Amicus Therapeutics Inc (FOLD) 2016 Q1 法說會逐字稿

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

I would now like to turn the call over to Sara Pellegrino. You may begin.

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

On this call, as referenced on slide 2, we may make forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business as well as our plans and prospects. Our forward-looking statements should not be regarded as representation by us that any of our plans will be achieved. Any or all of the forward-looking statements made on this call may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. You are cautioned not to place undue reliance on any forward-looking statements, which speak only 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 conference call to reflect events or circumstances after the date hereof. For a full discussion of such forward-looking statements and the risks and uncertainties that may impact them, we refer you to the forward-looking statements on slide 2 of the slide deck, as well as to the forward-looking statements and risk factors of our annual report on Form 10-K for the year ended December 31, 2015, which is filed 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, Sarah, and good morning, everybody. I'm pleased to host this call today on the heels of a very successful first quarter at Amicus. As we have discussed before, we have outlined four key strategic priorities focused on our three lead clinical programs, and we have made significant progress with each one during the first quarter.

The number one priority was getting migalastat approved in the EU as quickly as possible for all Fabry patients with amenable mutations. As we announced a few weeks ago on April 1, we have received a positive CHMP opinion recommending full approval of migalastat with a broad label for Fabry patients with amenable mutations, of which the current label lists 269 mutations that today represent approximately 35% to 50% of the total Fabry population.

This was the broadest label that we could have hoped to achieve, and I can tell you having just returned last week from the commercial launch meeting with the Amicus team in Germany, we are fully prepared to market migalastat to patients in the European Union upon final EC adoption, which we continue to expect in the second quarter. Brad will go into more detail about the launch plan, but I am extremely pleased with the very high caliber and passion of our team and the preparations that have gone into this launch planning to strongly position Amicus for success in the Fabry market.

Our number two priority is determining the optimal path forward for migalastat here in the United States. We remain fully committed to trying to identify an optimal US pathway based on our existing data set without the need for another phase 3 study. On that front, we have now substantially completed the integration summary of safety analysis as requested by US FDA. We have also collected and analyzed additional histopathology data and gastrointestinal symptom data as well as longer-term renal and cardiac data across both phase 3 studies, which were presented at the March World Meeting in San Diego.

We have not yet disclosed these data with FDA, but we received positive feedback from physicians at the world meeting and of course, in the CHMP's proposed label. I will also add that the CHMP conducted an in-depth and rigorous review of both phase 3 studies in reaching its opinion with respect to migalastat.

We are now finalizing the briefing documents for FDA, and we anticipate having a meeting with FDA by midyear to clarify the US regulatory pathway for migalastat. We currently plan to provide an update on the US regulatory pathway following the receipt of formal minutes in the agency of that meeting.

We continue to believe that this medicine, migalastat, should be commercially available for all amenable Fabry patients in the United States, and we will continue to collaborate with FDA to identify the most rapid path to approval.

Our third priority, obtaining important early clinical data for a novel Pompe ERT, also remains on track. We were very excited to report in our press release this morning that we are actively enrolling patients across multiple sites and that patient dosing with this novel ERT, which we refer to as ATB200, is underway for our phase 1-2 clinical study of this drug for Pompe disease.

These initial patients have switched from Lumizyme to our ERT ATB200 which, again, is a highly phosphorylated ERT with optimal [fly consolation] to deliver what we hope to be significant benefit to patients with Pompe disease where such an extraordinary unmet need still remains.

As a reminder, this proprietary ERT in Pompe is enhanced with the co-administration of a pharmacological chaperone. I will review more about this study in an update in the coming part of this call. But I will state here that we are very pleased to be dosing patients and remain on track for interim data by year-end.

Finally, we continue to make good progress on our fourth important priority: the successful execution of the phase 3 study in EB, or Epidermolysis Bullosa. Since the acquisition of Scioderm, we have added significant resources to augment the Scioderm team's efforts. We have applied our successful global clinical operations expertise in the rare diseases to open new clinical sites globally. Through our strength in medical affairs, we have enhanced our presence within the physician community at key dermatology meetings. And we continue to strengthen our collaborative relationships with the EB patient community.

Indeed, we have made significant progress in execution as it relates to these four key strategic priorities, and we very much believe that these three clinical programs in Fabry, Pompe and EB, each with a potential $500 million to $1 billion in potential market opportunity, will be the cornerstone of a much stronger and bolder vision at Amicus to build a leading global biotechnology Company focused on rare and devastating diseases.

I will refer you, if you have the slides following along here now, to slide 4. As you see here highlighted, we have transformed Amicus over the past few years due to the development of our internal pipelines, including our chaperone technology. With technologies and, importantly, biologic capabilities that we have acquired through the acquisition of Callidus Biopharma, as well as our expansion into rare and devastating diseases beyond lysosomal storage disorders with our acquisition of Scioderm in the EB program.

And in 2016, we expect this to be a very important year that has already brought to us the most important achievement so far in our Company's history: a positive CHMP opinion for migalastat.

Before I turn the call over to Brad to discuss in more detail our launch plans for migalastat, let me highlight on slide 6 the strength of the broad label recommended by the CHMP and emphasize why this is so significant. This is the first oral therapy for Fabry. It was recommended by the CHMP for full approval as a first-line therapy, and it represents a very innovative use of personalized medicine for patients with amenable mutations in Fabry.

Also, too, you'll see that it is for all patients with amenable mutations; 269 mutations listed in the label. These amenable mutations covered in the label represent 35% to 50% of the diagnosed Fabry population today in a market that generated $1.2 billion in global sales in 2015 and which continues to grow at a double-digit rate annually as new patients are diagnosed.

The label also includes the first-ever searchable website for pharmacokinetic medicines where physicians will quickly and accurately determine if a Fabry patient has an amenable mutation. So, again, a real advancement here for migalastat, and we believe in the field of medicine.

Having just spent time with our commercial team in Europe last week in preparation for our migalastat launch, I can tell you that they are very excited. This is an extraordinary team, and they are committed to this program. Very excited about the strength of this label as we prepare to introduce migalastat into the market in Europe.

I am extremely grateful for the ongoing support, especially from the Fabry community, in particular those patients -- I'm sorry -- those physicians who led the clinical studies in migalastat, as well as the patients who volunteered for these studies over the past decade, in many cases giving up access to an approved therapy to switch to a then-unproven technology. We believe that we are well-positioned for success.

And with that, I will turn the call over to Bradley to discuss our preparations now for launch in the EU.

Thank you, John. As John mentioned, we truly are launch-ready at this point, and the international team is eager to begin marketing migalastat as soon as we reserve formal EC adoption, which we expect in the second quarter. Let me provide a little bit more color there.

Under David Allsop's leadership, we have built a team of over 50 people to support our EU-and-rest of world launch, including country managers and medics in the major markets in Europe and heads of all of the key commercial and G&A function. The individuals have significant experience in leading rare-disease companies and launching rare-disease products and have already done an excellent job with prelaunch preparations over the last year, as noted on slide 7.

We've completed extensive payer research and payer ad boards and received positive feedback around our projected label, which is now very much in line with the actual label that was provided by the CHMP. The clear feedback from payers in all of our international markets is that they would support price parity and enzyme replacement therapy based on the value that they saw in our projected label and in our data, which support the value of migalastat.

And behind the scenes, we been working diligently on developing the global value dossier and have begun to submit the dossier in certain countries where the reimbursement process is initiated upon positive CHMP opinion. We now expect to begin the country-by-country process in the remainder of the EU member states upon formal EC adoption.

We feel very well-prepared and pleased to have kicked off the country-by-country process, and we've gotten great receptivity and we are very confident in the value proposition that Galafold will bring.

As a reminder, on slide 8, as John mentioned, the $1.2 billion global Fabry market today is large and continues to grow at a double-digit pace annually. We prioritized the EU, Japan, US and other countries with large Fabry markets for initial launch.

And, importantly, of the 5,000 to 10,000 diagnosed patients around the world, we estimate that 40% to 50% of them are not currently on treatment and that there is further opportunity for growth and diagnosis through newborn screening and other initiatives, such as screening in high-risk populations and general elevation of disease awareness. We believe that the product profile for migalastat is an innovative new treatment -- oral treatment option will strongly position us for a successful launch.

Turning to our global regulatory strategy on slide 9, it's important to reiterate that the positive CHMP opinion and potential EC adoption provide a platform to address more than 70% of the global Fabry market including the EU member states as well as several international territories that accept the European approval as the basis for authorization.

We won't outline the full launch sequence for competitive reasons, but it will be similar to other products in rare diseases, the Germany launch first. And now our entire German team is in place, including the key account managers, or KAMs, who are trained and ready to launch upon EC adoption.

As a reminder, Germany is currently the third-largest Fabry market behind the US and Japan and has about 550 patients on enzyme replacement therapy today, with a roughly equal number who are diagnosed but untreated. So this is a great first country to launch migalastat in.

In the rest of the EU, each country has its own reimbursement process, which can take six to 12 to 18 months, and we are pursuing each of them vigorously.

In countries that offer specific pathways for innovative products for high unmet need -- with high unmet needs, we are pursuing those channels where we can. In the UK, for example, we have been selected to go through the HST process, or highly specialized technology process, that was designed for orphan diseases with unmet need where, among other things, the reimbursement will not be determined by quality or quality-adjusted life care.

And in parallel with the reimbursement process, we have initial patients being treated in France through our temporary authorization of use, or ATU, and the positive CHMP opinion that allows us to now broaden our expanded-access program, or EAP, to additional countries that recognize the EU opinion.

The EAP program is important because it allows us to provide the earliest possible reimbursed access to migalastat for Fabry patients while we are in the process of securing formal country-level pricing, reimbursement and marketing authorization.

And in the US, as John mentioned, we anticipate meeting with the FDA in the middle of the year and intend to provide an update on the US regulatory pathway after we receive formal minutes from that meeting.

Finally, I would like to touch on one more important market, which is Japan, outlined on slide 10. Japan represents another large Fabry market. In fact, it's the second-largest Fabry market in the world, with an independent regulatory process that we are actively pursuing.

Today in Japan, there are more than 650 Fabry patients on enzyme replacement therapy -- again, with a similar number who are diagnosed but untreated. And physicians tend to initiate treatment early in the course of the disease, so this is a very progressive and supported Fabry community.

To date, we've done a great job of laying the groundwork in Japan to deliver on our mission to make migalastat available as broadly and as quickly as possible. We are fortunate to have had multiple sites in Japan as well as several Japanese patients who participated in our pivotal phase 3 study, so we already have data in about half a dozen Japanese subjects with Fabry disease who have taken migalastat, in addition to a phase 1 PK study in healthy Japanese volunteers that was completed earlier in development. Migalastat was also granted an orphan drug designation, and we have already begun the process of interacting with the Pharmaceutical and Medical Device Agency, or PMDA, on the optimal regulatory path forward. We hope to have an update on this process later in the year.

And, finally, beyond the initial Fabry market opportunity, we would like to remind you on slide 11 that this is a significantly underdiagnosed and may be one of the most prevalent human genetic disorders. Through newborn screening initiatives, diagnosis is on the rise, and these data suggest that Fabry may be up to 10 times higher than historically reported in the literature. A majority of patients identified through newborn screening have amenable mutations. And as a reminder, when one patient is identified, typically three to five additional family members are also identified.

I am happy to address questions about launch preparations during the Q&A. But for now, we'll turn the call back to John to outline our Fabry franchise strategy.

Great. Thank you, Brad. On the heels of a successful positive CHMP opinion, I would like to reiterate our commitment at Amicus to delivering a highest-quality therapies for all individuals living with Fabry disease.

We begin, of course, with migalastat as a personalized medicine for patients who have amenable mutations, as identified in our proposed label. For all of the patients with Fabry who do not have an amenable mutation, there has been a lack of innovative new treatment options now for more than a decade. We hope to change that with our development of a novel proprietary biologic, our own Fabry ERT.

As we have outlined on slide 12, our target product profile is a Fabry ERT with improved drug targeting, and we expect our CHART platform technology to further differentiate this product for co-formulation with migalastat. The cell line has been identified based on the work done over the last several years by Dr. Do and his scientists here at Amicus. That cell line has now been transferred to our manufacturer, and we expect to provide more information including pivotal free clinical data in the second half of the year.

As you can see on slide 13, it is our vision that patients with amenable mutations receive a personalized medicine with oral migalastat as a monotherapy, while patients with non-amenable mutations may receive one infusion, a novel ERT that incorporates the stabilizing properties of this chaperone and that in the future, we have all Fabry patients on an Amicus product, driven entirely by their human genetics. Beyond that, we continue to innovate as part of our commitment to the Fabry community to discover the future next-generation therapies and in the months ahead, we will have more to say about our Amicus pledged to patients in Fabry disease.

Turning now to our Pompe program, you can see here on slide 15 -- building, again, on the biologics capability that we've developed here at Amicus, our manufacturing relationships with key contract manufacturing organizations, we set out a number of years ago to address three primary challenges with enzyme replacement therapy, the current standard of care.

The first is activity and stability. What you see, of course, with the current standard of care, the approved ERT is a rapid denaturation of ERT in the pH of the blood. You also see protein aggregation.

Secondly, the challenge of tolerability and immunogenicity. You see infusion associated reactions in greater than 50% of late-onset Pompe patients. And antibody titers have shown to affect treatment outcomes. It's also been reported that all patients develop antibodies to the current standard of care.

The third challenge -- and this is a challenge owing to the structure of the primary protein and its carbohydrate structure, and that's the challenge of uptake and targeting. What you see with the current standard of care is very low mannose 6-phosphate receptor uptake into skeletal muscle. In fact, the vast majority of that GAA or Pompe protein is not delivered to the target lysosomes of muscles.

The challenge I have put out our science teams a number of years ago was to develop a novel ERT that would address all three of these major challenges. To do that, our team has incorporated the CHART technology, or chaperone advanced replacement therapy, which is the addition of a chaperone to stabilize the ERT, enhance activity and stability, and potentially reduce tolerability in immunogenicity.

They also needed to invent an entirely new ERT that had a high level of mannose 6-phosphates and was properly glycosylated. We believe that we have now achieved that and are very, very pleased that that is now in-patient.

Let me briefly turn over on slide 16 the discussion to our Chief Science Officer, Dr. Hong Do, who has also been a chief architect of this exciting new drug.

Great. Thank you, John. As John mentioned in the previous slide that the key component of our particular approach for Pompe disease is the development of an ERT that can be effectively targeted to key disease-relevant tissues. To this end, we have developed a robust and proprietary cell line which, in fact, does produce an enzyme (inaudible) ATB200 that has optimized like population for efficient drug targeting. We have worked diligently to scale up this process so that we can develop this ERT at large-scale manufacturing. So we actually have maintained these critical qualities of this protein during the scale-up of this enzyme; in particular, maintaining high levels of mannose 6-phosphate to ensure good drug targeting.

We have verified that this -- the glycosylation of our product has been maintained throughout this process, as can be seen on slide 16 on the left. The graph represents the ability of our enzymes to bind the intended mannose 6-phosphate receptors to ensure good femoral uptake.

As can be shown on the right-hand side, this is a vial of our drug product. To date, we have generated multiple GMP batches of our drug, which is supplied by our clinical study that is being enrolled now.

With that, let me turn it back over to John to discuss our clinical study design.

Great. Thank you, Hung. And, again, great that this is now in patients. I will emphasize that what we've done is also -- it's not just differentiated, it is in the current approved standard of care. We also think that this is highly differentiated from any other ERT in development today, specifically in terms of addressing the three key limitations of the Pompe ERT.

The other point that I will highlight, we went through, and Hung showed the chromatography slide, of what we have done in not only designing this novel ERT, but in successfully scaling it due to manufacturing process and maintaining high levels of mannose 6-phosphate. And the entire carbohydrate structure, including the proper glycosylation is a remarkable achievement. It is something to our knowledge that no one has ever been able to do in the Pompe field before and we think really reflects well on our growing and unique capabilities in biologics design and now manufacturing.

On slide 17 we are -- you will see here we are actively enrolling patients in our ongoing phase 1-2 clinical study to investigate this proprietary Pompe ERT, ATB200. Again, co-administered in a fixed-dose regimen with our chaperone, AT2221. As a reminder, this is an 18-week safety and PK study beginning with three ascending doses of ERT -- the ATB200 alone, followed by that ERT plus chaperone. Following this 18-week treatment period, patients are eligible to continue to receive ERT plus chaperone. Initially, the clinical study will look at patients switching from Lumizyme, the ERT standard of care.

Key things we are looking for in this study to differentiate our product candidate includes safety and plasma PK that demonstrates potential benefits of the addition of the chaperone to inform dose selection for our next study. Also, tolerability and infusion associated reactions will be observed as well as antibodies and the characterization, importantly, of the types of antibodies, some of which are now based on proprietary assays that we have developed here at Amicus.

We expect to include patients naive to ERT in the study after we have the initial switch data. We will continue to follow these Pompe patients in an extension study where we will look at longer-term functional measures of the disease and assessments. So, again, over the last several months, a great achievement now with this drug in patients.

I am happy to answer questions on the clinical programs during the Q&A. But for now, let me turn the call over to Dipal Doshi, our Chief Business Officer and also General Manager of our Scioderm business unit focused on EB.

Thanks, John. I am pleased on slide 19 to provide an update on our EB program for the progress with our ongoing phase 3 study, which we have named the Essence study for patients with all three major types of EB.

In the third quarter of 2015, we acquired SD-101, a late-stage potential first-to-market topical treatment of EB. EB is a chronic, rare, genetic connective tissue disorder with no approved treatment options. While the blisters and lesions typical of EB are visible on the skin, it is not a skin disorder. It is a rare genetic disease that can affect all layers of the skin and internal organs. EB is a debilitating, excruciatingly painful and potentially fatal disease. It is a disorder with 30,000 to 40,000 diagnosed patients in just the US, EU and Japan.

We are fully aligned with the sense of urgency among the EB community to get a treatment approved. And since the acquisition, we have made significant progress in adding our Amicus resources, experience and clinical operations capabilities to this program. Since the acquisition we have applied our previous success in global clinical trial recruitment in rare diseases to increase the number of clinical sites in our phase 3 ESSENCE study. And today we have 16 sites, with many more sites coming online in the coming weeks. We believe it is important to have this wide geographic experience with SD-101 among several leading physicians and their patients. We are more than 50% enrolled today and expect momentum to begin picking up even more as these new sites have come online.

We've also spent quite a bit of time building relationships and visibility within the dermatology community. We presented the phase 2B data to the dermatology community first at the American Academy of Dermatology and now at the upcoming Society of Investigative Dermatology. We've also continued to strengthen our relationships with the EB patient community and continue to believe we are well-positioned for success in our phase 3 study. We remain on track to complete enrollment midyear, and we continue to expect to report top-line data in the second half of this year.

I will now turn the call over to Chip to review our financial position.

Great. Thanks, Dipal. Good morning, everyone. I will start today's financial discussion with a few comments on our current cash position and our overall 2016 financial guidance. I will refer you first to slide 21. \

Amicus continues to maintain a strong balance sheet. Cash, cash equivalents, and marketable securities totaled $165.9 million at the end of March, as compared to $214 million at the end of December last year.

During the month of April we strengthened our cash balance with the addition of $16.2 million of net proceeds from the sale of 2.1 million primary shares under our aftermarket, or APM, financing facility. We also intend to access an additional $10 million of debt under an existing debt facility during the second quarter. Based on the detailed financial review, after the positive CHMP opinion and through the continued careful management of expenses, we expect to remain within the original 2016 net cash spent guidance of between $135 million and $155 million.

The current cash position, including proceeds raised from the APM and the additional debt, is projected to fund our operations into mid-2017 through several important inflection points that John outlined previously on the call.

Turning to the first-quarter results, I will be referring to slide 22, and additional details will be found in our Form 10-Q which will be filed later today. Total R&D expenses for the first quarter of 2016 increased to $23.4 million, as compared to $15.1 million for the first quarter of 2015. The increase was primarily due to higher contract manufacturing and clinical research investment driven by the scale-up of our Pompe ERT manufacturing efforts as well as advancement of our Pompe and EB clinical development programs.

Total general and administrative expenses for the first quarter of 2016 were $15.7 million, as compared to $6.4 million in the first quarter of 2015. The increase in G&A was primarily due to investment in pre-commercialization activities.

Net loss for the first quarter of 2016 was $43.7 million, or $0.35 per share, compared to a net loss of $24.3 million, or $0.25 per share, in the first quarter of 2015. The wider loss is attributable to an increase in total operating expenses. And as of March 31, 2016, we had approximately 125.2 million shares outstanding.

This summarizes our key financials for the first quarter of 2016. As I said, more information on our financials will be available in the 10-Q, which will be available later today.

I'm happy to address any additional questions on the financials during the Q&A. And for now, I will turn the call back to John.

Great. And thank you, Chip. I will conclude on slide 23 by noting that it has been a remarkable start to the year for Amicus, and ours is a story of exceptional patient focus and perseverance. Amicus is about invention and healing. The development and approval path for migalastat was certainly not a straight line, and we had to overcome many obstacles along the way. And such is almost always the case for drugs that represent highly innovative technologies and meaningful differences for patients.

The result of all that hard work is a CHMP opinion that validates the effort and the perseverance and what it could mean for Fabry patients.

2016 is poised to be our most significant year ever. And much like the CHMP opinion, as it has validated migalastat as a meaningful therapy for Fabry patients, we expect to see phase 3 data from the EB program that, if positive, will validate our purchase of Scioderm last year. And, very importantly, we expect to see phase 1-2 data from our Pompe program, which we hope will validate both the program and, more broadly, our capabilities as a biologics Company.

Any one of these programs could be the basis of a promising rare disease company. But, taken together, we think that these programs and the technologies behind them and our pipeline position Amicus in the coming years to become one of the leading global rare-disease companies.

So with that, operator, we will turn it back to you, and we are happy to take any questions.

(Operator Instructions) Ritu Baral, Cowen.

John and Brad, you mentioned that you intend to price migalastat at parity, or at least you updated for parity pricing to enzyme in Europe. As you understand it now in your market research, what exactly is the price of enzyme in Europe after all the mysterious discounts the various countries get?

Sure, thanks, Ritu. I think you've articulated it well. That's been our strategy, and I think the data and the package that we have very much support that strategy. So we've said historically that the global average price for an average patient ranges around $250,000 to $300,000 -- that includes the US, by the way -- where ERT prices tend to be higher over time.

In Europe, that average price for an average patient from a gross perspective is about $250,000. And after gross to net, it is different by different country. But you can assume that there is something like a 20% discount off of that. So, perhaps $200,000 as a base point for a net price in Europe.

But, again, it is different country by country. There are some countries that have a higher average starting point and some that have a lower, but that's probably good rule of thumb at this point.

Got it. That's very helpful. And then if I could circle back to your US strategy, John, I think you mentioned that you intend to go back to the FDA with the integrated database, safety database, the new GI data and the new biopsy data including, I think, the proto-site data presented at WORLD. What is the strategy of your argument as you go back into the seating? What do you think, based on your interaction between receiving those very controversial minutes now -- what do you think is going to be most meaningful to them in the data package right now?

Ritu, I won't comment specifically on our regulatory strategy. I will remind everybody that our last discussions in the fall with FDA, they indicated that there were multiple potential approval pathways under either subpart H or full approval. We think we have a very, very strong data set here. It's only been strengthened since the fall. We think the EU approval and the strength of that approval is further validation and support. We also think the potential for the publication of the 011 US study in a top-tier medical journal could also provide further validation.

So, again, we've gathered all the data that we have. We've just about finalized the briefing documents, and we believe we'll have that discussion or potentially a series of discussions in the months ahead.

Got it. And very last question. The expanded-access program in Europe and other geographies that you mentioned, what are some of those -- what are some of the geographies that may kick that off near-term?

Sure. We've already mentioned the ACU process, which we did receive approval for cohort ATU. We announced that a few weeks back. The other countries that key off of either the CHMP opinion or the adoption by the EC are countries like Spain, Italy; Turkey is another one; Brazil is an important one. And they each have different nuances. In some cases, it's fairly straightforward, like the cohort ATU process in France. In other cases in Brazil, there's a very specific judicial process that has to be followed. So we will be, just as the reimbursement process, a country-by-country approach. But we are, in every geography where we can, trying to take advantage of that so we can provide access as quickly as possible for patients through those programs.

Helpful. Thanks for taking all the questions.

Anupam Rama, JPMorgan.

Maybe a quick one for Brad, just looking at slide 9 about your global regulatory strategy. Given some of the updates from your rare-disease peers this quarter, how are you guys currently thinking about the LatAm situation, and how does that impact your regulatory strategy in that region? Thanks.

Anupam, as I just mentioned, within the question from Ritu, we are pursuing the inpatient programs in Brazil in particular, which has a very specific judicial process that has to be followed in parallel with pursuing the regulatory process in that country.

We are looking at -- LatAm represents a large Fabry population, very much in need of new treatment alternatives, and therefore we are looking at that geography very carefully. And we will -- as we've done in Europe and elsewhere, we will judiciously target the largest unmet need first and continue to expand out from there.

So I would expect, in addition to our expanded-access programs, we will provide regular updates as we go through that process over the next six, 12, 18 months. But it's a very important market and one that we think very much deserves an opportunity for access to migalastat.

Great. Thanks for taking our question.

Joe Schwartz, Leerink Partners.

I was wondering, first of all, your Pompe program, what -- can you give us any order of magnitude on the type of data that we will see before the end of the year in terms of numbers of patients and potentially duration? And then I heard you mention safety PK tolerability, immunogenicity. Will there be any clinical measures captured and reported? And then, what will -- again, what's the right way to think about the form that you will release that data?

Joe, I think we will have more of an update as we get deeper into that study by midyear. But, again, to remind you that the first cohort of patients, about a dozen patients, that will be 18 weeks of data in the primary treatment period. We also do expect to study naive ERT patients and nonambulatory ERT patients as well in later studies.

So I think what you would expect to see in the second part of the year are data on those dozen or so patients at the 18-week point. So, once we have that or some cohort of that, that we will be able to provide data on the -- as you indicated very importantly, the plasma PK, the tolerability, the antibodies, the immunogenicity. And, again, while those are not clinical -- traditional clinical endpoints, we think they very much go to the nature of the mechanism of action here and the drug and the potential for clinical benefit.

In the extension study of those patients beyond the 18-week treatment period, we will be capturing -- compared to their baseline as they switch from Lumizyme, we will be comparing what they look like in some of the more traditional measures: the six-minute walk test, force vital capacity and other more clinical measures of disease.

So I think this will be a growing body of data throughout the course of the next year, with some important interim looks by the end of the year.

Okay, great. Thanks. That is super-helpful. And then if I could just ask on Galafold in Europe, what do you -- who do you expect to be the first adopters in terms of your understanding of how this market segments out? What does the market look like to you in terms of the types of patients? It is clearly large, as you point out, and growing. But there is patients that you have studied on ERT, those who have been on ERT but have been naive when you treated them. There's women; there is men. There's more or less severe patients on a number of different organ manifestations. So how do you see this very large market coming onto your drug over time?

Joe, this is Brad. Good question. And we've obviously thought a lot about the Fabry market and patient segments, et cetera. One of the great things you will recall is that, of course, we're studied the two major segments: both patients on therapy, so potential switch patients; but also patients naive to therapy. And so those data sets are what really lay the foundation for what we think is a very strong label and what CHMP indicated would be a first-line therapy for Fabry.

So we have very much identified, I think, patients in both of those segments who would eagerly look to take migalastat, both patients on ERT who are dissatisfied or who are looking for a treatment alternative -- an oral treatment alternative with a lower burden of treatment, or patients who are newly diagnosed and are looking for product with the characteristics that we have in the label.

So we think we have advantages in both of those segments. And as I mentioned in the call, you have a roughly equal -- you have about a roughly equal number of both patients on therapy -- on ERT today as well as patients who were diagnosed but untreated.

Perhaps I will leave it there versus going into the very specific commercial plans for those segments. But we think there's a robust opportunity in both.

Okay, great. And then I think on your last call, you were hoping to complete enrollment in the Zorblisa phase 3 by midyear. And I noticed today that you are still just saying over 50% enrolled, but adding additional resources. So can you give us any update/granularity there so we can have the right expectations?

We still expect enrollment completion by midyear and data by the end of this year, Joe. We don't -- what we will not do is provide such granularity here as we go step-by-step through the study except to say now that it's more than half enrolled. I think the next update will be when the study is fully enrolled.

Okay, great. Thanks for taking all my questions.

Roy Buchanan, Janney Montgomery.

I had a quick one on the ATM. If I read between the press release, I guess, and the slides, it looks like maybe the $16.2 million was all used in the quarter. Was there any used in April?

Yes, Roy, hey, it's Chip. That was 100% completed after the quarter so that the ending cash balance of $165.9 million did not include any of the proceeds taken down in April from the ATM.

Ah, okay. Okay, that's helpful. And then I had a speculative one, I guess, on Zorblisa. Have you guys ever considered maybe -- regardless of the phase 3 outcome, its potential to combo with either the cellular or gene therapies that are being tried? Thanks.

You know, I think those are all possibilities. We are constantly looking at all the new technologies being developed. As you know, Zorblisa is by far the most advanced program in the clinical study. It is the only program also for all subtypes of EB. For other specific subtypes, there are some very exciting, very early-stage programs and technologies and we are very familiar with them. And I think down the road there could be a potential to study those in combination. There could be great synergies with what seems to be the anti-inflammatory and healing aspects of Zorblisa together with other drugs that might get to the more fundamental mechanism of action.

Okay. Thank you.

(Operator Instructions) Salveen Richter, Goldman Sachs.

First, with regards to Fabry disease, when you talk to patients out -- when you do patient outreach programs or as you've talked to physicians, how much of a factor is brand loyalty going to play in terms of getting patients to switch from the existing ERTs over to your therapy?

And curious about plans and timelines for the Japan market.

And then a third question -- with regards to Zorblisa, with the complete target wound closure rates of 60% to 82%, can you help us frame what we should be looking for in the phase 3 study here? And then how would physicians use this cream? Would they use it on wounds or as prophylaxis, and what is clinically meaningful in terms of the outcome here?

Great, Salveen. Thank you for all three of the questions. I'll take the first one in terms of brand loyalty and Fabry. We have been actively involved for a decade now with this Fabry patient community. It is a community filled with great needs -- great unmet medical needs and a very, very sophisticated community. My assessment is that they have absolutely zero brand loyalty. Their loyalty is in finding the very best therapy with their physicians' advice. For they -- and given that it's an x-linked disease, for their family members. And that's where we hope that the strength of the data and having this as an alternative therapy available beginning in Europe and then hopefully around the world and ultimately in the United States as well. That will drive -- switching from ERT, we think some substantial numbers of patients.

And also, too, in that diagnosed but untreated population that is about equal to the treated population today. We think that this -- for those patients who have given up or failed ERT, and for those patients who have not elected to take on the great burden of an every-other-week infused therapy that this might offer a potential alternative treatment that they might not otherwise have. So we are very, very optimistic about the ability to deliver this medicine very quickly to a number of patients living with Fabry.

To speak to that just briefly further, if you look at our 012 study, which was a switch study, these were 60 patients, all with amenable mutations in Fabry disease who all were on enzyme replacement therapy, either Fabrazyme or Replical. Throughout the course of 2012 when we enrolled that study, every one of those patients voluntarily elected to give up an approved therapy for a fatal genetic disease in the absence of any pivotal data that we had. And this was at dozens of sites globally. The fact that they did that then and that they continued on that therapy, I think, bodes very well in terms of the potential uptake in migalastat and speaks specifically to their needs for newer and potentially better therapies.

And I think also, too, our significant physician interaction globally over the last several years, but intensely over the last several months, has told us that this will -- the decision to put patients on migalastat will be driven by data and good medicine. And there, I think, we'll be very well-positioned.

Your second question was about Japan. Let me turn that to Brad.

Yes, I think in Japan, Salveen, I think the best thing to do is to say that we will provide an update later in the year as we progressed that process. We have initiated discussions with the PMDA, so that is underway. And as I mentioned, we have laid a great groundwork for those discussions in our development so far. But why don't we wait for more detail after we've had the subsequent discussion with the agency, and we will come back to you?

And your questions around the Zorblisa and the treatment paradigm there -- Dipal, I will let you handle that question.

Sure. Salveen, I believe the first question was around the percentages that we saw on the phase 2B study and how that may correlate to the phase 3. I think the best way to answer that is that we've learned a lot about how to design the phase 3 study based on the data from the phase 2B and from the breakthrough and for the phase 2A, which is the breakthrough therapy designation. I think the best way to view that is that we are hopeful that the phase 3 trial results reflect those learnings, and that's how we have designed that trial.

In terms of how physicians will use the SD-101 on the wounds or prophylactically, we believe that if the drug is approved that they will use the SD-101 product on the different types of EB. And it's a very broad basis of utilization considering the fact that the trial design has taken into account the different major subtypes. So we plan on doing much more market research as the year progresses on utilization. But we are confident that if we see the trial results that we would like to see and the data shows what the data should show, that utilization from the physicians will be across all the different subtypes -- the major subtypes of EB.

Great. Thank you, Dipal.

Thank you.

Salveen, I hope that answers your questions.

Yes. Thank you.

There are no further questions. At this time, I would like to turn the call over to John Crowley, Chairman and CEO of Amicus Therapeutics, for any closing remarks.

Great. Thank you, operator. And thank you all, to the analysts, for the excellent questions. Have a great day. Thank you.

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