Amicus Therapeutics, Inc. (NASDAQ:FOLD)
Lazard Capital Markets Healthcare Conference Call
November 14, 2012 3:30 pm ET
William D. "Chip" Baird, III – Chief Financial Officer
John F. Crowley – Chairman and Chief Executive Officer
Bill J. Tanner – Lazard Capital Markets LLC
Bill J. Tanner – Lazard Capital Markets LLC
Okay, good afternoon. I am Bill Tanner one of the biopharma analysts at Lazard Capital Markets. I’d like to thank everybody for attending the 9th Annual Lazard Capital Markets Healthcare Conference. We hope the last couple of days have been useful and valuable to you.
Saving the best for last, very pleased to have Amicus Therapeutics presenting. As most of you know Amicus is a pioneer in the development of chaperone technologies and this had some exciting news recently as it relates to using chaperones with in combination with enzyme replacement therapies and obviously the big milestone before the end of the year would be hopefully the immunotherapy data for migalastat.
So Chip Baird, CFO, who will be presenting for us also want to acknowledge Bradley Campbell, he is the Chief Business Officer at table, as well as Sara Pellegrino. So thanks very much for coming to the conference. Chip report your comments.
William D. "Chip" Baird, III
Thanks Bill. And I’d like to thank not only Bill Tanner, but Steve Sands and the rest of the team at Lazard. We’re really pleased to be here and updating everyone on Amicus and everything we’ve been doing it’s been a great 2012 with a lot of very important milestones coming up here in the near-term.
We’ll refer to our Safe-Harbor provision. We will be making forward-looking statements today. So Amicus Therapeutics by way of background is focused on the discovery, development and commercialization of pharmaceutical chaperones for the treatment of rare and orphan diseases. Since our founding as a small research-based organization, we’ve made tremendous progress in our goal of developing a fully integrated biopharma company, delivering innovative therapies for patients living with rare disease.
Our company is built on three pillars of value. The first is our pharmacological chaperone platform technology, which utilizes small molecules that’s selectively target niche folded and unstable proteins. Our chaperones can bind to it stabilizes the patients own enzyme increased in the patients and dramatic activity. It can also work in combination with existing enzyme replacement therapies again stabilizing or trafficking and ultimately enhancing the activity in patients with lysosomal storage disorders.
Our second pillar value is our pipeline. Using our chaperone technology, we built it a deep and robust pipeline. We developed a significant expertise in global expertise and disease, in rare disease, clinical research, medical affairs and patient advocacy and using that expertise, we’ve developed the pipeline includes multiple programs in Phase 3 and Phase 2 development. I’ll tell you more about those today.
And then finally, the last pillar that we mentioned here is our collaboration with GSK. We’ve collaborated with GSK on our more advanced program migalastat for the treatment of patients with Fabry disease. GSK provides important financial support as well as clinical and regulatory expertise. And under the collaboration, Amicus has responsibility for the U.S. commercial efforts, while GSK leads commercial efforts outside the U.S. This arrangement preserves important value for our shareholders, while at the same time, accelerating the introduction of migalastat for patients living with Fabry disease outside the United States.
So at Amicus, we are developing pharmaceutical chaperones as next generation treatments for patients with lysosomal storage disorders such as Fabry disease, Pompe disease Gaucher disease. Chaperones work in two distinct ways. As a monotherapy, our chaperones selectively bind and stabilize the patients own enzyme, stabilizing the mutated and misfolded enzyme, traffic in that enzyme to the lysosome where it can have its intended activity of cleaning substrate.
Our chaperones can also be used in combination with existing enzyme replacement therapies. They work in that similar manner. In this case, you are taking infused exogenous enzyme replacement therapies and then binding those therapies with a custom targeted chaperone again stabilizing that the chaperone and stabilizing the enzyme increasing tissue uptick and ultimately increasing substrate reduction.
On this latter point on the combination approach, we’d now evaluated our chaperones in conjunction with seven different marketed or investigational enzyme replacement therapies in preclinical animal models and in all seven cases, we are seeing clear evidence of increased enzymatic activity.
So using our pharmaceutical chaperone technology, we build a late stage and diversified pipeline again most of as program migalastat for Fabry disease and here we have two phase 3 studies ongoing, Study 011 and Study 012 as a model therapy. We also have a combination of co-administration program that’s in Phase 2 development and we have a longer-term next generation coformulation product that’s in late stage preclinical development.
Second most advanced programs AT2220, this is a co-administration program for the treatment of Pompe disease and there we have a Phase 2 program ongoing. In addition to those two assets, we have programs in Parkinson’s, Gaucher and other non-disclosed lysosomal storage disorders.
With the exception of migalastat Amicus owns 100% of the world right commercial rights to all of our pipeline. Focusing a little more on the GSK collaboration, we originally enter the collaboration fall at 2010 and we extend that collaboration in July of this year. Key points on the expansion of that collaboration include additional $18 million investment that was done in this summer; we also gained the U.S. commercial rights to migalastat in all its forms which accelerates our path to becoming a commercial stage company. We also gained U.S. commercial rights to the co-formulated program. That’s a longer term asset but that’s a very exciting program and we’ll show you some data from that program at the end of the presentation. And finally GSK recommitted to their 60% cost sharing arrangement to support all forms of development of migalastat monotherapy co-administration and co-formulation.
Financially we’re in a very strong balance sheet position. We had $106 million of cash at the end of September and we expect end of the year with more than $90 million of cash so that $90 million cash combined with the ongoing 60% cost share from GSK provides sufficient funding to take us well through 2013 and fairly far into 2014. We strengthened the balance sheet this year not only through the GSK investment. Additional milestone received under the GSK collaboration but also through a $61 million equity offering that we completed back in March then, brought a number of new high quality investors into the story, and then increase and diversity the shareholder base.
Just quickly from a guidance perspective, we continue to guide to the upper end of our $37 million to $42 million of net operating expenses and that’s a number that’s net of the cost share reimbursements under the migalastat collaboration.
So, diving a little deeper in terms of the phase 3 studies that we have on going for migalastat as a monotherapy, we have two studies both valid in migalastat at 150 mgs every other day in patients with amenable genetic mutations. So study 011 is our U.S. registration study, this is a six month, placebo controlled study where the primary endpoint is kidney GL-3. We continue to expect to receive results from that study in December of this year so coming up very soon but we’re also gathering 12 month data from that study that will provide important support of safety and efficacy information as well.
Study 012 is our global registration study. We also think it has a good chance of serving as our phase 4 commitment here in the U.S. This study compares migalastat directly to ERT. So this is a switch study. Patients in this study will already be on an enzyme replacement therapy and either remain on that therapy or switch over to migalastat for the 18 month duration of the trial. This is a study that we had some concern in terms of its enrollment because you’re asking patients to switch away from their existing therapy but we were very pleased and gratified to do as well as we did enrollment this year, we had originally targeted a stretch goal of 50 patients enrolled by the end of the year. We’ve already beat that we have 57 patients now randomized, we’ve closed training and we expect the final few patients to randomize before the end of the year.
And the end point here is – I should mention the end point here is kidney function is measured by GFR. One of things that gives us good degree of confidence around the outcome of our study 011 which is coming up here very soon as the patient disposition shown here. So when we originally design the study we had hoped to enroll 60 patients and assume that 10% dropout rate. So at the end of the six-month primary achievement period we’ve had 54 valuable patients and we did better in that, we the 67 patients enroll and we have lower than anticipated dropout rate of only 6%. So we expect at the end of the six months we have 63 valuable patients.
And more than that we’ve had of the 63 completers, all 63 elected to continue into the six-month open-label extension period. That’s going to give us important additional information in terms of the safety and efficacy and I’ll show you a little more about those specific comparisons that we expect to make. Beyond that from the 63 of those 63 folks who elected to continue 51 have already completed now 12 months on the study, and of those 51, 49 of those 51 have elected to stay in a long-term extension study.
These will treat patients who have other treatment options in the form of existing market with ERTs and so we are encouraged by the continued use of migalastat participation in the study. So this scheme gives you a little more sense of the how we are evaluating the efficacy of migalastat in the six-month primary treatment period. It’s a 1:1 randomization between placebo are the treatment arm. At the end of the six months we are willing to measure kidney GL3 in the patients, so we take a baseline biopsy and then six-month biopsy and we’re going to conduct a responder analysis. So responders will be defined that patient who experience a 50% of greater reduction in kidney GL3. Just to highlight that this is the same end point kidney GL3 that was originally used for approval of Fabrazyme here in the U.S. about a decade ago.
The same time we are waiting on 12-month data and we should have the 12-month biopsy is completed by the end of the year. And that data we have on the first half of 2013, but that will have other important supportive comparisons that we can make about migalastat. So for example the treatment arm that bottom bar there will now have 12-months of continues therapy on patients on migalastat and be able to evaluate how patients do overtime, just the effect of migalastat improve between months 6 and 12 is there durability of effect.
We'll also be able to evaluate placebo patients against themselves. So they’ll receive six months of placebo followed by six months of active and that is another important comparison that we’ll be able to make. We'll also have long-term 12-month safety information for all patients. So that’s a data that will come in first half of 2013 and we expect to be supportive of the primary analysis which we expect to have at the end of this year.
To talk a little more about that primary analysis, we recently presented data at the American Society of Nephrology about two weeks ago out in Santiago. This is data from the long-term Phase 2 extension study, but what’s interesting about this data is this is value in the same primary end point that we're going to be measuring in our Phase 3 Study 011. So little more about kidney GL-3, GL-3 is the substrate that accumulates in Fabry disease, it affects all organs throughout the body but has particularly damaging effects in the kidney.
And so here we're looking at you see eight patients, five patients who have amenable mutation, these are mutations that would qualify for our Phase 3 study and over a year’s worth of therapy, we see an average or median decrease of about 78%. Four out of the five patients of those first five patients with the amenable mutations had a greater than 15% reduction in kidney GL-3. That would be a reduction that in our Phase 3 experiment, would be to find as responder, so four out of five of these amenable mutations were responders, just to find in the Phase 3 study.
The three patients on the right were enrolled prior to the lineation between amenable and non-amenable patients. We're not expected to see those patients show a GL-3 responder, a 50% reduction and in fact we didn’t see that, so that was also in its own way of re-sharing result. All of this was presented again two weeks ago at ASN and we can share those files with investors who have interest.
This is long-term patient disposition from that Study 205 the Phase 2 extension study and I’ll call your attention to the bottom two bars on the slide. The patients, originally enrolled 17 patients completed study 205, those 17 patients had an average of 5.2 years duration on the study. We think that is truly remarkable that for five years these patients again in the face of other approved products for the treatment Fabry disease took migalastat as their only treatment for their Fabry disease.
The 16 of those 17 continued today in a long-term open-label extension study. In addition to be an encouraging sign it also provides long-term safety and efficacy data that will be important for regulatory authorities. Finally, a word on the Fabry market, so today that market is a $660 million market, we expect that marker to grow to a number closer to $1 billion in the coming years particularly given that diagnosed Fabry disease in later on at patients, within that market we divided between patients who would be amenable to monotherapy which we think is about 50% of the overall market and patients with non-amenable mutations for that second half of the market that the red side of the slide there.
We still think the migalastat that can play a role in helping those patients, we think and we’ll show you data here in a moment that suggests that migalastat given in combination with existing ERTs can result in improved patient outcomes are relative to ERT alone. And so that’s a good segway to our ERT combination technology. Just a way back on ERTs have been around for 20 years and more now and they represent a very important first-generation therapy to the treatment of lysosomal storage disorders, but they are just a first step and they have important limitations fundamentally infusing enzymes into the bloodstream isn’t unnatural act.
These enzymes are typically live in a certain compartment of the lysosome acidic pH infusing those same enzymes into the neutral pH of the bloodstream resulting rapid unfolding and denaturing of those enzymes and that leads to a host of unwanted effects, it results in infusion side reactions, immunogenicity, reduced uptake into tissues and ultimately reduced efficacy of the drug.
We believe that we can overcome and address many of these concerns when co-administering or co-formulating these enzymes with the pharmaceutical chapra. This is an idea that’s been around for a while and importantly this year we’ve conducted now two Phase II studies that have proven this concept demand and we’ll show you some of that data here in a moment. A little more about those two studies, we’ve done study Fabry, study 13. This is a drug interaction study looking at a single-dose of migalastat given immediately prior to the patient’s normal infusion of Fabrazyme, Replagal. We are looking here not only at safety but asking important question which is can we increase the level of active circulating enzyme in plasma and secondarily can we then – and you see an increase level of active enzyme taken up into disease-relevant tissue. We are conducting a very similar study design in Pompe disease, Study 010. So here we are talking about a different chaperone AT2220 and we are giving it alongside Myozyme/Lumizyme. Asking similar questions not only about drug-drug safety interaction, but can we increase levels of active circulating enzyme in the plasma and then we can have an effect on tissue uptick and two tissue matter of disease state.
So this is the most specific schema on study 013 where we look at variety of ERT doses in part because of the shortage in the different dosing regimens that are being worked through as Genzyme was dealing with the Fabrazyme shortage. We also validate Replagal, which is the other improved product in Europe and other parts of the world. We validate in two dosage of migalastat and again we look at safety as well as plasma and tissue levels of the enzyme.
So this is the results on the plasma side, so you see three panels here. The one on the left is results of Replagal and the right two panels are different doses of Fabrazyme when given a conjunction with the migalastat 150 mg, so you can see in all cases this is 12 out of 12 patients showing an increase in (inaudible) levels of active enzymes in the plasma clearly demonstrating a pharmacological effect, so good to see in the pass of the next question is doesn’t have an impact in disease relevant tissues here we did skin biopsies to evaluate that and the answer is yes, we can translate that, increase in plasma two and increase in the skin.
So where do you see 12 patients across the X axis here the white bars represent that biopsy give immediately prior to an ERT effusion so that’s the patients on background and made up levels of enzymes which not surprisingly these patients is very low number.
The red bars represent day two after an ERT alone infusion, so ERT without the chaperone and then you can see the effect blue bars, so this is ERT plus migalastat at day two. So you can see in cases where we show the data here a very noticeable effect in terms of the level of tissue uptick.
Longer-term, we will be asking questions as we do repeat dose studies what kind of effect they have on substrate reductions and also what clinical outcomes, this is still a dose ranging study and this is the lower dose. We look forward to seeing the higher dose data presenting that in the first quarter of next year.
But important proof of concept even at the lower dose here, so shifting gears same idea Pompe disease we are talking about AT2220 given a conjunction with Myozyme/Lumizyme we’ve completed three dose cohorts here and the final dose cohorts we expect to have results by the end of the year. Again the same type as sixth block this is 16 patients and once again 16 out of 16 patient show an increase in circulated enzyme, and measured with the Chaperone versus ERT alone, very encouraging results. We then looked at tissue uptake, in this we’re doing muscle biopsies, a little more difficult to get out, a little more heterogeneous in terms of the tissue type but the red or, the red bars represent ERT alone and then the blue or green is ERT plus eight dose of 2220. And you can see several patients showing a nice increase in levels of enzymes, active enzyme in the muscle and again we expect to have the fourth and highest dose cohort. This is the dose that we associated with the greatest level of activity in pre-clinical models presented by the end of the year.
One other point we’re highlighting on the Pompe program is the work that we’ve been doing around immunogenicity. Immunogenicity can be an issue with all infused enzymes, these enzymes are fused into the blood stream and unfold a – can often elicit an immune response. This is a particular problem in Pompe and patients with infantile onset Pompe where the emergency standard of care is to oblate the infants’ immune system with Methotrexate and Rituxan so that they can better tolerate their Myozyme or Lumizyme.
We did a work with a company in the UK to better characterize just how immunogenetic these proteins are. And you can see here on the graph Myozyme and Lumizyme are amongst the most immunogenetic proteins that has ever been evaluated in this assay. When given in conjunction with 2220 we see a significant reduction in that same immunogenecity profile of the two drugs and we think that’s an important observation. It could be a real clinical benefit for patients and something that we’re actually thinking about is we plan a future clinical study.
So as we think about the longer term vision for the company we are focused on what we call the continuum of integration. We talked a little bit about Chaperone and monotherapy, Chaperone ERT co-administration both in Pompe and Fabry and we’re actually working even further downstream in terms of co-formulated proprietary ERTs where we have our proprietary Chaperone and proprietary ERT co-formulated in infusion bag which we think will be next generation of innovation for patients.
We got access to one of these programs through the extents of the GSK collaboration back in July so this now involves a collaboration not only with GSK, but with a company called JCR which is a biologics manufacturer in Japan.
We were working with them on Proof-of-Concept, preclinical Proof-of-Concept work with proprietary ERT that they have for Fabry disease. And we show some of the results here on the next slide. These were presented back when we announced the deal but worth repeating. The dark blue bars are measuring the reduction in GL-3 in a mouse model. These were doses that are similar to the indicated dose for Fabryzine about 1 meg per kg you see a net reduction, that reduction in GL-3 is enhanced when co-formulated with our Chaperone, what’s interesting is that we believe that when given with the Chaperone we maybe able to get to higher dose well of higher than 1 mg per kg.
And when you look at data on the far right you see even further reductions in GL-3 and in fact when you look at a higher dose JR-051 co-formulated with our chaperone. You see reductions that are approaching wild type levels of GL-3. So if these type of data hold up in clinical setting we think this would be a very important step forward for patients. And this is one of the reasons we are so excited to expand that deal.
This is our last slide. I think it’s been a very productive, a very successful year so far for Amicus we’ve validated our co-administration platform both in Fabry and Pompe Phase 2 studies. We’ve made terrific progress in terms of enrolling and executing our Phase 3 studies in Fabry. We significantly strengthened our balance sheet through financings and through business development activities. We’ve expanded our collaboration with GSK, we’ve accelerated our path in becoming a commercial company and we’re poised and very anxious to see our six month top line data for Study 011 coming up at the end of the year.
So with that I thank everyone for your time and attention here at the end of the day and invite any questions, thank you.
Bill J. Tanner – Lazard Capital Markets LLC
Thanks Jeff, questions
Just on the 012 study, you mentioned that it enrolled faster than you thought. What would be the rationale for that? I mean patients who are beyond the ERT they’d be presumably well controlled so that?
William D. "Chip" Baird, III
Yeah, we were actually just to give a little more color on that at the beginning of the year coming into JP Morgan Conference that was as we thought about our five corporate goals and that was – one of them was to enroll that study 012 by the end of the year that was the one that we felt was most vulnerable and most prone to slippage and not only are you asking patients to switch away from an approved therapy but we don’t yet have the migalastat study along one data. If we had successful data there you could see that moving faster, where I think is speaks to a little of unmet need in the space while again we believe that just seniorities are good first generation products there that prospects that and oral every other day. Therapy could provide a similar or superior clinical benefit was compiling for patients.
And I think the other thing that was a challenge for us is until the shortage was resolved here in the U.S. that was slowing down enrollment here in the U.S. So with that shortage resolved enrollment moves in faster than sort of our optimistic case scenario. So all those things were and reviewed as positive and sort of the continued level on that community. John, do you want to add any color on?
John F. Crowley
Yeah, the only thing I’d add to that too is that we spend a lot of time in the first quarter this year averaging to two physicians, what we call team Amicus that is with medical affairs, patient adequacy and some of our science team and senior management team. And I think that kind of interaction just gave further confidence to the states that it was – a worthwhile trial to participate in and as Chip said that there is just real demand there.
So this will be more just kind of treatment and people just taking infusions for years and years and getting tied to that or..
John F. Crowley
Well I think its both, so if you look at the literature I think its clear that for example in the U.S. (inaudible) only have their primary end point from their initial Phase III didn’t hit statistical significance in their confirmatory study and so they shown is sale-through reduction. And I think two that you can underestimate the burden of just getting enzyme replacement therapy I mean it’s a four to six-hour infusion patients are taking pre-med they’re spending a day of their life every other week dedicate to that – so that therapy and as you’ve said if there is a promise of every-other-day treatment that could provide similar or superior benefit I think there is just real demand there.
Bill J. Tanner – Lazard Capital Markets LLC
Great. Any questions from the audience. Okay, Chip thanks very much.
William D. "Chip" Baird, III
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