Amicus Therapeutics Inc (FOLD) 2012 Q2 法說會逐字稿

Good day, and welcome to the Amicus Therapeutics second quarter 2012 results conference call. (Operator Instructions). As a reminder, this conference call is being recorded. I would now like to introduce your host for today's conference, Sara Pellegrino. Ma'am, you may begin.

Good afternoon and thank you for joining our conference call to discuss our second quarter 2012 financial results. Speaking on today's call, we have John Crowley, our Chairman and Chief Executive Officer; Bradley Campbell, our Chief Business Officer; David Lockhart, our Chief Scientific Officer; and Chip Baird; our Chief Financial Officer. They are all available to participate in the Q&A session as well. Pol Boudes, our Chief Medical Officer is on vacation this week.

Today's prepared remarks coincide with a slide presentation that is now available on our corporate website at www.amicusrx.com. The slides are located in the investor section under Events and Presentations, right below the webcast link.

On slide 2, we have our reference to forward-looking statements in this conference call within the meaning of the Private Securities Litigation Reform Act of 1995, relating to the business operations and financial condition of Amicus, including but not limited to, preclinical and clinical development of Amicus candidate drug products, the timing and reporting of results from preclinical studies and clinical trials evaluating Amicus candidate drug products, and the projected cash position for the Company.

Words such as, but not limited to, believe, expect, anticipate, estimate, intend, likely, should and could, and similar expressions are words identifying forward-looking statements. Although Amicus believes the expectations reflected in such forward-looking statements are based upon reasonable assumptions, there can be no assurance that its expectations will be realized.

Actual results could differ materially from those projected in Amicus' forward-looking statements due to numerous known and unknown risks and uncertainties, including the risk factors described in our annual report on Form 10-K for the year ended December 31, 2011, and other public filings with the Securities and Exchange Commission. Amicus does not undertake any obligation to publicly update any forward-looking statements to reflect events or circumstances after the date on which any such statement is made or to reflect the occurrence of unanticipated events.

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

Great. Thank you, Sara. Good evening, everybody, and as Sara indicated, we will be using the slides that're up and available to everybody on the call. We got feedback after our last conference call that that was very helpful and hopefully that will be a format we will continue to follow here at Amicus.

So, with that in mind, I'll reference slide number 3 to begin just to give you a sense of the agenda for this call. I will provide an overview of some of the general Amicus corporate highlights, go through that together with the Fabry program. I'll then turn it over to Brad Campbell who will take us through the highlights of the Chaperone ERT program's highlights. Chip Baird, our chief Financial Officer, will go through the 2Q 2012 financial results together with updated guidance for full year 2012. And then, I'll take the call back for some concluding remarks.

So, if I can draw your attention now to slide 4, I'll just provide a couple of updates on Q2 highlights including the very recent development you've seen in the press release we sent out just about an hour ago based on a very recent and very positive Type C meeting interaction with the FDA which we think is going to bode very well for this program. So, we'll provide some more update and color on that, but just generally with our Phase 3 program, we're happy to report that in the second quarter, we completed the 6-month primary treatment arm.

And again, remember this is Study 011, our Phase 3 study for US approval. It's a randomized placebo-controlled study. Again, with a 6-month double-blind primary treatment program. And then, if you'll recall, a 6-month open-label follow-up period.

We are updating our patient disposition today letting everybody know that at the end of that 6-month primary treatment arm, we had 63 of the 67 patients completed. We did have 4 dropouts, none due to any SAEs or any concerns with the drug. They came off for various other reasons, as we expected. It was a lower than expected dropout rate for this study. So, we think another point that would further enhance our likelihood of success here.

So, we end the study with 63 patients. Of those 63 who completed the primary treatment arm, we had a 100% conversion of those patients to voluntarily elect to continue on the study. So, again, half the patients having been randomized to migalastat, half randomized to placebo. Patients blinded, of course, to either.

At 6 months, those patients who had been on migalastat continuing on migalastat. Those patients who had been on placebo, continuing on to -- coming on to migalastat. Again, blinded to that. Very importantly, as part of the protocols for patients electing to continue into this 6-month extension, we do have them consenting to and are collecting 12-month kidney biopsies for these patients. I'll comment here further about the FDA interaction, but again, very encouraging Type C that the FDA is going to allow us to not only compare with the 6-month primary treatment period to placebo, as we've talked about. We knew that they would require 12-month data for -- safety for filing and approval, of course. But based on the Type C meeting, the FDA has indicated that they will look at 6-month data, as we've always planned on. But also, that the FDA would consider not just safety but efficacy at 12-months and the totality of the data.

Again, we remain fully blinded to this data. We do intend to remain blinded. I'll comment a little bit more about that, which will push the unblinding into the fourth quarter. So, a delay on unblinding, but we think will bode very well for the chance of it moving the NDA forward once we do unblind the data.

Again, just move down the list here on Pompe. Our 182220 co-administered with ERT. We reported in the second quarter positive preliminary results in that Phase 2 study, the 010 study. In the first 2 cohorts, cohort 1 and 2, and Bradley will provide an update shortly on where we are in that study, but that continues to move very well for us.

Again, a very strong financial position ending the quarter with $95.8 million in cash and Chip will provide an update to that cash position and full-year guidance here shortly. Certainly having the strong balance sheet giving us the flexibility not only to advance the Fabry program, multiple programs with GSK, but allowing us to invest in the rest of our pipeline, and again, with our restructured arrangement with GSK and expanded collaboration, Amicus now having full US economics for all Fabry products we think will drive significant shareholder value in the years to come.

So, a very busy, a very successful first half of the year for us on many fronts as we ended Q2. And now, we're moving into an equally busy and hopefully equally successful second half of the year based on the expanded Fabry collaboration with GSK. Our transitioning and preparing to become a fully integrated biotech company within the US with commercial operations in Fabry. And again, advancing the core platform technology, especially the combination programs, the ERT plus chaperone programs that continue to advance at a very fast pace for us.

So, those are the highlights. If I could draw your attention then to slide 5, just to remind everybody again what we went through in our call a couple of weeks ago announcing the expanded collaboration with GSK. GSK having increased its investment in Amicus and the Fabry development program for Amicus, of course, transforming us into a pre-commercial stage, US biopharmaceutical company with the intent, upon approval of our Fabry drug, to launch in the United States.

Again, this is three separate Fabry programs and products now being developed with our partners at GSK. The migalastat monotherapy program currently in Phase 3. Again, with Study 011 results now anticipated in the fourth quarter. The co-administration program that's currently in its Phase 2, the 013 program that Brad, again, will provide an update on here shortly. And then, now, the development of a proprietary next-generation enzyme therapy developed with GSK. And of course, that enzyme that we went into some depth about over the last several weeks that we now have access to from JCR in Japan.

So, I won't continue to go through everything that's on the slide to highlight all the benefits of this field, but again, we think this is a not just transformational for Amicus in terms of becoming a commercial company here very shortly, but one that enhances the balance sheet, that validates the technology, and it expands our already strong relationship with our partners at GSK Rare Diseases.

So, turning to slide 6. Again, we have two ongoing studies for migalastat for Fabry disease as a monotherapy. Phase 3 global registration studies. The first being our 011, the US registration study with 150 mg of migalastat dosed every other day. The first 6 months of that being placebo-controlled and the primary endpoint versus placebo being the change at 6 months at the surrogate endpoint of GLC in the interstitial capillary of the kidney. That remains the primary endpoint, of course, in that 6-month primary treatment period.

Again, we're very encouraged that the FDA has indicated that they will consider the efficacy based on the totality of the data including the 12-month biopsies as well. So, we think that gives us lots of ways that we can be successful in this study.

We continue to have great confidence in that study together with the Study 012, which is our global registration study, still the same dose, 150 mg of migalastat given every other day. Again, this is a switching study. So, every patient beginning on ERT Fabrazyme or Replagal. 30 patients then randomized coming off of the ERT, coming on to migalastat. Patients with known responsive mutations. Those 30 patients would take migalastat for the 18-month treatment arm of the study. It is a clinical endpoint comparing that switched group to the 20 patients remaining on enzyme replacement therapy. Kidney function is measured by GFR.

We also expect this study to be our Phase 4 -- fulfill our Phase 4 commitment here in the United States. We remain on target for full enrollment by the end of 2012. Again, very encouraged. We continue to remain ahead of our enrollment curve and projections in that study. And we're still guiding that we'll enroll it by the end of the year. So, hopefully that study will remain on track. We've got every confidence that it will.

As we turn to slide 7, just to reiterate all the reasons why we remain very bullish on Study 011, given the nature of the design. Again, our Phase 2 experience now with more than 150 years of patient data. Those 17 patients from the Phase 2 extension study continue to remain on migalastat are chaperoned as their only therapy for Fabry disease.

Again, the positive results that we've seen on both renal and the urine GL-3 clearance, the key biomarker in the disease, together with long-term trends toward stabilization of the kidney function. All that remains true.

The entry criteria that hopefully we're all very familiar with that was part of patients gaining access to this study. The improved histological methodology, the BLISS methodology developed by Doctor Barisoni just published here recently. One that we think is a more sensitive and more objective advanced measure of the GL-3 inclusion bodies that will be used to gauge the primary endpoint.

And now, from what we continue to learn from our Phase 3 observations, the very low dropout rate in this study and the very high, the 100% conversion rate from patients finishing the primary 6-month treatment period into the 6-month extension arm. So, we think that all bodes well now with this very new data, based on the recent Type C meeting with the FDA. Again, where the FDA has indicated that they will consider efficacy as well as safety for the 6-month and the 12-month endpoints.

So, we think that, again, enhances the likelihood of our moving very rapidly toward an NDA submission for migalastat. And again, to be clear, we are pushing by just a couple of months the unblinding of this data. And the key reason for this is to maintain the integrity of this study. We still have patients who are in that 6-month extension arm. We need to collect the full 6-month extension data, giving us a full 12-month view into these patients' treatment. And with that, we'll be able to have completed all of the biopsies at the 12-month period prior to the unblinding.

We think this could prevent the chance of any bias in the study and is something that we think would be viewed very favorably by the regulators in submitting data with 6-month and 12-month endpoints.

But again, we think we could be approved on that 6-month primary endpoint that we've looked at and talked about for some time now. Together with also having the ability to look at safety and efficacy at the 12-month endpoint.

Slide 8 just shows you graphically again where we are with the low dropout rate and high conversion to the extension studies. Again, 63 patients having completed of the 67 initially enrolled. The end of the study in Q2 and all of those 63 patients rolling into the 6-month extension study. 40 of those 63 having already completed the 6-month extension arm. So, a year of study complete for 40 patients. And of those 40, 38 out of 40 have voluntarily elected to roll into the next year of study. So again, we think at least in terms of drug tolerability and patient compliance, we think that bodes very well for our ability to collect a very robust data set as we look toward hopefully an NDA filing.

So, with that overview and some more detailed commentary that I just provided in the Fabry program, let me go ahead and turn it over to Brad who will take us through our innovation continuum with the ERT chaperone combination technology and an update on some of the Fabry and Pompe programs.

Great. Thanks, John. Good evening, everybody. So, as John stated, our vision is to use the chaperone ERT combination platform to create better therapies for patients with the lysosomal storage disorders along this continuum of innovation, which is outlined for you on slide 9.

So, we're really focused on solving these broader issues with the ERTs to address the unmet needs that're still unique to each LSD. Our top priority is to improve efficacy and potentially reduce the immunogenicity by combining ERTs with our specific pharmacological chaperones.

So, the first step here has been our chaperone ERT co-administration work where we've already demonstrated positive preliminary results from Phase 2 studies in both Fabry and Pompe. And the next step along the continuum is the direct combination of our chaperones co-formulated with proprietary next-generation ERTs, which we're already doing in Fabry and I'll touch on a little bit later. And as John mentioned, we've already begun to explore in Pompe and other LSDs as well.

So, the overall goal here for both co-administration and co-formulation is to stabilize the enzyme, keep it in its active form, and increase the uptake of active enzyme into key tissues of disease. In the case of co-administration, the chaperone is orally administered just prior to ERT to bind to and stabilize the ERT in circulation. With co-formulation, the chaperone is combined with the enzyme to keep it stable from the beginning.

So now, let me go into a little bit more detail on how we've been validating this platform through each of our chaperone ERT programs. Let's move to slide 10. I'll go through a little bit more detail on both the Fabry Study 013 and the Pompe Study 010.

So, just a reminder, while our monotherapy studies are investigating an oral every-other-day dosing regimen to chaperone a patient's own endogenous enzyme, our co-administration studies are using the chaperone delivered just prior to the ERT infusion to improve the stability of the ERT while it's still in the circulation.

So, for each of these studies, patients will be compared to themselves at two subsequent ERT infusions. Patients come in, receive ERT alone, and then, come back just prior to the next infusion. They receive a single oral dose of the chaperone. Both studies are designed to evaluate safety and whether the presence of the chaperone increases active enzyme in plasma and in key tissues for skin for Fabry patients and muscle for Pompe patients compared to ERT alone.

So, as a reminder, earlier in the year, on the left-hand side here, we released positive preliminary results from the first two cohorts of the Fabry Study 013, which is the Phase 2, open-label study of migalastat co-administered with ERT for Fabry Disease.

Now, we're completed the cohorts with migalastat 150 mg co-administered with Fabrazyme or Replagal. And also, migalastat 450 mg co-administered with Fabrazyme. The cohort on migalastat 450 mg co-administered with Replagal is ongoing. And a poster with additional results from the study has been accepted for a fall 2012 scientific conference.

More recently, during the second quarter, on the right-hand side of the chart here, we announced results from the first two dose cohorts from the Pompe Study 010 evaluating our chaperone AT2220 co-administered with Myozyme or Lumizyme. And recall that among all 4 patients in Cohort 1 and all 6 patients in Cohort 2, we saw increases in active enzyme compared to ERT alone in the plasma.

So, at this point, in terms of how that study's progressing, we fully enrolled 3 out of the 4 ascending dose cohorts. A few weeks ago, our independent DSMB gave us the go-ahead to move into Cohort 4. And now, we're enrolling patients in this highest and final dose cohort of AT2220, and we continue to expect final enrollment and full results from all four cohorts by the end of 2012.

So really, importantly significant progress in moving forward with both of our Phase 2 co-administration studies with several important milestones and additional data expect for both programs later this year.

As we previously discussed, there are really differing degrees of unmet need across the group of lysosomal storage disorders that we're focused on. For Pompe disease in particular, remember that immunogenicity is a significant issue, where immune responses occur in a majority of Pompe patients receiving Myozyme infusions which have the potential to limit treatment outcomes with this ERT.

So now, I'd like to turn your attention to slide 11, and here, I'll turn it over to David who's going to comment briefly on some of the preclinical work that we're doing to better define the ERT-related immunogenicity. David?

Hello, everybody. I'm going to introduce you quickly to a new type of assay that we're using to look at the immunogenicity of Myozyme and Lumizyme. It can also be used for other protein therapeutics as well.

We have done, previously, studies in animals. And, of course, there's the issue of using a human therapeutics protein in animals to try to assess immunogenicity and there are shortcomings to that sort of approach.

So, instead, and to complement the animal work, we're using a new type of assay that looks at a T-cell response in cells derived from human beings with different HLA types. We're also supplementing a panel of 50 cell lines derived from healthy volunteers with a sub-cell line derived also from Pompe patients.

And so, if you look at the graph, this assay has previously been used to look at existing human therapeutics and what it's found is that the clinical immunogenicity on the X-axis, that's the percentage of patients who received these different drugs that develop antibodies. And then, on the Y-axis is the output from the Episcreen Assay which measure the T-cell response in terms of proliferation of T-cells and the cytokine secretion profile.

You can see on this plot that, overall, there's a good correlation between what's observed in this ex vivo assay using human cells but outside the body and the antibodies that're actually seen when patients are given the different drugs. And some of the drugs here you'll recognize. Herceptin, Avastin, interferon-alpha and -beta, and so on.

The correlation with other human therapeutics has been good. So, we decided to use this assay also with Myozyme and Lumizyme and later with other LSD ERTs as well. You can see that -- what we've seen so far is that we are seeing that Myozyme elicits a strong T-cell response consistent with the high antibody response that is seen in many Pompe patients. We will be able to correlate this T-cell response with the HLA types, with the observed IgG titer, the antibody titer that's seen in the patients, and also with the GAA genotypes. We'll be able to see which of these things are predictive of an antibody response to Pompe ERT, and most importantly, which of these things can be reduced in the presence of AT2220.

The preliminary results are already looking promising. That was with a smaller panel of cells. We're now using the full 50 healthy volunteer panel. As I said, we're supplementing that with a unique panel that we've derived from the patients in our Pompe clinical studies.

We'll have more of these data in Q3 and also be presenting these data at various scientific conferences. This looks very promising so far.

Let me just bring your attention to slide 12 before I hand it back to David to review a little bit of data. This is a high-level slide, but we really want to make sure we highlight our expanded relationship with GSK and their partner JCR.

Remember JCR is a Japanese biologics company with over 20 years of developing and commercializing recombinant proteins. As part of this expanded relationship, we now have the ability to develop our co-formulated chaperone ERT product, which is moving rapidly through preclinical development.

We're not going to spend a lot of time here because we covered this in great detail when we announced the expanded collaboration earlier. However, let us now turn to slide 13 and just provide you a quick reminder of why we're so excited about the development of migalastat co-formulated with JR051 as a proprietary next-generation ERT. Again, I'll turn it over to David to review the data.

I'll do this very quickly because we showed these data on our last conference call. But these data showed that when Fabry mice, these are Fabry knock-out mice, when they are treated with a single administration of JR051 co-formulated with migalastat, with a 30-minute infusion -- mimicking the infusion situation that is followed for Fabry patients -- we've been able to measure an increase in the circulating half-life, which we've shown before. We've been able to measure increases in uptake of the enzyme in the key tissue, which we've shown before. What's shown here is the reduction in the storage material, GL-3, in both the heart and the kidney.

So, if you look at the darker blue bars, you can see that if you just give 1 mg per kg or a medium dose of JR051 compare that to what's seen with Fabrazyme, there is a reduction in both the heart and kidney. If you do exactly the same experiment but with JR051 co-formulated with migalastat, you can see the light blue bar next to it, that there is a significantly greater reduction in the amount of GL-3. Again, this is only after a single co-formulated infusion.

So, that looks very promising. Clearly, the small molecule is making it so there is more activity from the enzyme and there's more activity where it matters and in a way that matters. Mainly, in the heart and kidney and that results in a reduction in the storage material. And in lysosomal storage diseases, the main job of the therapy is to reduce the storage material.

If you go to the right, we figured that it would be possible to do even better by giving more of the enzyme, not just stopping at necessarily the doses that had been used in previous studies with Fabrazyme or Replagal. But to go to a higher dose of JR051. And then, to combine the higher dose of JR051 with migalastat. You can see that the higher dose of JR051 on its own does a better job at reducing the GL-3. So, that's very encouraging. The best job of all was with the higher dose of JR051 in combination with migalastat.

You can see in the heart, even after only this single co-formulated infusion that the levels are nearly back down to wild-type levels. In the kidney, where the GL-3 reduction is always the most difficult, it's never been shown that the GL-3 levels can be brought back down to wild-type levels. But with the higher dose of JR051 plus migalastat, it's closer than it's ever been observed before getting to within about 25% of the wild-type levels.

So, very encouraging and this is something that we are going to continue. I should remind you that as part of the Fabry program, immunogenicity is also important. So, we'll have more to say about that in the future as well. So, it' snot only boosting the activity of the enzyme, reducing the substrate even further, but also, reducing the immunogenicity. That's important for both Fabry and Pompe.

Back to Brad.

Great. So, let me just close up the program update section by saying that we are extremely pleased with the progress we've made and encouraged by the data we've generated so far. The goal now is to really look to rapidly advance the co-formulated chaperone ERT products as the next-generation therapy along the continuum of innovation.

So, with that, let me turn the call over to our Chief Financial Officer, Chip Baird, who will review the financial results for the second quarter and full year 2012. Chip?

Great. Thanks, Bradley, and good afternoon, everyone. I'll start on slide 14 by reviewing our second-quarter 2012 financial results for the three months ending June 30, 2012.

Alternatively, these results appear in Table 1 of the press release we issued earlier today. Additional details can be found in our 10-Q, which will be filed later on today.

So, for the quarter, total revenue was $10.7 million compared to $4.0 million in the prior period. Our total revenue consists of research revenue and collaboration milestone revenue recognized under our collaboration with GSK for migalastat.

Research revenue for the second quarter 2012 was $5.5 million up from $2.4 million in the year-ago period. That increase was due to a higher reimbursement rate from GSK for shared development cost for migalastat, which is 50% in 2011 and 75% here in 2012.

As a reminder, each quarter, GSK reimburses us for the portion of our actual spend that exceeds our obligations. Amicus and GSK reconcile each party's spent from migalastat program on a quarterly basis to ensure that the costs are shared in accordance with the arrangement. Under the arrangement, research revenue is expected to fluctuate quarter to quarter relative to the proportion of total migalastat expenses and the percentage we're responsible for paying under the agreement.

Moving on, collaboration and milestone revenue for the second quarter of 2012 was $5.2 million compared to $1.7 million in the year-ago period. This was higher based on milestone revenue of $3.5 million recognized during the second quarter of 2012.

Collaboration revenue in both periods reflected the recognized portion of the $33.2 million upfront payment received from GSK upon signing the agreement back in 2010. This upfront payment is being recognized on a straight-line basis.

Total operating expenses in the second quarter of 2012 were $20 million, an increase from $18.8 million in the prior-year period. The total operating expenses consist both of research and development as well as general and administrative expenses.

R&D expenses for the period were $13.8 million including $921,000 of stock-based compensation expense. This compares to $11.6 million in R&D expense including $651,000 of stock-based compensation expense in 2011. The year-in-year increase in R&D expense was primarily attributable to higher contract research and manufacturing cost within the Fabry program.

G&A expense for the second quarter of 2012 was $5.8 million including $836,000 of stock-based compensation expense. This compares to $6.7 million of G&A expense for 2011 including $3.2 million of stock-based compensation in the prior-year period.

The decrease in the second quarter 2012 expense was due to a decrease in stock option compensation expense versus the year-ago period.

Moving down to P&L, non-operating income expense consists primarily of the change in valuation of the warrant liability, which is a non-cash expense along with interest income, interest expense, and other miscellaneous items. In the second quarter of 2012, we had a non-operating income of $4,000. That compares to non-operating income of $2.1 million in the second quarter of 2011. The change between the two periods is due to the change in the valuation of the warrant liability.

As a reminder, warrants were issued in connection with our March 2010 registered direct offer in common stock and were recorded as a liability at their fair value on the issuance date. The fair value of these warrant increases or decreases with the change in our stock price.

Net loss attributable to common shareholders for the three months ended June 30, 2012 was $9.3 million or $0.20 per share compared to a net loss of $12.6 million or $0.37 per share for the same period in 2011. Weighted average of common shares outstanding were 46.9 million and 34.5 million for the three months ended June 30, 2012 and June 30, 2011, respectively.

If everyone can turn to slide 15, I'll update you on our cash position and our full-year 2012 operating expense guidance. Our cash, cash equivalents, and marketable securities as of June 30 totaled $95.8 million compared to $56 million at the end of December 31, 2011.

With the strengthening of our balance sheet in the third quarter of this year through the $18.6 million equity investment from GSK as well as the receipt of a $3.5 million milestone payment, we expect to end the year with more than $90 million in cash, cash equivalents, and marketable securities.

We anticipate that this cash will be sufficient to fund our current operating plan beyond 2013. We continue to expect full-year 2012 operating expense within the upper end of the previously guided range of $37 million to $43 million, net of anticipated cost-sharing related to the GSK collaboration.

As a reminder, GSK's responsible for 75% of the development cost for migalastat monotherapy and co-administration in 2012. During the second half of this year, GSK will also begin investing in 60% of the development cost for our chaperoned ERT co-formulated product. However, that's a program that's currently in preclinical development. These costs are not expected to be material to Amicus for the remainder of the year.

As we mentioned in our conference call a few weeks ago, we're committed to building a commercial infrastructure using a stepped-up approached triggered by key de-risking events. So, we're looking to see positive results from our Phase 3 Study 011 of migalastat monotherapy prior to committing significant resources towards the commercial launch.

This summarizes our key financials for the second quarter and the full-year 2012. I'll also be available for the Q&A session if there's additional questions on any of the numbers here. With that, I'll turn things back to John.

Thanks, Chip, and Brad, and David. So, hopefully you get the sense that the activity here remains at Amicus. On slide 16, I'll just summarize some of the key activities, the checkmarks you see in Fabry, Pompe indicate the milestones we've already delivered on.

And again, to summarize for the Study 011, it is a change in guidance from Q3 to Q4. However, it's based on the encouraging Type C guidance that we've received from the US FDA. Again, this will allow the last patient to complete the 6-month follow-up period of the study and will allow us to collect that complete data for all 63 patients prior to the unblinding.

So, we think this will provide for an even more robust data set and further increase the likelihood of a successful NDA filing. Again, we remain extremely encouraged now that we've completed the primary 6-month treatment period and have seen 100% conversion. 63 of 63 patients completing the primary 6-month period moving now into the voluntary 6-month extension arm.

So, all of this taken together, we think, is a positive for Amicus. We like the FDA's indication that it will consider efficacy as well as safety data at both the 6-month and 12-month periods. We think all of this is a great example, too, of our strong working relationship in our Fabry program with our partners at GSK. We will look forward to all the data that will come in Fabry. Very encouraging. And likewise, in Pompe, that program, that combination study moves forward together with the results on the immunogenicity studies that David highlighted for us as well.

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

Thank you, sir. (Operator Instructions). Anupam Rama, JPMorgan.

In your Type C meeting with the FDA, did you have a chance to share any of the Phase 2 extension data? And if you did, to what extent did those data have influence in the FDA accepting 12-month safety and efficacy endpoints?

We certainly kept the FDA up to date, Anupam, on all of the data that we've collected in that extension study. It's been made public, of course. So, it was available to FDA. I think that is one piece of the puzzle.

Certainly from a safety standpoint, the drug continues to have an excellent side effect profile. In terms of the encouraging trends that we've seen in kidney and renal function, we think that's very positive as well.

We think, too, that while we're very confident in hitting the primary endpoint and seeing the appropriate P-value compared to placebo at the 6-month endpoint, we do know from our Phase 2 studies that at 12-months, you saw even further GL-3 clearance in the patients who remained on migalastat.

So, that taken together leads us to believe that it could be an even more robust data set at 12 months that could enhance the whole NDA package and hopefully make it a smoother NDA process. So, for all of those reasons together with GSK, we thought it was a wise investment to wait a couple of months on the unblinding.

Did you talk to any physicians about sort of the advantages of having a 12-months safety efficacy data in the label and what market implications this may have?

We haven't yet discussed that with physicians in designing the study. We did get significant feedback from physicians that 6 months would be an appropriate period compared to placebo to see a change. Obviously, more data over a longer period of time, we think, will give further confidence to physicians in prescribing this drug.

So, certainly, we think it could also not only enhance the NDA but our ability to effectively compete against other products in a market place.

Ritu Baral, Canaccord.

Forgive me, I dropped off for a second because of the signal, but could you comment on whether the FDA might accept positive statistically significant (technical difficulties) approvable endpoints to the (technical difficulties). What was your sort of general impression on that scenario from your discussions?

Yes, I think -- you cut out a little bit there, Ritu. Let me just rephrase it and make sure I heard the question correctly. I think you were saying that if we were to miss statistical significance, the P-value, at 6-months versus placebo, would the FDA consider filing on the efficacy data at 12-months. At which point, of course, all of that is going to include data for people who have all been on drug. Is that the question?

(technical difficulties)

You cut out again but I think that's what your question is.

Yes.

So, yes, that's very much -- and that's the primary rationale for waiting for unblinding and why we think it's very encouraging, the feedback from the FDA on this Type C guidance, that they would consider approval endpoints based on the 6-months data. And then, presumably, if we were to miss at 6 months, that they would consider the totality of the data in the full package based on 12-month efficacy.

So, that's why we're very encouraged by the feedback and why we are taking the couple of months extra to unblind the study to make sure that the data has the highest degree of integrity possible. For instance, preventing any potential for bias in the analysis period from the unblinding to last patient out of the 12-month period.

Ritu, this is David. If I can just add that the assessment is always based on the totality of the data. The nice thing about having the data at 12 months is that for roughly half of the patients, then, we will have data at both 6 months and 12 months. And then, for the other half of the patients who had been on placebo for the first 6 months, we will have 6-month treatment data for them.

So, the data package at 12 months is substantially larger. As people who believe that the drug actually does what it's supposed to do, we believe that works in our favor.

Again, we're encouraged by this. I think it is an expression of enhanced flexibility from the FDA that I think comports with the spirit and letter of the new guidelines you're seeing in PDUFA V regarding innovations in rare diseases and accelerating approvals in rare diseases. So, we again think it's very encouraging.

Joseph Schwartz; Leerink Swann.

I was just wondering if we could continue on that line of thought and maybe you could expand a little bit on why do you think the FDA is now focused on 12 months versus 6 months and what was different in those meetings versus your prior interactions with the FDA.

Just to be clear. It's not the FDA is now focused on 12 months and not 6 months. The FDA is still very interested in the 6-month data. To be very clear about this, the FDA has not said that they will look only at the 12-month efficacy for approval. It's that they will consider both the 6 month and the 12 months. So, to Ritu's prior question, to frame it that if, for some reason, we didn't reach statistical significance at 6 months, that we would also have a fuller data package at 12 months.

So, I think that's a very important -- that's why it's such an added advantage, we believe, and why it weighs heavily in favor of holding off a few months on the unblinding so that we can continue with the full data package to those 63 patients.

Remember, the primary efficacy endpoint is still the effect at six months during the placebo control period. That is the primary efficacy endpoint. So, what John is saying and what the FDA was saying is that there is a more complete data package at 12 months. Typically, the FDA likes to see safety data for a chronic disease treatment. They like to see safety data for 12 months.

So, that's something that we had always expected, but the primary efficacy endpoint is still the 6-month data. You can think of the 12-month data as being supportive, secondary. Of course, there will be the full 12 months of safety data across all of the patients.

Again, it will be a very robust data set that we'll have.

Thank you for the clarification. Could you explain to us a little bit more about why GSK returned the US rights to migalastat. And now, how you'll be addressing the commercialization there given it's still not too far away?

Again, to be clear, they didn't return the US rights. This was a comprehensive extension of our deal, Joe, where they bought up their equity in the company, of course, investing another nearly $20 million in the equity investment. We agreed to advance the next-generation proprietary ERT. They contributed the ERT to that collaboration. We contributed the chaperone component. We did acquire the US rights in the expanded collaboration here.

Again, the rationale is that there was significant value. We did give up our rights to milestones and royalties. So, very significant value that was exchanged here as well. In addition, throughout the relationship in the last year and a half, I think GSK has grown increasingly confident in Amicus's ability to utilize our experience in scientific and medical affairs and patient advocacy to lay a foundation for the commercial infrastructure.

Again, with that, give Amicus independence of pricing in the United States. So, for all of those reasons, I think it made very strong strategic sense, certainly for GSK as well as for Amicus to extend and expand the collaboration. Does that answer the question, Joe?

Yes, I think that's very helpful. Thank you. Just one more if I could ask another. That would be could you remind of us your patent position on migalastat and are you planning on expanding beyond those that have been granted? For example, could you patent the pharmacogenomic look-up table? At what point in the patent process is that? What would that add to the lifecycle?

Sure. So, we have issued patents around the method and use of pharmacological chaperones that we've talked about here. Those are issued from what we licensed from Mount Sinai. With further extensions, that will take us into the early 2020s on that. In addition, we have the protection of the Orphan Drug law in the United States of 7 years of exclusivity.

We do have manufacturing patents around the process and scale up that are pending. We've also filed certain other patent applications that we believe have the potential to further extend beyond the method and use patents that we would have.

We are also looking to, for instance, what you indicated, Joe, the pharmacogenetic look-up table. Other unique aspects that were unintended or unforeseen as we began the research that we think could be incorporated into the label that could significantly enhance the intellectual property of the program.

But typically, oftentimes in these orphan spaces, you just see the protection of the Orphan Drug Act. We think we have that and quite a bit more. So, we've built a very significant series of patents and a strong patent strategy around the program. Not just in Fabry, but broadly for what we're working on here.

Two other pieces. This is Brad. Two other pieces of color there. In addition to what John mentioned, have also filed dosing administration patents that go later into the 2020s, 2027 and 2029. Remember, too, through combination therapy, that extends the patent life as well.

So, for example, co-formulation patents, which we're filing now, we expect to take at least to 2033. So, a significant patent portfolio built around the monotherapy first. And then, extending out all the way into the 2030s.

It would seem as if you've added a lot to the arc. So, that's good to hear. Thank you.

Yes, we spend a lot of time and a lot of money, quite frankly, on patent development and patent prosecution.

Kim Lee, ThinkEquity.

I just wanted to delve a little more into your conversations with the FDA. Can you give us a little more color on who actually suggested the 12-month efficacy and safety data analysis? Was it the FDA who brought that up or you brought that up? What do you think the FDA saw in your data set so far that would lead them to possibly want to see 12-month efficacy data?

Again, to be clear, we, and GSK, and everybody remain completely blinded to the 011 study. So, the FDA didn't see anything in that. What the FDA has seen is the long-term extension study data that continues to have encouraging trends in renal function together with all the histological measures.

They've, of course, looked at the BLISS methodology in the recent BLISS publication. The FDA, and GSK, and Amicus, I think, were very pleased with the low dropout rate in the study and the high conversion past the primary endpoint, which is at 6 months and remains at 6 months in the study. And saw the ability to get a very robust data set because of that high, 100%, conversion rate in patients in that second 6-month period. So, a full year of data.

I think all of that taken together. We've always expected that we would have some added data at 12 months. Certainly for safety purposes, but actually now, being able to look to 6-months and/or 12-month efficacy for approval we think is a great benefit to this program. Especially since we didn't have to wait a full 6 months further for unblinding. It is just a couple of months delay in unblinding. Does that make sense, Kim?

Yes. No, I appreciate the clarity. If I may, one last question for Chip. Can you tell us, you've given the weighted average common shares outstanding. Can you give us the exact shares outstanding for this Q2?

Yes, at the end of 2Q is 46.3 million shares outstanding.

Thank you. This does conclude our question-and-answer session. I'd like to turn it back to management for any closing remarks.

Great. Thank you, Operator, and I think that was a good call. Hopefully a lot of updates and some added color. Hopefully even more confidence in our lead program in monotherapy for Fabry disease. Also, hopefully folks get the sense that all of the technology and programs at Amicus continue to progress together with a very strong balance sheet.

So, we're excited about the second half of the year and very excited to see more and more data in all of these programs. So, it'll be a busy 5 months coming up. Great. Have a good night.

Thank you, ladies and gentlemen, for attending today's conference. This does conclude the call. You all may disconnect and have a good day.

Great. Thank you.