Amicus Therapeutics' Management Presents at UBS Global Healthcare Conference (Transcript)

May.21.14 | About: Amicus Therapeutics, (FOLD)

Amicus Therapeutics, Inc. (NASDAQ:FOLD)

UBS Global Healthcare Conference Call

May 21, 2014 12:00 PM ET


William D. Baird – Chief Financial Officer


Andrew Terry Rosenbaum – UBS Investment Bank

Andrew Terry Rosenbaum – UBS Investment Bank

Good afternoon everyone. Welcome to the last session within this room for the 2014 UBS Healthcare Conference. My name is Terry Rosenbaum and I’m happy to be the host for this session. I would like to introduce our next speaker who is Chip Baird, the CFO of Amicus Therapeutics. And after he is done, there will be a Q&A session held in the breakout room Carnegie East, just across the hall. Chip.

William D. Baird

Thanks Terry and I would just like to thank UBS and the conference organizers for inviting us to be here today. I’m the CFO of Amicus Therapeutics and look forward to telling you a little bit about Amicus. We will be making forward-looking statements today and refer you to our Safe Harbor provision.

At Amicus Therapeutics, we’re focused on developing next generation therapies for rare and orphan diseases with a specific focus on lysosomal storage diseases. We’ll show here pictures of patients with lysosomal storage diseases to illustrate for you and remind ourselves of our company mission.

On the upper right hand side is the picture of a family with three generations suffering from Fabry disease that is a common occurrence in that indication and the left hand picture there are two siblings both of whom are living with Pompe disease. There are first generation therapies for these diseases, but as I’ll show today that remains significant unmet medical need in these indications. Our goal is to make meaningful improvements in the treatment of these diseases and in the lives of these patients.

From an investment highlight perspective we have both near and long-term catalyst that have the potential to create significant value for shareholders and for patients living with lysosomal storage diseases. Our near-term catalyst is Migalastat Monotherapy, we recently released top line Phase III data from our first study there and we are expecting results from a second Phase III study to read out in the third quarter of this year. As a reminder that’s a program that we own the worldwide rights to.

And then in the long-term we are executing our three-and-three strategy to advance three next generation ERTs into the clinical in the next three years. Our vision here is that we can develop bio-better enzymes for Fabry, Pompe and MPS1 by combining proprietary enzymes with our pharmacological chaperones and IGF2 targeting technology. First up is our next generation Fabry ERT which is poised to enter Phase II studies in patients in the second half of this year, and that will be followed up by our Pompe proprietary ERT which is expected to enter clinical trials in 2015.

And finally from a balance sheet perspective, we’re strongly positioned and well capitalized, we ended the first quarter with over $71 million of cash on hand and those dollars are sufficient in the current operating plan to get us into the second half of 2015 and through I think a number of important catalysts. We built a robust product pipeline pictured here and across the top you see the elements of our next generation three-and-three strategy and as I mentioned it’s led by the Fabry program followed by Pompe and then MPS I.

And then across the bottom you see our monotherapy programs and I’ll tell you more about Migalastat Monotherapy currently in Phase III. As well as our Parkinson’s program which is earlier stage and is the basis of our collaboration with the Biogen which we entered into last year.

So by the way of background Fabry diseases is a fatal lysosomal storage diseases caused by mutations in GLA enzyme, its one of the most heterogeneous genotypes for genetic disorders of over 800 known mutations. It leads to the accumulation of storage material in this case GL-3 and that accumulation of storage material causes a range of serious and debilitating symptoms including pain, GI problems, angiokeratomas and ultimately leads to premature death, death is typically caused by renal failure, cardiac failure or stroke. And while there are approved therapies there as I’ll show you significant unmet need remains.

The limitations of current available therapies are several, first and foremost is that ERT does not prevent disease progression, it can delay, but does not ultimately prevent diseases progression, patients on the ERT still die from their Fabry diseases. Second is the burden of the infusion, the IV infusions, patients spend one out of every 14-days of their lives hooked up in an infusion chair in addition to the impact on their daily lives is the cost of hospital administration of those infusion therapies.

And then finally, not only for Fabry diseases, but for ERTs in general you have the issues of tolerability and immunogenicity. In clinical trials over half the patients on Fabrazyme clinical trials experienced at least one infusion associated reaction and more than half of the patients develop antibodies against the enzyme itself, which have the potential to limit the therapeutic effectiveness of the enzyme.

And on the left hand side of the page here, a quote from Dr. Robert Desnick was a godfather of Fabry diseases treatment, has been treating patients for more than 40 years and was an inventor of Fabrazyme and was recently quoted as saying that there remains an unmet medical need among these patients and to hear it from someone like Dr. Desnick underscores the serious nature of the unmet need here in Fabry disease.

So, despite those limitations of ERT, that market is still close to a $1 billion market today and it’s in the U.S. it’s about 30% of that market, about $300 million in annual sales, driven by Fabrazyme, it’s the only approved product here in the U.S. outside the U.S. Fabrazyme and Shire’s Replagal are the approved products. The growth rate in this market has been double-digit for the last several years that’s driven by two factors; one is expansion into new geographies and the second is the ongoing identification of new patients.

In terms of how we see Amicus fitting into that market space and that commercial opportunity, we’re looking at two ways to use our pharmacological chaperones migalastat to address that market and develop better therapies for patients. For patients with amenable mutations and I’ll tell you more what that means in a moment. And we think that’s about 30% to 50% of the market, we deliver migalastat as pharmacological chaperones to chaperone the patient’s own enzyme to the lysosome where it can then reduce substrate and affect the disease state.

For other patients, we’ll combine migalastat with our own proprietary enzyme to buy and stabilize that [indiscernible] or infused enzyme, which increases the uptake of that enzyme into tissue and again will lead to increased reductions of disease substrate. So, one molecule, two ways of using it, but in the end our vision is developing two products that could represent better products for all Fabry patients.

I’ll tell you a little more about Migalastat Monotherapy, which is our most advanced program. And, start by this differentiating Migalastat Monotherapy versus enzyme replacement therapy. Enzyme replacement therapy is given once every 14-days; it results in a peak of enzyme activity followed by a long trough until that next 14-day infusion. In contrast, migalastat is given every other day and more closely approximates how healthy individuals make enzyme all day, everyday.

The delivery we talked about ERT is delivered in a multi-hour infusion, where as migalastat is an oral pill. And has potential to get to more of the disease relevant tissues that are difficult to reach with a large molecule. From a manufacturing perspective ERTs are based upon chose cell a recombinant protein manufacturing methods. In the past that has led to supply disruptions and there is complexity involved with that. In contrast migalastat just the trying to ensure the purchase of small molecules.

And finally migalastat is unique and that it is a more of a personalized medicine approach. As I mentioned before, there is 800 known mutations, we've identified a subset of mutations that we think represents between 30% and 50% of the market. And we know exactly which patients can benefit from monotherapy that has important advantages obviously from not only patient and physician but payer perspective as well.

A little more about amenable mutations and how we get to the size of the market. We’ve characterized over 500 of those 800 known mutations and we know which ones are amenable. The other thing that’s interesting about the market in what's been going on recently is that there has been a number of Newborn Screening studies and those studies have shown and conducted in Italy and Taiwan and Austria and here in Illinois in the United States. The reference rate of incidence in the literature has classically been one in 40,000 or one in 60,000 births.

These Newborn Screening studies have shown an incidence that’s far higher somewhere between one in 1000 to one in 4000 life births. Most of those mutations in those screening studies, where actually amenable mutations and when you find a newborn with one of the mutations you typically screened the rest of the family, because it is ex-linked and typically identify three to five additional Fabry patients. So we believe that there is still tremendous growth opportunity in this market and its one that could be particularly suited for Migalastat Monotherapy.

In terms of our global registrations strategy, we have two Phase III studies that we are conducting. The first is FACETS study, this is Study 011, we recently reported top line 12-months and 24-months results from this study. This was a placebo-controlled study and where kidney GL-3 the amount of substrate and interstitial capillary cells in GL-3 was the primary endpoint.

And we’ll show you more data from that study in a moment. The second study is the ATTRACT study or Study 012 this is an ERT switch study. So patients enroll and either stay on ERT or switch to Migalastat Monotherapy for 18-months of treatment. The primary outcome measured here is kidney function as measured by GFR. We are on track to report those results in the third quarter of 2014.

A little more about the study design for Study 011, the FACETS study. So you can see here the stage one was a double-blind, placebo-controlled, six month treatment period where we took baseline biopsies and biopsies of six months and measured the amount of GL-3 the number of inclusion bodies in the patient’s IC GL-3 cells.

After six months, patient switched over to migalastat for an open label extension, and at 12-months again they got into another biopsy to measure the level of GL-3 in the interstitial capillaries cells, and then from 13-months to 24-months those patients continued on migalastat and we monitored clinical outcomes including kidney function.

We announced at the end of April the key findings from the study and the results were positive from both an efficacy and safety perspective as we could have hoped. Importantly we showed that patients who crossed over from placebo to migalastat showed statistically significant reductions in their interstitial capillaries GL-3 levels at 12-months of P 0.013.

And that patient who remained on migalastat for that second six months of therapy from seven months to 12-months demonstrated a durable reduction in the interstitial capillaries GL-3 levels. We also measured another marker of disease substrate Lyso-GB3 and we saw similar pattern in terms of reduction and maintenance of reduction across these patients.

Kidney function as measured by GFR which is the primary endpoint for Study 012, we look at here in Study 011 and we saw important trends towards stabilization over 18-months to 24-months. The drug was generally safe and well tolerated, which is obviously important for a lifelong chronic therapy and I’ll show you a little more at the end, but the patient disposition in terms of continuation of this therapy has been excellent and has been very encouraging to folks of the company as well as our investigators.

So I’ll show you first the six month result, these are results that we presented at the 2014, LDN WORLD Conference back in February, that these show the number of inclusions per capital areas measured as a continuous variable across all patients. So the red line is placebo patients and you see the level of GL-3 going up over the first six months where as the patients on migalastat on the blue line the level of GL-3 going down P 0.008.

Our hope was for 12-months that the patients should cross over on that redline that begin receiving migalastat that they would show a similar reduction in GL-3 and that the patients in the blue line here would maintain the benefit that they saw in the first six months and so when we unblended the data that’s exactly what we saw. We saw those cross over patients show statically significant reductions in their GL-3 levels and the patients who maintained for the second six months on migalastat on a continuous basis had a durable reduction, so very encouraging results here.

We also then looked at Lyso-GB3, I’ll show you that slide here, Lyso-GB3 is another important and emerging biomarker in terms of the measuring of disease substrate levels. It’s an easier measurement to take than kidney IC GL-3 which requires biopsy. And again we see the same pattern, patients reducing over the first six months those that receive the migalastat in the first six months and then maintaining those levels and then patients who crossed over after six months showing a statically significant reduction in their Lyso-GB3 levels, so two important biomarkers both showing clear drug activity in this patient population.

The other efficacy measure that we highlighted in the 12-month to 24-month data was glomerular filtration rate or GFR. This is measure of how efficient the kidney is in doing its job of filtration and when we looked at it using two different measures of eGFR as well as measured or iohexol GFR. GFR is the primary endpoint for Study 012 and we’ll be getting those results in the third quarter. And what we saw on an annualized rate of change is that these patients had trends towards stabilization anywhere from a 0.79 improvement on the MDRD measurement to - 0.3 to - 1.51 declines.

That compares very favorably to the published literature on the natural history of patients who are untreated or even patients on ERT. And this by way of background for those whom are healthy and middle aged your kidney GFR is going down at - 0.5 to - 1.0 mls/per years. So even in healthy population GFR is going down, so to see this level of stabilization over 18-months to 24-months was also an encouraging sign.

A note about safety we detailed it here, but the overall summary is that migalastat today’s has been generally safe and well tolerated, and again that’s important for a life long chronic therapy and it really speaks to the broader patient experience that we’ve seen. This is something that has been something we've observed now for up to eight years patients have been taking migalastat as their only treatment for Fabry diseases. We have 97 patients around the world today taking migalastat.

And importantly when patients had a choice to continue in a long-term extension study or go back to commercially available treatment, on average 94% of those patients have elected to stay on the migalastat as their only treatment for their Fabry diseases. So these have all been encouraging, qualitative signals for us in terms of the drugs benefit risk profile.

Our global regulatory strategy is really divided between the U.S. and ex-U.S. and in the U.S. as we previously disclosed we’re going to bring the totality of the data from Study 011 and Study 012 back to the FDA to discuss the registration pathway. In Europe registration pathway is led by the results from Study 012, Study 011 will provide important supportive evidence and that will generally we believe to be the path and other regions of the world as well.

So this is a program we’ve been executing on since the first patient was enrolled in the first Phase III study back in the third quarter of 2009. So like most important things, it’s been a long path and but we’re very close to the finish line in terms of this global registration strategy and is an exciting time for the company as we get ready to un-blind that second Phase III study.

Backing up to the Fabry franchise, that we’re building, we've told you about Migalastat Monotherapy for the 30% to 50% of patients who have amenable mutations, we’re also focused unless other patients who don’t have a amenable mutations, and we’re developing a next generation ERT, which we expect to launch into clinical studies this year.

In pre-clinical studies, we’ve shown that this proprietary ERT when combined with the chaperone. Increases the amount of enzyme that’s taken up into disease relevant tissue and the reason that’s important is when we get more enzymes in disease relevant tissue, you see better reductions in terms of the amount of substrate, the amount of storage material and at the higher doses here you see the reduction that approach near well type levels. The enzyme – the chaperone also give us the ability to dose at potentially higher levels, which could further reduce the substrate level. We expect to have more to say about the Phase II clinical design and timelines coming up here soon.

Shifting gears to the second component of our three-and-three strategy, I’ll talk a little bit about our next generation ERT for Pompe diseases. And this is a program that was really catalyzed by the acquisition of Callidus Biopharma at the end of last year. by the way of background Pompe diseases is a severe progressives and ultimately fatal neuromuscular diseases like most genetic disorders, it’s a spectrum in terms of the age of onset, there is infant onset all the way up to onset in the adult years. There is an improved therapy, lumizyme is the only [approved] therapy and there are like Fabry diseases limitations to that approved therapy.

And the real challenges with the current approach of ERT are shown here. One is that the stability of the enzyme itself, infusing lysosomal enzyme into the blood is one of the most unnatural acts that you can do. The typical pH in the lysosome is 5.0, it’s an acidic environment and you take lysosomal enzyme and put into the neutral pH of the blood, it begins to rapidly unfold [indiscernible] eliciting an immune response.

Targeting [uptake] is also a real challenge in this disease, there have been studies that are shown that a very small fraction of the current standard of care was actually taken off the disease relevant tissue, most of the enzyme is cleared through other pathways. And finally tolerability and immunogenicity, it’s particularly pronounced in the infant onset patients where the immune’s responses can be so severe that the emerging standard of care is to ablate the infant’s immune system and deliver methotrexate and Rituxan to wipe out their immune system so that they can tolerate the lumizyme. So there are a lot of ways to improve upon the current standard of care and we think we have multiple tool sets to do that.

We are using our CHART technology, where we developed a pharmacological chaperone to stabilize the enzyme itself, which we think has benefits in terms of stability in the bloodstream. It protects it from unfolding and has a potential to deliver an improved immunogenicity profile. Through the Callidus acquisition, we also have a targeting technology that leverages a variant of the IGF-2 Peptide, which governs uptake into muscle cells.

By tagging the enzyme with IGF-2 we can further increase uptake and again that’s been one of the big challenges with current standard of care. Much like our combination studies in Fabry disease and Pompe disease, we’ve shown that when you add the chaperone to the enzyme itself you get greater uptick in disease relevant tissue and that corresponds to greater reduction in substrate in this case glycogen levels.

And some of the data that guide us so excited about the Callidus acquisition is shown here, so here you see across the X-axis increasing levels of lumizyme and not a big increase in terms of activity and uptick. When you compare that to AT-B200 which is our proprietary enzyme, you see 10 fold greater uptake into tissue. And then when you combine that with the IGF-2 targeting moiety the increase is now 50 fold greater than lumizyme.

So, a significant increase in uptick and that corresponds to increased activity in muscle cells and corresponding reductions of glycogen. These studies were all done without the benefit of the chaperone and that’s something that we are evaluating this year in further proof-of-concept studies. The goal here is to select a final drug candidate for our DNA studies this year and move into clinical studies in 2015.

From a financial picture, as I mentioned before, we’re well capitalized with just over $71 million at the end of the first quarter, we project to spend between $54 million and $59 million this year and that’s cash sufficient to get us to the second half of 2015.

Thank you for your time today and happy to take any questions in the breakout session after this presentation. Thanks.

Question-and-Answer Session

[No Q&A session for this event]

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