Amicus Therapeutics Inc (FOLD) 2016 Q2 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Amicus second-quarter 2016 results conference call and webcast. (Operator Instructions) As a reminder, this conference call is being recorded.

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

Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics' second-quarter 2016 corporate highlights, program updates, and financial results. 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 speak only as of the date hereof.

All forward-looking statements are qualified in their entirety by this cautionary statement and we undertake no obligation to revise or update this presentation 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 this slide as well as to the forward-looking statement and risk factor section of our annual report on Form 10-K for the year ended December 31, 2015, and our quarterly report on Form 10-K, 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 everyone to this call today to review what has been very strong second quarter of 2016 at Amicus Therapeutics.

So as we began the year at the JPMorgan conference, we had outlined several important catalysts throughout 2016 that we believed would make this a truly transformative year for Amicus. And through the first half of this year, we've accomplished many of these key milestones, as you will see in the left-hand side of this slide.

These milestones include the full approval and commercial launch of our precision medicine migalastat under the trade name Galafold in the European Union. We also saw significant progress with regulatory submissions of migalastat in other countries on the heels of this EU approval.

We saw also dosing of patients in our Pompe clinical study, a very important milestone for us. Of course, Pompe, now our first biologics program into the clinic, and a very unique and novel use of our ERT biologics and Chaperone technology platforms.

We saw, too, the expansion of our biologics pipeline with a new program for the disease CDKL5. And the completion in the first half of the year of $130 million in financing through what we believe to be a very smart mix of equity through our state-of-the-market ATM facility as well as debt.

So as we look forward to the second half of 2016, we are sharply focused on five key strategic priorities. I'll highlight these as an overview and then turn it over to Brad to begin speaking about the initial days of the launch in Europe.

So our five key priorities for the second half of this year. First, the international launch of Galafold, with continued execution in Germany and the initial EAP countries. And to focus on broader access as we navigate the country-by-country pricing and reimbursement in open-label -- I'm sorry, and open additional EAP programs in the EU and other international territories.

Second, the additional regulatory submissions for migalastat with a focus on major markets, including Japan and the United States. In Japan, we have accelerated our pathway, where we now expect to submit our Japanese new drug application or J-NDA in the first half of 2017. In the United States, we are continuing to work with the US FDA toward defining an optimal regulatory pathway, and we expect an update in the third quarter of this year on that progress.

Third, our priority to successfully execute our clinical studies in Pompe and EB. There has been tremendous momentum with enrollment in the Pompe program. There has been great interest in the study from both patients and physicians. And in Pompe, we remain on track for initial interim data by year end and we'll describe the data sets we expect to see from this study in a moment.

For our EB program, we have met with the dermatology division recently of US FDA, and as a result, we have elevated the time to wound closure from a secondary to a co-primary endpoint. And we are concurrently revising our SAP while still blinded to the Phase 3 study.

We believe that this change may potentially increase the likelihood of success in this study, which we will outline a little bit further on this call today. And again with data expected after we have the initial Pompe data, which we expect to come first. We expect the EB data in late Q4 or early 2017.

Fourth key strategic priority -- we are maintaining a strong balance sheet to support both our commercial launch as well as the advancement of our pipeline. And fifth, we continue to build out our biologics pipeline in areas where there are significant unmet need in patients with rare, devastating diseases. We believe we have one of the most robust pipelines in rare diseases.

So we also believe that our key achievements in the first half of 2016 and our strategic priorities for the remainder of 2016 will strongly position Amicus to move further toward our goal of becoming a leading global biotechnology company focused on delivering significant benefits to people living with rare and devastating diseases.

So with that introduction, let me go ahead and turn the call over now to Brad Campbell, our President and Chief Operating Officer. And Brad will go into more detail about the Galafold launch in Europe.

Great. Thank you, John, and welcome, everyone, to our first conference call where we can officially discuss the commercial launch of Galafold. This is a very exciting time for the Company. And on today's call, I'll introduce some of the metrics that we are using to track the success of the launch in these early days.

As a reminder on slide 4, a little over eight weeks ago we received a very strong label in the EU for long-term treatment of adults and adolescents 16 years and older with a confirmed diagnosis of Fabry who have an amenable mutation. The label references 269 amenable mutations, which we estimate are representative of 35% to 50% of the Fabry population. And this is very consistent with the data that we've uncovered through patient mapping with our physicians in our major markets.

The approval was a significant milestone for the Fabry community as well as for Amicus. It's our very first product approval and marks the completion of our transition to a fully integrated commercial biotechnology company.

As outlined on slide 5, we remind you that the EU is, of course, a very important region for Fabry, representing 34% of the $1.2 billion in full-year 2016 enzyme replacement therapy sales, a significant portion of which comes from the EU three. As you know, Germany was our initial launch country and the third-largest Fabry market globally, with approximately 500 patients treated and a roughly equal amount who were diagnosed but untreated.

In France, we've made significant progress with the initial patients coming onto treatment through our cohort ATU. And finally, in the UK, where we have engaged in pricing and reimbursement discussions under the highly specialized technology or HST process.

On slide 6, we were providing a snapshot of our initial success with the Galafold launch. In these early days, while we are unable to formally recognize revenue due to the time lag between selling prescriptions and receiving data, we think that these metrics will be most useful for tracking the launch, the number of patients on reimbursed drug, the number of countries where patients can access migalastat through some form of reimbursement, and the number of countries with ongoing pricing and reimbursement discussions.

We have already mentioned that within 24 hours of receiving the EU approval, our commercial team delivered the first prescription to our first patient in Germany, an excellent example of our strong commercial organization and the early demand for Galafold, plus the logistical coordination to ensure rapid shipment and delivery. Now, as of July 31, we had 21 patients on Galafold, with the majority of them in Germany, with other patients participating in our expanded access programs, including the ATU in France.

Two further comments to provide some additional color on the progress so far. First, it's important to note that these patients include both naive and ERT switch patients, which we believe bodes well for the long-term success of the product.

And second, all 21 patients are de novo patients with no previous experience with migalastat. We believe that this early uptake reflects the strength of our label and data package, the unmet need remaining in the Fabry space, as well as the relationships that our team has built in the field.

Another important launch metric is to track our progress with access and reimbursement. And fortunately, through our expanded access programs, we have a mechanism to obtain reimbursement in certain countries prior to approval or formal completion of the pricing and reimbursement process.

So today, we have reimbursement in a total of three countries, including commercial launch in Germany, as well as two additional countries with expanded access programs. And we expect additional expanded access programs to come online both in Europe and in international territories in the months to come.

Finally, as many of you know, the pricing and reimbursement in Europe is a country-by-country process which generally takes 6 to 12 to 18 months, depending on the country. We have submitted now the global value dossier to multiple EU member states, and we now have 12 countries with active pricing and reimbursement discussions underway. So we are very pleased with the launch so far.

Finally, on slide 7, I will turn to the global regulatory update. As John mentioned, we are pursuing global regulatory approval of migalastat in as many geographies as possible, as quickly as possible, while prioritizing the major Fabry markets like Japan and the United States. Slide 7 provides a snapshot of where we are throughout the world.

First, as an overall statement, the EU approval opens up our ability to access more than 70% of the global regulatory market in the EU member states as well as countries that allow expanded access programs or accept submissions on the basis of an MAA approval. Outside the EU approval, we have actually now successfully completed four additional regulatory submissions, with more to follow.

As we announced last week and as John highlighted earlier on the call, we completed a meeting with regulators in Japan and intend to submit our J-NDA in the first half of 2017, based on already completed studies. This is approximately three years earlier than we had originally anticipated.

And as a reminder, Japan represents the second-largest Fabry market by country, with approximately 700 Fabry patients on enzyme replacement therapy. So this is a great opportunity for us to continue to expand the access of migalastat globally.

And finally, the US, which is the largest Fabry market with 1,500 patients treated today, continues to be a top priority for Amicus. As John mentioned, we continue to work with the US Food and Drug Administration on defining an optimal pathway forward for migalastat, and we continue to anticipate a US regulatory update in the third quarter of this year.

With that, I'll turn the call back over to John to walk us through the Pompe program.

Great. Thank you, Brad. So why don't we go ahead and turn to slide 9 and we will talk about the Pompe program. Let me highlight the study here, which we refer to as ATB200-02.

This is our first clinical study for our first biologics program, again here in Pompe disease. It is rapidly advancing, with significant momentum in enrollment, to investigate our proprietary enzyme replacement products, the ERT known as ATB200, which is co-administered in a fixed-dose regimen with our Chaperone AT-2221.

As reminder, this is an 18-week safety NPK study beginning with three ascending doses of the ERT alone, followed by that ERT plus Chaperone. Following the 18-week treatment period, patients are then eligible to continue to receive ERT plus Chaperone. We have enrolled the initial group of ambulatory ERT switch patients and we continue to anticipate interim data in these patients by year end.

We are also preparing to begin enrollment in cohorts 2 and cohorts 3, which are the ERT-naive and the nonambulatory ERT switch cohorts. In these last two cohorts, these patients will immediately begin with ERT plus Chaperone right from the start.

As you will see on this slide, we have outlined what we call the cascade of data that we expect to see between the end of 2016 and throughout 2017. These highlights include in the fourth quarter data in the ERT switch patients who are ambulatory or cohort 1; in the first half of 2016 extension data in cohort 1 and the initial data in the ERT-naive patients, cohort 2; and then from 2017 through the second half of 2017 the extension data in cohort 2 as well as the complete data set from the nonambulatory ERT switch patients or cohort 3.

Data from the 18-week primary treatment period will include important safety, PK, biomarkers of efficacy, and immunogenicity data, while functional measures are being assessed in the extension study as well.

The current Pompe study has two primary objectives. First: to establish strong proof of principle of the effects of this highly differentiated approach to the treatment of Pompe disease. And secondly: to inform the dose selection and design of our next clinical study. In the months ahead, we expect to provide more information on the key data parameters, which we will be evaluating in order to define the study's success.

In parallel with the enrollment in this Pompe study, we are also scaling up manufacturing right now to the 1,000-liter scale. This will be our Phase 3 and our commercial scale, so we are actively preparing to run our next study with the commercial scale of ATB200 plus Chaperone. Indeed, another important manufacturing milestone for our first biologics program and an important proof of principle for the further expansion of our biologics platform.

Let me go ahead and move to slides 10 and 11 with an update on the EB program. If you focus on slide 11 here, let me just comment that these advancements in our EB program come on the heels of the debra Care Conference which was held in Dallas two weeks ago which a number of us from Amicus had the privilege to attend.

It was cross-functional Amicus team and a Scioderm team. We had the opportunity while in Dallas at the conference, the patient conference, to engage with many of the patient organization leaders and families as well as investigators and our first EB patient advisory board. I also had the honor of delivering the keynote address at the conference.

I can tell you that there is a very strong sense of urgency and need among the members of the EB community. And we at Amicus are fully aligned together to complete our ongoing Phase 3 clinical study and to advance toward a treatment for this devastating disease.

Since the acquisition of Scioderm in the fourth quarter of last year, we have outlined a strategy to complete successfully the Phase 3 ESSENCE study and to enhance the likelihood of that study's success. This strategy has included the addition of many new sites and the increased internal resources necessary for this program.

We have applied our previous success in global clinical trial recruitment in rare diseases, and today we have 21 active sites in the EB Phase 3 ESSENCE study, with more sites continuing to come online. We believe it is important to have a wide geographic experience with SD-101 among several leading physicians and their patients.

We are now well more than 50% enrolled in this study. And importantly, we continue to see a 100% conversion of patients from the primary treatment period to the extension study, with a high level of continued interest in the ESSENCE study from the EB community. We expect data from this study in the late fourth quarter of this year or the first half of next year.

After opening new sites and adding additional resources, we also wanted, as part of our strategy here, to review and refine the statistical analysis plan for this Phase 3 study. We wanted to do this to make sure that we could maximize the potential for success.

To that end, we have completed now a series of discussions with the dermatology division of the US FDA regarding the proposed revision from Amicus to the SAP, the statistical analysis plan, while of course remaining blinded to the Phase 3 ESSENCE study data. In these discussions, we have leveraged our breakthrough therapy designation to engage the FDA to discuss a series of analyses that we believe can be prespecified while still blinded to the study, again to increase the likelihood of success.

And now I am pleased to report that based on several conversations with FDA and written communication received from the Agency, the FDA has agreed to the proposed revisions from Amicus to the SAP. Importantly, the FDA has agreed that time to target wound closure may be elevated from a secondary endpoint to a co-primary endpoint. And again, that's together with the previously specified primary endpoint of proportion of patients with target wound closure.

And based on this feedback from the Agency, we believe that the study's success could potentially be based on the achievement of one or both endpoints, assuming appropriate analytical methodology. And that the overall likelihood of study success has now been further improved.

Let me turn to slide 12 and highlight that the time to wound closure is an acceptable primary efficacy endpoint per FDA guidance documents. And that indeed there is precedence for use of this endpoint for regulatory approval. We also had positive data in our Phase 2b study, if you will recall, where time to wound closure with a 6% concentration of SD-101 was 30 days in the evaluable population compared to 91 days in the placebo group.

So why is that important? Time to wound closure shows us the healing of wounds over time with greater precision for discriminating treatment effects or treatment difference. It also correlates with the incidence of complete wound closure, our primary endpoint. Statistical simulations also indicate that the addition of median time to wound closure may increase our probability of success and may control for any placebo response by looking at wound healing over time as opposed to at a single time point.

On slide 13, I'll highlight the study design. So here we have a snapshot of the study design based on our revisions to the SAP. We believe that the design of this study, including the strict entry criteria around wound size, will again enhance the likelihood of success.

As of July 31, we know that the average baseline target wound size in the Phase 3 study population is approximately 20 centimeters squared. Again, remember that the inclusion criteria stated that a patient had to have a wound of at least 10 centimeters squared. So the mean is double the inclusion criteria minimum.

And again, this is more than the average wound size that we saw in the Phase 2b study. There we saw an average wound size of 13 centimeters squared. And again, the 20 centimeters squared is also in line with the average wound size from our Phase 2a study.

I'd like to emphasize key updates to the study design here, including the elevation of time to wound closure as a co-primary endpoint. We have also defined additional secondary endpoints, patient-reported itching and patient-reported pain, that we will be evaluating in addition to body surface area, or BSA, of the EB lesion. To add further statistical precision, our analyses will also include adjustment for key covariance, such as age of the patient and also wound size at baseline.

So we are very pleased with the level of interaction with the Agency on our proposed revisions to the SAP. Again, all of this facilitated with the breakthrough therapy designation for this product. We are also very pleased with Agency's rapid turnaround in formal minutes from that meeting.

So we are happy to go into more detail in the Q&A. But for now, let me go ahead and turn the call over to Chip.

Thanks, John. And good morning, everyone. I'll start today's financial discussion with a few comments on our current cash position and our overall 2016 financial guidance. I'll refer you to slide 15.

Cash, cash equivalents, and marketable securities totaled $214.2 million at the end of the second quarter. I am pleased to report we strengthened our balance sheet significantly during the second quarter of 2016 with $57.9 million in net proceeds under the ATM or at-the-market financing facility and an additional $30 million in debt under an existing debt facility.

Following the second-quarter close, we raised an additional $39.3 million in net proceeds through the ATM facility and have now raised the full $100 million registered under that ATM facility, completing that financing transaction.

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

Turning to second-quarter results, I'll be referring to slide 16, and additional details will be found in our Form 10-Q, which will be filed later today. While we did not record revenue in the second quarter, we invoiced commercial product shipments. And I'm pleased to report that we have begun to receive cash payments for commercial product. We expect to record product revenue in the third quarter.

Total R&D expenses for the second quarter of 2016 increased to $18.3 million as compared to $17.2 million for the second quarter of 2015. The increase is primarily due to investment in our Phase 3 EB clinical development, which was not a part of Amicus at this time last year.

Total general and administrative expenses for the second quarter of 2016 were $19.3 million as compared to $8.3 million in the second quarter of 2015. The increase here was primarily due to investment in precommercial and commercial activities related to the Galafold launch.

Net loss was $51.1 million or $0.40 per share in the second quarter of 2016 compared to a net loss of $27.1 million or $0.27 per share for the second quarter of 2015. The water loss is attributed to an increase in total operating expenses. And as of June 30, 2016, we have approximately 134.4 million shares outstanding.

This summarizes our key financials for the second quarter of 2016. And as I said, more information on financials will be available in the 10-Q, which will be available later today. I'm happy to address any questions during the Q&A.

But for now, I will turn it back to John.

Great. Thank you, Chip. So let me go ahead and conclude on slide 17 by noting that this has been a very strong first-half year for Amicus. We believe that 2016 overall is poised to be our most significant year in the history of the Company.

We anticipate important interim Phase 1/2 data from our Pompe program, which should validate both this important program and, more broadly, our unique capabilities as a biologics company. After we have the initial Pompe data, much like the EU approval and launch of validated migalastat as a meaningful therapy for amenable Fabry patients, we hope to see Phase 3 data from the EB program that, if positive, will validate our purchase of Scioderm last year and our entrance into the EB community.

As outlined in the beginning of the year at the JPMorgan conference, any one of these programs could be the basis of a promising rare disease company. Taken together, however, we believe that we have never been in a stronger position here at Amicus with one of the best portfolios of potential first and/or best-in-class medicines for rare and devastating diseases.

So with that, operator, we will go ahead and turn it over to any questions.

(Operator Instructions) Ritu Baral, Cowen.

Thanks for taking the question. My first couple questions have to do with the Galafold launch. One: are you expecting any conversion of extension trial patients in Europe to commercial patients at any time soon?

Yes. So it's a great question. We thought it was important on the call to highlight the fact that the initial patients were de novo patients because it reflects the very strong demand in those markets. Remember, in particular in Germany, where most of the patients have come on to Galafold, that's actually a market where we didn't have any clinical trial sites. And so in that market, we are actually seeing really strong update in physicians and patients who have no experience previously with migalastat.

We do, however, as you know -- we are, however, proceeding with the country-by-country reimbursement process. And we would expect in countries where we have active clinical trial sites in Europe to begin converting those patients to commercial as soon as we have the ability to do so. And we would expect that to happen over the course of the second half this year.

Got it. And then the additional geographies where you are expecting EAPs and pending regulatory application, can you give us any more detail as to what those geographies are that may be expanded into by the second half of 2016? And specifically, are Brazil, Canada, and Australia geographies with pending applications?

So we are trying to be a little circumspect around the actual order of country launch, just given the competitive nature. But I can give you a little bit more color to get at some of your questions.

So the markets that you have identified are clearly ones that are on our priority list for global submissions. And in particular, Australia, Canada, for example, have independent regulatory approval processes, which we will pursue as quickly as we can.

From an expanded access program, there are standard programs in Italy and Spain that are more similar to the ATU, and we would expect to continue to pursue those as quickly as possible. But there are also markets that you know -- Brazil, Turkey, and others -- which have their own expanded access or named patient programs that can be pursued, and we will be pursuing those as quickly as possible as well.

So I would expect that you will see later this year some patients coming on board in new expanded access types of programs, like the ones that I have mentioned. And I would also expect to continue to pursue regulatory submissions in those key markets that you asked about as well as others as we can.

Got it. And last question -- Pompe or -- let's go first commercialization. How do you define within Amicus the low-hanging fruit in Europe right now? What is the profile of those patients and what is your internal estimate in, say, the European top five as to the number of those patients?

Well, I would describe it in terms of where is the most severe unmet need for patients. And there we see it equal, both for switch patients and for ERT-naive. And again, to Brad's comments, we are very pleased that we are seeing switch patients from both standards of care therapies as patients who have never been treated with ERT.

So I don't think there is one segment, if you will, of the patient population that is stepping forward with a greater unmet need. I think there's equal levels of unmet need for patients currently treated as well as patients never to receive ERT. And we think that's a very, very good dynamic for the product.

Got it. So if you look at just the German numbers, it would be equally distributed between the 500 that are -- would you say that all 1,000 are low-hanging fruit? Or how would you further subdivide those patients into very likely --

Well, I think that in Germany, yes, you've got a market of about 1,000 identified and diagnosed Fabry patients. About half of them are treated today with one of the two existing ERTs.

We would expect in the early days of launch that the majority of the initial patients will be switch patients from the early dynamics that we are seeing in the market. And I think that's because they are in seeing the physician more regularly than the ERT-untreated patients, and also there's an existing reimbursement mechanism in place for those patients.

So in terms of speed to coming onto Galafold, our guess is if current trends continue, you will see more switch patients than naive patients. But we think very quickly that that should even out to about equal numbers.

Okay. And then as you look at those switch patients, do you think that there is a subpopulation even more likely to switch quicker, those with cardiac involvement or males versus females?

No. I think it reflects the breadth of the label.

Got it. Thanks for taking the questions.

Anupam Rama, JPMorgan.

Thanks so much for taking the question. Maybe just a quick verification question on Zorblisa. Has the FDA agreed that statistical significance on one of the two co-primary endpoints would be sufficient for approval here? I know that meeting one out of two co-primary endpoints has been sufficient in the lysosomal disorder space in the past with, I think now, Naglazyme and Aldurazyme. But is there precedent here in the derm space as well that we should be thinking about?

Sure. So based on the discussions we've had and the written minutes we've received, we do believe that the success of this study could potentially be based on the achievement of one or both of those co-primary endpoints. What are doing now is just finalizing the statistical methodology around that approach.

Okay. And maybe just a quick one for Brad. Of the 21 patients that you highlighted, can you describe a little bit about the concentration here in terms of physicians and prescribers, where these patients are coming from?

You just broke up at the end there. Can you repeat the last part of your question?

Just in terms of the 21 patients, the numbers of physicians and prescribers and the concentration of those, where those patients are coming from.

We won't give specifics there, but I would say that it's a well-distributed group. I think that the important thing is that we have had good coverage of both the KOLs in Germany, for example, but also the top-tier prescribers and the second-tier prescribers.

So we feel like the organization that we put in place is well able to target the key physicians in Germany and the other markets where we have expanded access program. So the distribution so far -- the coverage has been strong so far and the distribution has been good so far.

All right. Thanks so much for taking my --

I will say there has been a remarkable openness to the physicians again in Germany. Since we didn't have any clinical sites, we've invested in a significant business and commercial infrastructure in Germany. It's a bit of a more diffuse market than you would see in other countries in Europe. You've got quite a few treating physicians. I think we've estimated that there were about 50 physicians who see about 90% of the Fabry patients.

Our sales teams have been to see every one of those 50 doctors at least a handful of times. So we've seen great reception from the physician community and openness to reviewing the data and the label for migalastat.

Great. Thanks so much for taking question, guys.

Joseph Schwartz, Leerink Partners.

First, on Galafold's launch in Europe, I was wondering how representative is the 21 patients on drug to this point, of trends that you expect going forward within that market and more broadly? And then are you able to obtain any insight into demand from monitoring Internet queries on your amenability table?

And is there any way to leverage that resource in creative yet still regulatory-compliant ways to drive more prescriptions? For example, ensuring that physicians have all of the information that they need or attention from Company reps?

Again, we are not going to be giving forward-looking guidance and projections on sales going forward. So I don't know that we could add a lot of color, Joe, except to state that there seems to be significant interest from both physicians and patients. And we are very pleased that in the first couple of weeks of launch that we've got 21 people who, at the end of May, were not treated with Galafold who are now being treated.

So we would expect to see those trends continue in terms of the interest and our investment in reaching out. So I think the next six months will give us a really good indication of what the launch metrics should be in Europe over the next couple of years. So again, it's hard to project out on six to eight weeks of data. But I think good early trends, for sure.

Brad, if you have any color to add?

On the second question, Joe, I think maybe you have a future role in our marketing team. But it's a great question. I'll say this is a new tool for us. And our key focus is that this is a regulatory tool to help physicians understand that amenability is an important part of the label and how to treat their patients. And so we will just be very careful to ensure that that maintains that level of integrity and won't be using it for marketing purposes.

Okay. And on Zorblisa, you have been hovering around 50% or more enrollment in the EB Phase 3 for some time now. I was wondering if you could talk a little bit about the main challenges to enrollment and what kinds of things you can do to give that program a boost.

I thought you added some additional centers. Have they been contributing as you would have hoped? And what needs to happen for enrollment to complete by the end of the year versus stretch into 2017?

Sure, Joe. So again, we put enormous resources to this program after the acquisition of Scioderm, both internal resources. And we knew upon closing that we would need to add significant sites to this program.

So we said back in the spring when we hit 50% enrollment that we would not give a further update until the study was completely enrolled. It's now well more than 50% enrolled, but it's not yet completely enrolled. So there are some additional sites that will be coming online over the next month or two, couple of months. So those will add additional patients.

What we have been doing, too -- if you remember, this was a very strict entry criteria, again focused on the identification of a primary wound as the primary endpoint. And now that we're looking at both overall proportion of wounds to close versus placebo as well as time to wound closure, that's just as important as it has always been.

And to give you some sense, we have had over 400 patients present to clinical sites indicating an interest and potential to participate in the study. With a rigorous evaluation and inclusion criteria, only about 20% to 25% of those patients have actually qualified to enter into the study.

So I think we're doing everything that we can and should be doing. We will closely monitor enrollment over the months ahead and we think by the fall will be able to provide an update.

But again, two things that are driving that data either by year end or first part of 2017 partly is the finalization of enrollment. And secondly, too, is with this modification in the statistical analysis plan, we want to get the final SAP locked in and then be able to determine when we will take a look at the full data set.

Thank you.

Tazeen Ahmad, Bank of America.

Just wanted to ask you a couple of questions perhaps on Pompe. BioMarin recently discontinued its program. And I was wondering if you could give us your thoughts on some potential takeaways that you took from that molecule or the way that the company has designed their trial. And where you think you might see an advantage over BioMarin in terms of how you've defined your trial and how confident you feel about going forward.

Sure. So again, BioMarin is a tremendous company and a great leader in the rare diseases. And I commend them for the enormous effort and resources that they put into the Pompe program over those many years.

We just think that we have a very differentiated approach. The BioMarin approach was a very different targeting technology. It also didn't include any Chaperone component to deal with issues around stabilization of the protein in blood or immunogenicity.

So again, we think that, as we've always believed, we have a very differentiated approach for the treatment of Pompe. We think that there are three major limitations of Lumizyme, the current standard of care. We think it has to do, number one, with the targeting that relates primarily to the carbohydrate structures and specifically to levels of mannose-6-phosphate on that protein.

The second problem is with the very high dose and the lack of a Chaperone to keep it blinded and stable and folded, that drug loses its activity. Third is problems around tolerability and immunogenicity. As you know, the Lumizyme product has a black box warning for some of the side effects.

So when we began this program here a number of years ago at Amicus, I challenged Hung and her science team to tackle all three of those limitations of the current standard of care. And we think based on preclinical models that we have a potentially very differentiated approach to the treatment of Pompe disease here, again, with our unique ability to glycosylate and engineer the carbohydrates on this protein and to maintain that high level of carbohydrate-optimized structure through the manufacturing process that reflects our biologics capability and a very unique biologic.

And again, with this fixed-dose combination with our Chaperone AT-2321 that's administered as a small molecule about an hour or so before the infusion so that the Chaperone is in the patient's plasma, they are ready to effectively meet the ERT when it hits the blood.

So again, we think ours is a very differentiated approach. The animal data was very, very compelling. And we are very eagerly looking forward to this initial data set in Q4 and then the cascade of data through the first half of the year.

Okay, thanks for that color. And then as you look for the first part of the data to read out at the end of the year, what would you consider to be compelling data?

Sure. There will be more over the weeks and months ahead that we are going to speak to that. But I'd refer everybody to the slide and the cascade of data, which is slide 9.

So when you look at the first data set that we will see from cohort 1 in the fourth quarter, we want to make sure, of course, these are all ERT switch patients from Lumizyme. Did they switch safely to be able to tolerate our drug, specifically the fixed-dose combination of ERT plus Chaperone?

Secondly, very importantly, are the pharmacokinetics, the PK. A key element of our fixed-dose combination is a different biodistribution and a different PK curve, a different half-life, than Lumizyme. So we are going to look at all of those parameters and see does it match with our expectations and with what we saw in the preclinical data. So that will be a very important data set for us.

We will also look at biomarkers, including biomarkers of efficacy. And we will have more to say about that in the coming months before we unveil the data about some of those specific biomarkers as well as immunogenicity. What were the antibody profile? What was the nature and type of antibodies, cytokines, other measures of the inflammatory response to ERT and what may be different in our data set?

And again, that will be the first of what will be many data sets that we will release over a six- to-nine-month period in this program. So that by mid-2017, we think we will have a very large and robust data set that again will prove the principal that this is a very differentiated approach to treating Pompe and also give us a path to Phase 3.

Okay, thanks for that color. Appreciate it.

Roy Buchanan, Janney Montgomery.

Thanks for taking the question. Just a quick one on Zorblisa Phase 3. You said the statistical plan is still not finalized, I believe. I just wonder if there's any thoughts of adding patients to the study.

No. We think that we will be able to keep within the target range of approximately 150 patients, even with these final revisions to the SAP. Again, now that we have agreement with FDA on the elevation of that time to wound closure to a co-primary endpoint.

Okay, thank you.

Salveen Richter, Goldman Sachs.

This is actually Kerry on the call for Salveen. Thanks for taking my questions and congrats on the progress. I have a few questions. First, what has the initial feedback been so far from patients and physicians that have started on Galafold? And what is the distribution of patients in terms of previously ERT treated versus ERT-naive patients? And I have a follow-up.

Well, the last part of that is of the 21 patients, the majority of them are ERT switch patients. In terms of color from what we are hearing, Brad, if you want to comment on that. I don't think anything new from what we have seen in terms of the clinical experience with Galafold.

No. I think it's in line with what we would expect and was the color we provided on the call, which is we have had good distribution for the prescriptions that have been written. We've seen good uptake with physicians and good receptivity to having discussions around the data around the program. So we are very pleased so far with the feedback and the progress.

Okay, thank you. And finally, just wanted to get some color around the rationale for elevating this secondary endpoint of time to wound closure to a co-primary endpoint. Was it primarily driven from your side or was it an FDA dermatology division-driven decision?

Right. No, this was entirely proposed by Amicus. Let me ask Jay Barth, our Chief Medical Officer, to comment further on the rationale.

There are several reasons that we sought to elevate the time to wound closure to a co-primary, and very happy that the FDA agreed to that. Based on FDA guidance in and of itself, it's an approvable endpoint in the wound healing study.

We also had very encouraging data from our Phase 2b study showing a difference in time to wound closure for SD-101 compared to placebo that was quite strong. And that we feel among the data that we are collecting, it is going to be a very sensitive and powerful way to look at that data in addition to the proportion of wounds healed at a particular time point. Because it is a cumulative look at all the wounds healing over time.

So for a number of reasons, we feel that it's a very positive development that we can have it as a co-primary endpoint. And as John mentioned before that with appropriate statistical methodology based on our agreement with FDA that hitting one of these two co-primary endpoints would be a successful study.

Okay, thank you.

(Operator Instructions) Ritu Baral, Cowen.

Thanks for taking the follow-up. I actually just wanted to go a little further on your answer to Tazeen's question on the biomarkers. Given you are not doing biopsies, John, what are the key biomarkers that you're going to be following, and what sort of changes in them are you looking for?

Sure. So we will look at a number of biomarkers, so things like the PK. As you know, there are isoforms of ALC and AFD that come from muscle. We will look at those. Both CK and the ALC/AFD are elevated in Pompe patients. But we don't know what we see in the ERT-experienced patients. We don't know what we will see in the short term, but we'll certainly look at those. We will also look at hex 4, which is analyzed from the urine of patients. We will look at that as well.

And again, this is an exploratory study. As you remember from the preclinical data, we saw a terrific uptake of the enzyme into target tissues. And compared to standard of care in preclinical models, we saw significantly better clearance of glycogen.

So these will be markers for is the enzyme getting into muscle, is it having an effect on the muscle architecture itself, and is it leading potentially to the further breakdown of glycogen. We think those are two equally important elements of the mechanism here. So we will get some early data.

Got it. One for Chip. Chip, what is the current shares outstanding now after the exercise of the ATM?

Yes. As of June 30, the number of shares outstanding was 134.4 million.

Got it. And last question, guys. As you think about the expansion of sites into Zorblisa and the Zorblisa pivotal study, how are you dealing with the potential for differences in treatment paradigm, especially given you said that you are going across different geographies. What geographies are you going across? And how different is background standard of care across these geographies?

I will say that all the study sites are in the United States and in Europe. So with that, we are looking at the potential for -- I think we have looked at sites in other parts of the world. A handful of those sites may come in, but only after they have passed rigorous quality control inspections by our teams, by our CROs.

So there will be no compromises in study site quality or ability to execute in this setting. These are all top advanced dermatology centers, major academic centers, and importantly, centers with experience in EB. Quality control is something we are very focused on.

And you feel pretty comfortable that standard of care is relatively equal across the ones you're looking at?

Yes, very comfortable.

And then just on your comments on covariance adjustments for wound size and age in this study. Is that sort of the same thing as stratification? And if not, do you have stratifications in your new SAP?

I'll let Jay comment.

It is a way of addressing the same issue that you are raising. We are not stratifying in our randomization, but a way to adjust for that when you analyze is to introduce the covariant. And we think those two, the age of the patient and size of the wound, will adjust for any potential imbalances between the groups. So that increases the power of our analysis.

Got it. Thanks for taking the follow-up, guys.

Just to comment further on Zorblisa and the EB program, we knew when we closed on the acquisition of Scioderm that there were three key areas we had to focus on and improve with the Amicus resources and experience.

One was the additional clinical sites, high-quality sites. Two was significantly more resources, internal resources -- people -- put to the program. We have done both of those two. By the time we had completed those activities in the spring of this year, we then turned our attention to the third area where we thought there could be a significant improvement. And that was around the statistical analysis plans and the definitions of success in this study.

So we, together with experts in the field, worked through our plan. We then presented that to FDA, and through a series of discussions and then written comments received from FDA, again, we feel really, really good about these changes and we believe that it has the potential to increase the likelihood of success in this study.

We continue to see enormous interest from physicians and patients to participate in the study. And again, I think that reflects the devastating nature of the disease and the significant number of people living with this just awful disorder.

Joseph Schwartz, Leerink Partners.

Thanks for taking my follow-up. I was wondering if you could just talk a little bit about your understanding for the drivers of placebo response in EB. Beyond spontaneous resolution and the potential for patients to get better skincare management, is there any other reasons for response rate in the placebo arm to be what it is?

No. I think you hit on those points, just based on the management of wounds in general and the nature of EB, there are wounds that heal on their own. Those tend to be the smaller ones, the ones that haven't been present for that long. But that is the nature of EB. And in the standard of care, there are wounds that do heal, especially, as I said, smaller and wounds of younger age.

Okay, thank you very much.

So again, Joe, with the inclusion criteria, the design of this study and now with these changes in the definitions of success, we think we've only further increased the potential and probability for this study succeeding. But ultimately, it will be driven by the data, of course.

Thank you. That does conclude today's question-and-answer session. I'd like to turn the call back to John Crowley for closing remarks.

Great. No, operator; thank you. That's all I have, everybody. Thanks for listening. Have a great day.

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