Amicus Therapeutics Inc (FOLD) 2011 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Amicus Therapeutics First-Quarter 2011 Financial Results. (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, Associate Director of Investor Relations.

Good afternoon and thank you for joining our conference call to discuss our first-quarter 2011 financial results. Speaking on today's call we have Matthew Patterson, our President and acting Chief Executive Officer; Bradley Campbell, our Senior Vice President, Business Operations; and Daphne Quimi, our Corporate Controller. We are joined by additional executive team members, David Lockhart, our Chief Scientific Officer; and Pol Boudes, our Chief Medical Officer, who are available to participate in the Q&A session.

As a reminder, this conference call will contain forward-looking statements 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, pre-clinical and clinical development of Amicus' candidate drug products, the timing and reporting of results from pre-clinical studies, 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 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 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, 2010, and our 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 Matthew Patterson, President and Acting Chief Executive Officer of Amicus.

Great, thanks very much, Sara. And welcome everyone to our first-quarter 2011 conference call.

It's my pleasure to lead today's call and to provide you with an update regarding our Phase 3 Amigal program for Fabry Disease and other significant developments for the Company during the first quarter.

I'm joined on the call today by Bradley Campbell who will provide some additional updates related to our development programs and Daphne Quimi who will review first-quarter financial results and guidance. We'll then open the call for questions.

First, I'd like to take a moment to thank John Crowley who recently transitioned from Chairman and Chief Executive Officer of Amicus to the role of Executive Chairman. John's been a tremendous leader for Amicus and has, of course, been instrumental in the success of the Company to date. As you all know, John's a passionate champion of the rare disease community and we intend to continue to pursue his vision of developing innovative new treatments for patients.

We end the first quarter of 2011 in a strong financial and strategic position and with positive momentum across all parts of our business, including our collaboration with GlaxoSmithKline rare diseases.

We have a strong organization that can execute on our strategy and I'm personally proud to be leading Amicus as Acting Chief Executive Officer during this important time in our Company's history.

Let me start off by saying we're very pleased with the continued progress of our multiple programs in development and feel that 2011 has been a great success so far for Amicus. This momentum is driven by our lead program, Amigal, which is in Phase 3 development for Fabry, in collaboration with our partner GSK.

First, and probably foremost in everyone's mind, is our ongoing US Phase 3 registration study, which we refer to as Study 011 and is intended to support US approval of Amigal.

In the first quarter and continuing through the month of April, we made significant progress towards completing enrollment in this study. We have 37 investigational sites open around the world with whom we are collaborating very closely.

Today we are pleased to announce that we are nearing completion of enrollment and expect to complete this effort late this quarter or in the third quarter. This continued progress is the result of a tremendous effort from the Amicus team, our partners at GSK, and our collaborators worldwide.

Now there's no question that this trial, like most studies in the rare diseases, has been challenging to enroll. And this is particularly true in our case with our Phase 3 study of Amigal due to the combination of strict entry criteria and the evolving Fabry market over the last two years.

However, despite this challenge, we've maintained focus on our strategy throughout this process with confidence that the protocol design we established gives this trial, and thus this program, the best chance for success. We remain confident and look forward to completing enrollment soon, which we will announce in a separate press release.

With that, let me switch gears to our Amigal Phase 2 extension study. We're excited about the continued progress with this study. The long-term data continue to suggest encouraging safety and efficacy outcomes after treatment with Amigal.

In February, we presented our annual update from this study, and again the data were very well-received by the Fabry medical community. As a reminder, 17 subjects are currently receiving treatment in this study.

The data update we provided demonstrated that Amigal remains generally well-tolerated, following up to four years of treatment. And in patients who have a genetic mutation responsive to Amigal, the data also suggests the treatment may result in maintenance or improvement of renal function, as measured by estimated glomerular filtration rate or EGFR. And in addition, importantly, reduced [progneria] continues to be observed in multiple subjects.

So these data from our Phase 2 extension studies are very encouraging. And we expect that the data from this study will be supportive to a future license application for Amigal. The long-term data combined with the robust design of the 011 study combine to give us a high degree of confidence in the potential success of Amigal.

And finally, let me touch on our second Phase 3 study which we call Study 012, which is intended to support registration of Amigal in Europe. We've made solid progress with the start-up activities for this study and have opened multiple sites globally. As a reminder, Study 012 is an 18 month randomized, open label Phase 3 study comparing the efficacy and safety of Amigal and ERT.

We expect to begin patient screening for Study 012 in the second quarter with dosing of the first patient anticipated in the second or third quarter of the year. Because this trial will enroll patients already receiving enzyme replacement therapy it will come as no surprise to you all that the global [Fabryzyme] shortage has had some impact on starting this study, especially at sites in the United States.

But we're taking steps to address this by adding additional sites and by working with our partners at GSK to open international sites as rapidly as possible. We will continue to work very hard to keep this study on track.

With that, I'll hand the call over to Bradley Campbell who'll give us an update on the continued progress of our work evaluating new applications of our chaperone technology, the use of our molecules when co-administered with ERT in lysosomal storage disorders, and the potential for our science in genetically defined subgroups of diseases of neurodegeneration. We expect important milestones from both our co-administration and neurodegenerative programs this year.

Bradley?

Thanks, Matt. Let me start with our programs to evaluate the co-administration of pharmacological chaperones with ERT, which are advancing in both Fabry and Pompe.

At a high level, we're pleased by the progress of these programs. We believe these studies have the potential to produce important data that will help us understand a completely new way to use our science and to expand the treatment options we can make available for patients.

In Q1, we announced important steps forward in both the Fabry and Pompe co-administration programs. First in Fabry, GSK and Amicus are currently conducting a Phase 2 open label, single dose study of Amigal co-administered with enzyme replacement therapy. Two cohorts of male patients will receive ERT alone and then ERT after a single administration of Amigal at one of two oral dose levels.

The primary outcome measure will be safety and a comparison of the ERT activity in plasma with and without co-administration of Amigal. We dosed the first patient in February and we're on track with our previous guidance to announce top line data in the second half of this year.

Importantly, this Phase 2 study is the first in-man clinical study of a pharmacological chaperone co-administered with ERT and could be a substantial opportunity for Amigal to address a larger percentage of the Fabry patient populations.

As a monotherapy, Amigal binds to the Fabry enzyme made naturally by patients with the responsive genetic mutation. When co-administered with ERT, Amigal binds to the recombinant enzyme, so genetic mutations are not a factor.

Our vision is that Amigal could be used as a monotherapy in patients with the correct genetic mutations, which we estimate will be about 50% of the patient population. For the other half of patients for whom ERT remains the only treatment choice, we hope Amigal will make ERT more effective through co-administration.

This additional use of Amigal thus has the potential to improve the ERT treatment option for patients, which of course would mean Amigal could be used in the treatment of all Fabry patients, in one form or another, and would significantly expand the potential market opportunity.

In addition to the work we're doing in Fabry Disease, the Amicus team is very excited to recommence clinical studies of our pharmacological chaperone, AT2220, in Pompe Disease.

In March, the FDA agreed with our proposal to conduct a Phase 2 study of AT2220 co-administered with ERT. After incorporating feedback from FDA and our physician collaborators around the world, we've commenced activities for this study. We anticipate dosing the first patient during the third quarter of this year with top line data results expected in the first half of 2012.

We're looking forward to advancing this program as we feel that there is significant medical need in Pompe and that our approach has potential to improve the ERT on the market today.

Both co-administration studies in Fabry and Pompe will provide important findings on whether the addition of a pharmacological chaperone prior to ERT can reduce the dosage or frequency of ERT infusions.

As a reminder, in pre-clinical proof of concept studies in animal models of Fabry and Pompe Disease, we have demonstrated that the addition of pharmacological chaperone can prevent the loss of ERT activity in circulation, increase tissue uptake, and increase substrate reduction over ERT alone.

Consistency in results between the Fabry and Pompe Disease models suggests that Amigal and AT2220 could be the first of many potential pharmacological chaperones for co-administration with ERT to address a variety of lysosomal storage disorders.

Now I'll turn to our pre-clinical programs evaluating pharmacological chaperones for the treatment of diseases of neurodegeneration, and in particular, our program in Parkinson's Disease.

These programs leverage our expertise in lysosomal storage disorders and rare diseases with an initial focus on genetically defined sub-populations of Parkinson's and Alzheimer's. AT3375, our lead pre-clinical pharmacological chaperone for the treatment of Parkinson's Disease, is on track to complete late-stage pre-clinical proof of concept studies, including IND-enabling activities in the second half of 2011.

AT3375 is targeted a glucocerebrosidase, or GCase, which is the enzyme deficient in Gaucher Disease, and leverages our knowledge in this indication. Mutations in the GBA1 gene for GCase are the most common genetic risk factor known for Parkinson's Disease. Not only are Gaucher carriers more frequent in the Parkinson's Disease population, but Gaucher patients have a 20 fold increased risk for developing Parkinson's Disease.

Finally, we continue to advance our pre-clinical work in evaluating the potential for pharmacological chaperones to treat certain sub-groups of Alzheimer's Disease.

That wraps up our program overview. At this point, Daphne Quimi, our Corporate Controller, will review the financial results for the first quarter of 2011. Daphne?

Thanks, Bradley, and good afternoon, everyone.

Before I review the first quarter financial results, I will comment briefly on our cash position and financial guidance.

As of March 31, 2011, cash, cash equivalents and marketable securities totaled $93.8 million, compared to $107.4 million at December 31, 2010.

In early January, we provided financial guidance and at this time we reiterate our expectations to spend a total of $45 million to $55 million on 2011 operating expenses, net of any cost sharing and milestones related to the GSK collaboration.

Additionally, our current cash position, including anticipated payments from GSK in connection with the collaboration, is expect to be sufficient to fund our operations and capital expenditure requirements through the anticipated commercial launch of Amigal in the United States.

Now, as I move to the financial results, I will be referring to Table 1 in our press release. If you have not already received this release, it is available on our corporate website at www.amicustherapeutics.com. Additional details can be found in our Form 10-Q to be filed later today with the SEC and available in the Investor Relations section of our website.

Total revenue for the first quarter of 2011 was $6 million, consisting of $4.3 million in research revenue and $1.7 million in collaboration revenue, compared to no revenue in the prior year period.

Research revenue reflects payments received from GSK for shared development costs of Amigal. Collaboration revenue reflects the recognized portion of the upfront payment received from GSK upon signing the collaboration agreement.

Total operating expenses in the first quarter of 2011 was $16 million, compared to $13.4 million in the prior year period. The increase was primarily attributed to an increase in research and development expenses which were $11.1 million in the first quarter, including $600,000 of stock-based compensation expense, compared to $8.9 million in research and development expenses in the prior year period.

The year-over-year increase in R&D was a result of contract research and manufacturing costs within the Fabry program.

General and administrative expenses for the first quarter of 2011 were $4.4 million, including $800,000 of stock-based compensation expense, up from $3.9 million in the prior year period. The increase in G&A expense was primarily due to an increase in third party legal and consulting fees.

Interest income for the first quarter was $60,000, as compared to $50,000 in the comparable quarter last year.

Net loss attributable to common stockholders for the three months ended March 31, 2011, was $13.4 million, compared to a net loss of $13.2 million for the same period in 2010.

This summarizes our key financials for the first quarter of 2011. I will be happy to address any questions during the Q&A part of this call.

With that, I turn things back to Matt.

Great, thanks, Daphne. So, as you can see, we've made significant progress in 2011 so far and we look forward to achieving multiple important milestones over the course of the rest of this year.

With that, why don't we stop the call, or at least our opening remarks and turn it over to any questions that you all may have. So, Operator?

Thank you. (Operator Instructions).

Ritu Baral, Canaccord.

First question is on the Amigal pivotal trial. Regional enrollment patterns, have you guys seen any sort of differential enrollment across the centers? Have you had any sort of new centers come on line? And has GSK been helping you with that?

No real trends, anything new in that regard. No new sites that have been added. We've been pretty much at that same number over the course of the year. And we're working actively with all of them from a recruiting standpoint.

I would say that GSK over time, not surprisingly, as they've gotten more and more involved in the program is more and more active in assisting. In particular, outside the United States where we tend to leverage a bit more CRO support than we do in the United States. So there's local people on the ground in countries where we don't have full-time staff that can help with talking to docs and the sites and helping with patient recruitment.

So, that's definitely a helpful aspect to our efforts right now.

And moving to the Amigal combo trial -- what percentage of normal ERT dose is required in sort of that one month lead-in period before your single combo dose?

Pol, is there a percentage that they have to be at for ERT? We know it has to be a stable dose, but there's not actually a requirement on that, Ritu. As long as they've been stable on a dose for that period of time, because when you think about the objectives there, we're just trying to look at the pharmacokenetic impact on the ERT.

So as long as we can know that they're stable and then compare the ERT alone outcome to the outcome when you co-administer the chaperone, we feel we can gain enough information from that, in particular because we're doing this in a decent number of patients.

Great. So that shouldn't essentially be sort of a rate-limiting step, as far as enrollment in that trial?

Right. I think that's our vision for it and we, of course, we thought that through as we were getting going on it, not wanting the Fabryzyme shortage to slow us down there. So we did build that into the study. It remains to be seen if people that are antsy about their Fabryzyme supply, if they feel uncertain about anything, maybe they'll be less inclined to participate, but that hasn't been a problem so far.

Okay. And remind us again what that percentage of normal ERT dose is for the European pivotal trial that you're starting?

So for the European dose, they really need to be within, they need to be very close to the labeled dose, 80% of the labeled dose of the drug, and on that stably before they can come into the trial, because obviously we don't want to enroll patients who partway through the study are going to have a significant increase in the ERT dose they're receiving, which could confound the results.

Got it. And then last question, moving on to 2220. What is the size, the patient number of that trial that you're considering? You think you'll have multiple cohorts, sort of like the Amigal combo therapy study?

Yeah, it's going to look a lot like the Amigal study and there will be multiple cohorts. And when we announce that study, in particular the dosing of the first patient, we'll be happy to provide more specifics on the patient numbers that we expect, number of cohorts.

And as far as the benefit of combo therapy for 2220, I guess what is the scientific rationale behind, do you think it will increase potency more than it will reduce immunogenicity? How do you think the sort of two benefits might weigh out?

Well, difficult to predict exactly how that will play out. But in Pompe in particular, we have aspirations of improving both safety and efficacy because of all the issues associated with that product and in particular the outcomes you see with those very high doses of ERT that are delivered.

So, we are very optimistic based on the animal data that we're going to have an impact on both aspects of efficacy by way of having a slower clearance of the ERT and more tissue uptake with even a lower dose of ERT.

And because we're using a lower dose and keeping it more stable when it's in circulation, we think that may have a very positive impact on the antibody reaction, the immunogenicity of the treatment and therefore, hopefully, produce a better safety profile for patients.

[Geoff Meacham], JPMorgan.

Hi, guys, this is [Anu Pamrama] in for Geoff Meacham.

A couple questions. The first one is should we still be expecting data from the Phase 3 Amigal study in the second half of the year? You've given us a little bit more definitive enrollment timelines.

Yeah, I think that's going to be difficult. And it's more likely the data will be in early 2012. Clearly, it's a 6 month study and you're going to need some time on the back end to analyze or get the data in, get the [database] locked and make sure everything is set in that regard.

So, I think what we plan to do is get to completion of enrollment and at that time we will provide more specific guidance on when to expect data. But I think at this point, unless something dramatic happens in the next couple weeks, it'll be difficult to get those data within the calendar year of 2011.

So, I expect it'll be early 2012 and we will provide more specific guidance on that as soon as we complete enrollment and announce that separately.

Great. And the other question is, when you kind of look at the Amigal development program and Fabry Disease, you've got a placebo control trial, and an ERT combo trial. You kind of briefly mentioned this in your opening remarks, but how to you ultimately see the agent being positioned? And I guess as a theoretical question, have you considered maybe a study as a potential maintenance therapy after ERT?

I guess the way that we thought about that, because it is an important question, is that for patients with addressable mutations, monotherapy will be the primary treatment choice for them. And so that will be positioned and you could consider, over time, how that might play out for [naive] patients versus switch patients which we'll obviously have to pay careful attention to. But in our opinion, for patients with addressable mutations, an oral treatment option is the ideal treatment option for them.

For patients with non-addressable mutations who can't take the oral treatment option, then you would consider a combination therapy approach. And so we see that as very much a market expansion kind of opportunity and one that should benefit more patients over time.

Joseph Schwartz, Leerink.

I was wondering, have you looked at the knock-out models for Pompe as well as Fabry and what have you seen there as far as the enzyme enhancement that is possible with your chaperone AT2220 relative to Amigal, in combination with ERT?

So, the data are extremely promising and it's really those data that we based our vision for going into the clinic. We have very good mouse models available for both Fabry and Pompe. So they're knock-out models, as you say. So they don't make any enzyme naturally. And as a result, they're easy to work with when looking at co-administration because you can see what happens with ERT alone, and then you can do the co-administration in both, in Fabry and Pompe.

In those mouse models we've shown that with the co-administration approach you get significantly more enzyme into key tissues, the tissues you care about in disease, like the kidney in Fabry. And you get a resulting larger decrease of the substrate that accumulates in these diseases.

So, we've seen that in both diseases. It was very repeatable in those models and that was extremely encouraging and gave us the confidence to invest in the Phase 2 clinical studies that we've started now. And I think with positive data out of those, we expect to try to move these approaches very rapidly into Phase 3 development as a new approach to using chaperone technology.

And what kind of overlap do you foresee, if any, in terms of the sites that you're using in the 011 study and that you might use for the 012 study?

Yeah, a pretty significant overlap. Because we've got such a large number of centers involved, there is a lot of overlap as we're working with [other world] experts of course and all the key centers that see Fabry patients.

We're actually right now looking at the possibility of even more sites for 012 than we did for 011, which is really a reflection of the Fabryzyme shortage issue and wanting to ensure that we just give ourselves every chance possible to enroll the trial in a reasonable time frame. And in our experience, the number of sites is the most important among many factors in trying to stay on timeline with enrollment.

So, that's our expectation and as we get, because that's a bit in flux as I described, we're just now continuing to add sites to that and bringing them all up globally. As we get closer to a final target number for that, we'll be happy to share that with everyone. But right now, it's a number we actually expect to be above 40 sites globally when we're all said and done.

And the reengagement of a lot of the same sites? Would you expect that to help significantly with the IRB process? Any thoughts on that for the 012?

Oh, it certainly gives us some help [if you do]. If you've already worked at the sites, there's two aspects to working with the sites that can be time consuming. One is the IRB or ethics committee process and the other is establishing a contract between the company and the sites.

And having worked with the site before is definitely helpful, in particular on the contract side. And then on the IRB side, you get to know their schedules and areas of sensitivity and you can predict those and hopefully move through the process a bit faster.

So, we'll leverage all the experience that we can to move it along, but both of those processes can still be frustratingly long in drug development, as you know quite well.

(Operator Instructions).

I'm showing no further questions in the queue.

Great, well, why don't we wrap up then? And once again, thank you everyone for dialing in today and look forward to speaking with you again soon. Bye-bye.

Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program. You may all disconnect. Everyone have a great day.