Sara Pellegrino - Senior Director, IR John Crowley - Chairman and CEO Bradley Campbell - President and COO Chip Baird - CFO Jay Barth - CMO.

Ritu Baral - Cowen Anupam Rama - JPMorgan Joseph Schwartz - Leerink Partners Roy Buchanan - Janney Montgomery.

Good day, ladies and gentlemen. And welcome to the Amicus Second Quarter 2016 results conference call and webcast. At this time, all participants are in a listen-only mode. Later, we will a conduct a question-and-answer session and instructions will follow at that time. [Operator Instructions] As a reminder, this conference call is being recorded.

I would now like to turn the conference 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 update 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 wells as our plans and prospects. Our forward-looking statements should not be regarded as representation by us that any of our plans will be achieved.

Any or all of the forward-looking statements made on this call may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. You are cautioned not to place undue reliance on any forward-looking statement, which speak only as 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 statement on this slide, as well as to the forward-looking statements and risk factors sections of our annual report on Form 10-K for the year ended December 31, 2015 and our quarterly report on Form 1O-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..

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, 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’ve accelerated our pathway where we now expect to submit our Japanese New Drug Application or JNBA 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 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 datasets we expect to see from this study in a moment.

Four, 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 advanced number of pipeline. And fifth, we continue to build out our biologics pipeline in areas where there are significant unmet needs in patients with rare devastating diseases.

We believe we have one of the most robust pipeline 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, we’ll 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 now over to Brad Campbell, our President and Chief Operating Officer, and Brad will go into details of 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. It’s a very exciting time for the company and on today’s call, I’ll introduce some of the key metrics that we’re using to track the success of the launch in these early days.

As a reminder on slide four, 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 the confirmed diagnosis of Fabry, who have an amendable mutation.

The label reference is 269 amendable mutations which we estimate a representative 35%-50% of the Fabry population and this is very consistent with the data that we’ve uncovered through patient mapping with our positions 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 five, 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 2015 and then 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 roughly equal amount to re-diagnose that untreated.

In France, we’ve made significant progress with the initial patients coming onto treatment through our cohort ATU and finally, in UK, where we’ve engaged in pricing and reimbursement discussion under the highly specialized technology or HST profit. On slide six, we provided you snapshot of our initial success with Galafold launch.

In these early days, while we’re unable to formally recognize revenue due to the time lag between filling prescription 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 on-going pricing and reimbursement discussion.

We’ve already mentioned that within 24 hours of receiving the EU approval, our commercial delivered the first prescription to our first patient in Germany, in that clinic map of our strong commercial organization and 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, but with other patients participating in our expanded access programs including the ACU in France.

Two further comments to provide some additional color on the progress so far, first it’s important to know that these patients include both naïve 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 needs 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 in 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 total of three countries, including commercial launch in German, as well as two additional countries in 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 six to 12 to 18 months depending on the country. We’ve submitted now the global value [indiscernible] to multiple EU member space and we now have 12 countries with active pricing and reimbursement discussions underway.

So, we’re very pleased with the launch so far. Finally, on slide seven, I’ll turn to the global regulatory update. As John mentioned, we’re pursuing global regulatory approvals 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 seven provides a snapshot of where we are throughout the world. First, as an overall statement, EU approval opens up our ability to access more than 70% of the global regulatory market in the EU member state, as well as countries that allow expanded access programs or accept submissions on the basis of 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 in the call, we completed a meeting with regulators in Japan and intent to submit our JNDA in the first half of 2017 based on already completed studies.

This is approximately three years earlier than we had originally than anticipated. And as a reminder, Japan represents the second largest Fabry market by country with approximately 700 Fabry patients commence on replacement therapy. So this is a great opportunity for us to continue to expand the access through Galastat 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 half hold pathway forward to Migalastat and we continue to anticipate the US regulatory update into 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 nine and we’ll 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 moment in enrolment to investigate our proprietary enzyme replacement product, the ERT noted ATB200, which had co-administered in a fixed dose regimen with our chaperone 80, 22, 21.

As a reminder, this is an 18-week safety and PK 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’ve 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 enrolment in cohorts 2 and cohorts 3, which are the ERT naïve, and the non-ambulatory ERT switch cohorts.

In these last two cohorts, these patients will immediately begin with ERT plus Chaperone right from the start. As you’ll see on this slide, we’ve 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 cohorts 1, in the first half of 2017 extension data in cohorts 1, and the initial data in the ERT naïve patients cohorts 2, and then from mid-2017 through the second half of ‘17, the extension data in cohorts 2, as well as the data - the complete dataset from the non-ambulatory ERT switch patients or cohorts 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 steps 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 to Pompe disease, and secondly, to inform the dose selection and design of our next clinical study.

In the month ahead, we expect to provide more information on the key data parameters which we will be evaluating in order to define study’s success. In parallel with the enrolments in this Pompe study, we are also scaling up manufacturing right now to the 1000 L scale, this will be our phase 3 and our commercial scale.

So, we are actively preparing to run our next study with 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 slide 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 had number of us from Amicus had the privilege to attend and it was a cross functional Amicus team and a Scioderm team, we had the opportunity well in Dallas that 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 that 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 on-going phase 3 clinical study and to advance towards treatment for this devastating disease.

Since the acquisition of Scioderm in the fourth quarter of last year, we've 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’ve 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’s 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've 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 pre-specified while still blinded to the study, again, to increase the likelihood of success.

And now, I'm 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 together with the previously specified primary endpoint of proportion of patients with target wound closure.

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’s success has now been further in progress.

Let me turn to slide 12 and highlight that the time to wound closure is an acceptable primary efficacy endpoint per FDA guidance document 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'll recall, where time to wound closure with a 6% concentration of FD-101 was 30 days in the evaluable populations compared to 91 days in the placebo.

So, why is this important? Time to wound closure shows up the healing of wounds over time, with greater precision for discriminating treatment effects with 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 cm², again, remember that the inclusion criteria stated that a patient had to have a wound of at least 10 cm².

So, the median is double of the inclusion criteria minimum, and again, this is more than the average wound size as we saw on the phase 2B study, there we saw an average size of 13 cm². And again, the 20 cm² is also in line with the average wound size from our phase 2A study.

I’d like to emphasize key updates of the study design here, including the elevation of time to wound closure as a coprimary endpoint. We’ve 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 lesions.

To add further statistical precision, our analyses will also include adjustment for key covariates, 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’re also very pleased with the agency's rapid turnaround in formal minutes from that meeting.

So, we’re 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’m 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 aftermarket 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 our 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 function 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’ve 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 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 pre-commercial 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 $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. Happy to address any questions during the Q&A, but for now, I’ll 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 and 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 amendable Fabry patients, we also 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 JP Morgan conference, any one of these programs could be the basis of a promising rare disease company.

Taken together, however, we believe that we've never been in a stronger position at here in 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’ll go ahead and turn it over to any questions..

[Operator Instructions] Our first question comes from Ritu Baral of Cowen. Your line is open..

Hi, guys. Thanks for taking the question.

My first couple of questions have to do with the Galafold launch, one, are you expecting any conversion of extension trial patients in Europe - to commercial patients anytime soon?.

Yeah. So, Ritu, it’s a great question, we thought it was important on a 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 onto Galafold, that’s actually a market where we didn’t have any clinical trial size. And so, in that market, we’re actually we’re 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 commercialize as soon as we have the ability to do so and would expect that to happen over the course of the second half of this year..

Got it.

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

So, we’re 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 to some of your questions.

So, the markets that you’ve 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’ll pursue as quickly as we can.

From an expanded access programs, there are sort of standard programs in Italy and Spain, they are more similar to the ATU, and we would expect to continue to pursue those as quickly as possible, but there are also market, as you know, Brazil, Turkey and others, which have their own expanded access or name patient programs that can be pursued and we’ll be pursuing those as quickly as possible as well.

So, I would expect that you'll see later this year some patients coming on board in new expanded access types of programs like the one that I’ve mentioned. And I would also expect to continue to pursue regulatory submissions in those keys markets [indiscernible] as well as others that we can..

Got it.

And last question, Pompe or commercial doubt, I go for commercialization, how do you define within Amicus the low-hanging fruit in Europe right now? Sort of what is the profile of those patients and what’s 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 naïve and again, Brad’s comment, we’re very pleased that we’re seeing switch patients from both standards of care and therapies, as well 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’s stepping forward with a greater unmet need. I think there is 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 - I mean, would you say that all one 1000 are low-hanging fruit or how would you further sub-divide those patients into sort of…?.

Well, I think - in German, you’ve got a market of about 1000 identified and diagnosed Fabry patients, about half of them are treated today within 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 we’re seeing in the market and I think that’s because they’re in - being in the position more regularly than the ERT untreated patients and also this - 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’ll see more switch patients than naïve patients, but we think very quickly that that should even out to that equal numbers..

Okay.

And then, as we look at those switch patients, you think that there is a sub-population 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..

Of course..

Thank you. Our next question comes from Anupam Rama with JPMorgan. Your line is open..

Hey, guys. Thanks so much for taking the question.

Maybe just a quick clarification question on Zorblisa, has the FDA agreed that statistical significance on one of the two co-primary influence would be sufficient for approval here? I know that meeting one out of two co-primary influence has been sufficient in the [indiscernible] disorder space in the past, but I think ecozyme and aldurazyme, but is there a precedent here in the derm space as well that we should be thinking about? Thanks so much..

Sure. So, based on the discussion we’ve had in 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, and what we’re 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, could you describe a little bit about the concentration here in terms of physicians and prescribers? Where these are patients are coming from? Thanks..

Sorry, Anupam, you just broke up at the end there, can you repeat the last part of your question?.

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

We won’t give specifics there, but I would say that it’s a well distributed group.

I think the important thing is that we’ve had good coverage of both KOLs in Germany, for example, but also the top-tier prescribers and the second-tier prescribers, so we feel like the organization that we’d put in place is well able to target the key physicians in Germany and the other markets where we have expanded access programs.

So, the distribution so far - the coverage has been strong so far and the distribution has been good so far - it’s been a remarkable openness to the physicians, again, in Germany, since we didn't have any clinical site, 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 - quite a few treating physicians I think we've estimated that there are about the 50 physicians who see about 90% of the Fabry patients.

Our sales teams have been to see every one of those 50 doctors, it leaves a handful of time, 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 the question guys..

You bet..

Thank you. Our next question comes from Joseph Schwartz with Leerink Partners. Your line is open..

Good morning. Thanks very much.

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 would 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?.

Yeah.

Again, we’re 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’re 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 were now being treated.

So, we would 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 the six to eight weeks of data, but I think good early trends for sure.

Brad, do you have any color to add?.

On the second question, Joe, I think maybe you’ve a role in our - 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 patient.

And so, we’ll just be very careful to ensure that that maintains that level of integrity and we’ll be using it for marketing purposes..

Okay.

And on Zorblisa, you’ve 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? And I thought you added some additional centers, have they been contributing as you would've hoped? And what needs to happen for enrollment to complete by the end of the year versus stretch into ‘17?.

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’d need to add significant sites to this program.

So, we said back in the spring when we get 50% enrollment that we wouldn’t give a further update until the study was completely enrolled, it’s now well over 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’ve been doing too, if you remember this is 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 if it though we’ve been.

To give you some sense, we’ve had over 400 patients present to clinic site, indicating an interest and potential to participate in the study with the 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 we can and should be doing.

We’re closing monitor enrollment over the month 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 as the finalization of enrollment, and secondly, two, it’s with this modification in the statistical analysis plan, we want to get the final steps locked in, and then be able to determine when we’ll take a look at the full data set..

Thank you..

Thank you. Our next questions comes from Tafin Umar [ph] with Bank of America. Your line is open..

Hi, can you hear me? Sorry, I am calling for Umar. [indiscernible].

Yes, Tazeen..

Just wanted to ask you a couple of questions from Pompe, BioMarine recently discontinued to its program and I was wondering if you can give us the results on potential takeaways that you took from that molecule or the way that the company had to find their trial and where you think you might be on an advantage over BioMarine in terms of how you’ve designed your trial and how confident you feel about going forward?.

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

We do think that we have a very differentiated approach, the BioMarine approach was a very different in targeting technology, it also didn't include any chaperone component to deal with the issues around stabilization of the protein and blood or immunogenicity.

So again, we think that we - as we’ve always believed, we had a very differentiated approach for the treatment of Pompe.

We think that there are three major limitations of lumizyme the current standard of the care, we think it has to be at number one with the targeting that relates primarily to the carbohydrate structures, and specifically, the levels of mannose 6 phosphate on that protein.

Second problem is, with the very high dose and the lack of a chaperone to keep it - find it in stable unfolded, that drug loses its activity.

Third is problems around tolerability and immunogenicity, as you know, 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 in our science team to tackle all three of those limitations of the current standard of care, and we think based on preclinical model that we have a potentially very differentiated approach to the treatment of Pompe disease here, again, with our unique ability to glycosylate engineer carbohydrates on this protein and to maintain that high level of carbohydrate optimize structure through the manufacturing process that reflects our biologic capability and a very unique biologic.

And again, with this fixed dose combination, with our chaperone 80, 22, 21, 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 year, what would you consider to be compelling data?.

Sure. There will be more over the weeks and months ahead that we’re going to see to that, but as we refer everybody to the slide and the cascade data which is slide nine.

So, when you look at the first data set that will be from cohort 1 in the fourth quarter, we want to make sure, of course, these are ERT switch patients from lumizyme, did they switch safely to be able to tolerate our drugs specifically the fixed dose combination of ERT plus chaperone.

Secondly, very importantly pharmacokinetics, the PK, a key element of our fixed dose combination is a different bio-distribution and a different PK curve at different half-life than lumizyme, so we’re going to look at all of those parameters and see doesn't it match with our expectations and with what we saw in the preclinical data.

So, it’ll be a very important dataset for us.

We will also look at biomarkers, including biomarkers of efficacy and 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 with the nature and type of antibodies on cytokines, other measures of the inflammatory response to ERT and what maybe a difference in our data set.

And again, that will be the first of what will be many data set that will release over 6 to 9 months period in this program. So that by mid-2017, we think we’ll have a very large and robust data set that again will prove the principle that this is a very differentiated approach to treating Pompe and also give us the path to the phase 3..

Okay. Thanks for that color, appreciate it..

Sure..

Thank you. Our next question comes from Roy Buchanan with Janney Montgomery. Your line is open..

Hi, thanks for taking the question. Just a quick on the zorblisa phase 3, is kind of specifical plans still not finalized I believe, I just wonder if there is any thoughts of adding patients to the study? Thanks..

No. We think that we would be able to keep within the target range of approximately 150 patients even with the 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..

Sure..

Thank you. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open..

Hi, this is actually Carrion that called for Salveen. Thanks for taking my question and congrats on the progress. I have a few questions.

First, what has the initial feedback been so far from patients and physicians that had started on Galafold? And what is the distribution of patients in terms of previously ERT treated versus ERT naïve patients that have to follow?.

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

No, I think it’s in line with what we’d expect and with the color we’ve provided on the call which is we’ve had good distribution for the prescription that have been written, we’ve seen good uptick with physicians and good receptivity to having discussions around the data, around the program, so we’re 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 co-primary endpoint with it, and primarily driven from your side or was it kind of a FDA dermatology to division-driven decision?.

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

There are several reasons to that. We thought the elevate the time to closure to co-primary very happy that the FDA agreed to that, based on FDA guidance [indiscernible] been approvable endpoint and we’ll be able to study.

We also had very encouraging data from our phase 2B study, showing a difference in time from enclosure for HD-101 compared to placebo, that was quite strong.

And that, we feel, among the data that we’re collecting, going to be very sensitive and powerful way to look at that data, and in addition through proportionate wound field at a particular time point, but this accumulative, look at all the wounds given over time.

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

Okay. Thank you..

[Operator Instructions] We have a follow-up from Ritu Baral with Cowen. Your line is open..

Hi, guys. Thanks for taking the follow-up.

Actually, just wanted to go a little further on your answer to Tazeen’s question on the biomarkers, given you’re 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?.

Of course, we'll look at a number of biomarkers, things like PK as you know there are isoforms of ALC, ASD that come from muscle, we will look at both PK and ALC, ASD are elevated in patients, well we don't know what we will see in ERT experience patients, we don't know what we'll see in a short term but look at those.

We will also look at Hex4 which is taken from analyzing the urine of the patients. So, we will look at that as well.

And again this is an exploratory sedate and as you remember from the preclinical data, we saw terrific uptick of the enzyme into target tissues and compared to standard of care and preclinical model we saw significantly better clearance of glycogen.

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

One for Chip, Chip what's the current shares outstanding now after the exercise of the ATM?.

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

And last question guys, as you think about the expansion of sites in the [indiscernible] pivot study, how are you dealing with the potential for differences in treatment paradigm, especially given you said that you're going across different geographies, what geographies are you going across and how different is background standard of care across these geographies?.

We 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've looked at sites in other parts of the world, a handful of those sites may come in but only after they've passed rigorous quality control inspection by our teams, by our CROs, other compromised and study sites quality or ability to execute in that study.

These are all top advanced dermatology vendors, major academic vendors and importantly vendors that are experiencing VD. Quality control is something we're very focused on..

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

Yes, very comfortable..

And then just on your comment 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 the way of addressing the same issues that you’re raising. We’re not stratifying, but await to adjust for that when you analyze is to introduce the covariant and we think those two, the age of the patients and size of wounds would 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..

Yeah. I would just comment further on the EV program, we knew when we closed on the acquisition of Scioderm that there are three key areas that we had to focus on and improve with the Amicus resources and experience.

One was the addition of, additional clinical sites, high quality sites, two was significantly more resources, internal resources, people put to the program.

We’ve done both of those two, by the time we get completed with the activities in the spring of this year, we then turned our attention to the third area where we thought there could be significant improvements 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.

It continues 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..

Thank you. And we have a follow-up from Joseph Schwartz with Leerink Partners. Your line is open..

Thanks for taking my follow-up.

I was just wondering if you could talk a little bit about your understanding for the drivers of placebo response and EB, beyond spontaneous resolution and the potential for patients to get better skin care 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 the few around, the smaller ones, the ones that haven’t been present for that long. But that is the nature of EB and the standard of care, there are wounds that you heal, especially if it’s smaller hand wounds of younger age..

Okay, thank you very much..

So again, Joe, with the inclusion criteria, the design of the 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..