through the DSMB. We'll see it here very, very shortly. So I think that's important to note with respect to the biomarkers and what to see.

And Tom, I'm sorry. Remind me of the second part of your question, or was that it?

And I'm showing no further questions. I would now like to turn the call back over to John.

Operator, the gentleman from Goldman Sachs, the analyst, Tom, I just wanted to make sure I covered his questions.

Sorry about that. So, the question was, since these are patients switching from Lumizyme to your drug, would we see a comparison of their baseline measurements in these biomarkers to their biomarkers on your drug?

Yes, we will.

Okay. Great. Thanks for the questions.

I am showing no further questions. I would now like to turn the call back over to John Crowley for any further remarks.

Great. No, thank you, operator. Everybody, it was a very strong third quarter for us. And again, we've begun to deliver on some of the important data, particularly with respect to the successful launch of Galafold in the very early days in Europe and more data to come, including the US regulatory update, the Pompe data, as well as the finalization of that important statistical analysis plan revision in our Phase III EB program. So more news ahead this quarter hopefully building into a very strong and successful 2017. So thanks, everybody, for listening. Have a great day.

Ladies and gentlemen, thank you for participating in today's conference. You may all disconnect. Everyone have a great day.