Amicus Therapeutics, Inc. (FOLD) Earnings Call Transcript & Summary

Welcome to the Morgan Stanley Global Healthcare Conference. I'm Jeff Hung, one of the biotech analysts. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/research disclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. For this session, we have Amicus with CEO, Bradley Campbell. Welcome.

Thank you, Jeff.

So for those who may not be as familiar with Amicus, can you provide a brief introduction?

Sure. Yes. And first of all, thank you to Jeff and to the Morgan Stanley team for hosting us. It's a great conference. Great to see everybody in person. Don't get to do that as much as we used to. So I appreciate the forum. So yes, Amicus Therapeutics, we are a biotechnology company focused on developing and delivering next-generation therapies for people living with rare diseases. I think the most important parts of our story for this year are number one, Galafold, which is our small molecule chaperone for people with certain mutations, amenable mutations living with Fabry disease. And we had a great quarter last quarter with Galafold, delivered $111 million in sales. We actually raised our sales guidance for the year to 14% to 18%. We see that as a long-term growth driver for Amicus, and it's great to see such strong numbers being posted so far into the launch, and we'll talk more about that as we go forward. The second piece of the story, of course, is Pombiliti and Opfolda, which is our 2-component therapy for Pompe disease. We delivered $16 million in revenue in the second quarter on our way to $62 million to $67 million in top line revenue for the end of the year. So really exciting to see that product take off and we'll talk a lot more about the launch, I'm sure. And all of that is underpinned by, I think, strong financial discipline on track to deliver our first full year of non-GAAP profitability. And I think that's just a measure of the financial discipline we have and also a sign of things to come as we continue to build the strength of the company.

Great. Let's start with Galafold. You raised revenue guidance for the year. Can you just talk more about what is driving growth and what aspects of those dynamics might change as you go out beyond this year?

Sure. Yes, it's an interesting story. So when we came into the Fabry market now and is 2016. So the year before, we did a ton of work looking at how big the Fabry market was at the time. And what we estimated was, there was about 10,000 patients who are diagnosed globally. About 5,000 of them were treated at the time with enzyme replacement therapy, which was the only available treatment and about 5,000 were diagnosed untreated. And we knew at the time, and we believe that Fabry was a significantly underdiagnosed disease, and we've learned a lot more about that since then. But one important driver overall, is just significant market growth. And so today, we estimate there's about 17,000 patients diagnosed globally with Fabry disease. The treated portion has actually more than doubled. So there's now about 11,000 treated patients living with Fabry. But there's still another 6,000 who are diagnosed untreated. So I think one big piece is that you've just continued to see significant numbers of new patients being diagnosed. Another important piece of that then is, how does Galafold fit within that sort of treatment dynamic? And of course, we are indicated for patients living with amenable mutations, and that's about 1/3 to 1/2 of the population. What we've been able to do is drive significant switching from what was standard of care at the time to Galafold. And the initial part of our growth is really focused on that portion of the population that's switching population. What we see now though, is that the big driver of our growth is actually either the diagnosed untreated or the newly diagnosed patients. And so in our big markets, the U.S. U.K., Germany, Europe in general, we're seeing 80% of our new patients coming from that either newly diagnosed or diagnosed untreated market. So that's, I think, a new phenomenon for us and one that I think will continue to fuel us for years to come. And so the biggest driver for me in the long term is continuing to penetrate into that existing diagnosed untreated market, of which, again, there are 6,000 patients today. And then also really working with the entire medical community to shorten the pathway diagnosis. And that's where if you really think about kind of AI, machine learning and all those pieces, you could see how we could find even more Fabry patients going forward and Galafold, hopefully would be the treatment of choice for those patients.

And you talked about 80% -- could you just clarify what proportion of the new diagnosed patients are being put on Galafold as the very first line of treatment? And then, how fast do you expect it to change? Like is there -- where you're here?

I mean I think at this point, we believe that we're standard of care for patients with amenable mutations. And so most of the -- at least in our mature markets, most of the switch patients have switched. So we're talking 80% to 90% market share of treated amenable patients. Now on a global basis, that's more like a 60% share of treated amenable patients, because there are some countries that we've launched in more recently. So there is still a switch market, but predominantly, the big growth is coming from these either diagnosed untreated or newly diagnosed. And from what we understand, we're 90-plus percent. If an untreated patient starts on a therapy, if they have an amenable mutation, we're getting 90-plus percent of those patients.

And so then how much more room do you think that there is, given that a fairly high percentage as it is for new patients?

Well, look, I mean, if you start with the 6,000 patients that are diagnosed untreated. Oftentimes, they're untreated because they're still progressing through the evolution of disease. And so maybe they don't meet the treatment criteria today, but they will continue to progress forward. So over time, we'd expect that all of those patients will be treated. And we estimate historically that 1/3 to 1/2 of them would have mutations amenable to therapy. An interesting change, though, and this is -- we've come to appreciate this more in the last kind of 3 to 5 years is actually the later onset patients, who are the ones that are predominantly being diagnosed today, they tend to be enriched for amenable mutations. And so in fact, if you look at those 6,000 patients, it might be instead of 1/3 to 1/2, it could be more like 50% to 60% have amenable mutations. And we've -- there've been some reports in the literature that show those kinds of numbers that sort of 60% to 80% of patients who are diagnosed with the late onset mutation, are amenable to the chaperone. So I think that will be a growth driver for -- if we just do that alone, that gets you almost all the way to the sort of $1 billion opportunity we see. And that's not even counting diagnosing more patients, which I think will continue to happen over time.

If I'm not mistaken, I think Galafold has about 60% of the global market now.

Of the treated amenable patients exactly.

And so what gives you confidence that you can reach 85% to 90% market share? And can you just talk a little bit about what's required to achieve those levels? And how long do you think that, that might take?

Yes. So what gives us confidence is that in mature markets and by that, I mean, again, Europe, U.K., separate from Europe now technically in the United States. We are already getting to 80% to 90% market share. So we know that's achievable. The places -- there's a couple of regions where we launched more recently, call it, in the last 3 to 5 years instead of 5 to 7 years. And in those places, you're still on that journey, so you're probably 50-ish percent share in those countries. And so you have room to grow. Interestingly, Japan, which could end up being the -- and I know that was one of the questions that you had in your mind, could end up being the third largest market at the end of this year. It's been a little bit slower from a launch perspective, still strong, but perhaps because of the culture there, but it's taken us a little bit longer. That has become a huge growth driver for us. And again, I think there, you could see us getting to those 80%, 90% share numbers. But the good news is, as I already said, that's only part of the journey. Probably the biggest journey from here to the end, is the newly diagnosed or diagnosed untreated patients.

Great. Maybe let's shift to Pombiliti+Opfolda. You said that the global Pompe disease market growth continues to be driven by diagnose new patients. How long do you expect this trend to continue? And do you expect that to be driven more by specific geographies?

Yes. So in Fabry, the diagnosis is driven a lot more by high-risk population screening, family screening, so you find an index patient, and then you look back into the family because it's next-link disease. Pompe in the United States, to your geographic question, is driven heavily by newborn screening. So because of the more immediately fatal -- infantile onset form of the disease, newborn screening has been adopted in almost every state in the United States. And so you're finding not just infantile onset patients, but interestingly, a growing pool of late-onset patients found through that mechanism. Now those later onset patients, or I should say, patients with late-onset mutations are not likely to be treated at birth but they will be treated in the next sort of 5 or 10 years. And in fact, there's a growing understanding that Pompe is because it's a progressive disease that actually pediatric patients with late-onset mutations are exhibiting signs and symptoms in their -- as toddlers. So I think that you'll actually see a move towards treating those patients earlier. But the U.S., for sure, is a big part of that. There is, however, another focus from a diagnostic perspective and Priya Kishnani, Dr. Priya Kishnani, was one of the investigators who looked into this. She and some others effectively just went to muscular dystrophy clinics and looked at patients with elevated CK, which is a measure of muscle disease, and they just said, hey, maybe they don't have a muscular dystrophy, maybe they have Pompe and they screened them for Pompe, and they found actually a significant number of patients trapped in those clinics with a differential diagnosis of generally muscular dystrophy. And in fact, they had Pompe disease. And that's really what changed the literature reports from incidents of 1 in 40,000 to more like 1 in 20,000, or even 1 in 15,000. So if you -- if you look at that patient population, I think that's a phenomenon that will happen globally. So I think you'll find patients that way as well. So to the overall point, how long is the Pompe market going to grow? I think you're going to see healthy growth for many years to come. And I think that's a pretty consistent pattern with all the lysosomal diseases. Once you have a therapy or therapies, more people are out there looking for it. There's more of a reason to find patients and you just see this kind of steady growth over time.

And you've launched in Spain and are in active reimbursement discussions with additional EU countries. Can you just talk about the launch trajectory in the recently launched countries and how those have fared relative to your expectations?

Yes. So Spain is a great example because actually, we launched before NexViazyme, which, of course, is Sanofi's second-generation ERT and came out of the gates really strong and have continued to see great momentum Spain. Now it's a smaller market compared to Germany or the United States. But I think that tells you that in those markets where we can get out ahead of the competitor, we can have an even potentially faster ramp. That being said, we're still in a great place in the U.S., in the U.K. and in Germany. I think that we're on track to do kind of 12% to 15% market share of the adult patients in the U.S. likewise in Germany, and I think we could be on our way in the next 2 years to be more like 25% to 30% in those markets. So significant progress in all of our core markets, but there are some opportunities to go faster when we can get out in front of Sanofi. And there are a handful of countries in Europe where that could still happen. Even still, if you think about Germany, where we kind of launched head-to-head with Sanofi, I think most of Europe will be more like that dynamic, and we've seen a phenomenal uptake in Germany so far. And I think we'll see that in those countries as well.

You indicated expectations for the overall time from prescription to infusion to improve from 65 down to 30 to 45 days by the end of the year. Can you just talk a little bit more about that trajectory, where you are in that process?

Yes. Yes. So when we started the journey when we launched, we said we -- our hope is that the average would be around 90 days, and we were largely successful in doing that. Our goal, though, was to get down to that 30- to 45-day window. The analog that we were looking at was Galafold, where we were able to do that. That's kind of how we started at launch. And then as you get on formulary, as the physicians get more used to writing the pre-off forms, you can get it down to kind of 30 to 45 days. With -- and in fact, Galafold, it's more like 30 days. The reason why in the case of Pompe or Pombiliti + Opfolda, it's 30 to 45 days is because you have kind of two components. You've got the insurance component and then you've got the infusion components. Patients typically will take their infusion of their last medication and then 2 weeks later, they'll take -- they'll start on a new product. And so that's why once you get to the insurance authorization, you can either catch them on the very next infusion or it might be up to 2 weeks later. So that's kind of the goal. Where we are in that process right now? As we came out of Q2, we were at 65 days for the end-to-end process. But what we shared on the call was that from an insurance perspective, so just the insurance phase, the most recent patients were more like 35 days. So we're shrinking and shrinking and shrinking the insurance process. We're getting better at scheduling those infusions. And again, I think we're on track to do that kind of 30 to 45 days by the end of the year.

And what proportion of growth is being driven by deepening with repeat prescriptions versus broadening with more sites? And what have you seen in terms of net patient adds?

Yes. So the net patient adds, I think, have been really strong. So we reported in Q2, we had 186 patients who were either on treatment or scheduled for treatment, 74 of them were actually on treatment that gives you a little bit of flavor of what that queue is, coming out of Q2. And from your broadening, deepening question, the metrics that we shared on the call where we had an increase in 50% of prescribing physicians in Q2. That's a great number, right? So now you're getting more and more docs to infuse the product for the first time. The other thing, though, is to the other point is we are having more and more physicians do repeat prescriptions. We didn't break down exactly what the ratio was there, but I would say it's probably roughly equal in terms of new prescriptions versus repeat prescriptions. And I think both of those are critical, right? You want to broaden the aperture in terms of numbers of places where you can treat new patients, but then you really want to see the strong prescribers prescribe again and again. And that's, I think, where you'll get -- as you get more experience, they try it with one patient, they see a good response and then they want to try to get it again.

And what factors have been encouraging patients and physicians to switch to Pombiliti + Opfolda?

The primary driver still, I would say -- well, first of all, I think it's the efficacy data, but I think really it's the real-world experience that physicians are having. So we're just hearing over and over again. And of course, there are anecdotes you can't necessarily promote on them per se, but physicians are trying the product in a patient. Oftentimes, these are declining patients, and they're seeing great results. And I think that's what gives them confidence either to view it again, or when they're in front of their peers to share their experiences. Now we are focused on doing everything we can to generate and share real-world evidence, and that may be a case study where appropriate. It might be coming out of a cohort of patients like the U.K. EMS patients have now come into a registry, and we're hoping to be able to publish on those patients in kind of the next 12-month kind of time frame. So that, I think, is a really big part of the story. There is, however, a not insignificant amount of word of mouth, coming from the patients themselves. And in the right forms like in the United States, you can support patient-to-patient conversations. And there, we've heard of a number of stories either from those patient meetings where you have kind of an organic, "Hey, I tried it, it's great. You should try it," kind of conversation. Or through, we've heard about siblings or friends who are involved in the study, who now want to come on commercial drug. So I think there is an element of a pull component from the community itself. And I think, that will be an increasingly important part of the story as well. And you could see that be a kind of momentum building over time.

And over time, where do you see the proportion of switch patients naive patients trending in U.S. and EU?

So in the United States, where we are indicated for switch patients only today, the majority of course, are coming from switching. And effectively, we're taking market share on a kind of based on the distribution of the available products. So today, Myozyme is the minority of patients in the United States, Nexviazyme as the majority, and we're taking a majority of our switch patients from Nexviazyme and a minority from Myozyme. It's kind of proportional to what's available to us. And that's what we had anticipated. In Europe, where we have all three segments available, again, it's roughly proportional. We're seeing a strong uptake in the naive patient population. We're seeing strong switching from Lumizyme, which is still the majority of the population in Europe, and then we're seeing Nexviazyme switches as well. So I think effectively, physicians, I think, care less about what drug they're on. They care more about how they're doing and how long they've been on that medicine.

And does that -- do those split differ across different insurance coverage? Or are they fairly comparable across?

In the United States, honestly, the payers don't really care what product they're on. We were very careful to negotiate in the label, that it was enzyme replacement therapy that it was referring to versus Lumizyme, specifically, one product specifically. So we've had no pushback on, hey, you studied Lumizyme patients, but you're trying to convert an exercise patients. So that hasn't been an issue at all, which is great. And that was intentional as we negotiated the label.

Yes. And you've noted that one of your goals is to achieve 30% to 35% market share within 3 years for each market launch, which you've seen in the U.K. And then you've observed that the launches in Germany and U.S., Spain, they are kind of on that pathway. Are there any regional dynamics though, that are worth noting?

I think the biggest difference really between the different geographies is the proportion of Lumizyme patients who are -- the proportion of patients, excuse me, who are on the first-generation drug versus Sanofi second-generation drug, when we launch into that market, or like the case of Spain where we launched ahead of the competitors. So I think I wouldn't be surprised if Spain as it is right now, if it's on a kind of faster trajectory. If there's a band of potential outcomes, they may be on the higher end of that band. Whereas Germany and the U.S. may be in the middle of that band. So I think that's probably the biggest regional difference. And then, of course, naive. We don't have naives available to us today in the United States. And so that is another pool of potential growth in Europe. It's a pretty small portion of the population, though. So it doesn't make a huge difference. I will say though that I'm very confident based on each of our launch markets that we are on track for that, as you said, 30% to 35% after year 3 which is phenomenal. If we can deliver that, it's going to be -- and then that's what we're on track to do. I think it's going to be -- continue to be a great launch and a great growth driver.

And then how do you think beyond that, beyond the 30% to 35% and moving on higher levels, like, say, 50% pathway, like what factors would further help accelerate?

Yes. The reason why I think that kind of makes sense, that timing -- and in the U.K., again, is a good example of that, is what we've heard from physicians is they feel like they need a year or two, to if they switch a patient to then think about switching them again, or when they first start a patient to think about switching them for the first time. When we look at the -- before we launch, when we ask physicians, like where are your patients on their disease progression journey, they generally said sort of 1/4 of them, 25% of them are declining or clearly declining. Maybe 50% of them are kind of roughly stable and then 25% of them are either too new to tell or they're having some improvement. So if you think about that journey, right now, aside from the naive patients in Europe, I think we're generally getting the decliners, whether they're declining on Nexviazyme or Lumizyme. I think those are those ready switchers, and we're kind of working through that population. After a year or two, everybody who started a year or 2 ago is going to be moving into that kind of ready to switch phase. And I think that's when you have that opportunity to interrogate them. And that's where I think we can easily get to that 30% to 35%. I think how you then change the curve is once you get physicians confident that, in fact, we shouldn't wait a year or 2. We're having a great experience. You should reset expectations. You should aim for improvement, not for stability, I think that's where you become standard of care. And predominantly physicians are starting to use or switch to Pombiliti + Opfolda, and that's how you become 50-plus percent market share.

And you touched upon this a little bit ago, but in the U.S., like how do you see the treatment-naive segment playing into the market share? And how much have you collected so far? And how do you think about what's needed to support potential label expansion?

Yes. So the clear -- we've generated significant data in the naive population that we think is very compelling. In the end, the FDA, because we didn't show superiority in that segment, we're not able -- or we're not willing to include them in the label. Obviously, other jurisdictions have taken a very different point of view of that. But that is what it is. So now I think the opportunity is to take both the real-world data -- sorry, both the naive data we've already generated, and then the real-world data from -- like the U.K. registry, from Europe where we're treating naive patients and put that into a supplemental BLA to expand the population into naive. That's probably a 3- to 5-year journey, frankly. But at the end of the day, again, it's probably 5% to 10% of the global opportunity every year is naive. So we'll -- there's lots of switch opportunity to focus on for today. We're getting naive outside the United States. And then I think, at the right time with a compelling package we can we can hopefully expand that label. And the good news is now there's precedent for that. If you look at Fabry disease, as an example, the agency accepted real-world data to confirm the Fabry -- the Fabrazyme conditional approval. So I think now there's good precedent in the agency and things like that.

Great. Can you just talk a little bit about your manufacturing plans? Any updates there, especially on your second-gen manufacturing process?

Sure. Yes, one thing that I think we've been very pleased to see is the evolution of the Biosecure Act. We came into this year, it was surprising, I kind of came out of left field a little bit from Congress. And the good news is we've seen a couple of really important evolutions in that legislation that gives us great confidence that it will no longer be any kind of barrier impact on Amicus. The first is, and this is kind of well, I think, observed -- is this idea of a transition period. So now going out to 2032. So if you were exposed to the Bio Secure Act, you'd have time to transition to another facility or another manufacturer. The other piece that I think is relatively new and maybe less understood is -- and you can go online and find all this through the publicly available information is that, they've effectively said that Medicare and Medicaid will no longer be prevented from reimbursing for prescription drugs that are manufactured by these named Chinese manufacturers. In other words, there should be no impact of Biosecure on the ability for Medicare and Medicaid to reimburse for these medicines. So I think those two things combined, remove the negative impact on a company like Amicus. There are other parts of the legislation that have other -- around genetic data capture and those kinds of things that I think may have different impacts on the industry. But for our purposes, it really takes away the negative -- potential negative impact of Biosecure. So that's really good. That being said, and by the way, we're well underway with the transition from the Chinese facility within WuXi to the Ireland facility within WuXi. That process is on track. We're hoping for commercial drug to start to hit the supply chain at the end of next year or early in 2026. So that's well on track, and that's great. The other piece, to your point about second gen manufacturing, the focus there is really on bringing the cost of goods down, we think, by 25% to 30%. So in the long term, that's a huge value driver by reducing the cost of producing that medicine. And that is -- we'll start to invest in that next year. That's probably a 3- to 5-year process. So you'll start to see the benefit of that, in the kind of the first quarter of the launch, if this is like a 20-year life cycle, it's the first quarter, but then you'll have a lot of time for the benefit of those savings.

Great. Can you just talk about any latest updates on your early-stage pipeline? And when might we expect to hear additional updates on this program?

Yes. We've been very careful, I think, as we've kind of gone on this financial journey over the last 2 or 3 years to say, look, we're -- we need to get the launch right for Pompe. We need to continue to grow Galafold. We need to get to a place of self-sustainability. And I think we've done a really nice job on delivering on that. Again, we're -- our goal, and we're well on track for non-GAAP profitable this year. You could see our way then to GAAP profitable and then positive free cash flow. So I think we're in a great job there. And so therefore, in order to do that, we had to reduce our investment in our Fabry and Pompe early-stage programs in particular. The good news is, we did still, at a very marginal way, we have still moved those forward to some extent. And there's some really exciting technology there. But I think at this point, that's probably a 2026 story. But again, that's when we're going to have our own resources to be able to fund our pipeline, and not have to go to investors and ask them to take risk on that. So I think right now, we focus on growing the core business, delivering value for shareholders that way, do just a little bit of work in the background to keep those programs going and then have much more to say about that in a couple of years.

And your response kind of answers the next question, but what are your thoughts about licensing or acquiring external assets? And if you were to consider that, what would be the ideal profile?

Yes. So in keeping with that theme, I think the answer for now is, don't take risk with the P&L to invest on something early, focus on profitability and top line growth, and I think we've done that so far. I do think there's an opportunity, though, in the nearer term to look at commercial assets or soon to be commercial assets, where we can leverage what we've built and add to, and accelerate the revenue story and the profitability story. And then in, call it, 3 to 5 years, again, when we have our own resources, when we have our own capital to put to risk, start to build a pipeline, so we've become a fully integrated company. So I think if we do business development, it will be focused on adding to the top line, to increase the scale and accelerate the path to getting to that kind of significant cash flow that we can then support our own kind of R&D.

Okay. Maybe one last question in the last couple of minutes. One of your key priorities for the year is achieving full year non-GAAP profitability, and you achieved that in 2Q. Any additional thoughts on that for the year and your expectations for what could drive acceleration in the second half?

Yes. So we -- just by nature of the curve, you add more revenue as you go into the second half, right? So that's -- we should see that happen, and that should help with that. I think we -- you saw us tighten our expense guidance. So we started with $345 million to $365 million in non-GAAP OpEx, we tightened that to $345 million to $360 million. I think we've done a great job over the years of making sure we keep expenses in line. So that's a big piece of it as well. And so yes, I think it's both more revenue coming in, in the second half, and then it's also continuing to be prudent in how we spend and always looking for ways to spend less.

Great. Looks like we'll leave it there. Thanks, Brad, for your time.

Thank you.