Amicus Therapeutics Inc (FOLD) 2015 Q4 法說會逐字稿

Good day ladies and gentlemen, and welcome to the Amicus full year 2015 results conference call and webcast. At this time all participants are in a listen-only mode. Later we will conduct a question and answer session and instructions will be given at that time. (Operator Instructions). As a reminder, this call is being recorded. I would like to turn the call over to Sara Pellegrino, Senior Director, Investor Relations, you may begin.

Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics full year 2015 corporate highlights, program updates, and financial results. Speaking on today's call, we have John Crowley, Chairman and Chief Executive Officer; and Chip Baird, Chief Financial Officer,Bradley Campbell, President and Chief Operating Officer, Dr. Jay Barth, Chief Medical Officer; Dr. Hung Do, our Chief Science Officer, and Dipal Doshi, our Chief Business Officer and General Manager of Scioderm, are also here and available to participate in the Q&A session. Before we begin, we wish to inform participants that today's call will contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, relating to preclinical and clinical development of our product candidates, the timing and reporting of results from preclinical studies and clinical trials, the prospect and timing of the potential regulatory approval of our product candidates, commercialization plans, financing plans, and the projected cash position for the Company.

The inclusion of forward-looking statements should not be regarded as a representation by us that any of our plans will be achieved. Any or all of the forward-looking statements made during the call may turn out to be wrong, and can be affected by inaccurate assumptions we might make, or by known or unknown risks and uncertainties. For example, with respect to statements regarding the goals, progress, timing and outcome of various regulatory authorities, and in particular the potential goals, progress, timing and results of preclinical studies and clinical trials, and the expected timing of the EMA's final decision with respect to regulatory approval of migalastat in the European Union.

Actual results may differ materially from those set forth in this release, due to the risks and uncertainties inherent in our business, including without limitation the potential that results of preclinical or clinical 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 including the EMA may not grant or may delay approval of our product candidates. The potential we may not be successful in commercializing our product candidates if and when approved, the potential that preclinical and clinical studies could be delayed because of the identified serious side effects or other safety issues, and the potential that we will need additional funding to complete all of our studies. Further, the results of earlier preclinical studies and/or clinical trials may not be predictive of future results. With respect to statements regarding projection 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 plan.

In addition, all forward-looking statements are subject to other risks detailed in the Annual Form 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 caution statement, and we undertake 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 Therapeutics.

Thank you Sara, and good morning everybody. As you know at Amicus, we have four key strategic priorities. Number one, getting migalastat approved in the EU as quickly as possible, for all Fabry patients with all medical mutations. Number two, determining the optimal path forward for migalastat in the United States. Number three, obtaining important early clinical data for our novel Pompe ERT. And number four, executing successfully on our Phase 3 study in EB, epidermolysis bullosa. We continue to remain very sharply focused on these four key strategic priorities, and we have made substantial progress during the past quarter in this regard.

On today's call we will focus on strategic updates for these three key programs, as well as our full year financial results. Let me begin this morning's call with a regulatory update for migalastat for Fabry disease. As you know, migalastat is an oral small molecule pharmacological chaperone that has the potential to be the first personalized genetic medicine for Fabry disease. If approved, migalastat will represent the first new therapy for Fabry patients in more than a decade, and it may represent an enormous step forward in the treatment of this disease. Migalastat has been investigated now in the two largest Phase 3 studies ever completed in Fabry patients.

In the EU right now, our marketing authorization application, or MAA, is under final review, and we are advancing toward a CHMP opinion. I am pleased to report that the Amicus team and several key opinion leaders completed the oral explanation earlier this week at the February CHMP meeting. As many of you know, an oral explanation is part of the MAA process for many novel Orphan drugs. As we have seen for other new orphan drugs, the opinion often comes at a subsequent meeting. The EU regulators do not want us to comment on the details of our preparation or on their feedback, but we at Amicus continue to be pleased with the level of collaboration and engagement with our reperators and the entire CHMP.

We greatly appreciated the opportunity to discuss migalastat with the broader CHMP team and its members. I am enormously proud of our Amicus team and the Fabry clinical experts, who presented before the CHMP on migalastat this week. The team did an excellent job, and was very well prepared for all of the questions and dialogue at the CHMP meeting. We continue to have confidence in the regulatory process and in our clinical data. We have been able to answer all questions from the EMA with our existing dataset. The decision on migalastat is now in the hands of the regulators, with an opinion likely during the next CHMP meeting, which will be held March 29 through April 1.

If approved our commercial team which is composed of individuals with significant commercial experience in leading rare disease companies, has already done an excellent job with prelaunch preparations, including appropriate medical outreach, and patient payor and physician understanding, and the Amicus team in Europe is ready to launch migalastat there and in other international territories. We have built, I believe, in the past year a premier orphan disease international commercial and leadership team, and that team is fully prepared and excited. hopefully to bring in medicine to people living with Fabry disease soon.

On the US update, and moving to our US strategy for migalastat, we had previously stated that we would provide an update in the first quarter. On this call I am pleased to report that our integrated summary of safety is on track and nearly complete. We have also collected now and analyzed additional histopathology data and gastrointestinal symptom data, as well as longer term renal and cardiac data across both Phase 3 studies.. Several parts of these new data analysis will be featured at next week's Scientific WORLDSymposium. We continue to believe that longer term data, as well as the new analyses from the existing studies, add to the totality of the data for migalastat. We expect a meeting with FDA to take place during the second quarter, to seek further clarity on the US regulatory pathway for migalastat, and following receipt of formal minutes from the Agency from that meeting, we will plan to issue further clarity on the US regulatory pathway for migalastat. We remain fully committed to identifying an optimal US pathway based on our existing dataset without doing another Phase 3 study. And as a reminder the potential US approval pathways include the potential to generate additional data on gastrointestinal symptoms, to support a request for full approval, or potentially to request accelerate approval under Subpart H, possibly based on surrogate endpoints beyond just Interstitial capillary GL3. We believe that clarifying this pathway is in the best interest of patients, as well as our shareholders, and we look forward to a further update in the second quarter.

Let me move now to our Phase 3 program in epidermolysis bullosa, EB. In the third quarter of 2015 we acquired a late stage potential first to market topical treatment FD-101 for EB. As you know, EB is a chronic rare genetic connective tissue disorder with no approved treatment options. EB is a debilitating excruciatingly painful and potentially fatal disease. It is a disorder with 30,000 to 40,000 diagnosed patients in just the US, EU, and Japan.

We are fully aligned with the sense of urgency among the EB community to get a treatment approved, and since the acquisition we have made significant progress in adding our Amicus resources, experience and clinical operations capabilities to the enrollment in the ongoing Phase 3 study, on top of the excellent work that the Scioderm operations team has done prior to our acquisition. As to today I am pleased to report that the study is just over 50% enrolled, and 53 patients have completed the primary treatment period, and all 53 of those patients, so 53 out of the 53 who have completed the three month primary treatment period, have all voluntarily elected to continue in the open label extension phase, we remain on track to complete enrollment mid-year, and we continue to expect to report top line data in the second half of this year.

By the time this study is expected to be fully enrolled in the number of this year, we will have doubled the number of clinical sites, and nearly tripled the overall resources in this program since the acquisition. In addition to opening additional clinical sites and augmenting the recruiting efforts, the Amicus team has been working diligently alongside the Scioderm team on publication and abstracts to report at dermatology conferences, to raise visibility within the medical community about SD-101, as well as the disease itself.

I am pleased also to report on the call today that as a result of these efforts, we have been accepted to present at the American Academy of Dermatology, or AAD. Dr. Amy Paller of Northwestern University, who is a leading investigator who also ran the initial single center Phase 2a study with SD-101 that led to the breakthrough therapy designation, will present the Phase 2b data on March 6th at this conference. While much of these top line data have already been shared publicly by Amicus, it will be the first time for these data to be presented at a very important dermatology meeting by a key opinion leader and investigator.

Moving to our Pompe program, we continue to be very, very excited about the potential for our novel treatment paradigm for Pompe disease, which consists of the novel ERT, our proprietary ERT ATB200, co-administered in a fixed dose regimen with our chaperone AT2221. This is an 18-week safety and PK study beginning with three ascending doses of ERT ATB200 alone, followed by that ERT plus chaperone. Following the 18-week treatment period, patients are eligible to continue to receive ERT plus chaperone. Initially the clinical study will look at patient switching to the current ERT standard of care.

Key things we are looking for to differentiate our novel treatment paradigm include, safety and plasma PK that demonstrate the potential benefits of the addition of the chaperone, to inform dose selection for our next study. Also, tolerability and infusion-associated reactions, as well as antibodies and the characterization of the types of antibodies. We will continue to follow these Pompe patients in the extension study ,and include patients naive to ERT in the study, after we have the initial switch data. We will also look at functional measures of the disease and assessments, and these patients will continue to be assessed on these functional measures in the extension study.

So a very, very important study for us in Pompe, and we will be happy to answer any questions on our Pompe program, as well as Fabry and EB. Before we do that let me turn the call now over to our CFO, Chip Baird. Chip.

Thanks John. Good morning everyone. I will start today's financial discussion with a few comments on our current cash position, and our overall 2016 financial guidance. Amicus continues to maintain a very strong balance sheet. Cash, cash equivalents and marketable securities totaled $214 million at December 31, 2015, as compared to $169 million at December 31, 2014. We strengthened our balance sheet significantly during 2015, with a $258 million public offering. We expect full year 2016 net cash spend of between $135 million and $155 million. The current cash position is projected to fund our operations into mid-2017 through several important inflection points that John outlined previously in the call.

Turning to the full year 2015 financial results, I will be referring to Tables one and two in the press release we released earlier today, and additional details will be found in our Form 10,-K which will be filed on Monday, February 29. Total R&D expenses for the full year 2015 increased to $76.9 million, as compared to $47.6 million for 2014. The increase is primarily due to higher contract manufacturing and clinical research costs, driven by the scale-up of our Pompe ERT manufacturing, as well as advancement of all of our clinical development programs. Total general and administrative expenses for the full year 2015 were $47.3 million, that compares to $20.7 million in 2014. The increase was primarily due to pre-commercialization organizational costs, as well as transaction costs incurred with the acquisition of Scioderm.

Net loss for the full year 2015 was $132 million, or $1.20 per share, compared to a net loss of $68.9 million, or $0.93 per share in 2014. The [waternet] loss is primarily attributed to an increase in total operating expenses, and as of December 31, 2015 we have approximately 125 million shares outstanding. Last Friday we amended our $50 million debt agreement with Redmile, this had no immediate impact on the balance sheet. However, the amended terms surrounding the initial $50 million traunch, increased our financial runway and provides access to an additional $25 million in funding upon certain clinical and regulatory milestones.

We also disclosed this morning we are establishing a $100 million at the market, or ATM, equity financing facility, and this is a matter of good corporate financial housekeeping. We have previously used an ATM facility with great success in 2014. The finalist's three prospectus for the ATM will be filed early next week, and while the revised debt agreement as well as the ATM can give Amicus future flexibility. It is important that we have no immediate plans to sell shares in the near term, we will continue our focus on carefully managing the cash, and being sensitive to dilution, as we drive towards value creating milestones throughout 2016. This summarizes our key financials for 2015. And as I said, more information on financials will be available in the 10-K which will come online on Monday. I am happy to address any questions during the Q&A. For now, I will turn it back to John.

Great. Thanks Chip. This quarter let me just highlight and conclude here with some of the key milestones over the coming months and throughout this year. Of course, the CHMP opinion on migalastat, an FDA meeting on strategy for migalastat, and a regulatory path forward there. The data on March 6th and presentations in EB. The data and presentations next week at the WORLDSymposium. The EB Phase 3 data in the second half of this year, and the second half the interim and full Pompe clinical data. Hopefully you can see all of these activities continue us on the path toward our vision, to create one of the world's leading global biotechnology companies, focused on rare and orphan diseases. With that, operator, we will open the call to questions.

(Operator Instructions). Our first question comes from Ritu Baral of Cowen. Your line is open.

Good morning guys. Thanks for taking the question. First question probably unsurprisingly is on the CHMP proceedings this week. Can you generally give us the topics that were covered during the oral explanation? I understand you don't want to give details, but just generally what were the angles, and were there any surprises on the topics covered?

I can't comment on the nature of the questions and the exact interaction with the CHMP. I will reiterate I was very pleased, and that the team did an excellent job and they were well prepared, as well as Fabry key opinion leaders there at the meeting to talk about migalastat as well, and that we continue to have confidence in the process, and in our clinical data that is now in the hands of the regulators.

I want to confirm you said there are no outstanding questions that any topics covered were answered in full?

I can't comment on the nature of the discussion as well. I just have to state that we believe it is likely that we will receive an opinion at the next meeting.

Okay. If you did receive another set of questions, sometime in the interim, would you publicly disclose that?

I don't think unless it changed our guidance on timing, I don't think we would comment again on the nature of the interactions. It is quite frequent at the end stages that you do have a back and forth with the regulators, but again we continue to have confidence in the process, and think it is likely they will reach an opinion at the next meeting.

Understood. Just to follow up on a point you addressed when discussing the US path forward. You mentioned that there was additional GI data that you already generated. Can you talk to at least the nature of the data without scooping WORLD, and then do you have any thoughts on a GI Fabry composite endpoint, that a Fabry competitor has been discussing for their pivotal study? And I will hop back in the queue after that. Thanks.

Part of that gastrointestinal data that we referenced there, Ritu, is the patient by patient data we shared at JPMorgan. I don't have handy the exact slide number, but we did show the patient by patient data in the placebo controlled study, so placebo versus migalastat, that showed very supportive trends in favor of migalastat over placebo, again on the patient by patient data set. There are other parts of the gastrointestinal symptoms that we continue to look at, and data that we evaluate that has not been made public, and has not been shared with FDA. Secondly to your question around the GI composites, we also are looking at potential GI composite endpoints to support approval, that could be for full approval, or potentially to request accelerated approval. I think that there are a lot of ways where that could be an important dataset for us, and obviously for others potentially in developing medicines in Fabry. GI and diarrhea in particular is a significant symptom of and life limiting aspect of living with Fabry disease, although the leading killers in Fabry, of course, are cardiac disease, renal failure, and cerebrovascular events.

Thanks for taking the questions. I will hop back in the queue.

Of course. Thank you, Ritu.

Our next question is from Anupam Rama of JPMorgan. Your line is open.

Maybe a quick one for Chip. When you are thinking about the cash position and the burn, what is included in the current guide for potentials or implicit milestones to side on shareholders?

The current guidance of $135 million to $155 million is based on the operating costs of our business, assuming full success across the programs. We are not factoring in individual milestones, due to Scioderm or any other contingent payments, but rather just the prosecution and full commercialization of migalastat and the other programs.

Again, just to add to that, we continue to believe that we will have significant financial flexibility to pay milestones with the success of those programs, of course those are all success based milestone payments.

Great. Thanks so much for taking the question.

Thank you. Our next question comes from Dae Gon Ha of Leerink Partners. Your line is open.

Thanks for taking my question. Calling in on behalf of Joe, two questions. One to follow up on Ritu's point earlier about migalastat, if you do get the positive opinion from CHMP, and a final approval in the EU, what is your expectation of how expensive of a label you can get, in terms of covering the various mutations? And I have one question for Pompe. I know it is kind of early, but at JPM, a competitor disclosed an interim analysis on their Pompe program, which I am sure that you are aware of. Looking forward at your program and juxtaposing what they disclosed, what are your expectations in terms of functional output, specifically in the pulmonary side, as well as the 6-minute walk test. Just want to get the superiority or non inferiority to the standard of care? Thanks.

Let me take the first part on the label. We continue to believe that migalastat and the data for migalastat across all of our studies support the use of the drug in all Fabry patients with all amenable mutations, and that is the label that we are pursuing. Secondly, in terms of Pompe, again this is a very differentiated treatment paradigm from anything that is approved, or any other product in the clinic today. It is a proprietary ERT that is uniquely engineered to have the appropriate glycosylation and a high degree of bis formulation, so different than any other therapy, and in addition, it is combined with the oral administration of a pharmacological chaperone, which binds to the ERT and plasma, stabilizes it, enhances activity, and importantly, we believe based on preclinical data, has the potential to be much more tolerable for patients, and have a significantly reduced immune profile.

As we go into this first series of clinical studies, we want to establish not only that the drug is safe, and that patients can safely switch from the current ERT standard of care to this regiment, we want to prove many of those important differentiating factors for this therapy, so we are going to look at tolerability. We are going to look at immunogenicity, we are going to look at antibodies, we have specifically developed some unique antibody assays, not only to characterize the titres, but also to characterize the nature and extent of the antibodies, which we think dramatically limit the efficacy of the current standard of care.

We will be able to capture all of that in our initial clinical studies, we are also going to do some careful PK modeling, to show what we think is a very different PK profile in bio distribution of our drug, and in addition to all of that, we are going to measure throughout this study and extension studies, all of the other traditional functional measures of the disease, so things like force vital capacity, 6-minute walk test, MIP, MEP, muscle strength, and measured in a variety of other fashions. We will look at all of that, and then we will see. We think this will be a very, very differentiated drug.

Are you able to provide though, in terms of those functional assessments that you mentioned like SEC, MIP, MEP and 6-minute walk test, what you would consider to be clinically meaningful to demonstrate superiority, in terms of a threshold?

Let me be clear, this is an additional clinical study. This is not setup as a superiority study. And I am not going to comment on the data from other people experimenting in the field. I think people can interpret the variety of data of those clinical studies over multiple years in many different ways.

Okay, great. Look forward to seeing the data at WORLD.

Yes. It will be very, very exciting to being to see the data here from these patients. A very important program for us, and one where we have invested enormous resources, and we think we have the potential for a very, very differentiated therapy, in a disease with such dramatic unmet need still.

Yes. See you in San Diego.

Wonderful. Thank you.

Our next question comes from Roy Buchanan of Janney Montgomery. Your line is open.

Hi, thanks for taking the question. Just wanted a little bit, maybe insight I guess on the possible outcomes CHMP process, if you don't get the opinion at the next meeting, are there other possible outcomes, and what would time lines potentially look like after that?

Thanks I will reiterate the final decision on the opinion is in the hands the regulators. We think it is most likely that they will reach an opinion in their next meeting. Of course, that could always be delayed, and it is in their hands. But our expectations are that it would be at the next meeting.

Do you think we could know if it is delayed before the meeting, or would it become known at the meeting?

I don't know.

Okay. Thank you.

There are no further questions at this time. I would like to turn the call back over to John Crowley, Chairman and CEO, for any closing remarks.

Great. All right, well, thank you everybody. Thanks for listening to this morning's call. A lot of work ahead of us still, but we feel very confident with the path that we are on. Thanks so much, have a great day.

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