Amicus Therapeutics Inc (FOLD) 2015 Q3 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Amicus 3Q results conference call and webcast. (Operator Instructions) Please do note that today's program is being recorded. I would like to now introduce Sara Pellegrino, Director of Investor Relations for our opening remarks.

Good evening, and thank you for joining our conference call to discuss Amicus Therapeutics' third quarter 2015 corporate highlights, program updates and financial results. Present on today's call we have John Crowley, Chairman and Chief Executive Officer; Chip Baird, Chief Financial Officer; Bradley Campbell, President and Chief Operating Officer; Dr. Jay Barth, Chief Medical Officer; Dr. Hung Do, Chief Science Officer; and Dipal Doshi, our Chief Business Officer.

The slide deck to accompany this call is available on our corporate website at www.amicusrx.com in the Investors section. This presentation will contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 relating to preclinical and clinical development of Amicus's candidate drug products, the timing and reporting of results from preclinical studies and clinical trials evaluating Amicus's candidate drug products, financing plans, and the projected cash position for the Company. Words such as, but not limited to, look forward to, believe, expect, anticipate, estimate, intend, potential, plan, targets, likely, may, will, would, should and could, and similar expressions or words identify forward-looking statements. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. The inclusion of forward-looking statements should not be regarded as a representation by Amicus that any of its plans will be achieved. Any or all of the forward-looking statements in this conference call may turn out to be wrong. They can be affected by inaccurate assumptions Amicus might make or by known or unknown risks and uncertainties. For example, with respect to statements regarding the goals, progress, timing and outcomes of discussions with regulatory authorities, and in particular the timing of an NDA submission for migalastat monotherapy, and the potential goals, progress, timing and results of preclinical studies and clinical trials, actual results may differ materially from those set forth in this presentation due to the risks and uncertainties inherent in the business of Amicus, including, without limitation: the potential that results of clinical or preclinical studies indicate that the product candidates are unsafe or ineffective; the potential that it may be difficult to enroll patients in our clinical trials; the potential that regulatory authorities may not grant or may delay approval for our product candidates; the potential that preclinical and clinical studies could be delayed because we identify serious side effects or other safety issues; the potential that we will need additional funding to complete all of our studies and our dependence on third parties in the conduct of our clinical studies. Further, the results of earlier preclinical studies and/or clinical trials may not be predictive of future results.

With respect to statements regarding projections of the Company's cash position, actual results may differ based on market factors and the Company's ability to execute its operational and budget plans. In addition, all forward-looking statements are subject to other risks detailed in our annual report on Form 10-K for the year ended December 31, 2014, and Form 10-Q for the quarter ended June 30, 2015. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. 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. This caution is made under the Safe Harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995. So, with that, it is my pleasure to turn the call over to John Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics.

Great. Thank you, Sara, and good evening, everybody. I am very pleased to be joined here tonight by our executive leadership team, and we're going to go ahead and highlight our recent progress with our development program, as well as an overview of our third quarter 2015 financial results. We do have a document online, for those of you who can accept it. I'll begin on page 4. And at the outset I really want to emphasize the enormous effort and commitment by this team and everybody at Amicus, together with all the folks that we work with to advance these programs. And in addition, I'll begin on slide 4 by highlighting the very sharp focus we have here at Amicus. We have four key business priorities, and let me begin by outlining those.

So, first is the approval and then the commercialization of our personalized medicine, Galafold for Fabry disease in Europe. We remain on track to receive an opinion from the CHMP by the end of this year or early next year. I also want to highlight that we have assembled an extraordinary commercial leadership team in place to launch Galafold in key regions once approved, and Brad will provide more color on that shortly. These individuals who will lead these efforts for Amicus have a successful track record in launching drugs for rare diseases.

Next, a key part of the focus for the Company remains our continued commitment to work to determine the optimal US approval pathway for Galafold. We are in the process of integrating the data from our Phase 3 studies and Phase 2 studies as requested by the agency, and we are further evaluating several US approval pathways including the potential to generate additional data on gastrointestinal symptoms to support a request for full approval, or potentially to request accelerated approval under subpart H, possibly based on surrogate endpoints beyond just interstitial capillary GL3. The timing of an NDA submission will be based on the completion of the required data integration as well as the determination of the optimal regulatory pathway. We continue to expect -- as we work on this diligently, we continue to expect to provide an update on the US strategy in the first quarter of 2016.

Our third focus in the Company and our third strategic priority is the initiation of our Phase 1/2 clinical study of our novel Pompe enzyme replacement therapy. On the manufacturing front, I am pleased to report that we continue with the successful GMP manufacturing campaign and we have now secured the necessary clinical supply for this very important Phase 1/2 study to commence. Earlier in October we held a pre-IND meeting with the US FDA, and based on the final minutes now received from that meeting, we plan to submit the IND for this Phase 1/2 safety and PK study in Pompe patients of the fixed dose combination of our novel ERT together with our chaperone. We will have more color on that shortly. Hung and Jay will provide that, but overall we are very pleased with the progress of this important program both on the manufacturing front as well as our preparations to enter the clinic.

And our fourth key priority and focus for the Company is our program in epidermolysis bullosa, or EB. And with that, our Phase 3 EB program, our novel topical therapy, Zorblisa, that we brought into our pipeline in the third quarter through our acquisition of Scioderm. We are currently recruiting patients in a Phase 3 study at sites in both the United States and Europe to support global registration. This study is currently approximately one-third enrolled. We have had excellent progress with this program and we are very pleased to announced this evening on this call that we have just now initiated the rolling NDA submission for Zorblisa. So, a major milestone to this program, a tremendous effort and an example of the early success of our integration of the Scioderm team into Amicus and those teams working together to advance this important therapy.

As many of you know, EB is a chronic, rare generic connective tissue disorder with no approved treatment options. It is one of the most devastating and excruciatingly painful and potentially fatal genetic diseases that I've ever seen. We are fully aligned with a sense of urgency among the community, in the EB patient community, to get a treatment approved. Jay will get into more specifics shortly on the EB program including some additional data that we will be sharing for the first time this evening on the Phase 2b study, but very positive momentum with this program.

So, again, I just want to emphasize the enormous commitment of this team, the enormous amount of work that is going into these programs, and our very sharp focus on these four key business priorities that I've just outlined. With that, I'd like to begin with the key updates beginning with Galafold in Europe. So, Jay, if you could begin with the regulatory update on Europe with Galafold, please?

Good afternoon, everyone. I am pleased to provide an update today on the European regulatory progress with Galafold, which you can see on slide 6. Our MAA is under review by the European Medicines Agency, EMA, under accelerated assessment, which is only granted to therapies for diseases where there is a significant public health interest and unmet medical need. And what this means is that the review period for the application may be 150 days under accelerated assessment instead of the 210 days for a standard review. Our MAA was validated at the end of June, and as part of the review process under accelerated assessment, the CHMP sends a list of questions after 120 days, known as the [Day 120] questions, and the review clock stops at that point. We have received that list of questions and we are in the process of finalizing our responses. And once we submit the responses, the review clock begins again and we expect to be on the CHMP meeting agenda to receive an opinion at the end of this year or early next year. On that note, I'll turn it over to Bradley to provide an update on commercial preparations in Europe.

Thank you, Jay. Good afternoon, everybody. As John mentioned, as we approach the potential launch of Galafold in Europe and outside of the United States, we have continued to build out our commercial team and have made significant progress with our launch preparations, which are detailed on slide 7. We do have leaders in place now in our key functional areas internationally as well as our key regions, who will be able to lead the launch of Galafold successfully. We also now have our distribution system in place and have started to fill in our field medical and sales teams in our initial launch countries. We believe that our world-class commercial team can build upon their prior experience in launching orphan and rare disease drugs, as well as the strong history that Amicus has established with our very broad global footprint in terms of our clinical trial activities, our very strong history of patient advocacy and medical outreach, and our other activities. With that, I'll turn it back to Jay to further discuss our EB program.

Thanks. I'd like to highlight our EB program, and there are two new data points from the Phase 2b study that we will be focusing on today, which haven't been previously disclosed. I'll start on slide 9, where we are showing the primary endpoint results in the Phase 2b study in both the intent-to-treat, or ITT, population, and the evaluable population. As a reminder, the primary endpoint to this study was the percent of patients with complete closure of target wounds. And, importantly, it's also the primary endpoint of the Phase 3 study, as you will see here, the results for the ITT population on the top table and the evaluable population below.

The results for the ITT population show the trends towards improved higher proportion of target wound closure for Zorblisa 6% versus placebo at month 1, and even more so at month 2. And in the evaluable population the same effects are present but even more strongly at month 1 for a higher proportion of complete target wound closure for Zorblisa 6% versus placebo. And at month 2, the effect is even greater, 82% versus 41%, which is associated with a p-value of 0.04. Month 1 is the prespecified primary endpoint in the Phase 2b study; month 2 is the Phase 3 primary endpoint. And these data are particularly significant because this treatment for EB is focused on closing open wounds. That is the primary endpoint here. These wounds were chronic in nature, so being able to achieve this high rate of closure and difference versus placebo in this double-blind Phase 2b study is of great importance in advancing a treatment for EB.

On slide 10, we are showing the results on an important secondary endpoint, which is the median time to wound closure, and this is both shown for the ITT population and the evaluable population. This is also an important prespecified secondary endpoint in the ongoing Phase 3 study. And, as you can see here, in both the ITT population and the evaluable population, Zorblisa 6% shows a faster time for wound closure compared to the 3% and placebo 40 days versus 91 days for placebo in the ITT population, 30 days median time to wound closure for Zorblisa 6% versus 91 days for placebo in the evaluable population.

So, for this call we focus on the new data, but for reference we have an appendix with additional details on the proportion with complete target wound closure over three months in the ITT and evaluable population, and also background slides that we have shared previously. We are happy to cover those during the Q&A session or in follow-up discussions.

On slide 11, we've shown this before, Zorblisa is shown to be well tolerated with adverse events that were similar across all three treatment arms. Slide 12 summarizes the results and key learnings from the Phase 2a and Phase 2b studies that have helped us in the design and conduct of the Phase 3 study. Of course, the Phase 2a study showed proof-of-concept, and we've seen in the Phase 2b study the safety being similar across the treatment groups. And the clear dose response favoring the 6% concentration over 3% in the percent of wounds closed as well as the median time to wound closure and the Phase 2b results are very helpful in being able to calculate the adequate sample size needed for the Phase 3 study. And with the sample size that we currently have for the Phase 3 study, the treatment difference of approximately 17% or greater will be associated with a p-value of less than 0.05.

The placebo response is minimized, because that is something that has been seen in these trials, by targeting baseline wound size of at least 10 centimeters squared. In the Phase 2b it was at least 5 centimeters squared. So, that is a learning from the Phase 2b that has been applied to the Phase 3 study in terms of eligibility criteria. Also, the wound closure within two months versus one month is really optimal time as the primary endpoint. In the Phase 2b it was one month, in the Phase 3 it is two months' time point, because that really increases the ability to distinguish between the Zorblisa treatment effects versus placebo. And, as we said, this endpoint, target wound closure, has been accepted both by the FDA and European regulators. And, importantly, there is a defined approval pathway based on the Phase 3 study, based on EMA and FDA feedback.

I'd like to close out this section with a brief mention of our regulatory pathways for Zorblisa. As you can see on slide 13, EMA and FDA have agreed to the study design. We have breakthrough therapy designation in the US and, importantly, able to announce today that we have just submitted the initial portion of rolling NDA to the US FDA. We are really pleased with the early success of the program integration and the significant momentum of our ongoing Phase 3 study, which is about one-third enrolled at this point. Also a highlight that 36 patients have completed the three-month primary treatment period in the Phase 3 study, and that all 36 patients have elected to continue into the ongoing open label extension study. We look forward to sharing the Phase 2a and Phase 2b data, including additional analyses and extension study data in early 2016 at the Scientific Congress. And now I'll turn it to Hung.

Yes, great. We'll go ahead and turn the call. Thank you, Jay. That was an excellent overview of the momentum in the Zorblisa program and specifically the significant milestones for Amicus and the Scioderm team of filing the first section of the rolling NDA. We will now go ahead and turn it over to Hung and then back to you, Jay, for the clinical section of this important Pompe update. So, Hung, let's go ahead and turn it to you and we'll begin at slide 15. Go ahead, please.

Great. Thank you, John. Hello, everyone. It is my pleasure to be here today to walk you through the recent progress of our novel ERT chaperone fixed dose combination for Pompe. We are now getting ready to enter the clinic and have made significant progress with our preclinical studies and our manufacturing activities, which are highlighted on slide 15. We have developed a proprietary cell line to produce a Pompe ERT designated as ATB200, which has optimal glycosylation particularly with high amounts of the specialized carbohydrate called mannose 6-phosphate for efficient drug targeting. Working with our partners at WuXi, we have successfully scaled up the manufacture of ATB200 and have completed GMP manufacturing campaigns necessary to initiate the Phase 1/2 study.

So, on the following slide 16, you can see that we have been successful in our manufacturing, where we have scaled from small scale to 5-liter scale up to our clinical production scale, which is 250 liters. Importantly, we have been able to maintain the critical quality attributes that are needed to ensure good drug targeting throughout the scale-up of this manufacturing process. As shown on this slide, ATB200 produced at 2- and 5-liter scales, as well as at the 250 liter scale all contain similar amounts of mannose 6-phosphate for binding the mannose 6-phosphate receptor, which is shown in the second and third peaks on these chromatograms. These were performed on an analytical mannose 6-phosphate receptor column to demonstrate the ability of the enzyme to bind the mannose 6-phosphate receptor. If you recall, high affinity binding to the mannose 6-phosphate receptor is required for efficient delivery of Pompe ERTs.

And just one thing I would like to remind everyone why we are so excited about this particular approach is that we have demonstrated strong preclinical proof-of-concept in preparation for entering the clinic. If you look on slide 17, you will see that we use the Gaa knockout mouse model for Pompe disease such that the deficiency in the GA enzyme activity leads to profound glycogen accumulation, as shown by PAS staining, the purple PAS staining in the upper panels. Further, the cumulative glycogen is contained within these internal cellular compartments, or vesicles, such that the apparent proliferation of these internal vesicles is the hallmark of Pompe disease. We use the staining of LAMP1, a known lysosomal protein within these vesicles to evaluate the effects of ERT for clearance of these internal vesicles, and as shown in the lower panels. Our cumulative studies indicate that the standard of care is only moderately effective for reducing glycogen and a turnover of these proliferated vesicles. These findings are in fact consistent with previously published data.

In stark contrast, ATB200 co-administered with our chaperone AT2221, was shown to substantially reduce glycogen levels as well as to facilitate their turnover and recycling of these internal vesicles as evidenced by the significantly reduced PAS staining as well as the LAMP1 staining to levels that are near normal levels. Taken together, these data suggest that our Pompe ERT approach has significant impact towards addressing the muscle pathology associated with Pompe disease and warrants further evaluation. And with that, let me turn it back over to Jay, our chief medical officer, to provide an overview of our Pompe clinical strategy.

Thanks. We are pleased to move our Pompe program into the clinic in Pompe patients, which we have summarized on slide 18. As John mentioned, we recently held a pre-IND meeting with the FDA. Based on feedback from the agency and the final minutes received from that meeting, we are now finalizing our Phase 1/2 safety and PK study protocol. I will highlight for you key parameters of this study as currently planned.

We will be in Pompe patients switching from approved ERT. The ATB200 plus chaperone will be viewed like a fixed dose combination, and we will not be required to study the chaperone component separately. The dose selection for a Phase 3 study may be based on PK and safety data from this Phase 1/2 study. The IND will be submitted very shortly and we expect to initiate clinical sites this quarter to begin the study. We believe that our clinical plan is a smart path into and through the clinic toward Phase 3 with what we believe to be a highly differentiated product that has the potential to offer a great benefit living with Pompe. Now I'll turn the call over to Chip to review the third quarter financial results and guidance.

Great. Thanks, Jay. Good evening, everyone. I will start today's financial discussion with a few comments on our current cash position and financial guidance beginning on slide 20. Amicus continues to maintain a very strong balance sheet. Cash, cash equivalents and marketable securities totaled $251 million at September 30, 2015 compared to $169 million at the end of last year. During the third quarter we successfully completed our acquisition of 100% of the capital stock of Scioderm, Inc. At the closing of Scioderm acquisition and the forecasted spending on the EB clinical development program, we expect to end 2015 with between $200 million and $225 million of cash on hand. Current cash is expected to fund our (inaudible) and including Zorblisa into 2017 through several important near term inflection points.

Turning to our third quarter 2015 financial results on slide 21, I will be referencing tables 1 and 2 in the press release that we issued earlier this afternoon, and additional details will be found on our Form 10-Q, which will be filed tomorrow morning. Total operating expenses for the third quarter of 2015 increased to $38 million compared to $17.1 million for the third quarter of 2014. The year-over-year increase was primarily due to increases in preclinical and clinical development costs on the Fabry monotherapy program and the Pompe ERT program, as well as investment in prelaunch activities for Galafold.

A net loss attributable to common stockholders in the third quarter was $37.8 million, or $0.32 per share compared to a net loss of $17.1 million, or $0.22 per share in the third quarter of last year. The [water] net loss is primarily attributed to an increase in operating expenses and as of September 30, 2015, we had approximately 119 million shares outstanding. This summarizes our key financials for the third quarter as well as our updated full year 2015 guidance. More information on our financials will be available in the 10-Q, which will be online tomorrow morning. Happy to address any questions during the Q&A, but for now we'll turn it back to John.

Great. Thank you, Chip. So, I will just finish up before we head to Q&A by reiterating again the sharp focus we have on the creation of shareholder value and advancing our mission around our four key business priorities in Fabry, Pompe and EB. We continue to believe we have the potential to create substantial shareholder value and, again, to deliver upon our mission for rare disease patients who remain at the center of everything we do here at Amicus. With that, Operator, we are happy to turn it to you and to answer questions.

Thank you. (Operator Instructions) Our first question comes from the line of Ritu Baral with Cowen and Company. Your line is open. Your question, please?

Can you give us any more color on the Day 120 questions received from the EMA? It seems like if you want to turn it around for a CHMP decision by the end of the year, you wouldn't have a whole lot of time to prepare the questions. Were there any surprises in what was asked?

I think it best, Ritu, if we don't comment on the ongoing regulatory interactions. I think I'll just reiterate that we remain under review, under accelerated assessment at this time, and we expect to be on track for that CHMP opinion by year-end or very early 2016.

Is there any indication that you may be moved to a regular review?

No. There is always the potential, but as part of the 120-day questions, they came back to us stating that remain under accelerated assessment.

Got it. And then any more color on the European hires that you plan to make as you prepare for Galafold launch over there, the number of reps, geographies and potential launch order of the countries based on reimbursement?

Yes. Let me ask Brad to add some more color there, please.

Yes, Ritu, I don't want to get into too much detail there, perhaps for competitive purposes, but I can tell you at a high level the key leadership is in place and those are across the (inaudible) expect, medical, legal, finance, in addition to the key regional structures in order to launch in the initial launch countries. From a launch sequencing perspective, again, I'll keep it at a high level, but I'll say that there is nothing necessarily unique about the sequence that we are moving towards. And we are very confident that we are ready to launch as quickly as we can in as many geographies as we can following the normal practice once we have the CHMP opinion.

Got it. And last question is on Zorblisa and some of the new data presented. The footnote on slide 9 goes through the three patients that were excluded from the evaluable population. Can you clarify a little more on the two patients? You stated that they did not have a total identified or qualified target lesion. What does that mean? What were the circumstances?

Yes, of course, Ritu. Jay?

Specifically, the eligibility criteria were that the target wound be contiguous, that it be one wound and meet the eligibility size. In this case there were these two patients who each had two wounds that were very close to each other and was touching, that were counted as a single wound initially. But then it was recognized that it did not meet the eligibility criteria of having one wound that met the target size, and that's why those patients were excluded from the evaluable population.

Thank you, that's helpful. Thanks for taking the questions, guys.

Thank you. Our next question comes from the line of Anupam Rama with JPMorgan. Your line is now open. Your question, pleases?

Just a quick one for me on the rolling submission for Zorblisa. I'm just wondering if you could give us a little color, if there is any ongoing preclinical or CMC work that needs to be completed between now and, say, the Zorblisa Phase 3 data later next year? A little color on that, please?

No, we have completed all the necessary preclinical requirements in the first section and the rolling NDA was the preclinical. We would expect the next section to be the CMC, and while there is still drafting work to pull that together, I don't believe there is any more CMC requirements that we have to meet specifically for that section of the rolling NDA.

Great. Thanks for taking my question.

Thank you. (Operator Instructions) Our next question comes from the line of (inaudible) with Leerink Partners. Your line is open. Your question, please?

Just a couple questions on Zorblisa. Just wondering, backtracking to the announcement of Scioderm acquisition back in August, you had mentioned a third of the enrollment was completed at that date, which is August 31. So, just wondering if you could comment on sort of the delays in terms of the enrollment and where you might be seeing that particularly, whether it's here or in the US? And, also, the second question would be if you could please comment on the IP protection surrounding Zorblisa? I understand that allantoin is highly insoluble, but just trying to get a sense of how much of a breadth you have in terms of usage? Thank you.

Sure, yes. To be clear, we don't see delays. Enrollment continues to advance. We continue to enroll patients. We are opening additional sites. I believe the update we gave is that the study was a third enrolled, and that was at the very end of September, I believe is the first time we had mentioned that. So, just about a month ago. The additional point to highlight is the original Scioderm plan called for 130 patients. We have modified that to meet the statistical plan at 150 patients, so that changes the math of it as well. But that program continues to advance well.

And the IP?

Secondly, around the IP, we have -- our IP counsel, Ken Peist, is here as well, and, Ken, if you want to comment about information we know around the IP of Zorblisa and specifically the formulation and some of the inventions there?

Exactly. So, the novelty around Zorblisa really is in the formulation of a high concentration of the active ingredient, and it's stable in the formulation at this high concentration at room temperature. That is the primary area of protection. And, of course, there will be data protection and orphan exclusivity for this product.

And just to highlight, given the pediatric investigational plan in Europe that would give us 12 years of exclusivity in Europe and with the pediatric plan in the United States would give us 7.5 years in addition to the intellectual property protection that Ken noted. And, again, that's a portfolio that we continue to strengthen as well. So, we feel it will be a very well protected franchise.

Great. Well, I will hop back in the queue.

I'm showing no further questions at this time. I'd like to return the program to John Crowley for any additional remarks.

Great. No, Operator, that's all we have. Everybody, thank you for listening. Hopefully, again, you get a sense of the commitment, the enormous amount of work that has gone into advancing the Company even just in the last 30 days with a couple of the key milestones we highlighted here around the Fabry monotherapy program, around the Pompe program, and that successful pre-IND meeting that has now formed the basis to advance our Pompe program toward the clinic, as well as the momentum including now the first section of the rolling NDA for Zorblisa. So, again, we will continue to work as hard as we can for patients and for shareholders, and thank you for listening and for your support. Have a good night.

Ladies and gentlemen, thank you very much for you participation. This does conclude the program. You may now disconnect.