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Amicus Therapeutics, Inc. (NASDAQ:FOLD)

Leerink Swann Rare Disease Roundtable Conference Call

October 2, 2013 1:20 PM

Executives

John Crowley - Chairman and CEO

Bradley Campbell - Chief Business Officer

Analysts

Joseph Schwartz - Leerink Swann

Joseph Schwartz - Leerink Swann

Without further ado, very pleased to have a fireside chat now with Amicus Therapeutics, a company we have covered for some time. We have John Crowley, Chairman and CEO; Brad Campbell, and Chip Baird joining us here, and I will get started by may be asking you in general, if you could just bring us up to speed with the state of the art for the Chaperone therapy, and where the company is evolving from there?

John Crowley

Yeah, you know -- thanks Joe, thanks for having us of course. I think the most important thing to remember is, there are really two distinct uses of the Chaperone technology, and the original basis on which the company was founded was the use of small molecule chaperones that selectively target bind to and stabilize a person's own natural enzyme, and that's what we have been developing for seven years with migalastat in Fabry disease. So that program continues to advance.

There are two Phase-III studies, we had the first readout that caused quite a bit of confusion back in December, it was based on the responder analysis. A certain number of patients who did or did not cross a threshold in terms of reduction of the GL3. So we now -- we have put out in December, the stage one analysis. We have had some regulatory interactions. The FDA of course made clear that they'd like to see the totality of the data and by that they mean the 12-month data from that study that's still yet to come, the 24-month data for that study that's still yet to come, and then also the data from the second Phase-III, which is the switch study we can talk more about.

So those are very late stage programs. It's one where the regulatory path in the U.S. is more complex than we think it is in Europe. That's the partnership -- the program already is partnered with GSK. So you have those late stage monotherapy programs in a drug that we think is a medicine, that we think can get approved in the U.S. and in Europe, and be a good effective medicine for about a third to a half of people living with Fabry disease.

Then you have the other application of the technology, which we think in the long run, has the greatest potential to affect the most people living with rare diseases and also have the greatest opportunity for shareholder value creation, and that's the use of the small molecules combined with our own proprietary enzyme replacement products that are in development, and we can talk more about where those stand, but the first of those, the next generation ERT in Fabry disease is poised to enter the clinic in 2014.

Joseph Schwartz - Leerink Swann

So, can you talk about where you are using -- where your chaperones might be agnostic to the ERT that's paired with it versus where you are developing proprietary formulations, what your strategy is?

John Crowley

Yeah, so the strategy is very clear. The initial studies that we had in Fabry with either Replagal or Fabrazyme or Pompe with Myozyme/Lumizyme were initial proof of concept. They were single dose PK studies showing can we safely change the PK profile and biodistribution in a positive way of those enzymes, and we showed in every patient that it was tried in like in every animal model, that yes we can have a profound impact on changing the biodistribution of those molecules.

Now, the strategy is to not make other people's ERTs better with co-administration or combination approaches, but to use these small molecules as a key part of the formulation in developing our own proprietary next generation ERTs, and that really is the Amicus strategy going forward to be a bio-better company in the biologic space, and of a classic second mover where the markets are established, reimbursement is set, patients identified, and we think we may have a better mouse trap. So, that's the strategy going forward to make a new ERT for every one of these at least lysosomal storage disorders; although the concept of unstable proteins infused in blood is not unique to the lysosomal disease space. We think there is a potential here to expand the technology, even beyond the lysosomal disorders.

Joseph Schwartz - Leerink Swann

And can you talk about how you selected the ERTs to pair your chaperones with for further development, and have you seen any intriguing animal data that suggests that the proteins themselves might be better than the legacy proteins before we even talk about what --?

John Crowley

Sure. Yeah. What the path forward is?

Joseph Schwartz - Leerink Swann

To go further with the chaperone?

John Crowley

Yeah again, it all fits into the concept of making biobetters in the lysosomal disease space; and to do that, we need to think about what's the problem that we are trying to solve for. So, our lead program is in Fabry disease, our own proprietary next generation biologic that incorporates the chaperone. The whole fundamental notion with Fabry or any other lysosomal enzymes is that you are taking a bioreactor made enzyme, you are giving it to a patient once every week or every other week, infusing it into their blood. The pH of our blood is about 7.5. These are lysosomal enzymes that for all of us without disease typically live and reside in the lysosome in a very low pH environment. The challenge is, when you do that, it's not only an unnatural dosing regimen, you are also putting it into the hospital environment of the blood, and basically these ERTs have a strong tendency in that hospital blood pH environment to just fall apart.

Where we intervene is by making ERTs that have a number of different, and we think improved, characteristics most significantly the incorporation of the chaperone in the manufacturing and formulation process, that keeps the enzyme stable and folded and more active, and by doing that when its infused in the blood, very simply the ERTs don't fall apart, they don't aggregate, and by doing that you can see enhanced uptake into target tissues, reduce substrate -- the substrate of course is what causes the disease in each of these different disorders, and we also believe reduce the immune profile of these ERTs.

So, when we think about where do we develop them, for Fabry, we think there is significant unmet need for a better biologic, something with better uptake, something that could potentially be given at improved dosing regimens, and something that's less immunogenic, and we have done significant amounts of animal data together with GSK to validate this approach in Fabry knockout animals, and we see significantly higher absorption of the enzyme and reduction of the GL3 substrate.

And we did the same thing again in Pompe, where there we think the need is even greater in the Pompe community, and the market potentially even larger and that's essentially what we are doing for each of these including our recently announced program in MPS-I, so that's the general approach.

Joseph Schwartz - Leerink Swann

In Fabry, with your co-formulated drug in animals, are you actually able to see reductions in GL-3 beyond the interstitial capillary and other tissues like the podocytes or other organs where traditional ERT that's not bound to a stabilizing chaperone can't have a chance to get to?

John Crowley

We think the effect is a couple of folds. We think that you are getting a more active form of the enzyme into key tissues of disease with the addition of the chaperone that confers hat added stability. We also think you are getting just more of it, and one of the advantages of using a chaperone is with a protein that's more active, more properly folded and less immunogenic, the patient can tolerate a higher dose. So, you have a more active form of the enzyme and more of it, and ultimately what we are seeing very consistently and in a pretty profound way is that you have a much greater clearance of the substrate in animals, and that was the data that we worked on from early 2011 until the initial preclinical work completed in mid-2012 that made GSK want to partner with us on this next generation biologics.

Joseph Schwartz - Leerink Swann

Okay. So when will investors see some more of this data in order to be able to ascribe some more value to these earlier programs?

John Crowley

So, some of the preclinical programs in the next generation biologics, we expect in the coming months at certain science conferences to be presented. So within the next two quarters, Joe, I think you will see a lot more of this data that people understand how we have translated the science into at least preclinical results. And in the meantime, these programs continue to advance towards the clinic, and that's something pretty important to remember that these are programs that are not years out, these are going to begin building into the clinic in 2014. So the first of our programs, the next generation biologic in Fabry will go into clinic in 2014, that's the program partnered with GSK.

And then our business strategy is basically every year for as far out as we can see to put another one of these into the clinic, so we would expect Pompe to enter the clinic in 2015, and we think then after for MPS-I and for certain other programs that we are yet to disclose, every year, we will have a new biologic into the clinic.

Joseph Schwartz - Leerink Swann

Have you seen the increased ability to get more of the protein into the lysosome? Have you actually been able to demonstrate improved trafficking to the target in animals?

John Crowley

Yeah, you can do the immunohistochemistry, you can actually show significantly more enzyme taking up into the lysosome of muscle cells, for instance, in Pompe disease. And of course, the proof is going to be, what does that mean for substrate reduction. So in the Pompe knockout animals, where we are administering our enzyme, our unique proprietary enzyme co-formulated with chaperone, we have also done this with lumizyme, co-formulated with our chaperone. At the end of the day, what you see is a greater reduction of a substrate in animals, in key tissues like quadriceps, the muscles, skeletal muscles or broadly cardiac muscles, the diaphragm.

Joseph Schwartz - Leerink Swann

And, what do you anticipate the clinical trial design would look like when you enter the clinic? You will probably do a first in man study, and then maybe straight to a pivotal study, because of the validation that already exists?

John Crowley

We think it may vary by disease, but broadly what we are thinking about, and this gets into a bigger kind of public policy question about how do you rapidly develop these medicines in these areas of still unmet need, and I had a meeting a couple of weeks ago with Peggy Hamburg to talk exactly about this, and that's rather than saying, okay, you are developing a drug for, call it, Pompe disease, Genzyme did this study 10-12 years ago, that's how they get approved to go do that study.

That doesn't really fit in the world today, especially when most patients, and certainly the most severe are already treated, and given that the patient populations are going to largely be switch populations, where you are saying, we think we have a new and improved product, we want you to switch from one therapy to another.

So that's how we are thinking about developing clinical programs where we can rapidly show safety of course, but also show that you can switch a patient from one enzyme to another, at least maintain their disease state for a reasonably short period of time, and build in, much like BioMarin is doing, and their Pompe study is coming up, building looks into superiority, but not necessarily have to have a superiority bar, so you can get these drugs approved, we think on a non-inferiority -- kind of a classic non-inferiority path, but actually have looked into the data in the short term that you could add into your label to show claims of superiority.

Joseph Schwartz - Leerink Swann

And we typically haven't had multisource ERT markets in the United States, anyone? There is a couple examples outside the U.S., with Protalix in Brazil and some others elsewhere. But how do you anticipate the reimbursers will respond to that in terms of requiring some price concessions or otherwise trying to play manufacturers off of each other?

John Crowley

Again, our strategy is to develop biobetters, and that -- and so we are not going to go in with a pricing advantage necessarily. Brad has done a lot of work in this space, and if you want to comment Brad, how do you think about pricing broadly in the next generation ERT?

Bradley Campbell

Sure. I mean, in general, we have seen the reimburser say, that if you are delivering value and if the prescribers are prescribing on label with prior authorization, but they are happy to reimburse up to the typically seen orphan prices that are out there. And as John said, we are doing a biobetters strategy, not an [E2] (ph), not a follow-on, and so we would expect to continue with that strategy going forward.

John Crowley

I wanted just to add to that, maybe Joe, one of the advantages you will have with the addition of the chaperone technology, the CHART technology that we call it, chaperone advanced replacement therapy, is you can have novel modes of administration. We have demonstrated some data. We have shown it recently at conferences, where if you take lumizyme for instance, and if you let it sit for 28 days at room temperature, it will degrade, it will aggregate. We have got a picture that shows assailing control that shows the enzyme -- the lumizyme after 28 days in kind of a milky, cloudy state. But then, they have the lumizyme in the exact same conditions, co-formulated with the chaperone, and it's as clear as the failing control. So, it's a very visually striking way to show just how much stability is conferred by the addition of this CHART technology.

But what it also means practically is you may be able to deliver these enzymes subcutaneously, so you can keep them stable in liquid suspension. Obviously, much more convenient for patients than being hooked up to an IV machine one out of every 14 days of their life. But it also means that you can do that, you may potentially be able to much more closely mimic, how you and I without disease make these enzymes a little bit all day, every day, and that's a key part of the technology going forward, it might not be in our first generation approach in terms of delivery. In some diseases it may, but it's certainly, I think an advantage that we would have, and again not just efficacy, but enhance patient convenience.

Joseph Schwartz - Leerink Swann

That's interesting. So this will be once a day or something?

John Crowley

Once a day, once every other day, we are doing a series of preclinical experiments right now looking at that.

Joseph Schwartz - Leerink Swann

Okay. So we should, I guess, expect that the Fabry co-administration program will kick off next year.

John Crowley

Into the clinic in 2014, right.

Joseph Schwartz - Leerink Swann

And then, how long do you think that that program will last, before we can --?

John Crowley

I hope it will last forever.

Joseph Schwartz - Leerink Swann

How long do you think it will take before the data?

John Crowley

So the -- right now the way we are thinking about it, is going into a short study, similar to other studies that have been done in Fabry to show that the enzyme in various doses, including doses that are more optimal, we believe than either Fabrazyme or Replagal today, that they are taken up into target issues, substrate is reduced, we think that would be a short, may be 12 or 18 person study. If you look at comparators, those tend to be 12 to 20 week studies. So we are not giving guidance yet on to when to expect data, but we think start to finish, those could be all-in six month type studies. And we are looking right now at could we then rapidly move into a Phase-III, perhaps that switch study that we envisioned, that's maybe a yearlong type of study.

So generally, we want to think about very aggressive timelines to develop this medicine.

Joseph Schwartz - Leerink Swann

What do you think about the endpoint that BioMarin has chosen in their Pompe switch study, and the endpoint that's powered for a four point improvement?

John Crowley

Look, the -- most people would later (inaudible) forms of Pompe, when they die, they die of respiratory failure. So it's typical of most neuromuscular diseases. So I think it's a very relevant endpoint, and broadly looking at another way to characterize respiratory insufficiency in these patients, and to capture a potential advantage, in talking of the doctors that we work in Pompe with and the regulators at FDA, they seem to be quite encouraged about that endpoint.

So we will see. I think it's great that patients will have yet another option to choose from, and we will see where that program goes with its data.

Joseph Schwartz - Leerink Swann

Okay. Great. Well thank you so much for joining us today, and keep up the good work.

John Crowley

Great. All right. Thank you. Thanks, have a good day.

Question-and-Answer Session

[No Q&A session for this conference].

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Source: Amicus Therapeutics' Management Presents at Leerink Swann Rare Disease Roundtable Conference (Transcript)

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