Amicus Therapeutics Inc (FOLD) 2008 Q3 法說會逐字稿

Good day, everyone, and welcome to the Amicus Therapeutics conference call.

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During this call Amicus may make various remarks about the Company's future expectations, plans and prospects that constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Company's most recent annual report on Form 10-K and our periodic reports on Form 10-Q. These documents are available from the SEC, the Amicus website or from our investor relations representatives. In addition, any forward-looking statements represent our estimates only as of today and should not be relied upon as representing our estimates as of any subsequent dates. While we may like to update forward-looking statements at some time in the future, we specifically disclaim any obligation to do so, even if our estimates change.

Before we begin we'd ask everyone to go to the Investor Relations section of the Company's website, AmicusTherapeutics.com, and print out the press release and related financial tables. These will be particularly useful when the Company reviews the financial results and reconciliation to non-GAAP financial measures discussed today.

And now at this time I would like to turn the conference over to Mr. John Crowley, President and CEO of Amicus Therapeutics. Please go ahead, sir.

Thank you, and good afternoon, everyone, and welcome to our third quarter 2008 conference call. I am joined on this call by other members of the executive team here at Amicus, including Matt Patterson, our COO, who will provide an update on our lead lysosomal storage disease clinical programs; by Jim Dentzer, our CFO, who will provide an overview of the financial results for the quarter; and also available is David Lockhart, our Chief Scientific Officer, who will be available to participate in the Q&A portion of the call that will follow our formal remarks here.

Let me begin by saying that in the third quarter we focused very intensely on continued advancement of our core programs. In our lead program, Amigal for Fabry Disease, you will recall that in August we announced successful completion of our end-of-Phase 2 meeting with the FDA. Since that time, we have continued to make excellent progress in our discussions with both the FDA and the EMEA in Europe in order to further define our global development plan for Phase 3 for Amigal. These discussions are ongoing, and we remain optimistic and on track to provide you with an update by the end of the year. Importantly, too, I'll note that where we are in this process is consistent with our expectations, and, most significantly, we continue to expect to begin Phase 3 development for Amigal for Fabry in the first half of 2009.

In our Gaucher and Pompe clinical programs, we continue to focus on running our ongoing Phase 2 clinical trials in each of those diseases, and we expect to report the Gaucher Phase 2 data in 2009. Separately, in our Pompe program, we continue our preclinical work to evaluate the potential for the combination of our chaperone, AT2220, and enzyme replacement therapy. This exploratory effort looking at the combination underscores the versatility of our chaperone platform, and I will ask Matt to elaborate a bit more on where we are and the next steps in just a minute.

During the third quarter, we also announced that we leased a small-scale research facility in San Diego which will be used to support ongoing research into new applications of our chaperone platform technology beyond the lysosomal storage disorders. In particular, the work done in the new San Diego facility will focus on diseases with high unmet medical need and larger patient populations, particularly in the areas of neurodegenerative and other genetic disorders. In 2009 we expect to provide more specifics on the R&D programs that we will focus on in addition to the ongoing work in our preclinical program in Parkinson's.

So, as we continue to execute on our lead clinical and preclinical programs, we look forward to achieving several important near-term milestones.

And, finally, I'll finish my upfront comments here by reminding everyone of our strong financial position based on a healthy balance sheet and our strategic alliance with Shire that funds 50% of our worldwide development costs for our three lead programs in the lysosomal storage disorders and provides for excellent -- I'm sorry, for success-based milestone payments for these lead programs. Jim will add some more detail later in the call, but obviously this is a very important subject at this time in the markets.

With that brief overview, I will turn the call over to Matt Patterson and ask that Matt further review in more detail our lead clinical programs in the lysosomal storage disorders.

Matt, it's over to you.

Thanks, John, and good afternoon, everyone.

I'll start with Amigal for Fabry and just elaborate a little bit on the introduction John just provided. As John mentioned, our focus over the last quarter has been to continue our discussions with both the FDA and the European authorities regarding our global Phase 3 development plan for Amigal. We continue to make excellent progress on these discussions. We're very encouraged, and, as John mentioned, the process has been moving along exactly as we predicted it would as we started this effort months ago now. And, as a result, as John mentioned, we're still on track to initiate Phase 3 development of Amigal in the first half of next year.

In addition, in parallel with this regulatory process, we continue to treat patients in the voluntary Phase 2 extension study, which we've spoken about before, but just as a reminder, 26 patients completed the initial Phase 2 protocols, and of these 26 patients, 23 have elected to continue treatment with Amigal in the voluntary extension study, which is a decision worth highlighting, because all of these patients have the opportunity to receive enzyme replacement therapy, but instead, along with their decisions, they're choosing to remain in our study. So we're very encouraged by that. And of these 23 patients, all of them have now been on Amigal for more than 1.5 years, and in fact eight of them have been on for more than two years, and some of them are approaching their third-year anniversary, so really an excellent study of continuing data collection for long-term efficacy and safety of Amigal. So we expect it will be an ongoing valuable source of data for us.

And, as mentioned before in previous calls and announcements, we are also using this extension study as an opportunity to evaluate two additional potentially optimized dose regimens beyond what we finished with in the Phase 2 primary protocols. And happy to report that we continue to be on track for getting those data and plan to announce those in Q1 '09 prior to initiating a Phase 3 study. As a reminder, we intend to look at those data and based on those make a final decision on a dose and initiate the Phase 3 thereafter.

So that's the Amigal update. Let me turn to the Gaucher program, our drug Plicera for Gaucher. Our focus here has been on continued execution of our ongoing Phase 2 study of Plicera in patients who have not been treated with enzyme replacement therapy previously. We're making excellent progress on this study, as well. As a reminder, this is a six-month study designed to evaluate safety but also to demonstrate trends of efficacy in the standard endpoints in Gaucher Disease, which include platelet count, hemoglobin level and spleen volume. We're studying two different dose regimens, repeating cycles of 225 mg three days on Plicera and four days off and 225 mg seven days on Plicera and seven days off. And, as John mentioned earlier, we expect to report the data in 2009, although I could say that earlier next year we expect to be able to provide more specific guidance on when in 2009 those data will be available.

So finally I'll turn to the Pompe program. As you know, this is a severe neuromuscular disease that continues to have very significant unmet medical need. In the second quarter we were very pleased to initiate our Phase 2 clinical trial of AT2220 as a monotherapy, which represents the first investigational oral therapy in development for Pompe patients and, of course, the third chaperone from Amicus to enter Phase 2 clinical studies. It's a multinational 12-week trial with an open-label design. Eighteen patients will participate. And upon completion of that 12-week time frame, patients will have the option of entering into an extension study designed to evaluate longer term effects of AT2220, both from a safety and an efficacy perspective, which will provide us further guidance on continued development of this drug candidate.

In addition to our work evaluating the product AT2220 as a monotherapy for Pompe, we continue to conduct preclinical studies to look at the potential therapeutic effects of administering AT2220 in combination with enzyme replacement therapy. We're evaluating this approach because we believe there are some patients who may not be good candidates for monotherapy but who may benefit from the combination approach. Therefore, we intend to continue our preclinical work, and based on these results we'll evaluate the potential for initiating clinical studies of combination therapy. But if both monotherapy and a combination approach prove to be successful, we have the potential to treat the entire Pompe population with regimens based on AT2220. So we're very encouraged by the progress on that program both clinically and preclinically.

So with that review of the lead LSD programs I'm going to turn the call over to Jim Dentzer, who's going to give us a review of the financial results for the third quarter.

Jim?

Thanks, Matt, and welcome, everyone. I'll provide a brief summary of the financial results for the third quarter.

Overall we continue to have a strong cash position. In Q3 we used $9 million of cash, ending the quarter with approximately $136 million in cash and marketable securities. That compares to $145 million at the end of Q2 and $162 million at the end of 2007. In this difficult market we continue to manage our cash carefully and expect our current cash, together with expected milestones and reimbursement from Shire, to enable us to fund our operations at least until 2011.

As we move to the P&L, I'll be referring to the tables in our press release, which use the same format as last quarter. Please note that GAAP financials are provided in Table 1. Table 2 and Table 3 are a reconciliation of the GAAP and non-GAAP financial results, highlighting charges for three non-cash items -- stock-based compensation, preferred stock accretion and changes in fair value for warrants. As with last quarter, the charges for preferred stock and warrants do not impact the current period, as they were converted to common stock in connection with our May 2007 IPO.

Total revenue for the third quarter 2008 was $3.7 million, comprising $0.7 million of collaboration revenue on the upfront payment and $3.0 million in research revenue for the reimbursement of R&D costs associated with our three lead programs. For the nine-month period, total revenue was $10.6 million for the period ended September 30.

On a non-GAAP basis, the net loss for the quarter was $6.6 million, as compared to $9.2 million for the same period in 2007. The reduction in operating loss was driven primarily by revenue resulting from our collaboration with Shire, under which, as many of you know, Shire pays 50% of global development costs in each of our three lead LSD programs. As a reminder, Amicus retains all U.S. rights to these programs as well as rights to all other programs in our pipeline.

Now to the R&D investment, we spent $7.6 million on R&D in the third quarter. This is higher than the $7.1 million in the comparable quarter last year, as we expected. And consistent with what we mentioned on our last quarterly call, we expected R&D expense to ramp up through the remainder of 2008 and into 2009 as we initiate and enroll additional clinical trials, invest in clinical drug supply and expand our discovery research activities.

Our G&A expense was $3.4 million, compared to $3.3 million in the third quarter of 2007. This increase was primarily due to hiring in key areas.

Our interest income for the third quarter was $1.0 million, as compared to $1.6 million in the comparable quarter last year. This decrease is primarily due to lower prevailing interest rates.

Our financial guidance for 2008 remains as follows. Our 2008 guidance for cash burn has been in the range of $40 million to $50 million. Despite expected Q4 payments for manufacturing royalties and license fees, we expect to finish the year at the low end of that range due to careful management of our cash. As a reminder, this cash burn guidance includes reimbursement of R&D costs but excludes milestones from Shire. We will continue to recognize the $50 million upfront payment from Shire on a straight-line basis over an 18-year period from the date of the agreement last November.

So that covers the balance sheet and income statement update. With $136 million in cash September 30, the potential for an additional up to $150 million in clinical milestones between now and regulatory approval, and Shire's commitment to fund half of our LSD development costs, we are well positioned to fund further advancement of our clinical and preclinical programs.

If there are any other areas you want to cover, I'll be happy to address them during the Q&A part of the call.

With that I'll turn things back over to John for closing comments.

John?

Great. Thanks, Jim.

We are now well into the fourth quarter, and our focus continues to be on executing against plan to advance into and through the clinic each of our three lysosomal storage disease development programs. By the end of this year we plan to have an update for you all on the status of our regulatory discussions for Phase 3 development of Amigal, and by Q1 of next year we expect to announce new data from the Phase 2 extension study with Amigal and then to initiate the Phase 3 study in the first half of next year, 2009.

In Gaucher we expect to have additional Phase 2 data in the program in 2009, and we also, of course, plan to continue progressing our Pompe program on multiple fronts, both as a monotherapy and in exploring the potential of a combo therapy there, as well.

We continue to have strong confidence that our business remains on track, and we look forward to executing on some very important milestones over the next six to nine months. And I will add, too, as Jim just added more detail to, that we are well positioned financially to continue to execute according to our plan with this business, and we'd like to thank each of you for your continued support. I'll remind you that in addition to Matt and Jim, David Lockhart is also here and available with the team for questions and answers.

And with that we'd like to open the call to questions, so, operator, please go ahead and feel free to open the call.

Thank you, sir.

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We'll take our first question from Matt Osborne, with Lazard.

Hi, guys. Thanks for taking the question. I have a question just to start with Matt, perhaps. Have you reached an agreement with either of the FDA or the EMEA of what would be an acceptable surrogate endpoint for Amigal?

Hey, Matt. No, we haven't finalized the discussions with either the FDA or the EMEA, so those continue to be ongoing. As we mentioned during the call, we expect to be able to provide an update on where exactly we are in that process by the end of the year, and certainly as we get to that update and then beyond we'll keep you totally informed. But right now it's not complete and we're on track to provide you an update by the end of the year.

Is there any risk that either group could arrive at a different endpoint, or do you feel based on the discussions and comments that you've received from both that they're moving in the same direction?

Oh, you know, I think it's difficult for me to speak to specifics of those ongoing discussions. I mean, they're both ongoing now. We're very upbeat about the progress with both. Sure, I mean, that's -- it takes some time to get through the process of working with both authorities, but we want to get, as we said before, we want to get the perspective from both regions so we can design the most robust Phase 3 program for global approval and successful marketing of the drug. So we're going to do our very best to tie it all together and come up with a plan that makes the most sense for this program.

Okay, great. Then, of the 23, of those patients in the extension study, have you started to see, with the dose optimization, are you seeing continued stabilization or are these patients starting to improve?

I don't have that data update for you at this time, Matt, but we'll give you an update in Q1, as projected earlier. But we are collecting ongoing safety and efficacy data, which does include the clinical measures of disease that we've spoken about before. And so we'll be happy to report on those over time. The focus for the Q1 update will be around those optimized and potentially optimized regimens, which means a focus on both safety but also enzyme levels and GL3 levels. So I think that's a reasonable expectation for Q1.

Is that likely at one of the conferences, [ACMG] or --

You know, a little difficult for me to predict exactly when, then, Matt, so right now I can't say any more specifically than Q1. But we'll do our very best, and of course we'll bring it to a scientific forum as soon as we can. But our expectation is at a minimum to provide everyone with a top-line update in Q1 by way of press release.

Great. Last question, for Jim, actually. You mentioned, Jim, that you have sufficient funds to last until -- through 2011. Does that include the milestone payments from Shire?

Yes.

Great. Thank you.

Next to Greg Wade, with Pacific Growth.

Good afternoon. Thank you for taking my questions. Matt, just with respect to the progress with the two agencies, first question would be, what criteria did you pre-specify in terms of your evaluation of the progress you'd be making there? Help us to understand how you're measuring that progress. And, secondly, in what forum do you anticipate updating us by the end of the year on where you're at with the two agencies? Thanks.

Sure. Hi, Greg. Well, you know, look, I think regulatory affairs is occasionally a bit of an art form on how things progress, and so I wouldn't say there's a set criteria for establishing a time frame. You need to work closely with the agency and do what's most productive and efficient. I think overall in the big picture we're making the progress we expected when you combine the multiple factors for us, which are that we want to work very successfully with FDA. We want to work very successfully with the Europeans. We have a corporate partner at Shire HGT that's very involved in this process.

And so I think when you combine all those factors the timeline we're working on is really quite reasonable, and the most important outcome here is that we get to a Phase 3 program that we can all have confidence in. And we have, I think, the luxury, also, of doing this in parallel with that Phase 2 extension. We're interested to see those data and make the best possible selection on dose for Phase 3, as well. So I think the timeline all kind of ties together quite well to ensure that we're giving the Phase 3 program for Amigal the very best chance of success.

Great. And how do you expect to update us before the end of the year?

Sorry. I think we'll -- right now, our expectation is to issue a press release, and it's possible that we'll have a Q&A session along with that, but honestly that's just a draft plan. We haven't finalized that plan at this time.

Thanks, Matt.

Sure.

We'll take our next question from Geoff Meacham, with J.P. Morgan.

Hey, guys. This is [Terry] in for Geoff today. Thanks for taking the question. Just you mentioned that you are excited about your discussions with the FDA. I'm just wondering if you can elaborate at all on that, on what specifically you're excited about in those discussions. And then I have a follow-up.

Yes, Terry, of course. This is John. I think what I'd refer you back to was the announcement that we had this summer about the end-of-Phase 2 meeting. And that had in it some very important information where it answered some very, very key questions that we had and the Street had, and it told us that the FDA said we're ready to move to Phase 3, which of course is a very important question. It said that we are eligible for accelerated approval. And it said that they are not opposed to the use of a surrogate primary endpoint in this study. So we think that's all good advancement. And we've commented before, and I'll reiterate it again here, that the tone of the discussions with the agency have been very positive and very helpful. So I think that's what gives us encouragement.

Okay. And then just in terms of moving some of the earlier stage chaperone programs to the clinic, do you think that that's a 2009 thing that we could be expecting, or is it something that's probably a little further out? And then I'm just wondering how much of that is dictated on the FDA's -- the duration of the Phase 3 Amigal study.

So, I think, Terry, you're talking about the earlier stage, the Parkinson's and other programs we haven't disclosed.

Exactly.

Right, yes. So there we've got a number of programs that are underway here at the Company, and the most advanced of those is the only one that we've disclosed, largely for competitive reasons, and that's our program in Parkinson's disease, where we're applying the chaperone technology to that disease of unstable and misfolded proteins. That is a program, as you're probably aware, that is partially funded by a grant from the Michael J. Fox Foundation. It is a terrific extension of our understanding in human genetic diseases and the use of chaperones.

We continue to make advancements there in the preclinical work. We've released some of that publicly. We would expect to continue to release the preclinical work that we're doing there into and through 2009, and we don't yet have any guidance as to when that program could enter the clinic, although I would expect to be able to provide more information in 2009. And, as you would expect with the other programs, they are earlier in the pipeline. And I think as we begin to disclose those programs over the next year or two that likewise we'll be able to provide better guidance about what the timelines look like for those programs.

Okay. So it's not at all predicated upon the potential cost of the Phase 3 studies for Amigal.

No, we've already budgeted, together with our partners at Shire, the expenses for the Phase 3 studies for Amigal.

Okay. All right. Thanks for taking the question.

Sure.

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We'll go next to Steve Harr, with Morgan Stanley.

Yes, good afternoon. Two questions. First, about a year ago you presented the Phase 2 Amigal data, and it was -- at the end of it you said we'd be -- you'd be going to the FDA and having discussions about moving to Phase 3, and we're at the same spot a year from now. So what have you learned in the interim, and what are the outstanding questions that you still have to get your hands around before you can go into Phase 3?

Yeah, sure, Steve. This is John. I'll take that. I actually think we've made quite a bit of progress in Fabry over the last 11, 10.5 months since we presented that first Amigal data, the first part of which was understanding the dosing, and that was in theory the preclinical studies and pharmacokinetic work that we did together with the folks at Shire that told us that there may be more potentially optimized doses. And based on that we've modified all the protocols on all three continents for that program to move all of those patients to the extension study, essentially giving us a whole new Phase 2 look in data, but with a population that we already knew quite well. And all of that has been done, including moving the patients to those doses and now being able to report that data early in 2009 in the first quarter. So I think that's really good progress there.

In addition, we have filed all the regulatory paperwork and held discussions now with the regulatory authorities, and just answering those questions, as I alluded to earlier, from -- that were out there, some pretty significant ones, about the ability to move forward into Phase 3, about whether a surrogate would be appropriate, whether we'd be eligible for accelerated approval, we've answered those questions here in the States, and we continue to advance the discussions. And I think having a pretty strong idea by the end of this year about what that Phase 3 global program looks like and being able to initiate it first half of 2009, I think that's pretty good progress in 10.5 months.

So is the outstanding question, though, data related, or is this just a -- you need some time to meet with the FDA and actually just dot the i's and cross the t's? Are there still outstanding questions that need to be figured out before you can go forward?

Yes, I think, Steve, I want to be real careful about respecting the confidentiality of the discussions we're having with FDA and EMEA. So there are parts of the program that still need to be resolved. So I think a lot of that will be answered over the coming weeks, and hopefully we'll be able to provide that update, we're confident, in December. So I think we've come a long way over the couple of months since we first began these discussions in the summer, and being able to take it to a very significant update in December I think will be real important for the program. And, again, I think the most important vote of confidence is that we're very confident that we'll be able to begin this Fabry Phase 3 in the first half of '09.

Then you guys said you have capital to get through 2011, assuming that you get your -- sorry, your milestone payments. Can you walk us through how long your capital will last without milestone payments? And then maybe you could give us some insight into what the events are that you need to see happen to reach those milestone payments to fund the Company through 2011.

Sure, Steve. So this is Jim. I can answer a little bit of that. Some of it, frankly, I'm going to want to defer until next quarter when we have the full year behind us and we have a more clear picture of what next year looks like. But the bottom line is you're right, we do need both the reimbursement from Shire and we need some milestones to get us to that 2011 figure. We do expect -- so far all of the programs are moving ahead very successfully, and we expect we're going to be funding all three programs aggressively in 2009 and 2010. I think for now what I really would like to say is let's wait until we get the full year results, and I can talk more fully about an outlook for 2009 and potentially farther next quarter.

All right. Thank you.

Thanks.

Thank you, Steve.

I have a follow-up from Matt Osborne, with Lazard.

Hi, thanks for the follow-up. And, Jim, just a quick question on the guidance for 2008. It looks like even at the low end of the range at $40 million assumes a step up in R&D expense for the fourth quarter. Is that safe to assume?

There is a step up, but you also see in the 10Q that we're filing today as well we've got some royalties and license payments, some cash payments, coming out in Q4 for $5.3 million. And there's also some extra manufacturing that we're going to do in Q4. So, yes, you're right, I mean, there is a gradual step up as we've said all along in R&D, and that will continue into 2009 as we further through all three trials, trials for all three programs. But there are some cash items coming up in Q4 that will push that number into the lower end of the range.

Okay, great. Thank you.

Yes.

And there appear to be no further questions at this time.

I'd like to turn the call back over to Mr. Crowley for any additional or closing comments.

No, that's it. Thank you, everyone, for participating in this conference call, and we look forward to keeping you updated on developments and hope this was a very helpful summary for everyone. Have a great night. Take care.

And, again, that does conclude today's conference call. Again, we'd like to thank you for your participation, and you may disconnect at this time.