Amicus Therapeutics Inc (FOLD) 2014 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Amicus Therapeutics full-year 2014 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 is being recorded. I would now like to introduce your host for today's conference, Sara Pellegrino. Ma'am, you may begin.

Thank you. Good evening. Thank you for joining our conference call to discuss Amicus Therapeutics' full-year 2014 financial results. Speaking on today's call we have John Crowley, Chairman and Chief Executive Officer; Chip Baird, our Chief Financial Officer; Bradley Campbell, our President and Chief Operating Officer. And Dr. Jay Barth, our Chief Medical Officer, is on today's call and available to participate in the Q&A session.

As a reminder, 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, cash runway, and 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 statement are based upon reasonable assumptions, there can be no assurance that our expectations will be realized. Actual results could differ materially from those projected in Amicus' forward-looking statements due to numerous known and unknown risks and uncertainties, including the risk factors described in our annual report on 10-K for the year ended December 31, 2014. All forward-looking statements are qualified in their entirety by this cautionary statement and Amicus undertakes no obligation to revise or update this conference call 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. Good evening, everybody. It's a pleasure to speak with you.

What a difference a year makes in biotechnology. So as we reflect briefly back on the full year 2014 results, it certainly was a major inflection point for our Company, both for the migalastat monotherapy program, which we'll highlight here in a moment, as well, but also, too, for our Pompe program and our Biologics platform.

And the vision, again, that we put in the press release that was just issued a short time ago, I think is very clear. And that's to build one of the world's leading and most significant global biotechnology companies focused on transformational treatments for people living with devastating rare diseases. Again, the notion that we are looking at areas where there are devastating diseases, dramatic areas of unmet medical need, even where existing approved therapies are in place today, and where we can bring novel technologies or create science or medical capabilities to bear.

We had a great Board meeting, I can report to you, last week, the Amicus Board met here in person. We reviewed our vision, our mission, our strategic plan, and our strategy to independently launch migalastat monotherapy globally. We believe we have the base capabilities in medical affairs, patient advocacy, clinical affairs, scientific affairs, that we can add significant value to these programs and deliver on the mission to get the drug to as many appropriate Fabry patients around the world as fast as possible, and with that mission, to be able to greatly enhance our shareholder value.

So let me just recap the WORLD meeting that was a couple of weeks ago in Orlando. So very, very successful meeting. It's amazing to see how much that venue has grown, now to over 1,300 participants in all the key scientific and medical leaders in the lysosomal storage disease field. We were very pleased, from our platform presentations and multiple poster presentations, at the very, very positive physician feedback that we received.

It was very heartening to see the data shown, and in some respects, data that we put out, for instance, on cardiac endpoints in Fabry and both of our Phase 3 studies just several months ago, and for some physicians, the first time we've had a chance to discuss it in depth. Again, very, very pleased with the physician feedback around the world.

We continue to see great momentum for our programs in Fabry and Pompe, again, with two oral platform presentations and six posters. What's increasingly clear to us, too, with the science and the data the way it's evolved and the physician feedback, is that migalastat monotherapy as a precision medicine for people with the appropriate mutations in Fabry is emerging as a clearly differentiated product. We've always known that it may have a unique and strong safety profile. Certainly, as an orally bioavailable medicine, it would represent a very convenient option, enhancing compliance for patients.

But as we see the data emerging, we and the key opinion leaders continue to be enthusiastic that this is not oral enzyme replacement therapy, that this is a unique medicine with a very distinct mechanism of action, and is a very small, small molecule, able to get into all key compartments of disease in a way that we think may be very differentiated from enzyme replacement therapy. Again, with the goal that we think we may be able to offer significant benefits for patients.

So lots of excitement building around what we believe, again, to be a distinct therapy in Fabry, but also excitement building around our next program to enter the clinic, and that's our enzyme replacement therapy for Pompe disease that remains on track to enter the clinic in the second half of this year. If I can remind you, the problem that we're trying to solve for is in this devastating neuromuscular disease, Pompe disease, or glycogen storage disease, one of the largest of the lysosomal storage disorders, where the existing therapy has been approved for nearly nine years, and we think to be a very suboptimal therapy.

What we tried to do is to solve for a number of key problems related to tolerability, activity and uptake of the program. The data that we showed in a platform presentation at the WORLD conference on the first day generated, again, significant enthusiasm, where we showed that we've built a novel enzyme replacement therapy, what we're referring to internally as ATB200. And it's distinct, because it has what we believe to be an optimized glycosylation structure on the seven glycan structures on the Pompe protein, or GAA; but not only an appropriate glycosylation pattern, very importantly, a very high level of nano 6 phosphate, which is the important targeting carbohydrate necessary for enhanced uptake in Pompe.

What we showed in that data set was significant glycogen reduction compared to the current enzyme replacement standard of care, Lumizyme. And this effect was even further enhanced with the addition of the chaperone. So what we've been able to do is to grow a homegrown product with our scientists, our scientific leadership, and two of our core platform technologies, one being our internal Biologics platform to generate uniquely glycosylated and highly phosphorylated proteins and the ability to scale those, as well as the combination of a specific chaperone designed to bind to the active site of that enzyme replacement therapy. Again, the notion that it's keeping the ERT folded, more stable, more active, we believe less immunogenic, and much better targeted to the muscle cells for people in Pompe.

A lot of momentum. We were busy -- Jay is on the call, as well, here, of course, our Chief Medical Officer -- and myself, Jay, and our senior leadership team are heading off to Europe tomorrow for a couple of days, with more than a dozen key opinion leaders and investigators from around the world in Pompe disease to discuss the clinical study. We're working on a very innovative, and what we hope to be accelerated approach to the clinical study that we'll put in place in the second half of this year. So, more to come on that, once we've vetted with these experts. But a very program that we're very, very excited about.

Just a brief update, turning back to migalastat monotherapy for Fabry patients with amenable mutations, starting with Europe and the European submissions, we remain on track for the MAA submission in mid-2015, the middle part of this year. And as a reminder, we've already had our first successful pre-submission meeting with the European authorities in December of 2014.

We've had our repertoires assigned. The team is actively -- and I can tell you that it's a great part of the focus of this Company, with this as our first marketing application in the world -- that we do this as timely as we can, but also submit the highest quality document that we can. So the team is very actively preparing for that submission. And in addition, we're also beginning to lay the groundwork for our commercial infrastructure in Europe, including key leadership that we're now in the process of evaluating to put in place.

With respect to the United States, we do have an FDA meeting scheduled this quarter, so in the next several weeks. We've, of course, been getting a lot of questions from many of you about the specifics of this meeting and how we would intend to communicate the feedback. So let me be very, very clear about this. I'm going to outline now the goals of this meeting, how we'll define success and how we plan to communicate.

So this is a Type C meeting. It is distinct from a pre-NDA meeting or a Type B meeting. We requested this Type C meeting, in large part, because we've not had a formal interaction with the agency since May of 2013.

And we want to review with the FDA what we believe to be a very, very robust prespecified data set from two Phase 3 studies, and to have a conversation with the FDA specifically requesting that we move forward with the ability to file an NDA, again based on the totality of these two successful and very large Phase 3 studies. This will be light years ahead of what the FDA has seen a couple of years ago.

As a reminder, the totality of the positive data from our Phase 3 studies has shown a number of important outcomes. We have shown that migalastat has number one, resulted in reduction of disease substrate. Number two, we've shown stability of kidney function. Number three, we've shown reduction in cardiac mass. And number four, as we just showed at the WORLD meeting, we've demonstrated a positive impact on patient reported outcomes, such as GI pain and quality-of-life measures.

So again, to highlight what we showed the agency in that meeting in May of 2013 versus what we have now. So in May of 2013, when we met with the agency, again in a Type C meeting, we had performed a post hoc analysis on an interim, or six-month data set, from Study 011, that was our placebo-controlled study. And that showed a statistically significant reduction on the quantitative change of disease substrate in the kidney biopsies of Fabry patients in their interstitial capillaries, who had amenable mutation based on our GLP HEK assay. Again, the notion of a targeted precision medicine approach here.

So at that time, we proposed to the agency that we would modify our statistical analysis plan while we were then still blinded to the outcome of the 12-month biopsies to prespecify that the primary outcome at 12 months would look at quantitative change in disease substrate, and that all of the subsequent analyses at months 12 and 24 of that Phase 3 study would be in patients with amenable mutations based on that HEK assay. The agency agreed to that revised statistical analysis plan and indicated that it could be prespecified from a statistical standpoint, but not from a regulatory perspective.

So what that means is two years ago, when the FDA only saw that biochemical endpoint on an interim look at the data in the 011 study, that that alone would not support approval; and they asked us to come back when we had the totality of the data from both of our Phase 3 studies. And that's exactly what we're doing this month.

So we're going into this meeting this month, and we plan to present the data to the FDA for the first time, all data sets from both Phase 3 studies and all data sets having been pre specified. Again, on reduction in disease substrate, stabilization of kidney function, reduction in cardiac mass, and positive impact in patient reported outcomes from both of our Phase 3 studies. And we'll show this in the naive patient population from Study 011, as well as the ERT switch population in Study 012.

So again, it is a significantly larger data set than the FDA has seen from Amicus and it is also the largest data set that the FDA has ever been presented for by any company. So we believe very strongly that the totality of the data suggests that migalastat is a very promising, truly differentiated therapy for people with amenable mutations living with Fabry disease, and we continue to believe very firmly that this data set should support a US approval.

So we've not yet had this meeting. It will be in the next couple of weeks. We've submitted the briefing document to the agency. We're very pleased with the briefing document. It has been a tremendous and extraordinary effort by the team here at Amicus, together with some of our key consultants and some of the key opinion leaders who have supported this work. We believe that a successful outcome of this meeting will mean that we will be able to move forward with an NDA, based on the totality of the current clinical data from both of these successful Phase 3 studies.

In terms of communication, we would expect to issue a press release to announce that we are moving ahead with an NDA submission and to provide guidance on the timing of that submission. Regarding the timing of the announcement, we may wait for formal written feedback from the minutes before we issue a press release, which is up to a 30-day turnaround.

We would also request a follow-up formal pre-NDA meeting. However, we believe that, based on what we hope to be a successful Type C meeting here, that this pre-NDA meeting would be more administrative in nature, to discuss the details to include in the NDA, since we will have already had a very thorough type C meeting.

Finally, let me conclude, before I turn it over to the team here for some comments, that we are going forward. One of the questions we've posed to the FDA is, does it agree with our perspective that the totality of the clinical data set and the breadth and strength of the data set support a full approval versus a sub Part H approval which, as you know, is based on a surrogate endpoint likely to predict clinical benefit. That, of course, was the initial path that we sought when we thought that we might seek approval solely based on biochemical data.

We don't know if this level of detail will come out of our Type C meeting. It may be deferred to a review issue, but it is a question that we're posing. So we were very explicit in our questions to the agency, very, very direct, with an enormous amount of supportive data in the briefing document. The team has prepared extensively and continues to prepare, and we continue to believe that this is a medicine that should be available to people in the United States living with Fabry disease with amenable mutations as quickly as possible.

So with that, let me turn it over to Chip to review the financials, and he can emphasize the strength of the balance sheet and the Company, as well. So Chip, go ahead, please.

Great. Thanks, John. Good evening, everyone. I'll start today's financial discussion with a few comments about our current cash position and guidance.

As indicated in this afternoon's press release, Amicus continues to maintain a very strong balance sheet. At December 31, 2014, we had $169 million in cash and cash equivalents, and that compares to $82 million at the same time last year.

Our balance sheet was strengthened during 2014 with a $40 million at-the-market financing in the second quarter, as well as a $103 million offering in the fourth quarter. As guided in early January around the JPMorgan conference, we expect full-year 2014 net cash spend to total between $73 million and $83 million. Based on this trajectory, we expect our current cash position to fund the operating plan into 2017.

Turning to our full-year 2014 financial results, I'll be referencing tables 1 and 2 in the press release we issued earlier today. Additional details can be found in our annual report on Form 10-K, which will be filed later this evening.

Total offering expenses for the full year 2014 increased to $69.9 million, compared to $64.5 million for the full year 2013. The year-over-year increase was primarily due to increases in preclinical and clinical development costs on Fabry monotherapy and Pompe programs, including carrying 100% of the development costs of migalastat in 2014, versus 40% of the costs in 2013 under the GSK collaboration.

Moving down the P&L, we had a non-operating loss of $1.3 million in the full year of 2014, compared to non-operating income of $1 million in full-year 2013. This change in non-operating expense, which is a non-cash item, was primarily due to an increase in interest expense on our outstanding debt, partially offset by the change in our warrant liability, which expired in March of 2014.

Net loss attributable to common stockholders in full-year 2014 was $68.9 million, compared to a net loss of $59.6 million in the full year of 2013. Net loss per share of $0.93 in the full year of 2014 was narrower than the net loss per share of $1.16 in the full year 2013. The narrower net loss per share versus the year ago period is attributed to an increase in the shares outstanding as a result of our ATM and follow-on public offerings. As of December 31, 2014, we had 95.6 million shares outstanding.

This summarizes our key financials for full year 2014, as well as our full year 2015 guidance. More information on our financials will be available in the 10-K which will be online later this evening. Happy to address any questions during the Q&A session, but for now, we'll turn the call back to John.

Great. Thanks, Chip. So let me just conclude by highlighting some of the milestones we expect across our entire Fabry disease franchise and, again, to remind everybody we think we have a unique platform and series of technologies to be able to help all people living with Fabry disease.

Of course, for those with appropriate mutations, it begins with migalastat monotherapy. We've already talked about the first quarter, the FDA meeting, and as soon as we can after that to issue the feedback from the agency on this Type C meeting. We would then, in mid-2015, the next milestone would be the migalastat monotherapy MAA submission.

We also in the second half of this year, at various scientific Congresses, since we still have more than 90 patients enrolled in our extension studies who continue to take migalastat as their only lifelong treatment for their Fabry disease, we continue to collect that data. We expect to see more of that toward the end of the summer and, from the extension studies, be able to report even longer term data, including at least 30 months of data on kidney function for the migalastat patients coming out of the 012 extension study.

So further important data that we'll see. We'll continue to follow their cardiac function and other measures of disease. So in the second half of the year, hopefully we'll have even more continued good news on the data with Fabry disease.

We're also working very diligently on the notion of combining chaperones with enzyme replacement therapy. We've talked to a number of you about the plans in the second half of this year for the initiation of a longer term Phase 2 study of migalastat co-administered with either Fabrazyme or Replagal, the currently marketed ERTs.

Again, a number of questions about this. The strategy there is to show further proof of concept that the addition of a chaperone can fundamentally change, in a very positive way, the nature of those ERTs, leading to what could be greater benefit for patients. We've got a number of different ways that we're looking at that. Whether that leads to a label expansion for us for co-administration or begins to seed the path toward out next generation Fabry ERT will be based on the data set that we see from those studies.

With that, we are in parallel actively working on the internal development of a next-generation enzyme therapy, so a bio better Fabry ERT cell line that is co-formulated directly with migalastat. And for patients with non-amenable mutations, we see this as having the potential for an advanced new option to treat their Fabry disease.

For Pompe program, a very, very important year for us. We have completed the engineering run successfully. We've talked to a number of you about the scale up in the second half of 2014 into the beginning of this year. We are in the midst of our IND enabling toxicology studies. Those will complete in the middle part of this year.

We have now begun the GMP batch runs with our partners at our contract manufacturing firm. We expect a pre-IND meeting in the middle part of this year and, again, to begin those clinical studies in the second half of 2015. So it was a great year in 2014, and we hope, in many ways, it will be just a great or even greater year in 2015.

So with that, Operator, those are our opening comments in 25 minutes, and happy to take any questions.

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

Thanks so much for taking the question. Just a quick question on where you are in terms of setting up an expanded access program for migalastat and which regions you guys are going to be focused on initially? Thanks.

Yes, we've been looking at that and working on it very actively. Brad, do you want to comment?

Sure. Thanks, Anupam. So as you know, we have been working on that. That program is set up, essentially the protocols are finalized. We're working with a great partner who has lots of experience in executing in those programs globally. We are essentially waiting to get feedback from the FDA before we initiate those programs. If they ask us to do additional work around the submission package, for example, we want to make sure that we have pools of patients available for that, really just a precaution.

That being said, we're ready to go once we have those regulatory interactions. And we would be looking to do that on a global basis, on a country by country basis, in particular where regulatory mechanisms exist for such expanded access programs. We'll have more to say on that as we come forward here and, again, finalize that regulatory feedback. But I would expect that that would be, again, on a global basis and a fairly significant effort.

Great. Thanks so much for taking our question.

You bet.

David Lebowitz, Janney Montgomery.

Thank you very much for taking my question and congrats on some great progress in the last few months. When you're looking at migalastat potentially entering the market, obviously the drug will be looked at in the amenable -- is going to be used in the amenable mutation population. But how do you actually view is the likelihood that doctors will implement the therapy? And the obvious would be in people who failed ERT, but theoretically the choice to use it could be earlier than that. And how do you think doctors will view that equation?

Yes. No, very clearly. I want to be very clear, this is not second-line therapy. This, we think, you look at the initial market of an opportunity for people already diagnosed and on enzyme replacement therapy. That's about 4,000 patients. That's part of a diligence project that we're working on with some consultants to narrow that. But about 4,000.

We think about a third of those patients have amenable mutations already today, so somewhere between 1,000 and 1,500. We believe immediately upon approval that physicians should strongly consider, based on the strength of the data we have, especially in the switch study that we've already shown you can safely and effectively switch patients, that if you have a genotype in one of those 1,000 to 1,500 patients, again, you should immediately switch, stop all ERT and switch to our drug.

We think it will have a good safety profile. It will certainly be more convenient, much less of a burden on patients. But most importantly, we think it may offer benefits for patients that ERT does not offer today. And again, that gets to the notion that this is a fundamentally different mechanism of action. It's getting into places like the podocytes in the kidney. We believe it gets into places like the cardio myocytes in the heart. We think the strength of the LVMi data on cardiac mass is very distinct from what's seen in enzyme replacement therapy.

So for those reasons, that's going to be a key part of our initial launch focus, I would expect. And then also, there are about 4,000 or 5,000 diagnosed but untreated Fabry patients. We think this could offer substantial benefit for many of those patients; well more than a third of those patients, we believe, have amenable mutations. And then beyond that, we think there may be a much larger patient population.

But we see this as a really unique, new therapy for patients. And yes, there are some patients who have failed ERT or who cannot tolerate ERT. If they have amenable mutations, certainly they should consider, with their physicians, migalastat. But we think very much this will be a transformative medicine in the space.

Excellent. And just quickly moving over to Pompe. Given the experience with migalastat and the challenges you had in the past, how has that guided you in designing the Pompe program?

So again, a fundamentally different approach to treating the disease. Migalastat, of course, being a small molecule precision medicine; in Pompe disease, what we've developed is a biologic product. We think it's a very advanced biologic product, that it offers significant potential benefits over the current standard of care, in terms of the potential to reduce immunogenicity, to increase tolerability, and very importantly, to increase tissue penetration of the enzyme into all key muscles of disease.

And that's a good part of the data that we showed at the WORLD meeting, the pre-clinical data was very, very compelling in places like the quadriceps and the soleus. Very difficult in a head-to-head study with the current standard of care. Our uniquely engineered cell line plus chaperone, that drug product combination was very, very distinct from the results seen with the current ERT, Lumizyme alone.

So as we think about designing a clinical study, this is a drug for all people living with Pompe disease, and we want to evaluate it in all key patient populations. And again, we're thinking about a very creative, adaptive and innovative design that can move the medicine to patients very quickly. So some general learnings on clinical operations and execution and patient advocacy, for sure, in our nearly decade work with migalastat. But the approach in Pompe is very different.

Thank you very much.

You're very welcome. Thanks, David.

Joe Schwartz, Leerink Partners.

This is [Mayam Contani] covering for Joe. Thanks again for taking my question and congrats on a very successful quarter. Just quickly, on this meeting that you have in two weeks. I was wondering, you laid out the four goals, but if you can help us understand what specifically would these goals be focused on, which ones, if you can help us identify?

I know you said you'd already presented the bio marker data in your previous meeting in May 2013 and you'll be generating more kidney function data from the long-term outcome study, which possibly can go into the NDA application eventually. If you can help us understand which components of this dossier that you have already submitted leading to that meeting would be the key focus for the regulators. Thank you.

Sure. So it's all the data sets on all the prespecified endpoints from both Phase 3 studies, the biochemical data, the kidney function data, the cardiac data, and the patient reported outcome data. So many, many ways to look at the drug's effect in many, many different respects.

And, again, to highlight, the purpose of the meeting is to share that data with FDA, very complete in the briefing document, and to discuss with them specifically our proposal that we move forward with the filing of an NDA and that the focus of that filing be on a full and final approval pathway for the drug. So very, very clear objectives to the meeting; and hopefully, we'll be successful.

Thanks. Good luck with that (multiple speakers).

Thank you. And at this time, I'm not showing any further questions. I'd like to turn the call back to management for any closing comments.

No, Operator, I think that's all. Thank you all for listening. I can see on the board here, we had very, very good attendance on the call, so I appreciate the effort and interest, and certainly, thank you to the analysts for the excellent questions. Great. That's all we have. Have a good night.

Thank you, sir. Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program and you may all disconnect. Everyone have a wonderful day.