Amicus Therapeutics, Inc. (NASDAQ:FOLD)
Q4 2012 Earnings Call
March 12, 2013 5:00 pm ET
Sara Pellegrino - Associate Director, Investor Relations
John Crowley - Chairman, Chief Executive Officer
Chip Baird - Chief Financial Officer
David Lockhart - Chief Scientific Officer
Bradley Campbell - Chief Business Officer
Ritu Baral - Canaccord
Anupam Rama - JPMorgan
Kim Lee - Janney Capital
Joseph Schwartz - Leerink Swann
Greg Wade - Wedbush
Good day, ladies and gentlemen. And welcome to the Amicus Therapeutics full year 2012 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 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 evening and thank you for joining our conference call to discuss our full year 2012 financial results. Speaking on today's call we have John Crowley, 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 session.
Today’s remarks coincide with the slide presentation that is now available on our corporate website at www.amicusrx.com. The slides are located in the Investors section under Events and Presentations right below the webcast link to today’s call.
On slide two, you will find a reference to our safe harbor statement. This conference call 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 this expectation 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, 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.
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 and good evening everybody. It’s a pleasure as always. We will recap where we were in 2012 and much of my discussion here before I turn it over to Chip for the financial overview will be focused on where we are today and what we see as some of the key milestones as we head forward into 2013 which as we have indicated through a number of investor meetings with many of you over the last several weeks will be an incredibly important year where I really believe we are finally going to realize in the clinic the true potential of these drugs being developed
Again, for a number of years, what we have sought to do is to use these pharmacological chaperone technology to make medicines, to build drugs that can fundamentally change peoples lives. As we ended 2012, we have the first glimpse into the most significant of the clinical studies we have ever done in Fabry disease and of course that’s Migalastat [for our] [ph] monotherapy.
So if you look in on the agenda slide here on slide three, you will see I will begin with Migalastat monotherapy for Fabry, an overview, give you the current state of that program and what to expect as we head into this year. I will also then highlight the new CHART, our Chaperone Advanced Replacement Therapy platform technology our proprietary platform and where that stands in now multiple programs including the clinical data as well and then of course turn it over to Chip for financial results in fiscal year 2012 and also for a guidance on fiscal year '13. And of course my full team will be here and happy as always to take any questions.
So as we started to do last year, we used PowerPoint slide. So for those of you who have your computer handy, feel free of course to run along. I am on slide four and here what we really want to highlight is where we are in Study 011. As you remember, as we ended 2012, we shared the preliminary data or the interim data from Stage 1 of Study 011 and that again is 60 person study, 30 people randomized to placebo, 30 people randomized to Migalastat looking on a primary endpoint to see if we would see meaningful changes and statistical changes placebo versus the active group.
On that interim analysis, we saw encouraging data. If you recall, we ended that study with 59 people having completed the 12 month period. 57 of those persons voluntarily elected to continue into the next year of the extension study. As we sit here today, all 57 people continue on that drug on Migalastat as their only disease modifying treatment for Fabry disease.
So I won’t reiterate much of what we have talked about over the last couple months in a couple of calls as well as numerous presentations including the updated data that we saw from WORLD meeting back in Orlando the middle of February. Again I would just reiterate that what we saw was encouraging and certainly merits continued study of the drug. We, in looking at that data, of course, looked at the primary endpoint where we did not achieve statistical significance at the six month period at the Stage 1 analysis.
But again, on a post hoc analysis, as you saw, we did see changes above a 0.3 inclusion body cutoff beyond that, though beyond the yes/no responder analysis. What we actually saw was looking at the total amount of GL3 analyzed as a continuous variable we saw very encouraging trends as well, almost meeting statistical significance even on this interim look. Again a median reduction of 41% versus just 6% in the placebo group. We also of course saw encouraging kidney function data, as measured by estimated GFR after six months and a very favorable safety profile with no treatment related adverse events.
Again we see patient compliance to be strong, as we have indicated over the last couple of weeks. We are spending a significant amount of time internally with our partners at GSK with some key consultants and now engaging the FDA in a review of the interim data as well as looking forward to the 12 months data.
It is important to remember that the people in this study, we have already collected all their 12 month data and samples including those very important biopsies. The analysis of the biopsies is ongoing by the pathologists. We are of course blinded to it. Moreover, we have not yet locked the database in that study. So as we engage in the further analysis of the data that we do have on the Phase 1 data set, we are also now working again with all those constituencies to make sure that as we look forward to the 12 month data that we are looking at the right data, the right data set, again with an eye towards the six and 12 month data efficacy and safety to support conditional approval of Migalastat for people with amenable mutations with Fabry disease.
So we continue to be encouraged. We think, based on the work that we are doing, the encouraging data that we have seen to date and these ongoing discussions with FDA, we have previously guided that the 12 month data would be late 2Q or early Q3. I think it is smarter now and we are now guiding to expect this in the third quarter. Again, it is very important to note that we continue to collect the data in a blinded fashion and we will not be un-blinded and once we are, of course, in a very timely fashion, as we have done before when we release it in a top line manner.
We want to make sure that we have the ability to put together the most compelling and rigorous data set possible once we see that 12 month set of data and it is also important to remember now as we are working on potentially even further revising the statistical analysis plan of 12 months. Then again, we want to do that in the most rigorous of fashion.
Also too, I will note that, when it comes to the patients for whom this drug would be appropriate that we expect to seek a label for patients with amenable mutation. We do not anticipate that we will have any label restriction for baseline interstitial capillary GL3. Of course that’s not practical, as kidney functions are almost never done in a clinical practice.
So we are moving forward. I think we are in good shape on Study 011 and we are very much looking forward to seeing that data. If it is consistent with what we saw in Phase 2, we would hope to be able to see that for patients who have been on Migalastat for the full 12 months of that study. That’s compared to six-month that they continue to show clearance of GL3 in those kidney cells and importantly for people who switched from placebo to Migalastat that we start to see a change in direction of their total amount of GL3, particularly as we look at it over time on that continuous variable.
So again the persistence and durability of the effect of this medicine critically important to evaluating the full safety and efficacy.
I will just note briefly, and again still following along on the slide four here, that our Study 012 continues to go very well. That is our second study for approval for Fabry disease for Migalastat. That was a study designed looking at a primary clinical outcome, 18 months study, looking at a direct measure of kidney function by iohexol GFR. Again over that 18 month treatment period.
If you recall from 2012, looking back we saw rapid enrollment of those patients. Every one of them has been stable on either Fabrazyme or Repligal as their only treatments for Fabry disease and we have 1.5 to 1 randomization again. Though 36 of those patients who enrolled of 60 stopping completely their ERT treatment and moving over to Migalastat and as we are on this call here today we continue to see very high compliance in that study which we think is very encouraging to-date. Again that, given that it's an 18 month study, last patient in was December '12. Data is anticipated in the second half of 2014. So that is where we are the Migalastat monotherapy program.
So let me highlight on slide five where we are on the combination therapy. And again if you remember, the whole concept here is that we are using small molecule chaperones to stabilize human recombinant proteins and bioreactor enzymes, either used as coadministration, as you will see at the top there, chaperones our proprietary chaperone together with currently marketed ERTs or the second application of this CHART platform technology is in the development of our own proprietary next-generation enzyme replacement therapies. Again, those are ERTs co-formulated with our proprietary chaperone and our proprietary enzymes. That all fits into the continuum of innovation that we have described before.
The third application that you will see on that slide there, five, is using the CHART platform technology to develop next-generation enzyme replacement therapies that have the potential for improved delivery regimens and if you recall a couple months ago, at the JPMorgan conference I had the opportunity to share for the first time some of the very promising data we have shown the ability to use these small molecules directly co-formulated with ERT to stabilize the ERT to such a degree that we may well be able to deliver these enzymes subcutaneously.
I will just highlight, we did at the Cowen conference last week had an opportunity to roll out this branding of the platform technology, again using CHART a Chaperone Advanced Replacement Therapy. The logo, I will commend our team here at Amicus for coming up with this internally. The logo here showing that forward-looking motion, again charting the future, for what we think could be the future of these treatment paradigms in the lysosomal storage disorders and the ribbon structures also looking forward representing the protein with the small dot of course at the active site or nexus of the protein. So a clever logo and one hopefully that we will continue to be able to use very effectively with all of our key constituencies patients, physicians, key scientists and of course investment community. Again we really think that this has the potential to be the greatest value driver for Amicus in the years to come, the ability to leverage this CHART platform.
If you turn to slide six, we will talk a little bit about where we are for Pompe disease. If you remember, again, at the beginning of January, we had the opportunity to share proof of concept data from our Phase 2 study or Study 010. That was our drug AT2220. It was orally coadministered in a single dose together with Myozyme or Lumizyme, the currently marketed ERTs for Pompe disease. The results of that study demonstrated that the coadministration increased the uptake of the Pompe enzyme or the recombinant GAA into muscle compared to ERT alone.
Again, in preclinical studies of that molecule coadministered with the ERT and co-formulated with ERT, we also saw increased enzyme uptake into tissue which also translated to further reduction of glycogen compared to the ERT alone. So we have moved forward.
Last year, actually when we first saw the early pieces of this data looking so positive, we at risk began a project to formulate this molecule in an IV formulation and we are doing that because we actually have preclinical data that it could potentially have an even improved PK profile and also very practical considerations that of course since patients who are still receiving their ERT with no burden to the patient and moreover it will actually allow better control of the administration of the drug and also in many patients, particularly the children with Pompe are actually unable to take oral medication.
So that again excellent proof of concept. This will be a very important study for Amicus, this next coadministration studies using the CHART technology. It will be a repeat dose clinical study. We are guiding again that this is expected to begin in the third quarter of this year. Manufacturing of the drug completed. It's now in its final preclinical studies and tox studies and the protocol development is nearly complete. We expect this to be a repeat dose study. Approximately 12 to maybe 24 weeks in duration. We will look at safety and PK in muscle. We expect people who have never been on ERT before to be in the study as well as treatment experienced people.
So this will give us a very important data set. Again, seeing can we change in a positive way the PK profile of Myozyme or Lumizyme? Can we enhance their tissue uptake? We will also of course look at the immunogenicity and what impact the chaperone addition might have on affecting the immune response to the ERT.
So that’s the coadministration and that is a program we fully intend to develop moving forward as a separate program. We also have on the continuum of innovation our next-generation enzyme replacement therapy. That is a proprietary ERT that we are developing here at Amicus. That is one will be co-formulated with the chaperone together with other changes to the ERT that we think might improve its profile and its ability to target muscle tissues.
So much work continues in the monotherapy and more and more, a good part of Amicus is focused on advancing our CHART technologies both in the coadministration setting as well as co-formulation with their own proprietary next-generation enzyme replacement therapy.
So that’s my overview of the programs. I will now turn it over to Chip and Chip can take us through the fiscal year '12 financial highlights and guidance of this year. Chip, all yours.
Great. Thanks, John and good afternoon everyone. I will start today's financial discussion with a few comments on our current cash position and guidance and I am on slide seven.
As previously announced at the JPMorgan conference in January, we began 2013 in a strong balance sheet position with $99.1 million of cash as compared to $55.7 million in the beginning of 2012. For the full-year 2012, net operating expenses were $40.7 million. This amount was net of cash reimbursed by GSK for shared global development of Migalastat and I am pleased to report that was within our guidance range of $37 million to $43 million.
Looking ahead, we continued to estimate full-year 2013 net cash spend of between $52 million to $58 million. Again, that’s net of anticipated cost-sharing under the GSK collaboration. As a reminder, GSK is responsible for 60% of the global development cost for Migalastat in 2013 and beyond. Our current cash position along with these anticipated GSK reimbursements is projected to fund our operating plan in this second half of 2014.
Turning over to slide eight, you will find snapshot of our full year financial results which also appear in tables one, two of today's press release which we put out after market close. Additional details can be found in our annual report on Form 10-K which will be filed later this evening.
For the 12 months ended December 31, 2012, total revenue was $18.4 million. That compares to $21.4 million in the year ago period. The slight year-over-year decrease is attributed to change in revenue recognition accounting under the expanded GSK collaboration. This accounting change does not impact cash and we will explain more detail on this on the following slides.
Operating expenses for full-year 2012 totaled $71.3 million compared to $72.3 million in full-year 2011. The year-over-year decrease in expenses was primarily attributed to lower research and development expense as well as a decrease in personnel costs.
Moving down to P&L, we had a non-operating income of $901,000 in the full-year 2012 compared to non-operating income of $2.8 million in the year ago period. The change in non-operating income, which importantly is a non-cash item, is primarily due to the change in valuation of how we warrant liability.
Finally, net loss attributable to common shareholders in full-year 2012 was $48.8 million compared to a net loss of $44.4 million in full year 2011. The wider net loss versus the year ago period is attributable principally to the change in the revenue recognition under the expanded GSK collaboration.
On a per share basis, the 2012 net loss was $1.07 compared to a net loss of $1.28 in 2011. The narrow net loss per share versus the year ago period reflects an increase and the shares outstanding as a result of our March 2012 follow-on (inaudible) offering and shares issued in conjunction with the GSK collaboration expansion in July 2012. As of December 31, 2012, we had 49.6 million shares outstanding.
Finally turning our attention to slide nine, I will provide a brief reminder on the change in revenue recognition accounting under the GSK collaboration. Beginning in the third quarter 2012, payments received from GSK expanded agreement are being recorded in the deferred reimbursements account on the balance sheet. Deferred reimbursements balance on December 31, 2012 totaled $30.4 million. That consists of $7.7 million in cash reimbursement from GSK under the Fabry cost sharing arrangement during the second half of 2012 as well as the $22.7 million for the unrecognized balance of the upfront payment and premium on equity received under the original GSK collaboration in October 2010.
Previously, research reimbursements from GSK were recognized as research revenue and straight line amortization of total upfront consideration was recognized each quarter as collaboration revenue. So while the recognition of these payments under the expanded GSK collaboration change, there is no cash impact and the mechanics of the cost sharing arrangement remain the same.
This summarizes our key financials for full-year 2012 as well as our full year 2013 guidance. More information of our financials will be available in the 10-K which again will be available later this evening. I would be happy to address questions during the Q&A session but for now, I will turn it back to John.
Great. Thanks, Chip. So I will go ahead and end here on slide number 10 which is our milestones for 2013. Again these are the clinical milestones. We are going to focus on the company and we look to make a difference for people with these diseases which we look forward to as well as of course building significant shareholder value. We see these, the three key drivers of value, hopefully this year.
Again the first being the Migalastat monotherapy program for Fabry disease. We have already delivered the full Study 011 interim data in science platform presentation of WORLD. Again now guiding for third quarter 2013 for the topline Study 011 12 month data or the Stage 2 data. That will be very important.
Again we are moving that to Q3, I think, to give us the time to continue to work with the FDA. We are fortunate that the study was designed that we have an interim look at the data. It's told us much about how the drug is working. It also now gives us an opportunity to potentially make yet further changes to the statistical analysis plan which I think will be important to understand the full effect of the safety and efficacy of the medicine and also to realizing that the FDA has already guided that they will look to the entirety of the data from both of those stages.
So we think that’s very encouraging and we are glad that we have a little bit extra time to complete those regulatory discussions as well as then to analyze the data once its underlined to us in the third quarter. And of course we will be able to topline release that very quickly after we look at it and digest the data.
We still plan for a pre-NDA meeting based on that 12 month data, that meeting to discuss a U.S. Regulatory pathway approval. We expect that in mid-2013. So that’s the Migalastat monotherapy program. Two major milestones still to achieve there.
The Pompe ERT coadministration program, our second clinical program, was significant the year. Again, very encouraging data. We saw the positive data at the WORLD meeting in February already delivered and everything in the Pompe program now geared toward the initiation of that repeat dose clinical study in Q3 of 2013.
Then our third program, again using that CHART technology. We intend to move forward still with the next-generation enzyme replacement therapy product in Fabry disease. That is the product that we are developing with GSK and with JCR Pharmaceutical, our partners in Japan. That is Migalastat, our chaperone combined with the JCR enzyme, the saline JR 051. That is on track for IND submission in the fourth quarter of 2013. We expect entry into the clinic in the first quarter of 2014.
So lots of work still to do. Of course there is an awful lot of research and development at Amicus ongoing in particularly application of the CHART platform technology to other programs and other rare diseases we have not yet disclosed. We think that we have the potential to this year once data is generated to begin to talk more about those programs. But on slide 10 we wanted to focus on the major clinical milestones.
With that, operator, that’s all we have and we are happy to take questions.
(Operator Instructions) Our first question comes from Ritu Baral of Canaccord. Your line is now open.
Ritu Baral - Canaccord
Thank you for taking the question. I just wanted to drill down further on the 12 month data that could come out, especially the potential changes to the statistical analysis plan that you discussed. What are some of those potential changes? Is filtering by baseline inclusion numbers one of them? Whatever you guys decide and decide prospectively to analyze the data? How you prospectively decide to analyze the data would you run it by FDA even before the Q3 12 months data?
Yes. The short answer is yes, Ritu. If you remember, if you look back historically over the last year, in this program, we had that type-C meeting last summer and that was the first time the FDA had indicated that we consider safety and efficacy of both six and 12 months. In fact referring to six-months as Stage 1 and 12 months as Stage 2. Through the fall of last year in 2012, we then worked with the FDA. We proposed three additional prespecified statistical comparison. We have gone through this before. Happy to review those again. But that’s already agreed to for the 12 month data set.
What we are looking at now is based on the six-month data as we know it. Can there be or should there be any other changes to the statistical analysis plan or different statistical comparisons, I do not want to comment specifically on what we are discussing with FDA. I want to preserve the integrity of those conversations.
So I will leave it at that, but once we have that guidance we will be able to release it outward.
Ritu Baral - Canaccord
Just as a follow-up. Because of the change at the six months point, the conversion of placebo patients to active, will we have hazard ratios for certain measures even if we don’t have P values and how historically has FDA looked at hazard ratios from small orphan trials?
I am not as familiar with that, Ritu. David, if you want to comment or we can certainly follow-up.
Yes, this is David. So we are still doing statistics. Sometimes people use the word descriptive statistics and it sounds like it is a less than rigorous comparison. But that’s now what we mean here. There is still direct comparisons. There is still calculations of means and medians. I think with the hazard ratio, comparable as to say, the 95% confidence interval. So standard [airs] [ph], confidence intervals and those sorts of things can be calculated.
The sensitivity is just to calculating a formal P value as technically that means there was a formal hypothesis testing. So if anything it's post hoc. There is sensitivity to calling it a hypothesis testing with the P value but essentially the same information comes from analyses with the confidence intervals.
Again, I think it is important, Ritu, to remember that what we are seeking here is that conditional approval. So looking for conditional approval based on a surrogate marker or markers likely to predict clinical benefit. We think GL3 is an excellent one and certainly the cell types in the tissues that we are looking at in the kidney are the very relevant ones that we think will be likely to predict a clinical benefit. We just want to make sure that as we look at the entirety of that data that we are able to pre-specify as many of those statistical comparisons as we can.
And I think there are two things that are important to be reminded of. One is that there is a lot more data when we have the 12 months collection. Because at that point the patients who were on drug for the first six months stay on drug. So we have will have data for of those patients for 12 full months. Then also the patients who were originally on placebo crossover to drug. So in effect you nearly twice as many patients. We will have data for nearly twice as many patients on drug for at least six months.
It gives us two things. One is data for nearly twice as many patients and it gives us data not only for a six-months treatment period but also a 12 month treatment period. As we saw in the Phase 2 studies there was an effect at six-months but that effect was larger at 12 months. That’s also what is seen with ERT.
So there is reason to believe that the effect could be even larger for the patients who have been on drug for 12 months not just six. So we can do that direct comparison. In addition, we have nearly twice as many patients with at least a six-month treatment period.
Our next question comes from Anupam Rama of JPMorgan. Your line is now open.
Anupam Rama - JPMorgan
Thanks for taking the question. Just on the repeat dose study for Pompe which is expected to start in 3Q, what sort of preclinical work or next steps need to be completed before the start of that study.
The manufacturing, we have to do the formulation work, moving from the oral formulation to the IV formulation. That’s completed. The GMP manufacture is completed. The aseptic fill finish is completed for the drug material. Then its just in the last of its toxicology studies. Brad you want to?
No, I think that’s a fair characterization. Of course the other elements of starting up a study are on the clinical operational side. So working with the sites which we have already identified, getting protocols approved, going through IRBs, Those kinds of things. So its really more in the clinical operations mode.
Yes. It is actually exciting to see that program now. I mean we were all here about two months ago when the contract manufacture had a live video feed from their aseptic fill finish facility and that was just an idea about 10 months ago at the company that it would be best to deliver this is an IV formulation for a host of reasons and the enormous amount of work here internally at Amicus to make that happen. Again, remember of course as you know. Anupam, this is an un-partnered program. So we are doing all of this with our internal resources and our key vendors. So it is exciting to see this move forward. And now we are only a quarter or two away from this going into patients in a repeat dose study. Obviously very, very excited to see the data coming out of that open label study.
Thank you. Our next question comes from Kim Lee with Janney Capital. Your line is now open.
Kim Lee - Janney Capital
Good afternoon. A quick question for you. What was the thinking that was behind the pushing out of the lead out for the Stage 2 of the trial? Is it some discussions with the FDA? If so, what has been that feedback? Thanks.
Again, we had been guiding to late Q2, early Q3. We think its prudent now that we say its Q3. Its really with all the data that we have, Kim, at six months, all the internal analysis that we have done, working with the pathologists to make sure that we have all the right types and numbers of pathology reads, together with the ongoing discussions with FDA and under Type C guidance, because there are timelines that are in two months or so period. So that will take some time to complete that. So again I consider it very much a positive.
Obviously we would love to have all the data sooner rather than later but the fact that six months data really look so encouraging, especially as we have dug deeper in to it on areas like looking at the overall GL3 level on that continuous variable. Just making sure that we do everything possible and take a little bit extra time so that we can analyze that data as comprehensively as possible and to set up as diligent a briefing package as we can into the FDA for the pre-NDA meeting.
Yes, the only other thing I would add, John, is from an operational perspective. Remember we have collected all those biopsies. Those were collected by the end of December last year. We are still blinded to the data. I know John mentioned both of those things. But as John said it is not an operational issue, more its just making sure that we get it right and we have the appropriate discussions and that we prepare appropriately.
Yes, to me, this was a strategic decision to take those extra couple of weeks and I think it is actually quite positive that we are engaging the FDA in this interim period between the six and the 12 months data. So I think it is very positive. Hopefully it will set us up even better.
Kim Lee - Janney Capital
And what --
Go ahead, Kim. I am sorry.
Kim Lee - Janney Capital
Oh, no. That’s okay. So you are in discussions with the FDA currently and can you help us understand what kind of guidance they are providing for you between now and your readout in Q3? Thanks.
I can't comment on specific items from the agency and the nature of the discussions. Only to state that we are sharing the data. We are proposing ideas for potential changes to not take away from but to add to the prespecified statistical comparisons. So that when we look and we describe what is the entirety of the data, we understand, the regulators understand, investors, physicians, really all the interested parties understand just how well we hope this drug is working and therefore how convincing of a package we can put together for that pre-NDA meeting. But I think its time well spent. Thankfully, we have got good data to look at.
Thank you. Our next question comes from Joseph Schwartz of Leerink Swann. Your line is now open.
Joseph Schwartz - Leerink Swann
Oh, hi. Sorry, I was on mute. Thanks. So, when will the FDA see 12 month data and how do you anticipate updating investors once they have seen and then that meeting has taken place and you are able to share with us whatever clarity you can at the end of that interaction.
Sure. So I think, Joe, in the third quarter, we will expect to be able to topline that data. As before, the full data that would be presented at a science conference most likely in the early part of the fall, I would suspect. Then in terms of the FDA, we intend to move once we analyze that data very, very quickly into the pre-NDA discussions with FDA. So you think about the monotherapy program. There is really three gates this year that we have to go through.
It's going to be the 12 month data in Q3. It is going to be the pre-NDA discussion after that. Then we are still on track and all the other work that we need to do is on track assuming that the 12 month data looks where need it to be, to file the NDA by the end of the fourth quarter. So those are the three gates that we will need to get through to continue to de-risk that program.
Joseph Schwartz - Leerink Swann
Okay, great. Then can I ask one quick follow-up on the IV AT2220 study in combination with the marker ERTs. I was curious, I think you said it was going to run for around 12 to 24 weeks. How many patients do you anticipate enrolling and how long do you think it will take to do that? Then what kind of immune response test do you anticipate you will be able to analyze? Will there be a ERT monotherapy arm as a control?
All right. So that’s four questions. Let me make sure I got them. So it’s the number of patients. Again we are still developing the protocols but I think it is fair to say this is probably going to be about 18 to 24 patients. Again, some on ERT, some naïve to ERT. We do expect afterwards that there will be an extension arm.
I think your second question was the time to enrollment. We expect this to enroll very, very quickly. We are not asking anybody to come off of their ERT. We are only adding an investigational medicine to explore whether we can change the PK profile, enhance the tissue uptake and potentially affect the immune profile of the ERT in a positive way.
So we think there will be significant interest. I could tell you we are talking to the key opinion leaders in the world, all of whom were investigators for the Myozyme pivotal studies. We are very excited about the data that we have seen including the clinical data. If you remember too. for Study 010, even though it was basically a Phase 2a PK study and it included multiple muscle biopsies, no chance to take the medicine our chaperone more than once, we enrolled that study very, very rapidly. In fact we had to turn some patients away.
The people living with Pompe disease are really, really eager for next-generation therapies that can either enhance the efficacy or safety of their current medicine potentially lead to the development of next-generation ERTs. I know at the end of the night, I don’t worry about enrollment of this study. We will do it in a rigorous fashion but we will enroll the study in a very, very expedited manner.
You had a question too also about immunogenetic. I was just scribbling down your questions quick. I apologize but immunogenicity was your third question, Joe?
Joseph Schwartz - Leerink Swann
Yes, thanks. Sorry to include so many but the immunogenicity aspect is obviously important and then we have ERT monotherapy as a control?
That’s not clear that we will need a monotherapy control right now but we are looking at that. Again, we will final protocols in the next short while here. But again since we are looking at ERT experienced patients, and remember of course, in Pompe you have a 100% pure conversion. So everybody develops antibodies. That’s known to the ERT.
We will have many of those patients in the study. We will look on a number of different parameters, including T-cell response antibodies to see if the addition of the chaperone and coadministration has any impact. We need to investigate that. Then we will also look at ERT naïve patient. If the medicine is coadministered with the ERT, chaperone with the ERT, what impact, if any, does that have on the immune response. So we will look at all the multiple parameters to measure the immunologic response.
I would stop there.
Joseph Schwartz - Leerink Swann
I think that was a, thanks very much, extremely helpful.
Thank you. Our next question comes from Greg Wade of Wedbush. Your line is now open.
Greg Wade - Wedbush
Thanks for taking my questions as well.
Hey, Greg, how are you?
Greg Wade - Wedbush
Hi, I am good, John. Good to hear your voice. The results of the 12-months study are complicated. You have got patients who had responded which could either continue to respond or fail, patients who had failed to respond who could respond or continue to fail. Then the same in the placebo group. So there is potential outcomes per group that you have already, responders and nonresponders. So I am curious, what you would prospectively define as a successful enough result at this 12 month time point to continue the program forward.
Then secondly, if I just might squeeze another one in. Your amenable mutation assessment hasn’t really been predictive of response at this point. I am just curious as to what the company is doing in order to create a sufficiently robust commercial test that would allow you to identify those patients whom, if you do go forward with the program might best be treated with Migalastat. Thanks.
Yes, let me address that last question first and I will ask David and Bradley to add any color that’s necessary. Actually we think it's one of the most powerful aspects of the technology is a very personalized medicine aspect of the monotherapy where, if you recall, we had develop the constructs of every known mutations that can cause Fabry disease, over 500 and even in the course of enrolling this study discovered several dozen new mutations that can cause Fabry. We are actually very confident that we can predict with nearly 100% certainty who is appropriate to this medicine based on that GLP assay.
So the amenable versus nonamenable is critically important to us. We think we have very good evidence. I think it indicated that we didn’t see evidence before. I am a little confused about that. Because if you look at our Phase 2 data that was presented at the American Society of Nephrology back in the fall, we actually had patients who had nonamenable mutations, and they actually showed an overall increase in their GL3 level compared to a 78% median reduction in the GL3 in people with amenable mutations.
So I don’t think that’s quite right but maybe I missed something. So David or Bradley, if you want to add any color on that point and then I will come back to your first part, Greg. I am sorry. So there is nothing there. So let me guess.
So actually, John's correct that from the Phase 2, we do have evidence that the in vitro study mutation by mutation does appear to be meaningful in terms of the response in vivo in patients with different mutations get the drug. We will have similar data from Phase 3. We haven’t shared the patient by patient data yet but we do have patients in the Phase 3 study who have mutations that based on the GLP pharmacogenetics assay are nonamenable.
So we are able to compare those with the preidentified nonamenable mutations versus those that are amenable and when we share the patient by patient data we will be able to compare those two groups and see whether there is good predictive power with the pharmacogenetics work.
Is that what you were asking, Greg?
Greg Wade - Wedbush
Well, everyone in the Phase 2 study was identified as having amenable mutation but last month it wasn’t 100%. So I am a little confused.
The confusion comes from the fact that when we were enrolled in that study, we had and R&D assay that was the basis of the inclusion. We tried to be inclusive. So there are patients who went into that study who then, when the full set of 531 assays were transferred to CRO so that could be done under GLP conditions. So every single one of the 531 were rechecked. There were some that had previously scored as amenable that were now determined to be not amenable.
We agree with the assessment of the CRO done under the GLP conditions. So those are, by the criteria we defined before the study started, they do not meet the amenable status criteria. So they were let in because of the R&D assay but with the GLP assay they are nonamenable. So that’s why they were in there. It was just a matter of time and the switching of the assay to a GLP setting outside of Amicus. So they will effectively serve as the control for the ability to predict based on that assay.
So let me just be clear, the vast majority of the patients in the study do have amenable mutations and that small number who don’t but we are still analyzing but I think, may be if I can just get to the first part of your question, I think it is very important, Greg, and a very good question around what to expect at 12 months and how do we know that’s going to support approval of this drug.
We know the drug worked. It has been patients now more than 200 years of patient data. Some people more than seven years on the drug. We think the compliance rate, the fact that the 57 of 59 people who agreed to go in the extension study in December before the six-month data was released, every one of them has continued on in the study. So there is really three things we need to show at 12 month advancing from six months.
First we need to show that the effect of the medicine is persistence and durable. So for instance, a lot of different ways and perhaps off-line, we can go through it in more detailed comparison but what we need to show is for people who were on the drug for six month, when you add another six-month of treatment, is that persistent and durable? Does it continue? Is it even greater in effect? If it is consistent with our Phase 2 data, it should be.
Again, for people who were on placebo, when they switch you start to see a change in the trend and the primary endpoint the six-month data, we look at peer responder analysis. As you saw with the post hoc analysis, it made sense that a cut of 0.3 and above, I think that explains that unexpected placebo response but much more importantly for 12 months we need to show that this entirety of the data on this biochemical endpoint supports that we see a persistent and durable change first.
Secondly that the change and the magnitude of the change we are showing is meaningful. We think it is actually quite encouraging at six months of the Migalastat treated group, it was already at a 41% median reduction. We think, in talking to all the experts in the field, that if that were to continue that would indeed be a meaningful changes likely to predict clinical benefit.
Of course, thirdly, we need to show that the drug continues to have strong safety profile, which thankfully it really does. When we put all that together we were hoping that all of that data will lead to a strong package for FDA seeking conditional approval.
Thank you. Our next question comes from Ritu Baral of Canaccord. Your line is now open.
Ritu Baral - Canaccord
Thanks for taking the follow-up, guys. One thing that’s not in your upcoming catalysts is a plan to take Migalastat, a sole Migalastat formulation for Migalastat alone into potential combo use. Can you take us through the strategy around that decision? Why bring it forward to the combo only as co-formulation.
Because we think it will be a better option for patients for number one. Number two, our co-formulation has essentially co-formulation program. It is eventually caught up with coadministration. So we think the 013 study was excellent proof of concept, again, showing of course we can change the PK profile, the tissue uptake of both Fabrazyme and Replagal and we did that in all patients for whom it was tested. Over the last two months we have work with GSK we have had many long meetings assessing whether we should move that into a pivotal study for coadministration and given how advanced the ERT and how well the ERT co-formulated product looks preclinically to be performing and how well the manufacturing is going, it doesn’t make sense to run those programs in parallel given that the next generation ERT for people with these nonamenable mutations will still need to the ERT. It should be and we think it has significant potential to be a better therapeutic outcome than just the coadministered chaperone with other ERTs. So we think it’s very important then to bifurcate the program. Migalastat monotherapy for Fabry disease for 30% to 50% of the patient population with anyone of these amenable mutations. Then the other half or more of the population we will have an IND we intend by the end of this year with a next-generation ERT. So I hope that makes sense.
Thank you, and at this time. I am not showing any further questions. So I would like to turn the call back to management for any further remarks.
No, that’s all we have, operator. Everybody, thanks for listening and always available to speak as needed. Have a great evening.
Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program. You may all disconnect. Everyone, have a great day.
You are welcome.
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