Okay, welcome everyone. It's my pleasure to lead this fireside chat with Amicus Therapeutics. I'm Joseph Schwartz from the equity research team at Leerink Partners, and it's my pleasure to be joined by Jeffrey Castelli, Chief Development Officer, and Simon Harford, Chief Financial Officer. Thanks so much for being with us and giving us an update.
Pleasure. Thank you, Joe. Great to be here. Thanks to Leerink, and it's great to be back in Miami for another investor meeting.
Yeah. Why don't we start by having you give us a quick level set of the company's latest progress and key goals for the year, Jeff?
Simon or me again?
Go ahead.
Yeah, so obviously this year it's continuing to execute on our commercial launches for Pombiliti. We're really excited about the additional launch countries this year. We're launching in 10 or so different European countries that we either have secured reimbursement or are in the process of securing reimbursement, and continuing to see the launch here for Pombiliti in the U.S. as it evolves. Galafold continues to be a great product and success story for us, and we continue to see a lot of promise there. Now, what we believe is a very long runway, lots of positive tailwinds for diagnostics to help grow patients. And really on that top line growth of those two programs and continuing to execute there commercially and medically, managing the bottom line, continuing to leverage that towards growing profits and becoming actually non-full GAAP profitable second half this year.
It is really a commercial financial discipline story. I know as the Chief Development Officer, I'm also very interested in our pipeline and looking at potential business development opportunities to grow the business. That is ultimately where Amicus sees ourselves as taking everything we're doing to actually start to generate money that we can now reinvest in the business, leveraging everything we have commercially, everything we have medically, even our clinical reg expertise. We view ourselves as a great partner or our own development company again for some of our early assets as we look to ramp some of that back up that we've sort of strategically kind of over the last few years, we've really focused more on growing the top line, minimizing the bottom line.
Now we're really looking at this as a great kind of, in some ways, a clean sheet of how do we invest, how we want to, and how do we leverage what we have moving forward. A lot of excitement for sort of the stormy seas we see a little bit out there in biotech. We feel like we're in a really, really great place and a pretty unique space.
Okay, great. Where are we in the Pombiliti launch in Europe and the U.S.? Before we start talking about all these additional markets, which I think might begin to kick in this year, this is not your first launch. As you alluded, Jeff, Galafold has got some nice dynamics to support further growth there. Sticking with Pombiliti first, what phase of the launch are we in in Europe and the U.S.? How do you think about where we are in the overall launch curve?
Yeah, maybe I can comment on that. I think where we are in the launch is we still have a ways to go because we've clearly launched in certain key markets. Germany, the U.K., Spain has been off to an incredible launch, but we still have Italy where we recently got reimbursements that are coming online step by step this year as we get on hospital formularies across the regions. We have the Netherlands where we recently got reimbursement, which is an important market for us because it was the sort of founding country of Pompe disease, so to speak. There are the others that you've sort of referenced that will come during this year. We recently got approval also in Australia, Canada, and Japan. We expect later this year. There's a journey that we are on to add patients in the international markets.
I think as far as the U.S. launch is concerned, I mean, obviously as a one market focus, we're progressing. What we saw in Q4 was actually an acceleration in prescriptions compared to Q3. It was a little bit sort of bumpy in 2024 in terms of quarter-on-quarter patient numbers, primarily because of two reasons. One, in the first half of the year, particularly, you had quite a lot of clinical trial patients ready to transfer to commercial drug. Secondly, obviously the timing of certain launches in new countries. We're pretty pleased with where we exited last year. 33% growth year on year as a company. Obviously, Pombiliti and Galafold were key contributors to that.
How has the overall reception to the product's label been, particularly in the U.S., now that you're in the second year of launch? You've got this unique statement or indication statement on the label, which implies that you can help patients progress or improve, rather. If they're not improving, then they should be considered as a candidate for Pombiliti. How is that reception to that aspect of the product profile going for the company?
Yeah, thanks for the question, Joe. Just as a quick reminder, outside of the U.S. so far, we've seen that we have a broad label for both naive patients and experienced ERT patients. In the U.S., we do have this somewhat unique label for patients not improving on their current ERT. Not unexpectedly, where we've really seen the initial uptake has been in patients that were not doing well on their current ERT, and that clearly falls into a not improving. I think the real opportunity moving forward for us is continuing to remind folks of what we saw in trials where more than half the patients after switching actually showed improvements and, in cases, meaningful improvements. In some cases, opportunity to regain function.
I think that is an aspect that is somewhat appreciated, but something we're really trying to continue to remind folks of that where stability is not necessarily the desired outcome here. You actually can potentially offer your patients an opportunity to regain function. I think we're looking at that as an opportunity, continuing, obviously, now that over 40% of patients here in the U.S. have now been on Nexviazyme for two years, which is the new product from Sanofi that launched a year to two years before us. We know that that now is a point where those patients are starting to be assessed of how are they doing on Nexviazyme, if they're progressing. We know they're starting to come over to Pombiliti. That is certainly something that will continue to progress. Obviously the 30% of Lumizyme patients, we can go in and keep reminding those doctors and those patients of the data that we saw.
Great. How large is this early adopter group, do you think?
Yeah, early adopter is an interesting term here for this market. In some way, that was those Lumizyme patients that had been on Lumizyme for years. Then when Nexviazyme came out, they all quickly switched to Nexviazyme. Sanofi was out there switching patients from their first-gen product to their second-gen product with no competitor. Not surprisingly, they got 60% of patients to switch over. In some way, that was early adopters. Now for us, it's really just a continued growth of those Nexviazyme patients as now they've been on long enough to now be considering a new switch. Those Lumizyme patients that for whatever reason didn't switch, and we think we have a great proposition to offer those patients. It really never was a great early adopter pool, I guess, out there for us, particularly in the U.S., given the dynamics.
I will say outside of the U.S., where we are launching more contemporaneously with Lumizyme, we're seeing really great uptake. In that case, I think there are sites and patients that have sort of been waiting for the next best ERT to come along. That's an area where we are doing really well and seeing great uptake.
How do conversations vary depending on the treatment center or the physicians that are at these centers? Is there a lot of variance between the level of appreciation and the need to be thinking about whether a patient can do better on a new treatment option?
Yeah, it's a little, you know, some of the bigger centers that have lots of patients that are more academic in nature, many of them were in our studies, for example, those sites tend to be aware of the different products and some of the data. Interestingly, though, they put all their patients on either Pombiliti through trials or onto Nexviazyme. It's actually some of those second-tier sites that weren't as quick to adopt Nexviazyme where there's more opportunity for us to find those Lumizyme patients. Overall, it's really one message of the theme of the data that we have from our trials, the mechanism that we believe is very differentiated in our emerging long-term data. It is the same kind of message out there, but it is a little different in terms of some sites were much more quick to switch all their patients to Nexviazyme or to Pombiliti, and other sites have been sort of waiting on the sidelines.
Okay. Since Pombiliti sales ended up coming within the higher end of the upwardly revised guidance, can you talk about any of the specific dynamics that ended up being better than you expected last year? How should we think about what kinds of things you consider when you establish your guidance, such as for this year?
Yeah. So Joe, I mean, clearly we were happy that in 2024 we ended up with $70 million worth of Pombiliti Opfolda sales, as you say, at the actually sort of over the top end of the guidance. A lot of that, frankly, is related to just underlying performance of speed of frankly patients being slightly ahead of what we were expecting at the time we set the guidance. I think as you think about 2025, really when we set guidance, we do it based on the trends that we see of what we think is reasonable. The components, though, that really build towards that year-on-year growth are really threefold. One is obviously the rate at which we switch patients in the U.S. from Nexviazyme and Lumizyme to Pombiliti Opfolda.
Second component is the sort of the trends in those markets where we were already launched last year, particularly the bigger ones like the Germanys, the Spains, the U.K.s, et cetera, and their continued growth. The third component, which is a smaller component when it comes to absolute dollar revenue, but is important for number of patients as we continue to grow into 2026, is those markets where you've got pricing and reimbursement during the year. What I would say to you is probably the biggest variable, because we guided to 65%-85% growth this year, which equates to roughly $115-$130 million. The biggest variable between the top and the bottom end of the range is realistically the speed at which we switch patients in the U.S. Why? Because if you take a patient, for example, that switches in March, that's a different dollar number than someone who switches in September.
Makes sense. What about the naive patient population? Is there an opportunity to expand Pombiliti's indication into that setting? What's the latest on that front?
Yeah, outside of the U.S. and the countries where we're launched and we have that broader label, we are seeing good uptake into naive patients. We're compiling that data as part of our registries. We've continued to collect our long-term data from our trials in naive patients and in all of our patients, frankly. With all of that data, there certainly are opportunities to go back and interact with FDA to try to expand the label for naives. It's sort of a matter of how much data and when, but it's certainly something that we're looking at actively and is in our plans to do, but a little early to give you specific timelines. We think that that, not a huge opportunity per se every year. Maybe there's 40 naive patients in the U.S. going on to treatment, and ultimately they do become switch patients.
It is not insignificant to have an opportunity to treat those patients earlier in the U.S. I think it also has somewhat of a halo effect of not necessarily then having Pombiliti be viewed as sort of really the drug that we are keeping there for any patient who finally declines, but really looking at it to move it up earlier in the process, which is where we believe it should be, is what we believe is really the most efficacious product in our minds.
Right. That makes sense. In Europe, where you've got the naive label, you're going to be adding some new markets like you alluded to. Can you talk a little bit about the timing of those new opportunities?
Yeah. Really as relates to 2025, I think we said at earnings time, we sort of have reimbursement now in Italy, the Netherlands as two key markets, Sweden, and a number of others. The rest will come sort of throughout the year. I would say the way to think about it is for those handful that we already have reimbursement for, you should probably start to see revenue flow through starting in the Q2. For those that are later in the year, they are probably more relevant to numbers of patients to get on drug for 2026, realistically.
Okay.
All that outside of Europe where a lot of that is, we have approvals, it's more going through the reimbursement processes and approvals. We also just did recently get approval in Australia, which was a full review of both products. Making great progress in Canada. We expect an approval here in the first half, in Japan in the second half. It does take time on the reimbursement side for those. Actually, we will launch first in Japan, even though that is the one that kind of comes in the second half of this year because reimbursement is much faster there. We look at Canada and Australia really as key drivers of growth for next year.
Okay. I need to ask you about the potential impact of any tariffs given you manufacture the product in China currently, although you're working on second source manufacturing, it sounds like you're making good progress on that front. Can you just give us your thoughts on those items?
Gosh, changes every day, so it was slightly difficult. What I can say for 2025 is the vast majority of the inventory related to product sales for the U.S. for 2025 is already in the United States. Therefore, it really doesn't have any material impact as far as this year is concerned, at least as we see the tariff situation today. 2026 onwards, obviously we'll have to wait and see where we are given the variability in this discussion at the moment. We're not anticipating anything that would sort of change course or anything from that perspective, but it's still a bit premature to comment.
Makes sense.
In terms of our second source manufacturing in Ireland with WuXi, we're on track to have product from that site actually going into the commercial pipeline here at the end of this year in Europe first.
Great. Okay. Let's shift gears a little bit. I'd love to hear your thoughts on the company's relatively large presence at the World Symposium lately, both on Pombiliti, and then maybe this provides a good segue to talk about Galafold.
Yeah. As usual, we had a great presence at World. I think we had somewhere close to 20 abstracts, I believe this year, across Pombiliti and Galafold and some other just Fabry, Pompe disease areas broadly. We had lots of great interactions with physicians as we normally do through our team being there, through one-on-one conversations, through sort of ad hoc advisory boards for various work we are doing, through our symposia that we offered. From a new data perspective, we continue to focus on insights coming out of our clinical work that we did, in particular showing actually the improvements that were observed and characterizing those improvements in patients that switched from long-term Lumizyme over to Pombiliti.
I think that data was very well received that we presented there, showing that half of patients had met a threshold for a meaningful improvement in either six-minute walk or forced vital capacity in those trials. Ongoing mechanism of action data on the differentiation there. Some of our long-term data, we'll continue to see that data coming out throughout this year too on our durability of effect.
I think we'll also be, from a data perspective, some of the data that will be impactful. Last thing I will add is we also continue to hear from physicians positive anecdotal real-world reports of how patients are doing. I think that you'll see this year, there will be more and more independent reports coming out from sites that have significant pools of patients on the three products. We're hearing that physicians are interested in actually starting to report some of those kind of indirect longitudinal comparisons among products, which we think could bode well for us coming this year as well.
Excellent. Galafold also had, there were some interesting initiatives that are underway with Galafold. You alluded to diagnostic enhancements earlier on in the discussion. Can we switch gears and talk about where we are in terms of the launch phase for that product?
Yeah, I'll start and Simon, please chip in. Galafold, remember we first got approved in Europe in 2016 and the U.S. in 2018. It's amazing just in the last two years, the growth we've seen and really growth driven by new patient ads and improving diagnostics and from our mature markets. We've seen 18% plus year-over-year growth the last two years. If we look back when we launched, it was maybe 5,000 diagnosed treated patients in Fabry across products and 5,000 diagnosed untreated. I think last year that was over 12,000 diagnosed treated up from the five. Actually the pool of diagnosed untreated had grown from 5,000 back then to 6,000. We're just seeing a lot of growth.
When you look at all the numbers from newborn screening, from at-risk screening, there still are probably five to ten times more people living with Fabry that do not even know it and are not diagnosed versus those that are diagnosed. There is just a continued opportunity to find those patients. When you find the patients, offer screening for the whole family and find three to five family members on average with being an X-linked dominant disease. We are investing in things as we can and AI and medical record screening. We have talked about the project with OM1 and Penn that we are excited to start to see the readout. We have taken over 500,000 medical records from the Penn system and ranked them from one to 500,000 on risk for Fabry disease.
We are offering the top 100 at risk to be worked up to see if they have Fabry. We will start to see some readouts from that later this year. There are a lot of opportunities to continue to help make a difference there in the diagnostics. In the U.S., what's great is there are five states doing newborn screening. As you find that newborn in Missouri, with good family screening, you can find family members that live all across the country. I think that is part of the growth that we are seeing here in the U.S. It is also the seeding from newborn screening of finding infants, and then they might not need treatment, but you can find the whole family through that process.
I think then you add onto that with what, about 65% market share in amenable patients globally, yet in major markets we're sort of well over 80%, which says there is still growth opportunity there. I think you then combine that with the intellectual property settlement with Teva means essentially out to 2037, we've got another 12 years of exclusivity. Obviously, we're still working through the follow-on Aurobindo discussion, but I think the Teva settlement was a good signal of how we think about things.
That creates a certain level of additional certainty. I think the last thing I would add is particularly with Galafold, now that we've built the infrastructure, we're not really adding expense related to Galafold. That is actually the biggest single contributor to leveraging the P&L in the nearer term. Pombiliti, Opfolda, we're still in the launch phase. We will start to leverage that too as we get slightly further out. That is a real important contributor not only to revenue, but also to the profitability.
Speaking of profitability, it's great to hear that you're on track to have positive GAAP income this year. How do you view the company's overall runway and path to sustainability? That's a term that we've heard management use for quite a while. What's the latest on that front?
I think we've gone in that direction since Bradley became CEO step by step to turn, first of all, fully non-GAAP profitable is what we guided to in 2024, and we achieved that this year. As you correctly say, we've sort of guided to becoming GAAP profitable during the second half of the year. That's really the next step to the pivot to sort of long-term profitability. The third step eventually will then be free cash flow positive. I think this year is a real pivot year. Why is that profitability important? That profitability is important primarily actually to be able to reinvest back and grow the business beyond just Pombiliti, Opfolda, and Galafold for the long term.
On that front, how does the company think about BD now? You've had a broader pipeline in the past, some of which was developed in-house, some of which was brought in externally. When's the right time for the company to be revisiting that kind of a strategy? What kind of a shape do you think that would take now?
The word I would use for business development is thoughtful approach. What do I mean by that? What I mean by that is I think our desire is sort of, first of all, potentially to license in sort of commercial type assets where you can leverage the infrastructure, whether that be on a global basis or potentially more likely on an international basis, given our broad infrastructure across sort of 40-odd markets remains to be seen. That is sort of the thought process because that leverages, you can typically find assets at more reasonable prices, which for us for the nearer term does play into the calculus, so to speak. Then beyond that, as the free cash flow and profitability starts to ramp up, obviously then we will look to build on top of that to kind of start addressing the question of for the next decade, what's the next discussion?
I would just add, as we're looking to sustainably leverage what we have in a thoughtful way, as Simon notes, the areas we're looking to do that would, Fabry continues to be an area of interest for us for the non-amenable patients in particular. We have some internal programs that we've been slowly trying to optimize, and we're also keeping an eye on everything that's out there in that space. There are a lot of adjacencies for Fabry and Pompe, rare neurology, rare metabolic, rare neuromuscular. Lots of areas where we could highly leverage what we have. There is also the infrastructure where we could leverage that and even go into slightly new space in rare.
We can really, we're always going to be focused on rare, but we're really looking for ways to unlock the value that we have already in our company through our global commercial medical, commercial team, our late-stage rare clinical regulatory expertise. We think there's a lot of ways we can take that and sort of have value add in the next area where Amicus wants to really put our time and energy to make a difference.
That makes sense. Anything that we did not touch on that we should make sure that we note before we close?
I don't think so.
No, I think we covered a lot, Joe. You did a pretty good job on your questions.
Thank you.
There is definitely a lot to discuss. Keep up the great work.
Thank you.
Thank you.
Appreciate it.
Thank you, everyone.