I'm Max Skor, a biotech analyst with Morgan Stanley. I'm happy to be hosting Amicus Therapeutics. With us today: Sébastien Martel, Chief Business Officer; Jeff Castelli, Chief Development Officer. But before we dive in, I just want to note for important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. So with that, maybe if we have anyone who's not as familiar with the Amicus story, we'll open up the floor with any high-level takeaways to introduce the company. That'd be great.
Thank you. Thank you so much. So look, you know, as you know, Amicus is a bit of a unique biotech story with significant growth potential and profitability as well. So we're just coming out of a strong set of Q2 numbers. For the first time, we reached more than $150 million of sales. We saw great traction for our Galafold therapy for patients with amenable mutations in Fabry disease. And we continue to see strong growth in our Pombiliti and Opfolda combination therapy for Pompe disease. So we look to grow these two products this year at a very nice rate. For Galafold, we've given guidance for 10%-15% growth in 2025. And for Pombiliti and Opfolda, 50%-65% growth. We just also recently, in the second quarter, signed an exciting in-licensing deal for an asset for FSGS, a rare kidney disease, currently in phase III.
So very excited also by that opportunity. And we're turning to the second half of 2025, where we expect to continue to build momentum and reach GAAP profitability for the first time. So an interesting turning point for the company.
Yes, definitely. So maybe if we can dive a bit deeper, could you give us a snapshot of your business today and your plans to sustain Galafold momentum and accelerate Pombiliti adoption through year-end and into 2026?
Yeah, so let's start with Galafold. So we operate in a Fabry market that is a nicely growing market. It's a sizable market for rare disease. Sales were $2.1 billion last year for the whole of Fabry. And we've been on the market for now six years in the U.K., sorry, in the U.S., and seven or eight years in Europe. And we continue to grow at a double-digit rate. The key drivers are really identification of naive patients. And so we're seeing a sustained level of newly diagnosed Fabry patients. We're seeing also a greater number of women being treated for Fabry disease, a growing proportion of patients with late-onset Fabry disease being diagnosed. So those are really driving the patient numbers.
If I think back to where we were prior to the launch of Galafold, we were estimating the market to be about 10,000 Fabry patients diagnosed and half of them being treated. Fast forward to 2024, and we estimate that there are 18,000 Fabry patients diagnosed, 6,000 still untreated, and another 12,000 currently being treated. So there's been very strong growth. We're in a unique situation with having the only oral therapy for Fabry disease, only indicated for a subset of Fabry patients with amenable mutations. We continue to see strong growth even in the countries where we've been the longest. That is, again, really mostly driven by new patient identification.
Okay.
Do you want me to jump to?
Yeah, no, Pombiliti would be great.
Pombiliti is a more recent launch. We're coming into a market slightly smaller than the Fabry market. 2024 sales for Pompe were $1.5 billion, growing close to double-digit. Again, a healthy market and sizable rare market. We've been launching by the end of 2024. We were in actually five countries. Our commitment this year was to launch in 10 additional countries by the end of Q2. We were already launched in six new markets. Last week, we launched in Japan. Yesterday, we got approval for pricing and reimbursement in Belgium. We're getting close to eight markets now. We've got a couple more that we'll hope to launch in the fourth quarter. We're definitely on track and building momentum here. Growth will come from both an acceleration of switches from competing products in the U.S., as well as our geographic expansion that I just mentioned.
I think, if I remember correctly, in the first quarter, the team addressed a rebate issue, an unexpected rebate issue in the U.K. that seems to have been dealt with. And you've been guiding to acceleration in Pombiliti sales in the second half. Could you give any more clarity or expectation around what that curve looks like?
Yeah, so we continue to believe that we'll see stronger overall sales in the second half of 2025 than we saw in the first half. This is driven by the new launches that we've had, so back in late Q2, for example, we initiated our launch in the Netherlands. We won here a significant place where Pombiliti and Opfolda is now seen as first-rank treatment, if you want. So we're going to earn 70% of the Pompe patients in the Netherlands. That's a bit of an interesting market because it's a highly concentrated market. The disease is very prevalent in the Netherlands. The disease is managed through one main treatment center, so very concentrated, and so they're planning to switch roughly 70 patients from Myozyme onto Pombiliti over the next 12 to 18 months. And this has started towards the very end of Q2. We had our first patient switched.
And since then, we've continued to see patients move onto Pombiliti and Opfolda. And the other part, besides geographic expansion, is really the dynamic that we're seeing in the U.S. So you may remember that our approval into the U.S. got a little bit delayed because the FDA wanted to inspect a manufacturing site in China. And that gave almost a couple of years as a head start to Nexviazyme. And so by the time we got into the market, there were a number of patients who had fairly recently switched onto Nexviazyme. Now, what we've seen from longitudinal data on Nexviazyme or Myozyme even is that over time, there's a proportion of patients who start declining. And it seems that the two-year endpoint is a bit of a turning point. There's close to 50% of patients that start to experience some signs of decline after two years on therapy.
As we entered the year, there was about a third of patients in the U.S. who had been on Nexviazyme for two years. As we'll exit the year, there'll be close to 66% of those patients. So a growing pool of patients that could potentially see decline and would therefore be more prone to look for alternative therapies. And so that's what's driving the acceleration in the U.S.
So through your market research, talking to doctors, obviously, you're starting to see that switch dynamic play out. Is there any guidance in regards to where we could expect the greatest inflection? Would it be second half of the year, or is it more cautious to say maybe in 2026 we'll see more of the switch patients come on?
So we definitely stick to the guidance that we'll see stronger sales in the second half this year. It's a bit early to get into 2026, but we would expect, as a result of both U.S. acceleration and then further geographical expansion, to continue to see an acceleration into 2026. If you think of new markets, we got approval for Canada and Australia, for example, this year, but have not launched yet because we're in the midst of pricing and reimbursement discussions. These will lead us to launch in 2026. And next year, we'll still have three or four smaller European markets where we intend to launch as well. So there'll be some further new countries to come into play in 2026.
Okay, that's helpful. So in regards to Pombiliti, where are you seeing the most friction? We can also highlight the tailwinds. You've talked about expansion. But in regards to the most friction or issues you're trying to address currently, is it on U.S. payer coverage, step-throughs, site-of-care dynamics, switching dynamics? Any additional color on that?
No, so on the payer side, we're not seeing any specific issues. On just the logistics of getting from prescription to actual infusion, we've seen since launch a gradual improvement into those timelines. And now we've kind of reached what I would say is normal expected timelines for this process. So this is now a well-oiled machine. I think we continue to invest a good amount of our time, and especially through our medical teams, in helping educate physicians and patients as well on, in some way, resetting expectations, what goods look like. And for too long, the expectation was that stability was okay. So if the patient treated was stable, that was good enough. Trying to shift the mindset and make people realize that given the data we've generated with Pombiliti, people can hope for improvement while on therapy. And that takes a bit of time.
We're adding, and maybe, Jeff, I'll ask you to build on that, but we're collecting data, building our real-world evidence data, and those will become also critical as we continue to differentiate Pombiliti and Opfolda.
Yeah, that was my next question.
Great segue. Thanks and good afternoon, everyone. So yeah, as Seb mentioned, our phase III data, the initial studies in PROPEL showed patients actually, after being on Lumizyme for long-term, had improvements in motor function after switching and stability in forced vital capacity, two of the key measures in Pompe disease. Actually, we just came off a very successful JSIMD meeting in Japan just in the last couple of days. Some great data presented there showing that on motor function, over four years in the extension, those initial improvements in motor function were maintained over four years. And similarly, we've seen up to seven-year durability of effect from our phase two patients. We're starting to see now also a lot more real-world evidence, not only of patients going on to Pombiliti having good experiences, but interestingly, Nexviazyme switching to Pombiliti case studies.
We've had some of those reported at conferences. We're continuing to hear that that is a very positive experience for those patients, seeing things like biomarker improvement, muscle strength improvement, some functional improvements in some of those case studies. We also, for the first time, just had presented independently from Amicus at IEM in the U.K., some of the sites that had the most experience with Pombiliti that were involved in the Early Access to Medicines program had large pools of patients. And one of the sites put about half their patients on Pombiliti and half on Nexviazyme. And they just reported out how those patients did across different measures.
It was very favorable for those patients going to Pombiliti, and especially on the motor function and different measures, that there was a noticeable improvement in the patients' move to Pombiliti and not so for the patients that went on to Nexviazyme. So I think additional data like that is going to continue to highlight the differentiated profile that we believe we have with Pombiliti and hopefully move beyond, as Sebastian said, waiting for patients to be worsening to switch to Pombiliti and start to actually have patients switch when they're actually stable on their treatment because they have that potential to get improvement.
Can you clarify in regards to new patient starts, let's say treatment naive patients, what that opportunity looks like, who's capturing that market now, and any color around that?
Yeah, so outside of the United States, Pombiliti has a broad label, naive patients, switch patients. And we are winning more than our fair share of those naive patient starts. Generally a small number, but we believe, and I think the physicians in those countries believe, the best time to start Pombiliti is right away to have the most time to be on that product. In the United States, we have a different label. That label is for patients not improving on their current ERT, which means naive patients typically have to go under one of the other treatments. Physicians interpret that if my patient is not actually experiencing improvement, then they can consider Pombiliti. So that would be stable or worsening patients. Currently now, it is probably used more for those patients where there is some worsening.
I think as we continue to build on that body of evidence and really start to win over kind of the mindset of Pombiliti is differentiated, we'll start to hopefully get into that stable group as well. But we're really excited about that opportunity in the U.S. Maybe even in the future, we'll continue to collect data on naive patients. Patients in our trials have done well when they started on Pombiliti. And at some point, hopefully, we can actually work with FDA and get the label expanded to naive patients like it should be.
So what is the gating factor there? Is it just more data, receptive FDA?
Both.
Okay. Maybe I'll take a quick, this is an opportunity just to ask, in regards to the regulatory landscape, how have interactions gone with the FDA? Are you having any sort of regular interactions?
Yeah, we continue to interact with FDA. We still have ongoing pediatric studies on both Fabry and Pompe, and we've worked with FDA on those studies. We are getting ready to start to interact with FDA more on FSGS, which we'll talk about in a bit. We are always looking to engage as there might be opportunities to, as I mentioned, maybe look for naive labeling for Pombiliti, for example. But so far, it's not a high interaction time with FDA for us, just based on where we are with our products. But certainly for DMX-200, I think we'll have some very substantial meetings with FDA probably early next year.
Okay, that's helpful. And now switching over to Galafold, where are you focusing medical education now? Amenable mutation testing workflow, adherence support, or expansion into newer geographies?
Yeah, so I mean, with Galafold in our mature markets, Galafold is now standard of care in amenable patients. We have upwards of 80%-90% plus of share of treated amenable patients. We still are having geographic expansion in some countries. I think we're up to about 60%-65% global market share of treated amenable patients. So still some significant opportunity to get that closer to 80%-90%. Where we're really seeing the most growth, even this far into launch, six to eight years into launch, is in new patients coming on to treatment. Fabry remains one of the most underdiagnosed genetic diseases. There's a lot of tailwinds for diagnosis. It used to be that patients or physicians would do everything in the world before they'd actually get a genetic test because it costs too much.
Now there's low-cost genetic tests for cardiac panels, renal panels that as soon as the physician suspects I have a renal patient or a cardiac patient or a patient I can't figure out what's going on, they'll pretty quickly defer to those tests. And we can have Fabry diagnosis much more easily. So that's one tailwind. Another big tailwind in the U.S. is newborn screening. For Fabry, there's eight states that are actively screening for Fabry. That's about 15% of newborns covered in those states. And what you're finding there is not that that newborn needs treatment right away, but you find a whole family when you diagnose that newborn because Fabry is an X-linked dominant disease and you can do family screening. I think that contributed to the 25% or so growth we had last quarter year- over- year in the U.S., bless you, for Fabry.
So we think there's a lot of tailwinds to keep growing that market. And the last thing I'll mention, so Galafold is only for amenable Fabry patients with certain types of mutations. Most of the patients in the Fabry community left to be diagnosed are later onset Fabry. They don't have the early onset mutations that are easier to diagnose. Most of the late onset mutations are amenable to Galafold. So all this continued growth in the future of growing diagnosis is going to be slanted towards people amenable for Galafold. So I think we'll continue to see, like we have seen, that Galafold growth is much higher than the overall Fabry market.
Okay, and remind me the compliance rate. It's high. It's greater than 90%.
Yeah, we've continued since launch to have over 90% adherence compliance, which for an oral medication administered every other day is quite remarkable, and I think speaks to the experience that the patients are having on the product.
Okay. Then I get questions around the IP discussion around Galafold. Could you just frame how the Teva Settlement supporting protection through January 2037 should be interpreted by investors? How are you thinking about remaining legal overhangs and potentially the Aurobindo challenge?
Yeah, so we had three generics that filed for Galafold, so Teva, Aurobindo, and Lupin. Lupin took a stay, which means they're sort of now dependent on what happens with the other two parties. End of last year, we settled with Teva for a January 2037 entrance. Our patent estate, actually over 40 patents go into publicly listed, goes into the early 2040s. So that was a settlement with Teva where we felt like it was appropriate that we gave up some of the long term for that settlement. Aurobindo is still actively looking towards a trial. As you look, we've said of most cases, Aurobindo, when a lead sort of party has settled, they would generally settle. The trial date is set for September 29th. We still think there is a good chance of a settlement up until that date.
But that being said, if we go to trial, we're still very confident. We still feel very confident in our patents and would look forward to the outcome of that trial.
Should we be anticipating a summary judgment from the judge coming out at any point now before the 29th?
No, that's a great question, Max. And so one of the things is Aurobindo did file for summary judgment. So they've already acknowledged the potential for infringement. So if they are not successful, they will be infringing our patents. They've acknowledged that. What they're trying to do is look at obviousness claims to say these were sort of obvious inventions. So they filed for a summary judgment. The judge does not have to rule on that. The judge can actually say, "I'm just going to let the trial happen." One of the things that could be a factor out there that could weigh in on a settlement would be if there is no summary judgment, that does sort of put more pressure a little bit on Aurobindo to settle. Or they go to trial where they run the risk of all the expenses of the trial.
If they're not successful, they would be dependent on waiting for the 2042 patents to end, whereas Teva could enter the market in 2037.
how's the timing around the trial? How long would this process generally take?
So trial, typically it'll be four to five days starting on the 29th. And then that's the sort of oral arguments. And then the judge can take up to six months typically after that to actually issue a ruling.
Okay, helpful. So maybe let's switch over to DMX-200, a product of a recent business development deal that the team signed. Maybe if you can introduce this asset, the indication you're going after and catalysts that we can look forward to.
Yeah, so I mean, we're very excited to be partnered with Dimerix on DMX-200 for FSGS, which is focal segmental glomerular sclerosis. It basically means that the glomerulus, which is the filtering unit of the kidney, has parts of its segments that are sclerotic or fibrotic. And basically the kidney is in an ongoing cycle of kind of losing activity. And eventually those patients will end up needing transplant or dialysis. And it's a very serious disease. No current treatments approved. About 40,000-80,000 patients in the U.S. are estimated to have FSGS. The deal that we did, Amicus has U.S. rights. Dimerix has ex-U.S. partners. And the DMX-200 is a CCR2 inhibitor. So CCR2 is one of the key receptors that leads to monocyte or macrophage-driven inflammation. So a key aspect of FSGS is the kidney gets damaged.
And then to compensate for that, because the kidney needs to filter the blood, the body starts to put more pressure into the kidney to try to get the filtering to happen. That's sort of the hyperfiltration damage that can happen. And drugs like ARBs and even Filspari that's out there for FSGS are addressing that component. Another component is that leads to inflammation that further kind of causes fibrosis and sclerosis in the kidney that makes it work even less well. So more hyperfiltration pressure. So you get in this pathogenic loop of high hyperfiltration, high inflammation. And what we're really looking with DMX- 200 is to break the inflammatory side of that cycle on the monocyte macrophage inflammation. So no other agent is addressing that aspect of this disease.
The product is in phase III for the ACTION3 study targeting final enrollment by the end of the year of 286 patients. We're very excited to continue to work with Dimerix to enroll that trial. That would mean a top-line readout. The study is a two-year study currently as designed. We just recently got agreement with FDA that proteinuria can serve as the primary endpoint, which is a big win and was really part of the final bit of data that we wanted to see before we executed the deal. We feel that the power is, the study is extremely well powered for proteinuria. We're gearing up for that two-year top-line data end of 2027, early 2028, based on the proteinuria with supportive data on GFR. One upcoming event here is Filspari, another drug from Travere that's in FSGS.
It approaches a different mechanistic side of the disease, more in that hemodynamic hyperfiltration damage I talked about. They have an AdCom in November. They have a PDUFA date in January. So we're looking forward to that AdCom to really see how FDA is sort of, or we see advisors and FDA are looking at the data package of proteinuria and GFR so we can then finalize the protocol, the SAP, for our study.
For the phase III study.
Yes.
Is there anything more you can tell us about the design of the proposed phase III study or it's really hinging on this AdCom?
I mean, the study is well underway. So it is in patients with primary genetic FSGS that despite ongoing treatments, corticosteroids, angiotensin receptor blockers have high proteinuria. The patients are sort of put on to stable ARBs, which is important, and then randomized to either DMX-200 or placebo. As I mentioned, a two-year study, proteinuria will be the primary endpoint. We'll sort of look from the AdCom how to sort of measure that, how to position it. FDA said GFR needs to be a secondary endpoint and supportive. If you look at the Filspari data set, we interpret that as meaning GFR trending in the right direction, but not necessarily significant. Although we are looking to power the phase III study for superiority in GFR as well. That's important for Dimerix and partners outside of the U.S..
The study is designed. I would say we're really just looking to finalize the statistical analysis plan and sort of how we tier the endpoints, how we measure the proteinuria.
Okay. And so hypothetically, how do you envision positioning it commercially given the lack of FDA-approved therapies in the space, but there is a lot happening?
Yeah, well, assuming Filspari is successful, they would be on the market. Let's assume that it's a two-year study for us and then an approval on a launch. We'd be about two and a half, three years behind Filspari. I think clearly they'd be out there educating the market about new treatments. I think there will certainly be patients that initially don't respond to Filspari's mechanism of action that could be where their issue is more of a monocyte macrophage inflammation that could then be candidates for DMX-200. I do think there also are ways that physicians can start to look at their patients and figure out which ones are likely to benefit from DMX-200, for example. There are some things you can measure like the levels of the MCP-1, which is the chemokine that is really being kind of inhibited with DMX-200.
Other inflammatory markers that you can measure. I think there'll be a way that physicians can start to identify that these are patients where we think DMX-200 could really have a benefit. And I think at some point you'll see that there's generally different populations that are responding better to one or the other. And we could actually see some combination use possibly as well. There certainly seems that logically there could be a synergistic effect of having an ARB, an endothelin inhibition, which really is Filspari bringing that component to the story and then a monocyte macrophage anti-inflammatory.
Okay. And just going back to the U.K. reimbursement dynamic one more time. This will reset next year, correct? It won't carry through. Is there any clarity on what it looks like for 2026?
You're talking about the VPAG?
Yes.
Yeah, so earlier this year or very late last year, we finally got what the rate was going to be for 2025, and it was a higher level than what was expected last year. It was running at about a 15% rebate, and this year this was ultimately set as 22.9%, so ABPI, the industry body in the U.K., has been having discussions and negotiations with the U.K. government. Our understanding is that those have stalled for now, and so we're still under the same scheme. I think for financial modeling purposes, I would expect to essentially assume a rate very similar to the current one, maybe very slightly higher than the 22.9, but I don't know, between 0% and 1%-ish, and so what that means is that the year-over-year impact should for now be expected to be limited or minor.
Okay. So just touching on BD potentially, I know we just talked about DMX-200, but on future BD, what are some of the priorities that define a fit for Amicus? Payer comparability, geographic overlap, current assets, center-based care, time to cash, development stage. How are you thinking about future BD potential?
Yeah, look, we really think that the Dimerix in-licensing that we executed earlier this year was the right deal at the right time and at the right price for us. As you know, we've made some important commitments with regards to profitability. Amicus is becoming GAAP profitable in the second half of this year and hopefully thereafter. Now, interestingly, if you look over the next five years, we're going to have continued significant growth in the top line. We don't expect our OpEx to grow at a high rate, probably low to mid single digit rates. So that actually means that we offer over the next five years some fairly significant operating leverage. So we're going to see our profitability and operating income margin grow in a significant way. This will over time give us space to take on more R&D spend.
I would say that our focus is more on late-stage assets. We continue to look for opportunities for things that could be adjacent to the therapeutic areas we're in. So rare renal diseases, rare neuromuscular diseases, but with a very strong focus on ongoing phase III or even post-phase III without products in registration. Ideally, we like in-licensing where you put a relatively small upfront at risk and then pay for success and look for things that could be fairly accretive to both top line and bottom line. So looking for ways to further accelerate the growth profile that we offer with the current setup.
Okay. Great, so we've been asking some of our companies some survey questions. I think it's appropriate now to ask this question regarding China's rise in biotech innovation. How are you thinking about your competitive position here and will it at all influence your R&D or BD strategy?
So we're kind of agnostic as to where the potential licensing opportunities may come up. The Dimerix transaction was with an Australian company with whom we had built relationship for the last two years. So there's an awful lot going on with U.S. biotech companies as well. We nurture relationship with a number of partners across different countries in the world, including Chinese companies as well. Our framework is very much around some specific therapeutic areas. We pay a lot of interest on the unmet need, on the probability of success of a phase III trial. We look at the manufacturing aspects as well. They play a big role also. There's nothing wrong with small molecules. And yeah, so we keep an open mind about where innovation may come from.
Great. One more question then in regards to what's been most impactful from a regulatory side? Would you say it's the FDA, MFN, or tariffs?
I'll leave you this one.
Yeah. I mean, tariffs for us, when you look at Galafold, very low cost of goods. So tariffs really not much impact there. When you look at sort of government payers, sorry, so finishing off tariffs for Pompe, obviously a little bit more cost. Most of that for this year is fully accounted for. Next year, we've said fully manageable with our P&L what we might project for tariff costs. We have been very successfully transferring manufacturing from WuXi, China to WuXi, Ireland. So we feel tariffs are pretty mitigated. FDA, so there's gives and takes, I think, there. Where we are so far, Dimerix has had great interactions with FDA. So I view that as not really an issue right now at all.
MFN theoretically could be a challenge, but again, as you look at the political stance where that is, it's likely that rare disease could be carved out or whatever happened similar to IRA. Also, if you look kind of our government, U.S. government sales are about 10% of our sales as a company. And that's really what leads most at risk is maybe having a 50% haircut in that. So while 5% of revenue is not great, certainly that is manageable. But again, we think it's probably low likelihood for rare disease. So none of the above would be my answer.
That's great. And I think we're up on time. Thank you very much. Really appreciate it.
Thank you.