Amicus Therapeutics Inc (FOLD) 2017 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Amicus Therapeutics First Quarter 2017 Financial Results and Corporate Update Conference Call.

(Operator Instructions)

As a reminder, this conference call today is being recorded May 9, 2017.

I would now like to introduce your host for today's conference, Ms. Sara Pellegrino, Senior Director, Investor Relations. Ma'am, you may begin.

Thank you. Good morning, and thank you for joining our conference call to discuss Amicus Therapeutics' first quarter 2017 financial results and corporate update. Speaking on today's call, we have John Crowley, Chairman and Chief Executive Officer; Bradley Campbell, President and Chief Operating Officer; Dipal Doshi, Chief Business Officer and General Manager of Scioderm; and Chip Baird, Chief Financial Officer. Dr. Jay Barth, Chief Medical Officer, and Dr. Hung Do, our Chief Science Officer, are also here and available to participate in the Q&A session.

On this call we may make forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business as well as our plans and prospects. Our forward-looking statements should not be regarded as 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 presentation and conference call to reflect events or circumstances after the date hereof.

For a full discussion of such forward-looking statements and the risks and uncertainties that may impact them, we refer you to the forward-looking statement on Slide 2 of our first quarter 2017 results slide deck; the Forward-Looking Statement and Risk Factor sections of our Annual Report on Form 10-K for the Year Ended December 31, 2016, as well as our Quarterly Report on Form 10-Q for the Quarter Ended March 31, 2017, to be filed later today with the Securities and Exchange Commission.

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

Great. Thank you, Sara, and good morning, everybody. Let me begin by drawing your attention to Slide #3 in the deck and highlighting the significant progress that we've made in the first quarter of this year toward fulfilling our 5 key strategic priorities for 2017.

So, to begin, we are executing very successfully in terms of our first priority, which is the international Galafold launch. We're tracking extremely well in terms of patient and physician adoption as well as pricing and reimbursement milestones across this country-by-country process in the EU.

Brad in a short while will review the launch metrics in more detail, but, again, let me just state that I'm very pleased to say that as of the end of April we have 101 Fabry disease patients on reimbursed Galafold, with the vast majority from our initial launch country, which of course is Germany. And with the launch very recently initiated in several new countries we are very confident that we can achieve our target number of 300 patients on Galafold by the end of this year.

Our second priority for the year is to submit our Japanese new drug application, or J-NDA. That remains on track for the second quarter of this year in this, in Japan, which is of course the second largest Fabry market in the world.

Third, we hope to establish definitive proof of concept in the clinic for our highly differentiated treatment approach for Pompe disease. We are extremely pleased with the initial positive clinical data that we have previously reported, including biomarkers of disease substrate and muscle damage, in the first set of switch and naive patients that we saw in this study.

We have important data to share in this program in the weeks ahead. We believe -- we continue to believe that our Pompe program, our flagship, home-developed biologics program, will be a crucial driver of shareholder value.

Fourth, we hope to successfully complete our Phase III EB program. With enrollment now complete in that study, data is on track for the third quarter of this year.

And, finally, our fifth priority is to remain diligent in maintaining a strong balance sheet.

So, we hope that these 5 priorities are clear and transparent, and we look forward to updating you on further progress throughout the year. With our 3 lead programs offering a potential $3-plus billion in total revenue and an opportunity to touch and transform the lives, we believe, of more than 5,000 people living with Pompe, Fabry and EB within the next 6 years, we believe we are on track toward building a leading global biotechnology company focused on the rare and orphan diseases.

So with that as an introduction and background, let me turn the call now over to Brad, who is in London, and Brad will highlight the Galafold launch for us. So Brad, please, go ahead.

Thanks, John. Good morning, everybody.

I'll begin on Slide 5 with an update on the same metrics that we've been providing since launch, all as of April 30. As we've said before, the start of 2017 has been all about opening new markets and continuing to drive successful launches in the markets that are open. Today we really want to emphasize that the launch is going exactly as we've outlined, first with the initial EMA approval last year, followed by immediate success with our launch in Germany, and now key achievements with pricing and reimbursement as well as an increased rate of patient growth over the past 2 months.

Turning first to patient numbers, as John highlighted, our most important metric for our early launch, we now have 101 patients on reimbursed Galafold as of April 30, again, a majority of whom come from our initial launch country in Germany. But we've also secured pricing and reimbursement in 11 countries, including 4 of the top 5 EU markets.

And with France and Italy recently converting from expanded access to commercial reimbursement, we also have 2 ongoing expanded access programs in Europe. To support the launch in additional geographies, we have an Amicus footprint either directly or indirectly through partners on the ground in 27 countries around the world.

Overall, we do have an ambitious goal to put 300 patients on reimbursed Galafold by the end of 2017. Let me provide you a little bit more color on how we plan to get there.

As a reminder, on our last call we highlighted that during the first 9 months of launch, from the end of May to the end of February, we had delivered a consistent 5 to 10 new patients per month. With continued momentum in Germany and with success with market access in opening new countries, we've seen an initial uptake in growth during March and April.

Now with the U.K., Italy and France launches getting fully underway, we expect growth to continue to accelerate in the second quarter as these additional large markets begin to contribute meaningfully to our patient numbers as well as to our revenue. I would note that coming into the summer months we do expect the typical European summer slowdown, but then we anticipate that we'll resume our momentum in the fourth quarter, keeping us right on track to achieve 300 patients on Galafold by year-end.

Our patient demographics continue to be encouraging, as well. We're seeing adoption from switch as well as naive patients, which I'll highlight in a moment, and we see a good mix of males and females, classic mutations, late-onset mutations, really a representation of the great utilization across the spectrum of Fabry patients with amenable genetic mutations who meet our EMA label.

As we begin to launch in new countries, we do continue to look to the success in Germany on Slide 6 as a strong predictor of our potential success in additional markets. Let me give you a quick update on where we are in Germany.

Looking at those metrics, we estimate that after only 11 months of launch, we have approximately 45% market share of all treated patients with amenable mutations. This includes a majority of ERT switch patients, but also now a meaningful number of patients who were previously naive to treatment for their Fabry disease. And, again, we think that this trend is consistent with what we would've expected with this launch: an initial adoption from switch patients followed by naive patients who are already diagnosed but chose not to take enzyme replacement therapy.

And, as a reminder, all of these patients and their physicians are newly experienced with Galafold in Germany because we didn't have any clinical trial sites there during the clinical development program. And now with most major prescribing centers having treated patients with Galafold, we believe that this depth of experience speaks to the broad interest thus far for a majority of the top key opinion leaders in that country.

One other important milestone, we've just successfully concluded our price negotiations in Germany. We expect a final price to be effective later in the second quarter, which is aligned with our parity pricing strategy and our expectations for timing. And, again, we think that reporting these indicators in Germany provides a sense of our early launch success, but, as we've said before, as more countries begin to contribute meaningfully to the launch, we don't expect to provide this level of granularity in every country.

However, moving to Slide 7, I would like to highlight some of the U.K. market dynamics to give a sense for how important we think that market will be, as well. In early March we began to promote Galafold in the U.K. following the final NICE publication, and funding will very soon become effective as we reach the end of the statutory 90-day period between final NICE guidance and NHS funding. So initial patients in the U.K. will begin to be reflected in our second quarter patient numbers.

Overall, though, we think there are 3 key factors that strongly position us for success in the U.K. First, we have more than a decade of patient and physician experience there. This is a highly concentrated market among a handful of major centers. The leading KOLs at the largest treatment centers were primary investigators in our 2 pivotal studies and lead authors in our journal publications, and they're currently treating clinical trial patients in extension studies who will soon begin the transition to commercial drug.

Second is the large pool of addressable patients. The U.K. represents the second largest EU market behind Germany. Approximately 450 patients are currently on enzyme replacement therapy treatment. And based on detailed market mapping that we've done and chart reviews, we estimate that amenability rates in the U.K. are actually at the high end of that 35% to 50% global range.

And third is the value of Galafold stated in the NICE recommendation under the HST process. NICE specifically points to the potential benefits of Galafold as well as the cost savings of an oral therapy that foregoes the infusion-associated costs that come with the standard of care.

We think this is a great example of where our parity pricing strategy gives us a great advantage, and together with our strong data package allow us to bring real value to the health care system as we continue to treat more Fabry patients with Galafold. Overall we think that our early market access successes bode well for our discussions in other markets, and we've already seen this play out in key countries like Italy as well as France.

So, turning now to Slides 8 and 9, I'll reiterate our global regulatory strategy to reach even more Fabry patients. The EU approval provided us the gateway to access approximately 75% of the global Fabry market. Europe, of course, is an important region that represents 34% of that global ERT market in 2015, a significant portion of which comes from the EU5. And, as I mentioned earlier, we currently have 2 ongoing expanded access programs.

Outside of Europe we've approved -- received approval and launched in Switzerland and successfully completed 6 additional regulatory submissions, with more to come, including, as John mentioned, our Japanese submission, which remains on track for the second quarter this year.

In the United States, we're continuing to work collaboratively with the FDA on the most expeditious approach to making the Galastat available in the U.S., including our planned intermediate access program, and we will provide an update once our work with the FDA is concluded. And, finally, over the remainder of the year we continue to expect additional expanded access programs to open up in multiple geographies around the world, including the planned intermediate EAP in the U.S.

In summary, we continue to believe that the progress with the European launch to date as well as our global regulatory progress reflect the strength of our data, the significant value of our precision medicine approach, and the unmet need among Fabry patients. We're on track to meet our goal of 300 patients by the end of the year and we remain committed to providing broad access to Galafold for all Fabry patients with amenable mutations.

And for patients with non-amenable mutations we continue to design a novel proprietary Fabry enzyme replacement therapy, co-formulated with migalastat to enhance that ERT activity, so that in the future patients and physicians may have an Amicus treatment option driven entirely by their genotype.

With that let me turn the call back to John to provide a further update on our clinical pipeline. John?

Great, thanks, Brad.

So let me now turn your attention to Slide #10 and then 11 on Pompe disease, and I'll provide a summary of our important Pompe program and where that stands to date. I truly believe that our Pompe program reflects biotech at its best, a highly differentiated combination of our expertise in glycobiology, our patient focus, and a clinical program that's designed to make a meaningful difference in the lives of patients.

Today I'll recap why we believe our treatment approach is highly differentiated based on its design and clinical data to date, and then I'll provide a bit more color on the clinical outcome from the published literature, which we view as a useful benchmark as we look to our data cascade as it continues later this quarter and then into the third quarter of this year.

So just briefly on Slide 11, again to remind everybody, we have developed here at Amicus a highly differentiated approach to the treatment of Pompe disease. It begins with the same base protein that others have developed, which is a recombinant enzyme known as rhGAA with 3 key differences, however. We have developed an enzyme with high levels of mannose-6 phosphate and a focus on carbohydrates and optimal glycan structures. These 2 differences, the mannose-6 phosphate level and the optimal glycans, are designed for efficient targeting of the protein.

Third, we also have the oral co-administration of an Amicus chaperone. Known as AT2221, this chaperone helps to provide a scaffold for the enzyme to remain stable in plasma until it's delivered into muscle cells. So our treatment regimen here in Pompe of the enzyme with chaperone, which we designate as ATB200/AT2221, is indeed very distinct from what others have developed or are developing.

Turning to Slide 12, this is just a reminder of the study design and the 3 patient cohorts. The Phase I/II Pompe study was fully enrolled with 20 patients, including 11 in our first cohort of ambulatory ERT switch patients, 4 patients in our second cohort of nonambulatory ERT switch patients, and 5 naive patients, ERT-naive patients, in this third cohort.

To date we have reported positive safety data in 13 patients across all 3 cohorts in addition to positive PK and biomarker data on 10 patients. That includes data on 8 switch and 2 ERT-naive patients, which I'll highlight on the next slide, on Slide 13.

So what you see here on Slide 13 is a snapshot of the preliminary clinical data that we've highlighted in detail earlier this year at the World Symposium in San Diego in February and also during our full year results conference call in early March. These results reflect initial Pompe patients who were switched from the standard of care, ERT, onto our regimen, as well as the first few treatment-naive patients in the study.

So, as a reminder, we've seen excellent safety and tolerability as well as a distinct PK profile. The improvements in key biomarkers of muscle damage and substrate over the first 18 weeks suggest that ATB200/AT2221, our Pompe treatment regimen, is having a positive effect on muscles in patients who had previously been stable on the standard of care ERT for several years as well as in ERT treatment-naive patients.

So to date we could not be more pleased with the data, and it's certainly very exciting, and we are looking forward to more data from this study in the second and third quarters of this year. And you'll see this outlined here on Slide 14.

So, key opinion leaders as well as many of you on the call today have expressed your enthusiasm for this program. We've spent a lot of time talking to the investment community about these results and why we believe this program is such a crucial driver of shareholder value for Amicus ahead.

We are fully committed to advancing through the clinic as rapidly as possible this program. We continue to invest significantly and scale up the manufacturing now to the 1,000-liter scale, which -- for later clinical studies and for commercial scale. We do that so that we could begin a registration study as soon as possible with our commercial-scale material. We very much believe that this program, again, is critically important first and foremost to people living with Pompe disease, but also to Amicus as a company, and certainly for all of our shareholders.

So, moving now from Pompe, we'd like to highlight some additional detail on our Phase III program in epidermolysis bullosa, or EB, so let me hand the call over to Dipal Doshi, who will provide further detail, our Chief Business Officer and General Manager of our Scioderm business unit. Dipal, please.

Thanks, John.

I would like to review our EB program and our important Phase III ESSENCE study on Slide 16. On the heels of significant momentum, we have completed enrollment with more than 160 patients enrolled. We exceeded our target of 150 patients, and we are on track to report top-line Phase III data in the third quarter of this year from this pivotal study.

And, as a reminder, we have elevated the endpoint of time to wound closure, and we are near final with our statistical analysis plan, or SAP, which is designed to optimize the study for success. We intend to provide more detail once we have formal written agreement from the FDA on our final SAP, in which we will outline what success looks like prior to unblinding and announcing the data.

With the potential to offer a first-in-class treatment, we very much look forward to announcing data from this study, and we continue to be pleased with positive patient participation, with more than 95% of patients completing the initial 12-week treatment period and continuing in the ongoing extension study where all patients can be treated with SD-101. It is our vision that all patients who elected to continue in this extension study can remain on SD-101 until approval, and, indeed, providing continued access to SD-101 in the extension study is a high priority for Amicus and our expanded access policy.

So with that, Chip, let me go ahead and turn it over to you now for the financial overview.

Great. Thanks, Dipal, and good morning, everyone.

Our financial overview begins on Slide 18 with our income statement. In the first quarter of 2017 we recorded product revenue of $4.2 million. This represents an increase of 50% over product revenue of $2.8 million in the fourth quarter of 2016. Total product revenue for both periods represents commercial sales of Galafold in Germany, which commenced in May of 2016, as well as reimbursed expanded access programs, or EAPs.

Moving down the income statement, total R&D expenses for the first quarter of 2017 increased to $30.9 million, as compared to $23.4 million for the first quarter of 2016. The increase here is primarily due to investment in Pompe manufacturing scaleup as well as continued investment in our Phase III EB clinical development.

Total selling, general and administrative expenses for the first quarter of 2017 were $19.1 million, compared to $15.7 million in the prior year period. The increase here was primarily due to investment and commercialization activities related to the international Galafold launch.

Net loss was $55 million, or $0.39 per share, compared to a net loss of $43.7 million, or $0.35 per share, for the first quarter of 2016. The wider loss is attributed to an increase in total operating expenses, and as of March 31, 2017, we had approximately 142.8 million shares outstanding.

Moving on to Slide 19, a few comments on our current cash position and 2017 financial guidance. Cash, cash equivalents and marketable securities totaled just shy of $280 million on March 31, 2017, compared to $330 million at the end of 2016. Total net cash spend for the first quarter of 2017 was $50.5 million. So we are tracking well against our full year 2017 guidance.

And, as a reminder, we expect full year 2017 net operating cash spend of between $175 million to $200 million and full year 2017 total net cash spend, including third-party milestone payments and capital expenditures, of between $200 million to $225 million. We continue to project that our current cash position is sufficient to fund operations into the second half of 2018, and, importantly, through several key catalysts that John outlined previously in the call.

So this summarizes our key financials for the first quarter of 2017. Additional details will be found on our annual report Form 10-K, currently on file with the SEC, as well as our Form 10-Q, which will be filed later today.

I'm happy to address any questions during the Q&A, but for now I'll turn it back to John.

Great. Thanks again, Chip.

So before we go shortly to the Q&A, let me just point out on Slide 1 (sic) [21] here are a summary of upcoming 2017 milestones. Again, this is what we're driving toward. We've reviewed this in detail throughout the call this morning, and this is what we're very sharply focused on, delivering on these objectives, these milestones throughout the course of this year.

On Slide 22 you'll see a snapshot of everything that's going on here at Amicus, so quite a busy time and exciting time at Amicus. We believe all of this together will position us to build a top rare disease biotechnology company.

Today we have 1 commercial product, 2 clinical-stage programs with important data readouts this year, and a platform for future growth that's grounded in strong science, drug development, a patient focus and an expertise in glycobiology and protein engineering. As we sit here today we own the global rights to all of our products and technology platforms.

There continues to be significant -- a significant amount of interest in partnering or licensing full programs and/or certain geographies from a number of parties, which could provide a source of funding, but only if it also provides a better and faster way to get our therapies to patients living with these rare, devastating disorders.

So our vision at Amicus continues to be a very big one: to become a leading global biotechnology company focused on rare and devastating diseases.

So with that, operator, I'll turn it over for Q&A, please.

(Operator Instructions)

Our first question comes from the line of Ritu Baral, from Cowen and Company.

I wanted to ask about how pricing is shaking out in the EU, especially since you are getting naive patients into the mix. One, is there any market that is looking to be significantly different pricing-wise than parity with the ERTs? And as more -- it sounds like more naive patients are going on to treatment. Can you sort of describe the demographic of those naive patients, maybe patient numbers or the geographies, and also how that proportion of patients will factor into your parity argument for pricing.

Sure. I think there were a couple of questions embedded there, Ritu. Let me turn it over to Brad to offer kind of a broad perspective on our, again, our pricing philosophy in Europe and some of the dynamics that we're seeing as more and more countries have now approved Galafold in their respective geography. So, Brad, go ahead, please.

Thanks, Ritu and John. So, yes, all good questions. I would say overall as a reminder we have been very clear about our pricing strategy, which is generally parity to enzyme replacement therapy in each individual country. And so with that pricing strategy we do have the ability in some cases, as was reflected, I think, in the U.K. NICE findings, to give some savings back to the system in the form of the infusion-associated costs that are avoided with an oral therapy. And I could tell you in general, as we've highlighted here today, that strategy has gone quite well. In particular, if you look at the update we gave on now having approved prices in 4 of the 5 EU5 markets, that's 75% of the total EU value in the EU5, and having those come in within 12 months of launch we think is great progress and reflects exactly where we hope to be, which is that the reimbursement agencies see the value that we think our total package brings to them in our value dossier. So overall things are going very well. To your secondary question around naive patients coming in, it's really exactly as we had predicted. The low-hanging fruit are the switch patients, and in most markets those are the ones that are active in the system. They're getting reimbursed for their product. But over time we have already identified that probably in most markets it's 50 to 40% of diagnosed patients actually remained untreated, and that's for a variety of reasons that we've talked about before, but we would very much expect to start to see some of those patients come on to Galafold. And so far that has fit exactly within our parity pricing strategy. So, again, the initial focus is on the switch patients, but we will continue to see in more mature markets, now like Germany, for example, to see a growing number of naive patients come in, as well.

And those first naive patients, do they have any particular common profile?

Only that they are largely diagnosed and untreated, with an amenable mutation. And they have largely followed the demographics that we've seen with our switch patients. So it's males and females, it's late-onset and classic mutations. Some patients have trouble accessing infusion centers. Others should've been on treatment but weren't for some reason. So it's a mix of patient demographics, and it's what we've been saying all along, which is amenability cuts across the spectrum of disease, and the uptake so far has been across that spectrum.

Our next question comes from the line of Tazeen Ahmad, from Bank of America Merrill Lynch.

Mine is on Pompe. So, John, in the prepared statement you had mentioned looking forward to definitive proof of concept for your Pompe program. Can you give us a little bit more detail, and maybe, Hung, can you chime in as well with your view about what exactly should we be looking for both in the 2Q and 3Q data releases in terms of number of patients, and what data beyond biomarkers can we look forward to? Thanks.

Sure, Tazeen, thank you. So, again, just top line let me state -- reiterate that we are extremely encouraged by what we've seen to date in our Pompe program and are certainly very optimistic in the future of this program. And we continue to believe it'll be a crucial driver of shareholder value ahead. Let me just remind everybody again, a 20-patient study. We did on this call give numbers in each of these cohorts. We, again as a reminder, the 18-week study we're looking at plasma PK, safety tolerability, importantly, infusion-associated reactions. In time we'll look at antibodies, as well, pharmacodynamics. And in the extension period at 6 months compared to their baseline we are looking at key measures of functional improvements in these patients. So we're looking at 6-minute-walk test, a number of respiratory measures, including forced vital capacity, other measures of strength. We're not giving detailed guidance right now in terms of what to expect in Q2 versus Q3 except to state that by the end of Q3 we expect all of that data to be there. So, again, this will be important data this quarter, but also important data in the third quarter. Sorry to be a bit vague, but we're not giving guidance in terms of what exactly to expect in the data release this quarter, as that's just now coming in and we're assembling it.

Okay, so would you be willing to make a decision on whether or not to move this forward just on biomarker data, or would you need to see the functional data that you mentioned?

No, it'll be important to see the functional data, absolutely.

Our next question comes from the line of Anupam Rama, from JP Morgan.

Maybe just a quick one on the Fabry ERT. When should we be thinking about sort of the finalization of the cell line development and optimization and moving that program into the clinic? Thanks so much.

Sure, thanks. So, again, to remind everybody, this is our own homegrown biologics program that under Hung's leadership we have developed in our science organization. It is a novel enzyme replacement therapy, again, same concept as in Pompe, same base protein that others have used. However, the carbohydrates that have been added and engineered in the cell line and selected in the cell line are distinct from other ERTs. And, again, in this one we're actually incorporating into the formulation the chaperone migalastat to provide confirmational stability. So that's what the product is. That's completed its preclinical proof of concept. It's been transferred to a manufacturer. There's process development work that's ongoing. I would expect in the second half of this year that we'll be able to provide additional preclinical data proof of concept and then also be able to give guidance on when that would go into the clinic.

Our next question comes from the line of Joseph Schwartz, from Leerink Partners.

I also had a question on the Pompe program. As we look forward to the first clinical data that you'll be reporting, what degree of improvement would you hope to see on the clinical endpoints like 6-minute walk and respiratory function at 6 months in order to feel as if the Phase III program made sense to initiate and was de-risked?

I think you have to divide it in 2 populations, Joe, that we're studying. You have your ERT-naive population, patients who have never received an enzyme therapy in Pompe. And then you have your switch patients, and those are patients, ambulatory and nonambulatory, who have been on ERT for some time. So I think if you look at what others have seen and reported, those have been in the naive population over a period of time from 6 months out to, in some cases, 1.5-plus years. Modest increases in ERT treatment-naive patients. Those generally tend to -- I think that have been reported are in the 25 or so meter range. So that's kind of the bogey, if you will, for the ERT treatment-naive patients. In the switch population, if you look at other studies that have been done, they generally haven't seen improvements. So if you saw stabilization in a switch population, given the profile of these patients and the historical analyses, that could be encouraging. It would certainly be very, very encouraging, and I think a real home run, if you were able to show consistent and large improvements in a switch population and if that was tied to continued improvements in biomarkers. So that's a -- that would be a big home run, and we'll see where the data comes in. Let me -- well, we'll get to it when we report the data, so I'm sorry. Go ahead.

Right. No, that's super helpful. Thank you for that insight. I was just wondering also if there are similar types of bogeys, if you will, on the respiratory function. I think the absolute numbers might be less, and so therefore it's a little bit difficult for me to know what figures would you be looking for for like FVC and MIP.

Yes, you know, FVC I think is much more commonly accepted in practice and by the regulators, certainly, although we're measuring a range of functions, MEP, MIP and others. I think if you look at what others have reported, Joe, they have shown in ERT treatment-naive patients very low single-digit improvement in absolute forced vital capacity over certain periods of time, generally 6-plus months on therapy. In switch populations they tend to be stable to even declining still. So obviously the respiratory measures tend to be much more variable. I think that's what we've seen in the literature and in other studies. So we're studying it. We'll look at it. We'll report the data. So we think it could be very, very relevant, as well, together with the 6-minute walk and other assessments of muscle strength improvement, skeletal muscle strength.

Our next question comes from the line of Mike Ulz, from Robert W. Baird.

Just with respect to the U.K. launch, maybe you can remind us how many patients are on the Galafold extension study and then how quickly you think those patients can convert to commercial therapy.

Sure, Mike. Brad, do you want to go ahead and get that one?

So we haven't given quite so specifics in terms of the number of trial patients, but it's in the single digits in most of the markets throughout Europe. I will say, though, that we're already coordinating very closely with the active investigators in the U.K., and it's really a matter of once the funding becomes available, which is a statutory mandate and is coming up soon here, then to coordinate with the physician that when the patient comes in to then manage the transition between clinical drug and commercial drug. So it does take a little bit of logistics, a little bit of time. But we are already working on that, and we would expect it to add incrementally to the first parts of the launch in the U.K. for sure.

Our next question comes from the line of Salveen Richter, from Goldman Sachs.

First, as Galafold launches in other EU countries, how should we think of the ramp-up in terms of sales through the rest of the year, and do you anticipate achieving a similar market share of about 45% of amenable patients in other countries? I just have one follow-up question. Thank you.

Sure, so those 2 questions, Galafold in the EU, how do we see it rolling out through the rest of this year, and secondly market share. Brad, I'll let you go ahead and (inaudible) both those, please.

Thanks, John. So, yes, for rolling out into additional countries, again, as our pure launch country so far we do look to Germany to say how do we think we'll do in those other launch countries. Each of them have their own individual dynamics, but yes, we would assume that we should be able to do something similar to what we've done in Germany as we launch into other markets. So that's how we expect to get to that 300. If you think about what I offered in the call, what we said earlier this year is we need to see an initial uptake at the start of the year, as some of the smaller markets opened as we gained momentum in Germany. Now we've seen that in the last 2 months. Now, really, with U.K., Italy, France coming onboard, as well as a number of smaller supporting markets in Europe, we would expect that rate to continue again, and that's the rate that gets us on the path to 300, although, again, accounting for what we would expect to see, which is a European slowdown, which is pretty typical. In terms of market share, so, as you've said, we are at 45% of treated amenable patients today in Germany, and, yes, we would aspire to get to that and even more, frankly, over time. We don't at all think that Germany is maxed out in terms of market share. But we do look to that ramp as a good proxy for what we hope to see in other markets.

And just moving on to (inaudible), could you guys provide any color around what a potential statistical analysis plan could look like, and what are you thinking in terms of your powering assumptions, and how are you splitting the alpha between the 2 co-primary endpoints? Thank you.

Yes, so given that we are nearly final, waiting for final FDA sign-off on that, we're not going to comment on any of the specifics until we have that fully agreed to in writing by FDA. I'll just remind you that we've previously stated that FDA is in agreement for us to elevate a previously designated secondary endpoint of time to wound closure to a primary endpoint together with the previous primary endpoint, which is proportion of wounds closed. So that remains the general framework that we're working with, and the exact details of p-values and other statistical measures, we've got our final plan in and hopefully we're on a very good final path here with the FDA, but until that's finally signed off by FDA we can't comment further.

Thank you. And I'm not showing any further questions at this time. I would now like to turn the call back over to John Crowley for any closing remarks.

Great. Thanks, operator. So hopefully everybody gets the sense, a very busy, very active and very successful first quarter, with much more to do yet here in the second quarter and throughout the year. So we know what the plan is, and now we have to continue to execute. So thanks, everybody. Have a great day.

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.