Amicus Therapeutics Inc (FOLD) 2013 Q1 法說會逐字稿

Good day ladies and gentlemen,and welcome to the Amicus Therapeutics first quarter 2013 results conference call. At this time all participants are in a listen-only mode. Later we will conduct a question and answer session, and instructions will follow at that time. (Operator Instructions). As a reminder, this call may be recorded. I would now like to introduce your host for today's conference, Sara Pellegrino, Director of Investor Relations. Ma'am, you may begin.

Good evening, and thank you for joining our conference call to discuss Amicus Therapeutics first quarter 2013 financial results. Speaking on today's call we have John Crowley, our Chairman and Chief Executive Officer, and Chip Baird, our Chief Financial Officer. Bradley Campbell, our Chief Business Officer, and David Lockhart, our Chief Scientific Officer, are also on today's call and available to participate in the Q&A. Today's prepared remarks coincide with the slide presentation that is now available on our corporate website atwww.amicusrx.com. The slides are located in the Investors section under Events & Presentations, right below the webcast link to today's call.

Turning to slide two, you will find a reference to our Safe Harbor statement. This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, relating to business operations and financial conditions of Amicus including but not limited to, preclinical and clinical development of Amicus candidate drug products, the timing and reporting of results from clinical trials evaluating Amicus' candidate drug products. Words such as but not limited to, look forward to, believe, expect, anticipate, estimate, intend, plan, would, should, and could, and similar expressions or words identify 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 on our Annual Report on Form 10-K for the year ended December 31st, 2012. All forward-looking statements are qualified in their entirety by this cautionary statement, and Amicus undertakes no obligation to revise or update this presentation to reflect events or circumstances after the date hereof.

With that, it is my pleasure to turn the call over to John Crowley, Chairman and CEO of Amicus.

Great, thank you Sara, and good evening everybody. As you see on slide three, I will go through the first two sections here. The update on the Migalastat monotherapy program for Fabry, as well as the Chaperone ERT Combination Programs, then turn it over to Chip to go through the details of Q1 financial results, and then I will come back and handle the milestones, and certainly as we always do turn it over to the Q&A.

Let me just begin by commenting, that as you see the first quarter really was one where we focused on execution. Primarily the clinical operations execution for Migalastat monotherapy, as well as the regulatory strategy and interactions around Migalastat monotherapy as well. You saw from the press release that we issued, that we have a type C meeting now scheduled an in-person meeting with the FDA this quarter. That meeting has not yet occurred. Although the briefing documents have all been submitted to the Agency.

And again with the CHART program as the Company continues to evolve more and more in addition to our monotherapy program toward developing these programs, multiple programs using the CHART or Chaperone Advanced Replacement Therapy platform technology. The goal here of course is to develop next generation proprietary enzyme replacement products for the lysosomal diseases and potentially beyond. So that is the overview of what we are going to cover.

Let's go ahead and please turn to slide four, and again this is here for reference. I will be providing some more specifics around these studies as well. As we know that we have two Phase III studies for monotherapy in Fabry disease. Study 011 and Study 012.

Study 011 is an ongoing Phase III study looking into the use of migalastat given 150 milligrams every other day compared to placebo in patients with Fabry disease. It is a 12 month study. As you know, we have taken earlier, or late last year a look at the interim six month data or the Stage 1 data. That has been announced. It has been presented at the World Meeting back in February, and we are reconfirming again on this call, that the 12 month data is anticipated in Q3 of this year, and this is a study intended to support the US registration.

The original statistical analysis plan for this study at six months was a yes /no responder analysis, and again that was looking at the number of patients who had a 50% or greater reduction in the interstitial capillary GL-3. The 6 month interim data set favored Migalastat versus placebo, but did not achieve statistical significance. We presented back in February at the World Meeting some further detail through a platform presentation at that meeting. It showed a wider separation from placebo in the patients who had higher levels of the interstitial capillary GL-3, notably those with 0.3 or above inclusion bodies.

This was an important analysis we think for explaining what happened, and why we got above the noise of the Bliss methodology on this histological measure. It was however a post hoc analysis, it wasn't predefined, and it was in certain sub groups of patients. We do think it is very important in understanding the mechanism of action, how the drug is working, and we think very clearly showing in patients for whom there is measurable levels of the GL-3 substrate in the interstitial capillaries of the kidney, what is actually truly going on, and we think speaks to the effect that the drug is having.

As we move forward with the further analysis, we had also presented originally, and continue to evaluate what was a prespecified secondary analysis of this primary, and that was looking at the overall burden of GL-3 in the kidney as a continuous variable in the same sub type. Again we didn't separate out any patients. It was all patients. 30 placebo,30 active group, and there we came very close to achieving statistical significance, even on this interim analysis. Where we showed a median 41% reduction of the GL-3 in the migalastat treated group versus 6% in placebo. The P of 0.093 and again, this captured all patients with any level of GL-3. So no subgrouping whatsoever.

Again to remind you, we did see and this was presented at the World Meeting, a trend encouraging in terms of kidney function as measured by eGFR favoring migalastat over placebo and again we continue to see a very strong safety profile for this drug with no drug-related SAEs,No withdrawals related to NAEs. So that is where we have been. We have spent quite a bit of time, and spent an enormous effort at Amicus together with our partners at GSK, to look at this data in great detail, to go back to review all of our Phase II data. We brought in quite a few consultants to help us with some expertise in areas like, biostatistics, for instance.

Now that we have the FDA guidance that they will consider the risk benefit analysis of this drug, and the totality of the data, we have been thinking quite a bit in preparing for, and want to ask the FDA's guidance in terms of what would define the totality of this data, and what are the key areas to look at. So as we get ready for the 12 month data in Q3 we are here today still being blinded to that data, both Amicus and GSK. The 6 month data is what it is, and we think it is very6 very encouraging, and we think it gives us based on our Phase II experience, good reason to believe that for the group treated with placebo at 6 months, that crossed over to migalastat, those patients with response limitations, we would expect to see a drug effect, and further reductions in their GL-3. For those people who in the Stage 1, the interim analysis who were treated with migalastat for the first 6 months, at 12 months we would hope to see based again on our Phase II experience, that the effect of the GL-3, or the effect of the drug on the GL-3 would be to see a persistent and durable effect and a greater level of GL-3 reduction. Those are the key things that we are looking for.

We set about to ask a couple of months ago the FDA for further guidance. We requested a Type C meeting. The FDA granted that request. They didn't have to. The FDA also granted that as an in-person meeting, again to take place this quarter. It has not yet taken place. It is one where we expect to be able to add to our statistical analysis plan, not take away from, and further define what is going to be success at 12 months, so we can communicate that to all of our interested outside constituencies. So the key purpose of this meeting really is to allow us to get feedback from the Agency on how we plan to analyze the totality of the data at 6 months, and if the data looks consistent with what we hoped for, and again based on Phase II, to allow us to move forward very quickly toward a preNDA meeting in the second half of this year. And again, we continue to expect this topline data in the third quarter of this year. So that is where we are with the Type C meeting.

As we look at the migalastat monotherapy program, it is very clear to us we have a couple of important gates to get through. This Type C meeting this quarter. The 12 month data release in the third quarter. Assuming we are good on those two gates, we would then move in the second half of this year toward the preNDA meeting. So very important points for the Company. Very important points moving forward with this 011 Study, as the study for the basis of regulatory approval, again seeking conditional approval on a surrogate endpoint likely to predict clinical benefit. So that is where we are with the monotherapy.

I will remind you we do have a second Phase 3 study, the Study 012 that is an ongoing study. It like Study 011 also overenrolled. We were targeting 50 patients, 60 patients came in. In terms of what do we know today. We know of those patients 36 randomized coming off of ERT completely and switching to migalastat monotherapy, 24 patients with a randomization schedule remained on the ERT product either Fabrazyme or Replagal. That is a study with a clinical endpoint, looking at kidney function measured by iohexol GFR. Patient compliance to date in that study has been excellent, and we expect that data in the second half of 2014.

So lots of progress with the analysis of the data in the 011 Study in the first quarter of this year, the development of a very strong regulatory strategy, the early interactions with the FDA. The preparation of the briefing document. The submission of the briefing document , and now this Type C meeting here in the second quarter. So that is where we are with our monotherapy program.

If we could move to slide five, and we will talk just a little bit more about the co-administration programs. Again an increasingly important part of our pipeline, the focus of our activities, and we think a very important part of value creation for our shareholders going forward. So the Fabry co-formulation study again, this is using the enzyme that has been developed by JCR Pharmaceuticals and partnered with GSK. This was the basis of our revised and extended agreement last summer with GSK, and it is great for us as we sit here looking to this as an IND planned for the end of this year, and we are still on track for that. And entry into the clinic in early 2014.

This was an idea first just over two years ago that we proposed to JCR and GSK, that led to a series of preclinical studies, and now that drug is in very advanced development, again scaled to 2,000 liters, and one intended, a product intended for patients that are non amenable to migalastat as a monotherapy. So for that part of the population that still would need to take enzyme replacement therapy as their primary treatment for Fabry disease, we think that this could be a very, very good option for those patients. Again, a drug that in preclinical studies has been shown to be better targeted to the key tissues and the key organs in Fabry disease, with the potential for reduced levels of immunogenicity. We again intend to file that IND this year.

We continue, though, to move forward with a very important program for us as well in Pompe disease. Two applications of the CHART technology we are utilizing in Pompe disease. One is our Chaperone AT2220 now formulated in an IV formulation, preparing for entry into its repeat dose study combined with Myozyme or Lumizymein Q3 of this year, that remains on target. A repeat dose clinical study we are finalizing the protocol with key investigators. A novel intravenous delivery of a coadministered Chaperone, building on the results of the co-administration PK and safety study that we did last year, Study 010.

And with that a good focus of our R&D efforts under David's leadership at Amicus has been the development of a proprietary next generation ERT. Basically what we did in Fabry disease with our partners at JCR and GSK, we intend now to do independently at Amicus. We are moving forward with a cell line that has been developed, we again have a contract for further development and manufacturing of that with our partner, our contract partner at Laureate Pharmaceuticals here in New Jersey. We are looking at multiple ways in which we can produce an enzyme that we think has the potential to have improvements on the current standard of care for enzyme replacement therapy in Pompe disease, looking at the targeting of the enzyme, its immune profile, as well as the addition of a small molecule in the manufacturing process that could further stabilize it.

We don't have it on this slide, but many of you whom we have met with over the last couple of months, we have shown our pipeline slide, and we also indicate other next generation ERT programs in development. We haven't yet disclosed that. We are not yet prepared to disclose that, but again a good part of our R&D efforts are to build this very robust pipeline utilizing the CHART platform technology to develop these next generation ERTs, the first of which is poised to enter the clinic again in early 2014. The pipeline continues to advance both the early stage and the late stage, and I feel very good about where we are positioned in the Company.

Let me turn it over now to Chip to go through the financial guidance and the Q1 results.

Great. Thanks, John. And good evening everyone. I will start today's financial discussion with a few comments about our current cash position and guidance starting on slide six.

As indicated in this afternoon's press release, Amicus continues to maintain a very strong balance sheet, and we are on track to achieve our full year operating expense guidance. At March 31st, we had $84.8 million in cash and cash equivalents, compared to $99.1 million at the end of last year. We continued to estimate full year 2013 net cash spend of between $52 million to $58 million, and that is net of anticipated cost sharing under the GSK collaboration. As a reminder, GSK is responsible for 60% of the global development costs for migalastat for Fabry disease in 2013 and beyond. Our current cash position along with the anticipated GSK reimbursements are projected to fund our current operating plan into the second half of 2014.

Turning over to slide seven, you will find a snapshot of our first quarter financial results, which also appear in Tables 1 and 2 of this press release we issued earlier today. Additional details can be found in our quarterly report on Form 10-Q, which will be filed later this evening. For the three months ending March 31, 2013 no revenue was reported whereas we recorded total revenue of $7.8 million in the first quarter of 2012. The year-over-year decrease is entirely due to a change in revenue recognition accounting under the expanded GSK collaboration. This accounting change does not impact cash, and we will explain this in further detail on the next slide.

Moving down the P&L, total operating expenses for the first quarter of 2013 totaled $17.3 million, compared to $18.5 million in the first quarter of last year. The year-over-year decrease was primarily attributed to lower research and development expenses, as well as a decrease in personnel related costs. We had non operating expense of $207,000 in the first quarter of 2013, compared to non operating expense of $2.4 million in the first quarter of last year. The change in non operating expense which is a noncash item, is primarily due to the change in the valuation of our warrant liability.

Net loss attributable to common stockholders in the first quarter of this year was $17.5 million, compared to a net loss of $13.1 million in the first quarter of last year. The wider net loss versus the year ago period is attributed to the change in revenue recognition under the expanded GSK collaboration. Net loss per share of $0.35 in the quarter of 2013 was unchanged from the year ago period, and reflects an increasein shares outstanding, as a result of our March follow-on public offering, as well as shares issued in conjunction with the GSK collaboration expansion in July of 2013. As of March 31st, 2013 we had 49.6 million shares outstanding.

Turning over the page to slide eight. I will provide a brief reminder on the change in revenue recognition accounting under the expanded GSK collaboration. Beginning in the third quarter of 2012, payments received from GSK under the agreement are being recorded in the deferred reimbursements account on the liability side of the balance sheet. The deferred reimbursements balance on March 31, 2013 totaled $31.7 million, and that includes $9 million in Fabry cost sharing since the expansion of the GSK agreement in the summer of 2012, as well as $22.7 million for the unrecognized balance of the upfront payment and premium on equity originally received back in 2010. Previously research reimbursements from GSK were recognized as research revenue, and the straight line amortization of the total upfront consideration was recognized each quarter as collaboration revenue.

While the recognition of payments under the collaboration has changed, there is no cash impact, and the mechanics of cost sharing remain the same. GSK continues to reimburse Amicus for the portion of our actual spend that exceeds our 40% obligation. Each quarter the deferred reimbursements balance will increase by the amount of reimbursement that GSK pays Amicus for shared development costs. Any future milestones payable by Amicus to GSK will then be applied against the balance of the deferred reimbursements.

This summarizes our key financials for the first quarter, as well as our full year 2013 guidance. More information on our financials will be available in the 10-Q, which will be available online later this evening. I am happy to address any financial questions during the Q&A session. For now, we will turn the call back to John.

Great, thank you Chip. On slide nine, I will go ahead and just summarize, again Q1 was a really important quarter for us to buckle down to work on the clinical execution, and work on the regulatory strategy for monotherapy, to make sure all of the rest of pipeline advances, and I am pleased with the Company's performance in the first quarter and heading now into mid-year. If you look on the slide, you can see the migalastat monotherapy milestones going forward.

Very importantly now after this Type C meeting,the first important piece of communication is going be the topline Study 011 12-month data in Q3, and then providing that looks positive, we would move forward with an FDA meeting, preNDA moving to discuss the US approval pathway in the second half of this year. I can tell you getting even deeper into the data, with all of the work that we did to prepare this document to the FDA, the briefing document and preparing for the meeting, I feel even more confident that the data shows that the drug is having a positive benefit in the patients for whom it is intended to benefit. So consistent with what we saw in Phase II, we think this could be potentially a very, very strong option for people with amenable mutations living with Fabry disease.

Pompe is again an increasingly important part of Amicus. The Pompe ERT co-administration program, the first data was released at that World Conference back in, or the complete data released at the World Conference back in February. We continue to move forward with that on target from a timeline perspective, working on finalizing the protocols with the lead investigators in the world in Pompe disease, and we expect to initiate that repeat does clinical study in the third quarter of 2013. Again, that is an open label study. And very exciting, the second application of our CHART technology, seeing that move forward in its final IND-enabling studies, and still on track for that IND submission for fourth quarter of 2013, and entry into the clinic in 1Q of 2014.

A lot of milestones moving forward, and still a lot in R&D behind the curtain. I could also comment that we continue to be very active on the business development front. Lots of interest. Again we are partnered in our strong partnership with GSK in the Fabry program.

Beyond that for Pompe and the rest of pipeline and our platform technology, Amicus continues to retain 100% rights to that technology and that platform, and our standard continues to be, that if there is a partner who can help us move those programs better and faster together than we can do independently, then we will certainly entertain that, and certainly as a potential tool for further financing of the Company while retaining significant residual financial rights in the program, and control over the program development given our expertise in the field. We will certainly entertain that as well.

We have many sets of robust discussions in Pompe, Parkinson's, and other programs continuing, and we will continue to provide updates as appropriate. With that, those are my closing comments, and Operator, I think we are happy to take questions.

Thank you. (Operator Instructions). Our first question comes from the line of Anupam Rama. Your line is open.

Hey guys, thanks for taking the question. A quick question on the Pompe program. Have you finished all of the formulation runs for AT2220, and how many doses are you going to be studying in the repeat dose study?

We finished all of that formulation work in fact back in early Q1, we did the aseptic fill finish with the contractor, that was completed successfully. The formulation is in very good shape, it is in its final tox studies, and so far so good. In terms of the protocol we are just finalizing that now, Anupam.. I would imagine in the next month or two, we will be able to provide more clear guidance in terms of what that study is going to look like from a repeat dose perspective. I can tell you and we have shared this publicly before, that we are considering this to be a 12 to 24 week open label study. We are just finalizing a lot of the details right now.

Great. Thanks for taking my question.

You bet.

Our next question from the line of Joseph Schwartz with Leerink Swann. Your line is open.

Great, thanks very much. I was wondering if you could talk set it some more about the interactions with the FDA that you have had, and expect to have, and in particular, if you could give us some insight into what the main arguments you think that might resonate with the FDA based on the existing data, first of all, and then what would be positive data that you think would enhance your case from the 12 month endpoints?

Sure, Joe. I want to be somewhat sensitive since these discussions are going on in real time, but when we first got the data, we obviously reviewed it with the Board, and we immediately released it, and our partners at GSK, we didn't have plans for a Type C meeting prior toe unveiling the Stage 2 or 12 month data. However, given the FDA's guidance that they would consider the entirety of the data, such that there is not one primary endpoint that would be dispositive, our Board and I felt very strongly that it is better to interact with the Agency as frequently and as in depth as possible, to try to understand what that means. And I think a good part of that reflects the very changing regulatory environment, especially in the rare and orphan diseases, where there is still such much unmet need, and the FDA much to their credit working very hard, trying to figure out the right and best solutions to bring these medicines forward, especially under PDUFA V and [FDSA].

So with that, we went ahead in early Q1, requested a Type C meeting, again the FDA didn't have to grant it for the middle of an ongoing Phase III study. They quickly came back and said yes, that is fine, and they agreed to make it an in-person meeting. That led to quite a bit of work and activity here for probably the better part of 6 to 8 weeks, to draft that briefing document. In terms of what is in, I can't release, of course, what is in there. It is very important that we maintain those confidences going into this FDA meeting. What I can tell you though, is it is not cherry picking or cutting the data. Even that point three cutoff that we talked about before, and the stratification of patients by baseline GL-3. We discuss that certainly in the briefing document and we will in person with the FDA, but more as an explanation in terms of why we didn't hit statistical significance at 6 months on the interim analysis, and why we saw that large placebo effect. I think that data speaks very strongly to it.

We think the most powerful arguments for the key part of what should constitute the entirety of the data are going to be based on what we have already discussed, and that the overall level of GL-3, and again the FDA has indicated that GL-3 is an appropriate surrogate endpoint, the reduction of which correlates with a likely prediction of clinical benefit. We have shown very good results even at 6 months. Again almost reaching statistical significance on that continuous variable, migalastat versus placebo. We would want to look for instance, and we think very important to look at 12 months for that migalastat-treated group. Do they continue to have a consistent and durable effect and further reduction at 12 versus 6 months. For the placebo group crossing over, we would like to see, do they begin to move in the direction of that first 6 months of treatment for the migalastat group. So a lot of different ways.

Again at every point what we have done in the briefing document is to add to the statistical analysis plan, not to remove elements of it, and to highlight what we think will be the important factors for the FDA to consider as they view the entirety of the data. I hope that is clear, and I am confident that doesn't go into too much of the confidences of the preparation for that meeting, and what will be I think a very good exchange with the FDA.

Okay. That is very helpful. Thank you. Can I just ask as a quick follow-up?

Yes.

As far as your plans to share with investors the insights that you are able to gain, can you gave us some more granularity on when and what form that might take?

We need to go through that meeting first, we need to digest the results with GSK. Our bias at Amicus is always to be as transparent and real time as possible. Of course, I need to be respectful of the GSK needs. I think it is unclear right now, Joe, whether we would be able to release the feedback from FDA, and to provide further guidance on what any changes or additions to the statistical advance plan could be in advance of the 12 months data. But certainly it would come at the very lease, come with the topline 12 month data in Q3. So stay tuned.

Thanks again.

Yes.

Our next question comes from the line of Greg Wade with Wedbush. Your line is open.

Good afternoon. Thanks for taking my questions as well. John, are you proposing with the FDA a new statistical analysis plan for the 12 month data?

We are proposing a revised statistical analysis plan. Our original plan, Greg, had that primary endpoint being the 6 month responder, yes/no, the percent of patients who showed that 50% or greater reduction, that had been in place for several years. If you recall we had a Type C meeting last summer, where we went through a number of different aspects of the program, and the FDA discussed with us potentially expanding that to look at the entirety of the data. We actually put in place additions to the statistical analysis plan back in the fall of last year, and now we are looking for further additions to this statistical analysis plan.

So this is somewhat unchartered territory. The advantage here for us is that the FDA has already characterized that 6 months as interim Stage 1 data. The FDA is viewing this as a 12 month study for safety and for efficacy. It is somewhat unusual, because they are looking at the entirety of the data on this risk benefit analysis, and what we are trying to do again is to define as best we can what success is going to be when that 12 month data comes, so we can communicate certainly to investors, but also to a number of key interested parties, including physicians and patients, and very importantly, be able to set up the guidelines and the grounds and the framework for that preNDA meeting in the fall. Does that answer your question?

It does. I think what we are trying to get at a from this side of the phone call is the parameters around which you are looking to change things. So for example, if you are successful in convincing FDA to allow you to look at the continuous variable as the primary endpoint in the 12 month study, while that would more likely because of the success of the 6 month study lead to potentially a statistically significant result, there is also the flip side too, which is the risk.

On the continuous variable side, if those responders show less of a response at 12 months, then that would suggest not a durable impact of the therapy, and obviously with this being a chronic disease, that is not going to be good from a business perspective. I think it would be helpful to us to understand what your preference is with respect to this negotiation of the statistical analysis plan, so that we at this end can make an assessment of what the risks are, if that is what you end up getting?

Sure. I will answer, and then I will ask David to add just a little more color to it, to make sure that I capture it all accurately. Our preference and we think the better way to look at this, is rather than a responder pure yes/no analysis, to look at the overall burden of GL-3 in the cell, and the reduction of that over time. As such we think the continuous variable is going to be a more accurate and more telling way to see what the impact is actually going to be.

Let me just comment, there is not going to be one primary endpoint at 12 months. The FDA has already been very clear that given the nature of this disease, it will be the entirety of the data including the safety components. What we do want to do is to emphasize the importance and to elevate the importance of that already prespecified secondary analysis, so it becomes a very important part of the FDA analysis at 12 months. Whether it is dispositive or not is ultimately going to be seen at I think a preNDA meeting. Buy I certainly to help give you guys, because I understand that there is some confusion Greg, in terms of how do we view success. I do agree with you that if we were to see the migalastat treated arm regress at 12 months, that would give us some pause for concern as to whether or not this is having the effect that we saw in Phase II, and is persistent and durable. But I think that we need to look at the data to make that judgment. David, anything to add, please?

Hi, Greg, this is David.

Hey, David.

Just to follow-up with what John said, so we are past, there is no primary at this point. We are past it. That was at 6 months, and so at this point, our job is to put together the best view of the data, and what it tells us about the treatment effect of the drug. And about the safety of the drug.

And so it is by its very nature multi-component, and so there are multiple parts of the analysis, and there will be multiple analyses from different ways of looking at the data, in order to determine whether there really is a clear treatment effect in the patients with amenable mutations versus patients who were either on placebo for the first 6 months or who do not have amenable mutations. There is no simple answer to saying what do you hope to see on the primary, because there is no primary. We are past the primary.

When it come to the durability effect the key is that for the first 6 months, half of the patients were on drug, and of half the patients were on placebo, and then at 6 months to 12 months everybody is on drugs. So we have the chance to see whether the initial placebo group when they are on drug for 6 months, whether that looks like what happened in the original group that was on drug for 6 months. And then we also get to see the patients who were on drug for the first 6 months, if when they are on drug for a subsequent 6 months whether they have maintained what we saw in the first 6 months, and whether that got even larger.

I think exactly as you said as in any study, there is a chance that the data won't go in the direction you hope, but we have reason to believe that with longer treatment things get better, because that is exactly what we saw in Phase II. So you are exactly right, there is always a chance it won't go as hoped as with any study, but we think we have the right analyses in place in order to make that assessment, and we have reasonable confidence there will be both a durable effect, and potentially even a greater effect when the patients are on longer, based on what we saw in Phase II.

Okay. And just lastly based upon the things you are thinking that, do you think you will have to have sequence level efficacy results by genotype, in order to support the use of the drug across the board in patients, or will we use a biochemistry, biochemical analysis of amenable mutation? Thanks.

John, do you want me to answer that?

I am sorry. Go ahead, David, please, yes.

So the selection of the patients that should go on drug will be, we expect it to be the same as what we have done in Phase III, where that decision is based on their mutation. So it is based on sequencing. It is based on the sequencing of the entire coding region of the GLA gene. And the patients that have a mutation that we have determined in a cell-based assay to be responsive to the drug, those are the patients that we believe should go on the drug. And those that do not have such a mutation, are ones that we are saying should not be on the drug, and that is exactly what we did in Phase III as part of the inclusion and exclusion criteria. So we expect it will be consistent with what we did in Phase III, based on the mutation, based on DNA sequencing.

Okay. And in the Phase III results that you have presently, you believe they are supportive of identifying the right patients, because the response rate looks like it doesn't quite match up with the number of patients that were included?

So the answer to that is, yes. We do believe that. And we have data from Phase II as well that is supportive of being able to identify the patients who are likely to respond based on their personal mutation. So yes, everything is pointing in that direction. Of course, that we will be getting more data as part of the Phase III study, and we will be getting more data for patients who for example in the first 6 months they were on placebo, and with what we now know to be non amenable mutations, who for the second 6 months will then go on drug, and we will see whether the amenable group showed an effect, where the non amenable group didn't.

Okay. Great, thank you.

Our next question.

Go ahead, please.

Our next question comes from the line of Kim Lee with Janney Capital. Your line is open.

Good afternoon. Apologies if you already addressed this, but I got on late.

Don't worry, it is okay.

What exactly do you expect from this Type C meeting besides going over the statistical plan? Thanks.

I think we actually did cover that in pretty good detail Kim, so I think that is in the transcript, but I just will kind of highlight, that what we did was to prepare a very thorough briefing document, based on the 6 month Stage 1 analysis, the interim data from the 011 Phase III, and a more detailed analysis of all of our Phase II studies, to add to the statistical analysis plan, focusing on a number of different elements, including this notion of the continuous variable that was a prespecified secondary endpoint, but to elevate the importance of that in the assessment of the drug from a risk benefit perspective, in terms of defining the entirety of the data.

I think it will be very important to have this good exchange with the regulators, to be able to explain and lay out the data as we see it. We think again it shows very encouraging results, that the drug is having a positive benefit in those patients with amenable mutations, and as best we can to frame how we should look at the entirety of the data once this 12 month data is unveiled. Again we and GSK are blinded to the data still. It is a very unique and important aspect of this study to remember, that the primary reason, maybe the only reason that we can add to this statistical analysis plan in an ongoing Phase III, is that we have not locked the database, and we still remain blinded to that 12 month data, although remember of course, all of those patient samples were collected by the end of 2012.

Okay. And just as a follow-up, and I appreciate you reviewing this for me.

That is okay.

But also, so would this be an agreement with the FDA after this Type C meeting, or could things still be flexible and move around and change, as far agreements go after you unblind the data?

It certainly could be subject to further analysis and interpretation after the 12 month data. We are trying to though, before we get to the 12 month data. to as best we can, define what the key elements of analysis should be. So stay tuned. We will see. I am very, very pleased with the FDA accepting this request for a Type C meeting. They are making it an in-person meeting down in Maryland, and I think hopefully speaks to their interest in seeing therapies for Fabry advance.

Great. Thank you.

You are very welcome.

At this time I am not showing any further questions in queue. I would now like to turn the call over to John Crowley for any further remarks.

Great. Operator, that is all I have. Thank you everybody for listening, for the great questions, and a lot more to come in the months ahead. So thank you.

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