Ready.
Okay, good morning, everybody. I'm Kristen Kluska, one of the biotech analysts at Cantor. Very happy to be hosting Bradley Campbell of Amicus Therapeutics. Thanks so much for being here.
Thank you, Kristen. Thanks to Cantor for having us. It's a great conference so far.
Awesome. I'm glad to hear that. Maybe just to start, do you mind giving us the typical high-level overview?
Yeah. So, as a reminder, we're Amicus Therapeutics. We develop therapies for people living with rare diseases. We have two commercial products today. The first is Galafold, which is our legacy product. We launched that in 2016, have seen great growth over the years with Galafold.
And I know we'll talk more about how we see that product evolving over time. But importantly, in the second quarter, we did over $128 million in global sales for that product. And that's within our 10%-15% growth rate.
So, very excited to see that product continue to evolve. Of course, we also have our second product, which we launched, Pombiliti Opfolda, for the treatment of people living with Pompe disease. And there, too, seeing robust growth in the second quarter, $26 million in global sales there, which is within our 50%-65% guidance range as well.
So, really excited to see some progress. And we'll talk a lot more about the drivers for Pompe, of course. And then the new part of the story, which I know we'll talk a little bit more about today, is we did, earlier this year, license a product called DMX-200 from a company called Dimerix, which is in late phase III development for the treatment of FSGS, which is a rare kidney disease.
Really excited to have another product in the portfolio and one that we think can help thousands of people living in the United States. And then last but not least, very strong financial position. We're on track to be GAAP profitable for the first time during the second half of this year. So, we think an exciting story and one that we're really eager to talk more about over the course of the year.
Okay, awesome. So, yeah, next spring, 10 years on the market for Galafold.
Yeah.
Hope you have something fun up your sleeve for the Amicus team to celebrate. But take us back in time when you had that launch. What did you think the Fabry disease market looked like in terms of number of patients, size, and then also what percent of patients might ultimately end up being candidates?
Yeah. So, remember, great questions. Galafold is a small molecule chaperone. And we did a whole host of work to characterize what causes Fabry disease. There are thousands of mutations that can lead to the disease. And we estimate that about a third to a half of people living with Fabry disease would have an amenable mutation, is what we call them.
At the same time, at that time, this is now 2015, 2016, there were about 10,000 patients globally who were diagnosed with the disease, and about 5,000 of them were treated. You can figure about a $200,000 average net price. So, it was a billion-dollar market at that point in time.
And honestly, at that time, we thought, if you're treating about a third of those patients, maybe they all go in therapy at some point, could this be a $700 million market for Galafold eventually?
So, that was kind of our initial ambition. What's been really exciting to see is a couple of things. So, first of all, we've established Galafold as standard of care for people with amenable mutations. So, in terms of execution, in terms of is the product delivering, I think the answer is yes. So, that's been really important. But interestingly, we've really learned two things over time.
The first is Fabry disease is probably even more diagnosed than we could have ever imagined. Where we sit today, the treated market has more than doubled. So, now there's 12,000 patients that are treated with a Fabry treatment today. And that's both Galafold, but then also the legacy enzyme replacement therapies.
So, that's pretty unusual in and of itself to see a market double, a treated market double over a period of time. However, there are now 6,000 diagnosed untreated patients.
The total diagnosed market is actually 18,000 patients. That's a really exciting opportunity to continue to provide patients with a new treatment alternative with Galafold. The other piece, though, to your point about eligible populations, and this is something that has been hinted at over time, but we're seeing it now more and more.
That initial population, those 10,000 patients, represented probably a more severe form of the disease. They were easier to diagnose. It just so happens that those patients had more of that 30%-50% amenability rate. What we've learned over time with newborn screening, looking at late-onset patients who are newly diagnosed, actually it looks like a high preponderance of those later-onset mutations could be amenable to the chaperone.
More like 80% or 90%. We're successful from a commercial perspective. That's really important.
The market is growing and growing at a really healthy rate. And it may very well be that more patients are eligible to take our medicine than we ever thought.
Okay, so now, instead of looking behind, let's look ahead. I'm curious, when you and I sit together here at the Cantor 2030 conference and have this fireside chat, what do you think diagnosis is going to look like? And it's hard to not give a shout-out to things like AI that are kind of brand new, right, which might even help with some of these ongoing initiatives.
So, we'll all get here in our flying car, and our avatars will actually do the talk. We won't even do the talk. But what do we think? So, if you were just to project forward the rate of diagnosis that we saw over the last decade, that puts you at like 25,000 diagnosed Fabry patients, which on the one hand sounds really significant.
It would be by far the largest pool of diagnosed patients with a lysosomal storage disorder and maybe starts to creep out of a hyperorphan disease into something larger. What's interesting, though, is there should be 100,000 patients living with Fabry disease out there in the world who haven't been diagnosed. So, you know that the opportunity is there. For sure, new technologies will play a huge role in finding those patients.
Interestingly enough, probably the biggest change over the last 10 years has just been the availability of low-cost genetic testing. So, that if a patient comes into increasingly a cardiologist or a nephrologist, they can just order a genetic test to confirm that it could be Fabry, or it could be a whole host of other genetic diseases that we now know cause a lot of these idiopathic, broader cardiomyopathies, et cetera, and end-stage renal disease, et cetera.
So, that in and of itself has been huge. We've learned a lot more about what a Fabry patient looks like. So, we have better questions to ask. Interestingly, newborn screening, which, while falling way behind Pompe in the United States, as an example, there are only eight states that currently screen for newborns or screen newborns for Fabry disease, I should say.
You do family screening when you find those, we call them index patients. You typically find four or five family members who have the disease, so that in and of itself is actually making a difference, and so all that's kind of going on, and that's great.
Where we still don't know the impact, and where maybe that's the difference between, I hope, the 25,000 and more than that, is how is AI, machine learning, going to improve our ability to diagnose patients, and I think that's, frankly, still unknown.
We are doing some work with OM1, which is a machine learning company that's helping us, has helped us deploy an algorithm into the Penn Medical System. We hope to have more information on what we're finding there at the end of this year.
We did do an interesting study in the U.K. looking at health inequity, which found that a significant portion of patients, 80% of the patients diagnosed with Fabry, were in the top two socioeconomic deciles, and I think 90% of them were white, which tells you you're missing a huge chunk of patients who are of color and are of lower socioeconomic means, so clearly, there's something going on in there.
We're doing that in other markets as well, and then you have a whole host of companies, Komodo and Genomenon and GeneDx and a whole bunch of folks that are out there aggregating data, looking in health records and improving their diagnostic capabilities, and so I have to believe in the next three to five years, you're going to see some improvement there as well.
I hope then to be able to say, hey, maybe Galafold could be even bigger than we think it is today.
Yeah. So, I know we talked about this 10-year milestone. Obviously, other regions came on board afterwards. But typically, when you see a drug on the market for 10 years, it starts to either reach or has surpassed its plateau. We're not even close to seeing that here. So, besides the fact that there's just been, frankly, more patients diagnosed, what are the other drivers that have led to this growth pattern continuing?
Yeah. I mean, I think first and foremost, it's the evidence and the impact we're having on patients. And I think there's two places to look at that. The first is we still have over 90% compliance and adherence. This is a chronic oral medication. And I think, I suspect, haven't done this in a long time, that we're one of the leading compliance and adherence rates for a chronic oral medication.
So, clearly, that says it is having some sort of impact. There's high satisfaction on the part of physicians and patients because you do have a proven technology in enzyme replacement therapy that they could switch to. I think the other piece of that is we're also, we have a large registry that we've had since we launched the product.
We continue to publish real-world evidence that shows the impact we're having on things like proteinuria, like cardiomyopathy, like Fabry events. So, I think that evidence continues to support the use of the medication as well. We talked a little bit before around being standard of care. So, we're about a 70% global market share of treated amenable patients.
So, there's still 30% more to switch. And in some countries, we're up at 90-plus% share. So, you know there's still an opportunity there. But the other interesting thing is that when we launched the product, it was all about switching. Now, 80%, like in the U.S., U.K., Germany, 80% of our demand is naive patients, newly diagnosed patients. And so, that's been an interesting evolution.
That's where, again, continuing to fuel the diagnosis and finding of patients so you can offer them a treatment, I think, is really important.
Three years from now, you're expecting total revenue could surpass $1 billion, much of which, at least we expect, is going to be driven by Galafold. Help us tie it all together to allow your confidence towards this prediction.
Yeah. If you put all those dynamics in place, I hope it's clear that the patients are there to come on the therapy.
So, if you just run the math, it's pretty obvious that you'll be able to have a significant opportunity to continue to bring patients on. In terms of kind of how we guesstimate, project what's going to happen between now and then, I think it's probably going to be 60% Galafold of that $1 billion, plus or minus a few percentage points. How do you get there? We're going to grow at 10%-15% this year.
We think that the growth rate stays in the low teens, high single digits, frankly, through the end of the IP lifecycle. So, you're still in a very kind of robust growth time for Galafold.
I think you can pretty easily run a line that gets you to that sort of 60%-ish number of that $1 billion in combined sales.
Okay. Last year at our fireside chat, I remember sharing with you that investors, there was an interest in seeing you build out a pipeline, and today, we can fortunately talk about that with your new addition for Focal Segmental Glomerular Sclerosis. I'm just going to say FSGS.
FSGS, yeah.
Much easier in biotech land.
Oh, that's good. I'm impressed. It took me a while. I had to practice quite a bit before I was ready to do it.
Tell us a little bit more about this indication, please.
Yeah. So, loosely translated, that's some segments of the glomeruli, which is the kidney filtration units, are scarred. That's sort of the lay translation of the fancy scientific name. Really high unmet medical need, no approved treatments for FSGS today. We think that there are at least 40,000 patients living with FSGS.
I think it could be much more than that. We know that actually there's an inequity of diagnosis. There's a predominant genetic subtype, which impacts the African-American community. So, I think a lot of what you'll find with FSGS is that it will look a lot like some of these other diseases where you'll find more patients as you have therapies approved.
Unfortunately, these patients have significant morbidity and mortality within five to 10 years of diagnosis. They're typically in end-stage renal failure. Like I said, there's no approved treatments.
There are ACEis and ARBs and steroids can address a subpopulation. We can talk more about that because I think it's relevant here, but just really excited to have the ability to now partner with Dimerix on a unique mechanism, a CCR2 inhibitor, but in and of itself, it's a unique CCR2 inhibitor, which we should talk about.
A nd we think there's a real ability then to disrupt the inflammation cascade that is hallmark with FSGS and hopefully lead to significantly improved outcomes.
Whenever there's one of these larger orphan indications with no approved therapies, that often begs the question of why. Is it that the disease course hasn't been understood traditionally? Companies that have tried in the past, maybe the targeting wasn't right. Do we have a good sense of maybe why this might be?
Yeah. I think part of it is it's a complicated disease. And there's multiple different subtypes. So, there's a genetic subtype. There's a primary subtype. There's a secondary subtype, which is caused when you have things like diabetes and other risk factors. So, part of it is it's unlike a Fabry or Pompe, which is just a monogenic disease where you can target that one gene that's impacted. Here, you have a lot going on.
It's also a fairly complex process. And I think we've learned a lot about the kidney and its function over time. And so, effectively, you're caught in this sort of inflammatory cascade where you start to get the scarring, which then leads to proteinuria, which then leads to increased inflammation, which then leads to more scarring. And you get into this kind of vicious circle.
I think people have had a hard time trying to decide where to target to sort of block that cascade. There's multiple types of inflammation. So, it is, I think, complex. Although you are seeing, I think, more interesting things on the horizon.
Obviously, Travere has a drug that's in late-stage development, which is a different mechanism, but eager to see them continue to move that forward. Yeah, so I think it's been a challenge of the complexity of the disease and then within that, sort of where do you target to make a real impact?
Yeah. We're rooting for all of you because these patients need something.
100%. 100%.
Let's talk about the targeting a little bit more. How has CCR2 been shown to mediate glomerular injury? Considering it's a relatively fast-progressing disease, at what stages of the course might interrupting the chemokine potentially slow down or maybe even reverse disease?
Yeah. So, it's long been associated with elevation in MCP-1, which is another inflammatory marker. And what is interesting is the other CCR2 inhibitors acted in a very different way and, in fact, ended up increasing MCP-1. So, there was almost like a rebound or echoing effect that led to increasing MCP-1 levels, which then were not able to show differentiation.
Our CCR2 inhibitor, and I wish there was an opportunity to name it a different class or call it something different because it would help differentiate from some of the other ones. It actually binds to both the heteromers and the monomers of CCR2 and the complex they form to prevent and to lower MCP-1 and then also lower proteinuria. And so, it's a very different mechanism. We have lots of data.
We could talk more about kind of why we're excited about the data that we've seen and confident in the outcome of the disease. But fundamentally, it leads to a reduction in monocyte-driven inflammation. And so, technically, we don't know that CCR2 inhibition would lead to better outcomes. But what we do have is a really, I think, important analog, which is corticosteroids.
So, corticosteroids have been shown to reduce monocyte inflammation and other forms of inflammation. And when they work, they actually lead to a 10-year survival rate of the kidney of 70%-80%. So, significant preservation of kidney function and kidney survival over a long period of time, which is really exciting. The challenge with corticosteroids is they only work in about a third of the population. So, a significant portion of the population don't see that benefit.
We believe the mechanism and the pathway is sound. That refractory population, which is what we're targeting, they need something much more. I should clarify, the Dimerix approach, now our approach, is to combine DMX-200 with ARBs, with standard ARBs, to lead to that monocyte reduction in monocyte inflammation.
Okay, and then if one is able to reduce the damage or proteinuria, how has this been shown to correlate with delaying transplants or kidney failure even?
Yeah. I think if you look at that stat I just shared with you, that tells you that if you can reduce that proteinuria and the inflammation, you can get to, at least with steroids, you got to a 10-year survival rate of 70%-80% of that kidney. Right? So, that is a significant benefit.
Whereas I think the reverse is true. Jeff, I'm going to have to phone a friend here. From onset of diagnosis of disease to end-stage renal failure is 5 to 10 years. Right? So, if you're not treated, in 5 to 10 years, you're going to be losing a kidney, effectively. Whereas if you can control that inflammation, you can actually preserve it for 70%-80% of people are preserving it out to 10 years.
Okay. So, the trial design is a bit de-risked as you get these interim analyses to make sure that things are trending well. How has this given you confidence to date and a positive outcome ultimately?
Yeah. We were really thrilled with the data package that we saw when we did diligence on the asset. So, of course, we had the preclinical safety and efficacy data. That was all very positive. And in fact, the FDA has said that's sufficient to support a filing of the product, which is great. So, there wasn't a lot of leftover work that we had to do there.
They did do a number of phase II studies in a number of rare kidney diseases and saw consistent reduction in proteinuria and other positive benefits. And it was generally safe and well tolerated in those phase II studies. So, you had a nice phase II data set to look at, which was great. What was really exciting to your point, though, is then they designed a phase III study. And there were a couple of important things.
The first is that they had received feedback, and then we actually had the minutes from that feedback prior to doing the deal where the FDA agreed to two-year proteinuria outcomes as an approval endpoint. This is the first time that we've seen this by the agency.
A large part of that is due to the PARASOL group, which is that group of nephrologists, thought leaders who have looked at the connection of proteinuria to GFR, so we knew that the agency was open to proteinuria as an approval endpoint, which is fantastic.
B ut then the second thing they did is they did an interim analysis where they disclosed previously, before we actually licensed the product, they disclosed that the treatment group statistically favored the placebo group on proteinuria.
In about a third of patients, we know already that you're seeing the statistically positive trend in favoring the treated group with DMX-200. You've got great preclinical data. You've got some very, very supportive phase II data. You've got a clear endpoint that the FDA provided support for. Then you have an interim analysis that confirms at least at that stage in the study that you were on track to meet that endpoint.
Okay, and then what level of evidence do we have to suggest durability, especially as patients naturally are becoming more advanced in their disease progression given the shorter timelines here?
Yeah. And I think maybe that's a little bit related to what you had said earlier, which is like when to intervene and is there too late. I mean, of course, at some point, end-stage renal disease is hard to reverse. But it does look like having an intervention kind of anywhere during that time period can have a positive outcome in preserving proteinuria or improving proteinuria and preserving kidney function.
I think, frankly, the reality is, again, the best thing we have to say, like long-term reduction in inflammation, I'd look at ARBs and I'd look at corticosteroids and the patients where they're effective in, they do show a long-term benefit. We don't have enough data yet in FSGS for DMX-200. But of course, part of the objective of the phase III study is to show two-year benefit in proteinuria.
If we can demonstrate that, I think we'll have an approval product. I think we'll have a great intervention for patients.
Okay. So, we understand the full phase III final analysis will come in 2027. But are there any near-term milestones to be aware of for this program?
Yeah. A couple of exciting milestones to look forward. The first is the PARASOL group has been continuing to analyze a new set of data, in particular thinking more about the primary endpoint of proteinuria for this study. They're starting to report that data to us and to DMX-200 and a couple of other collaborators.
We'll look to digest that data. I'm sure at some point, either at a conference or some other place, we'll share the outcomes there. That will give us all, I think, better confidence in the connection between proteinuria and GFR, which will be great.
There is also, of course, the enrollment of the study. We're 75% enrolled today in the study. We're on track to fully enroll that by the end of this year. That keeps us on track for the 27 date that you're talking about.
A couple of other interesting things. The first is we know, of course, Travere has an AdCom. And so, again, different mechanism and a different set of circumstances. But I think importantly, whatever the FDA tells them and the AdCom tells them about proteinuria and the trial design, et cetera, et cetera, will help us inform our final statistical analysis plan.
And then the last piece of the puzzle, which you kind of hinted at, is we do intend to go back to the FDA and talk about another interim analysis where we could, at the very least, again, run a futility and see whether the trial is on track. So, over the next kind of three, six, 12 months, I think you'll see some interesting and supportive milestones towards that progress.
Okay. And what is it going to take for this to be a billion-dollar product?
You know, look, I think we tried to be pretty conservative in how we thought about the market opportunity. So, we say kind of at least 40,000 diagnosed patients with FSGS today. I think there are statistics that say that's more like 40,000-80,000. This is in the U.S. alone. I should clarify, our rights are in the U.S. for this product. So, in the U.S. alone, it could be upwards of 80,000.
But we are very conservative there. Again, we've taken patients who are refractory to corticosteroids, who have primary FSGS. And so, that leaves you with like a 5,000-10,000 patient population. They have no available treatments today. If you apply kind of a standard orphan pricing for a small molecule and kind of a standard penetration rate, I think you can easily get to a billion-dollar product opportunity.
I do think there are some upsides for DMX-200, in particular around second indications, other indications. So, we also have rights to develop this in other indications. We have to solve some IP opportunities there, which we were very successful doing with Galafold as an example.
But I do think, I hope that we can come back in a year's time and have perhaps even more indications that we could pursue this in if we can get the IP in a place that gives you enough time to do it.
Okay. Definitely wanted to make sure I could cover Pombiliti and Opfolda. But thanks for all that background. I know it's a new program for a lot of folks. But so, for Pompe disease, how are you thinking about the projection here for the next three years, especially as it relates to the 2020 revenue guidance?
Yeah. So, again, if you do the opposite, if Galafold's about 60% plus or minus, Pompe is then about 40% plus or minus of that billion-dollar sales projection. And so, how do you get there? Well, today, or I guess at the end of last year, it was about $1.5 billion globally for all Pompe treatments, the legacy ERTs, and then Pombiliti, Opfolda. We believe that's growing to $2 billion.
So, underdiagnosed, not quite to the same tune as Fabry, but still healthy growth in that market based on finding new patients and based on having new therapies available. Again, we're growing at 50%-65% this year. We could talk about all the exciting things we saw over the second quarter. But this will be a very fast-growing product as we're still in the meat of the launch.
Our ambition to kind of square all that away is that we want to get to about a 50% share in every market that we launch into. We'll be right about that five-year mark for a number of those markets in another three years. You could see a significant contribution of revenue from Pompe.
Okay. And to close, do you mind sharing your current financial situation and then, of course, anything else our audience should take away today?
Yeah. Our focus is really on after kind of a tumultuous six months in the market and for Amicus specifically, building on our strengths. We know we've been successful in commercializing Galafold. Again, we hope to grow that product 10%-15%.
And we see low teen, high single-digit growth rates really through the life of that product. I think we understand now the dynamics in Pombiliti, Opfolda, and the Pompe market space that took us a little while to get our handle on.
But we're seeing that momentum. And again, we can draw on the strengths that we had with commercialization with Galafold. I'm confident that will be a billion-dollar-plus product at peak. And I think now we're on a trajectory where we can have a better handle of how we get there. As we talked about, DMX-200, totally unappreciated part of the story.
I'm super glad that you asked the question, Kristen. But I think very few folks have done real work for Amicus in that space. But it is a very exciting space. And I think over the course of the next six months, we'll spend a lot more time talking about that. And I hope people start to give us some credit and opportunity there.
And then our financial strength. I mean, look, it's a tough time. People are having a hard time raising money. And we took two years to get to profitability and get our own house in order. And I think we were able to do that successfully. And now we get to build on that. As you said, we have the start of a pipeline.
I think we can incrementally add to the Amicus story over the next six months or so and do what we do best, which is bring great medicines to patients.
Thank you so much for being here, Bradley. Really appreciate it.
Thank you.
We are rooting for you on all these fronts.
Thank you very much. Appreciate it.
Thank you.
Thanks, guys.