Amicus Therapeutics, Inc. (NASDAQ:FOLD) Q4 2024 Earnings Call Transcript

Amicus Therapeutics, Inc. (NASDAQ:FOLD) Q4 2024 Earnings Call Transcript February 19, 2025

Amicus Therapeutics, Inc. beats earnings expectations. Reported EPS is $0.09, expectations were $0.02.

Operator: Good morning, ladies and gentlemen. And welcome to the Amicus Therapeutics Full Year 2024 Financial Results Conference Call and Webcast. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Faughnan, Vice President of Investor Relations. You may begin.

Andrew Faughnan: Thank you, operator. Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics’ full year 2024 financial results and corporate highlights. Leading today’s call we have Bradley Campbell, President and Chief Executive Officer; Sebastien Martel, Chief Business Officer; Dr. Jeff Castelli, Chief Development Officer; and Simon Harford, Chief Financial Officer. Joining for Q&A is Ellen Rosenberg, Chief Legal Officer. As referenced on slide two, we might make forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business as well as our plans and prospects. Our forward-looking statements should not be regarded as representation by us and any of our plans will be achieved.

Any or all the forward-looking statements made on this call may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. You are cautioned not to place undue reliance on any forward-looking statements, which speak only to the date hereof. All forward-looking statements are qualified in their entirety by the cautionary statement. And we undertake no obligation to revise or update this presentation and conference call to reflect events or circumstances after the date hereof. For a full discussion of such forward-looking statements and the risks and uncertainties that may impact them, we refer you to the forward-looking statements and risk factors section on our annual report on Form 10-K for the year ended December 31, 2024 to be filed with the Securities and Exchange Commission today.

At this time, it is my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer. Bradley?

Bradley Campbell: Great. Thank you, Andrew. And welcome everybody to our full year 2024 conference call. I’m very pleased to highlight what was a remarkable year for Amicus, exceeding expectations across our global business in 2024. In this time, we delivered significant top line revenue from our global commercial business to provide us with a solid platform for sustainable growth in the years ahead. With our portfolio in global rare disease capabilities, we have a clear path to deliver continued revenue growth and accelerating profitability in 2025 and in the years ahead. We have firmly established Amicus as a unique biotechnology company with two growing medicines with long commercial runways, a leverageable global infrastructure, and the financial strength to continue to build the business.

We are confident Amicus is in a great position to achieve our vision of becoming one of the leading rare disease biotechnology companies, delivering great medicines for patients and creating great value for shareholders. As we did in this morning’s press release, let me highlight several key points about 2024 on slide four. First, we continued our excellent commercial execution and delivered total revenue of $528 million for the full year, representing 32% growth year-over-year, or 33% on a constant currency basis. At the product level, Galafold continued its outstanding performance and we’re very pleased with the robust commercial growth of this precision medicine globally. At the end of 2024, there were more than 2,700 people living with Fabry disease taking Galafold.

For the full year, Galafold revenue was $458 million, which represents 18% growth year-on-year, or 19% at constant exchange rates. Galafold continues to be one of the fastest-growing products within the Fabry treatment space, and in 2024, the number of new patients actually grew with the largest rate since the first years of launch. This growth was driven primarily by net new patient starts in both the naive and switch populations in our leading markets, including continued penetration into the diagnosed untreated population, which we expect to be a major driver of growth in 2025 and beyond as the Fabry market continues to grow through improved diagnosis and medical education. To put these numbers into perspective, when we first launched Galafold in 2016, market research suggested that there were about 10,000 people worldwide living with Fabry disease who had been diagnosed.

About 5,000 of them were treated at the time and about 5,000 were untreated. Fast forward to 2024 and there are now 18,000 patients globally diagnosed with Fabry disease. The treated market alone has more than doubled to 12,000 people globally on some form of treatment for Fabry, while the untreated market has also grown now to 6,000 patients. So, there’s been significant growth from diagnosing and treating more patients. Regarding Galafold’s long-term outlook, we announced last year’s settlement with Teva in our ongoing IP litigation, with the agreement allowing Teva to enter the market with a generic in January 2037. This is a huge milestone that represents a major step forward in ensuring Amicus can continue to support the Fabry community with Galafold for many years to come.

These underlying market dynamics, combined with some additional market expansion, our strong IP protection, and the over 90% compliance adherence rates that we continue to see, will provide Galafold with the opportunity to grow for many, many years to come, including next year, or excuse me, this year in 2025, with projected revenue growth of 10% to 15% at constant exchange rates. We are extremely pleased by the meaningful impact this medicine continues to make for people living with Fabry disease with amenable mutations in countries around the world. And we believe that we have a very clear path to surpassing $1 billion in product sales from Galafold before the end of its life cycle. Second, let me highlight the continued strong global commercial launch of Pombiliti and Opfolda, our novel therapy for late-onset Pompe disease.

Pom-Op [ph], as we like to call it, was a huge driver of growth for us in 2024, having had multiple successful launches around the world. For the full year, Pombiliti and Opfolda revenue was over $70 million globally. As we’ve mentioned, our number one focus for the year was to maximize the number of patients on therapy by year-end. And as we shared earlier in January at the JPMorgan conference, there were 220 people living with late-onset Pompe disease who had been treated or scheduled for treatment with commercial product at the end of 2024, with 25 new prescriptions in Q4 alone. We are pleased with the global demand for this new therapy and consistently hear inspiring feedback from healthcare professionals around the world on how their patients are responding to Pombiliti and Opfolda, most recently at the WORLD LDN conference, which we think will help to further fuel the uptake in 2025 and the years to come.

We’re continuing to build momentum in our current launch countries with strong switch dynamics in the US, Europe and the UK, as well as seeing great uptake by naive patients in markets outside the United States. We’re also making significant progress on the reimbursement front globally. This includes moving patients through the insurance process in the United States in under 30 days, as we anticipated. Additionally, we’re still highly focused on increasing patient access and expect geographic expansion to be a big part of the launch story in 2025. We’re seeking two new approvals in Canada and Japan, and we’re very pleased to announce the most recent approval of Pom-Op [ph] in Australia and there are now 10 markets we hope to get reimbursement and launch in over the course of the year, including the four countries that had already received reimbursement agreements by the end of 2024 or early 2025 and now, most recently the Netherlands, an extremely important market for Pompe disease.

Sebastian will provide more details on all of these activities later in the call. Given the strong global launch to date and expected geographic expansion for the full year 2025, we project 65% to 85% Pombiliti and Opfolda revenue growth at constant exchange rates, which will be, of course, a significant contributor to our overall revenue growth. This sets us on a great course to achieve our ambition for Pombiliti and Opfolda become the new standard-of-care for this devastating disease. We are incredibly pleased to be providing a real choice for people living with Pompe disease and challenging therapeutic expectations for both physicians and their patients. Finally, as we continue our excellent commercial execution approach across both therapies, we are focused on delivering significant long-term revenue growth and anticipate surpassing $1 billion in total sales in 2028.

Amicus achieved well over $0.5 billion in global revenue from our two commercial products in 2024. We judiciously managed our OpEx within our guidance range and we achieved our goal of full year non-GAAP profitability. We continue to believe that our highly leverageable global rare disease organization can allow us to continue delivering strong revenue growth to come as the commercial business grows and we expand our portfolio over time. Finally, on slide five, let me highlight our key strategic priorities for this year. First and foremost, continued delivering total revenue growth of 17% to 24% at constant exchange rates. That includes double-digit Galafold revenue growth of 10% to 15% at constant exchange rates. As I mentioned previously, Pombiliti and Opfolda revenue growth of 65% to 85% at constant exchange rates.

We will continue advancing our ongoing studies to broaden labels and strengthen our scientific leadership in Fabry disease and Pompe disease. And finally, we look to deliver positive GAAP net income during the second half 2025. With that preview, now let me hand it over to Sebastien Martel to further highlight our commercial performance. Sebastien?

Sebastien Martel: Thank you, Bradley and good morning to everyone on the call. I’ll start by providing you with more details on our Galafold performance for the year. On slide seven. For the full year 2024, Galafold reported revenue reached $458.1 million driven by strong patient demand, particularly from our leading markets. In 2024, we delivered Galafold sales growth of 19% at CER which was above our latest guidance range of 16% to 18% at CER. We ended the year with more than 65% of the global market share of treated Fabry patients with amenable mutations. We’re very pleased to see that prescribers continue to position Galafold as the treatment of choice for Fabry patients with amenable variants. The great news is there’s still many more potential patients eligible for our therapy.

Turning to slide eight. Our results in the full year highlight the strength of our commercial efforts. The demand for Galafold globally continues to be strong with patients added in all major markets. We’re very pleased to share that in 2024, despite being on the market for eight years, Galafold grew at the largest rate of new patient demand since the first years of launch. Our leading markets such as the US, the UK, top EU countries and Japan remain the biggest drivers of patient demand. In fact, in 2024 this was the highest year for US gross patient starts since launch. This growing demand gives us great confidence in this therapy’s outlook over the long-term. Within a global mix which is about 60% naive and 40% switch, we’re seeing stronger uptake in naive populations.

So, we continue to achieve high market shares in countries where we’ve been approved the longest. There’s still plenty of opportunity to continue to switch patients over to Galafold and to keep growing the market as we penetrate the diagnosed, untreated and newly diagnosed segments. So, we know that there’s significant patient demand for Galafold and it is the fastest growing treatment in the Fabry disease space today. We also foresee the segment of the global Fabry market made of patients with amenable variants to potentially reach up to $1 billion in annual revenue by the end of the decade. For the full year 2025, the company currently forecasts revenue growth of Galafold of 10% to 15% growth on a constant currency basis. We anticipate sustained goals in 2025 and beyond to be driven by several key drivers.

First, the Fabry market is growing robustly, with a significant portion of growth coming from finding new patients and reaching the diagnosed untreated population. Second, we continue to make progress on expanding Galafold into new markets and extending the labels. Third, we’re also seeing many diagnosed, untreated patients transition to treatment as the need for earlier treatment, especially in females, becomes better appreciated. Fourth, the other piece is continuing to drive Galafold’s market share of treated amenable patients through continued commercial execution. As I said earlier, Galafold currently has more than 65% of the global amenable market, but we’re seeing in our most mature markets that we can reach up to 85%, 90% of market share.

So, we know that there’s the potential to reach those levels in the global market share as well. And last, all of that is underpinned by sustained compliance and adherence rates that continue to exceed 90%, reiterating our belief that those patients who go on Galafold predominantly stay on Galafold. Finally, as I mentioned in past calls, due to a variety of factors including uneven ordering patterns and FX filtrations, the rate of growth within the year is typically non-linear. We have historically seen Q1 revenues coming below the prior Q4 due to the timing of orders and the reauthorization process in the US, and we expect that to continue into 2025. Looking ahead, we expect double-digit growth for Galafold in 2025 and we remain confident that with our strong IP protection, Galafold has a long runway well into the next decade and clear path to surpassing $1 billion in revenue in the next 12 years.

Let me briefly turn the call over to Jeff Castelli to provide you with an update on some of the initiatives we’re currently supporting to improve diagnosis in Fabry disease. Jeff?

Jeffrey Castelli: Thank you, Sebastien and good morning, everyone. Moving to slide nine. We know there is still a significant diagnostic unmet need in Fabry and have done a lot of work recently to further understand the size of the undiagnosed population and importantly, what we can do to help them have a proper diagnosis and the opportunity for treatment. Encouragingly, we’ve seen many new patients coming onto treatment through newborn at risk and family screening initiatives, and continue to see increased patient identification through ongoing medical education and the support of novel screening initiatives. We’re making great progress on one of our own initiatives with the machine learning AI diagnostics company OM1, where we’re piloting that technology at Penn against over 500,000 medical records, and through that process, we’ve identified the top 100 people in the system with a significantly increased suspicion of having undiagnosed Fabry.

Those individuals are identified, are in the process of being offered a diagnostic workup and genetic testing to determine if they have Fabry and then to further characterize and validate this AI algorithm. We’ve also been collaborating with the NHS on a pilot program in the UK to assess diagnostic disparities in rare disease, which has revealed that 85% of the people diagnosed with Fabry in the UK are within the highest socioeconomic deciles. This means there’s a lot of work that can be done within and outside of the system to help identify people with undiagnosed Fabry disease who otherwise would not have been diagnosed. And focused outreach efforts are underway. Fabry remains one of the most under diagnosed rare genetic diseases, so the more people that can be identified, the more people may benefit from treatment, including Galafold for patients with amenable mutations.

And now I’ll turn the call back to Sebastien to continue reviewing the 2024 performance of Pombiliti and Opfolda. Sebastien?

Bradley Campbell: Sebastien, I believe you’re mute.

Sebastien Martel: Thank you, Jeff. So now let’s turn to slide 11 and we outline here our global launch progress with Pombiliti and Opfolda. We had a very successful first year of launch in the US, Germany, Austria, Spain and the UK. And we’re getting great early feedback from physicians and patients as they continue to build their body of evidence using this therapy. For the full year 2024, Pombiliti and Opfolda reported revenue reached $70.2 million in line with our latest guidance range. This is really strong growth coming off the base of roughly $12 million in 2023. When looking at the geographic mix of revenue over the course of the year, we observe 57% of sales coming from ex-US and 43% within the US. That’s the global average for all Pompe sales today.

We expect that number to move closer to a 50/50 split over the course of this year, with the US being the largest market in terms of LOPD [ph] patients and the highest price point, but also at the same time launching in up to 10 countries this year. Moving on to slide 12. Overall, we’re very pleased with the launches of Pombiliti and Opfolda in the first wave of countries over the course of 2024. And we remain very satisfied with the ongoing demand for this therapy. As Bradley mentioned earlier, our focus for the year was to maximize the number of patients of Pompe by year-end and we ended 2024 with about 220 patients treated or scheduled for treatment in five countries. That’s about 209 patients who have been treated and also about 25 new prescriptions added in Q4.

And as we’ve stated before, all eligible clinical trial patients in a launch market have been converted to commercial therapy by the end of the first half of 2024. Our launch has leveraged our highly experienced cross functional teams and we’ve had great outreach with KOLs. We’re seeing an increase in the depth and breadth of prescribers across all five markets, indicating to us that physicians are having positive experiences with the therapy and are gaining greater confidence in using it again in patients. All core treating centers are engaged and we continue to receive very positive feedback from HCPs and other stakeholders as to our business approach, support and patient focus. As it relates to our progress with access and reimbursement, our highly experienced team continues to interact in positive conversations with payers to demonstrate the value of Pombiliti and Opfolda and we’re very pleased to say that the overall time to the US insurance process has dropped to less than 30 days.

This was exactly where we had hoped to get it. In the US, we continue to see a majority of patients switching from Nexviazym about 68% and the remaining from Lumizyme. This means we’re switching patients proportionally from both products. We continue to see a broadening and deepening of prescriptions with more sites coming online and multiple new prescriptions from physicians. Outside of the US, we’re seeing patients from all three segments, some switching from Myozyme and from Nexviazym at a proportional rate to the respective market shares and some from the naive population. On slide 13, we’re expecting Pombiliti and Opfolda to be a huge driver of overall growth this year and we anticipate around 65% to 85% in revenue growth at constant exchange rates.

We see the following key drivers of growth allowing for this to happen in 2025 and beyond. First, continuing to increase the number of net new patients. We’ve talked about in the US that about 40% of next year time patients will be coming up to the two-year mark on therapy versus 10% last year. This means a larger pool of patients are more likely looking to switch to a different therapy, particularly given our data and improvement in experienced patients demonstrated in our Phase 3 study. Second, we’re also going to keep increasing the depth and breadth of prescribers. Third, as I said, we’ll be launching in up to 10 countries, new countries throughout 2025. Next, we’re continuing to drive differentiation of our therapy through evidence generation and real-world evidence.

In addition to continuing to look more closely at our Phase 3 extension studies which continues to be an important part of the conversation with physicians, also starting to see a number of case studies presented to physicians at congresses over time, as well as large enough cohorts of patients where physicians can actually compare their experiences over time on the three therapy. All of these publications we hope to be able to see coming out over time as well. And finally, we’re anticipating a 90%-plus compliance and adherence rate. So, all of these growth drivers will help us get to that 60% to 85% growth guidance range. Moving to slide 14 and looking more closely at the geographic expansion growth driver. We have emphasized a few times now that this is going to be a major driver of growth for Pombiliti and Opfolda over the course of this year.

Today, we launched in the US, Germany, Austria, Spain and the UK, and as mentioned in January we received pricing and reimbursement in Italy and now in the Czech Republic, in Switzerland and in Sweden. We’re very pleased to announce today that we have also received pricing and reimbursement in the Netherlands. That’s an incredibly important Pompe market. This is the country in which the disease was actually discovered and one that has a very high prevalence of Pompe disease in Europe. As a result, the Netherlands is a highly regarded research hub with a globally renowned center of excellence and respected treated physicians. In Sweden, Pombiliti and Opfolda has received first line positioning and has had their first patient treated with commercial therapy.

In Italy, the regional process approval is now progressing nicely with the first patient that’s anticipated to occur in the first quarter of this year. We expect the first commercial patients from all of these respective countries to begin treatment in the first half of 2025. In addition, we have the regulatory dossier under review with anticipated approvals in Canada and Japan. And as Bradley highlighted, Pombiliti and Opfolda was recently approved in Australia. We continue to be focused on securing broad patient access throughout the EU and we anticipate launching in up to 10 new countries in 2025, including the five that I mentioned, that represents around 650 LOPD patients age 18 and older. This will be key to driving commercial uptake in youth countries this year.

So, overall, we’re very pleased with the ongoing launch. The strength of our clinical data, the depth of experience and talent we have at Amicus gives us great confidence in our ability to make a very real difference for people living with Pompe disease. And with that, let me hand the call over back to Jeff to highlight our ongoing clinical studies.

Jeffrey Castelli: Thank you, Sebastien. On slide 15, we outlined how we are continuing to grow the body of evidence for Pombiliti and Opfolda through our ongoing clinical studies and our registry. Importantly for the younger Pompe community, we continue to enroll the ongoing open label ZIP study for children living with late-onset Pompe disease and the open label Rossella study for children living with infantile onset Pompe disease. We see this as an important opportunity to address the significant unmet needs and opportunities in these children and to support label expansions into these patient segments. Through ongoing clinical studies and the Amicus Pompe registry, we continue to generate evidence on the differentiated mechanism action and on the long-term impact of Pom-Op across endpoints and across patient populations.

Our medical conference presence and scientific publications continue to be an important part of our education efforts, including an exceptionally strong presence at the WORLDSymposium earlier this month. Moving on to slide 16. We once again had a very significant presence at the World Conference with 20 posters and two oral platform presentations highlighting our ongoing work across both Fabry and Pompe. This year’s symposium focused on a number of key themes relevant to our ongoing work in Fabry and Pompe. One important theme is the accelerating number of patients continuing to be diagnosed across rare diseases, in particular for Fabry and Pompe, driven by advances in screening and access to lower cost genetic testing. A lot of work is also going on to determine the best time to treat these newly diagnosed patients and we see evidence that symptoms occur much earlier than historically believed and therefore, we’re seeing a lot of forces moving us towards earlier treatment in these newly diagnosed patients.

Another important theme was on the impact of the various new treatment options and Amicus presented a range of data including an analysis on the number of Pompe patients experiencing clinically important improvements in clinical trials. For Fabry disease, we also highlighted our ongoing studies to expand the real-world evidence of Galafold and on the machine learning initiatives I spoke to earlier. And for Pompe, we also highlighted a number of important case studies and additional data generated from real-world evidence supporting the use of Pombiliti and Opfolda for all of those patients living with late-onset Pompe disease. Our team had a number of discussions with key stakeholders to further drive awareness of Galafold and Pombiliti and Opfolda and overall, we were highly encouraged by the engagement we received and look forward to presenting additional data for both of our therapies at future medical congresses this year.

And finally, we continue to focus on novel approaches to next generation therapies in both Fabry and Pompe. With that, I would like now to turn the call over to Simon Harford, our Chief Financial Officer, to review our financial results, Guidance and outlook. Simon?

Simon Harford: Thank you, Jeff. Our financial overview begins on slide 18, with our income statement for the full year ending December 31, 2024. For the full year, we achieved total revenue of $528 million, which is a 32% increase over the same period in 2023. At constant exchange rates, revenue grew 33%, which was above our latest guidance of 30% to 32% growth at a constant exchange rate. The global geographic breakdown of total revenue in 2024 consisted of $322 million or 61% of revenue generated outside the United States and the remaining $206 million or 39% coming from within the US. Cost of goods sold as a percentage of net sales was 10% for the full year 2024 as compared to 9.3% for the prior year period. Total GAAP operating expenses increased to $450 million in 2024 as compared to $439 million in 2023, increase of 3% On a non-GAAP basis, total operating expenses increased to $348 million in 2024 as compared to $342 million in the prior year, an increase of 2%.

We define non-GAAP operating expense as research and development and SG&A expenses excluding stock-based compensation, loss on impairment of assets, changes in fair value of contingent consideration, restructuring charges and depreciation and amortization. On a GAAP basis, net loss in 2024 reduced to $56 million or $0.18 per share compared to a net loss of $152 million or $0.51 per share in 2023. In 2024, non-GAAP net income was $74 million or a profit of $0.24 per share compared to a non-GAAP net loss of $39 million or a loss of $0.13 per share in 2023. Cash, cash equivalents and marketable securities were $250 million at December 31, 2024 compared to $286 million at December 31, 2023. As highlighted on slides 19 and 20, we are reiterating our full year financial guidance for 2025 as follows: Total revenue growth guidance of 17% to 24%; Galafold revenue guidance of 10% to 15%; and Pombiliti and Opfolda revenue guidance of 65% to 85%.

All growth rates are at constant exchange rates. As in prior years, we anticipate non-linear quarterly growth of Galafold to continue. In Q1, we anticipate Galafold to represent approximately 22% of its full year sales as we have seen historically in the last five years. As we announced on our Q3 call, gross margin is expected to be in the mid-80s percent range. Today, we are introducing our 2025 non-GAAP operating expense guidance of $350 million to $370 million and GAAP net income to be positive during the second half of the year. With our commitment to full year non-GAAP profitability during the first full year of launch for Pombiliti and Opfolda, we kept our operating expense growth in low single digits year-over-year at the midpoint of guidance.

As a reminder, we continued to have R&D commitments including registry studies in both Fabry and Pompe. The ongoing Pompe Phase 3 study in countries not yet reimbursed as well as next generation manufacturing process development for Pombiliti. As previously noted, we anticipate 2025 to be a hybrid year for Pombiliti and Opfolda COGS as we expect to work through the previously expensed inventory during the first half of 2025. Total gross margins for the full year ’24 were approximately 90%. Again, we expect gross margins in the mid 80% range for this year as we begin to recognize Pombiliti and Opfolda COGS through the P&L. Given the proportion of Amicus sales generated outside the US of 60% approximately we see significant FX exposure to our reported revenue numbers.

The euro, British pound and Japanese yen are the currencies we are most exposed to. We note that a change in US dollar exchange rates of plus or minus 1% compared to year-end 2024 rates could lead to a $4 million approximately move in total reported revenues in 2025. And with that let me turn the call back over to Bradley for our closing remarks.

Bradley Campbell: Great. Thank you, Simon, Jeff and Sebastien. As we’ve highlighted today, we have been highly focused on commercial execution and the performance of our two approved therapies across the global business as well as sustained financial discipline. We believe Amicus is a unique company in the biotech industry today with several key drivers of growth along with significant operating leverage and that over time will lead us to become one of the leading rare disease biotechnology companies. We have laid a solid foundation for Amicus to continue delivering life changing therapies for people in 2025 and for many years to come. With that operator, we can now open the call to questions.

Q&A Session

Operator: Certainly. [Operator Instructions] Your first question comes from the line of Tazeen Ahmad with Bank of America Securities. Your line is now open.

Tazeen Ahmad: Hi, guys. Good morning. Thanks for taking my question. Brad, I wanted to ask about Pom-Op, as you go through the launch and as we look at let’s say the switch patient population, on average how long are doctors keeping their patients on, let’s say, the first or second gen, the ERTs before moving patients over to Amicus because we’ve done checks which indicate there’s excitement about the third option being available for patients who have undermet needs. But there’s also been talk about keeping patients on the first two gen drugs as long as possible. So, we wanted to get a sense of what you’re hearing from your field force on that. Thanks.

Bradley Campbell: Sure. Thanks Tazeen. Appreciate the question. Totally agree. We continue to hear great excitement for the prospects of Pombiliti and Opfolda. And I think Sebastien highlighted the great uptake that we’ve seen and Jeff too highlighted all the data that we’re seeing and continue to see come out through WORLD and other publications. We hope to continue to support that. But as you said, I think there’s clearly a portion of physicians who’ve suggested that they want to see a year or two of experience once they’ve switched to patient. And I think that’s why we’re so excited about the US situation where we estimate now up to 40% of patients who have switched to Nexviazym will be entering into that kind of two years of experience.

We have seen instances where that switch happens much sooner. I think anytime where a physician sees their patient declining, they’re going to look for new answers. And as we came into this market, we did share some market research that suggested that about 25% of all patients are in some sort of decline phase on a previous medicine. And I think those are the sort of clear target opportunities. But about 50% may be in some stable portion of their disease. And I think that’s where we’re waiting for that kind of one to two years of experience. So, really excited to see the trend so far and we think this year is going to be an important year to get to that kind of — especially in the United States, that large bowls of patients getting to that two-year mark.

Operator: Thank you. Your next question coming from the line of Ellie Merle with UBS. Your line is now open.

Ellie Merle: Hi, guys. Thanks so much for taking the question. You mentioned that there’s a high prevalence of Pompe in the Netherlands. Can you elaborate a little bit more on the number of patients there and specifically a bit more on the timing for when you expect to start dosing and recognizing revenues from that region? And then just generally, I know you mentioned that there are a lot of countries where you expect the first commercial patients to begin in the first half of the year. Can you maybe give us just a little bit more detail on the country-by-country timing for the revenues for Pom-Op? And your expectations there, particularly as we think about the quarterly cadence of revenues throughout the year. Thanks.

Bradley Campbell: Sure. I’ll have Sebastien comment on most of that. I will say, just as a reminder Pompe disease was first described by a Dutch physician. Dr. Pompe, and the key opinion leader in the Netherlands is a world-renowned key opinion leader. She’s an incredibly well respected and important researcher and clinician and treater in the Pompe space. And either because of the long-term sort of evolution of the disease or because of the higher awareness or because of potentially both, there’s a much higher diagnosed population in the Netherlands versus what has been historically described in some other markets from a population perspective. And so, for all of those reasons, we think it’s incredibly important now to be able to provide Pombiliti and Opfolda to that community.

And to your question on timing in the Netherlands, we do think that we could start to see first patients coming on to Pombiliti and Opfolda sort of towards the end of Q1 or into early Q2, but it will be an important driver for us this year. With that further detail, Sebastien, do you want to talk a little bit more around some of the other dynamics that Ellie asked about?

Sebastien Martel: Yeah. Thanks Brad, and happy to do so, Ellie. So, I mentioned that we’re targeting up to 10 new countries in 2025. All in all, these 10 markets could represent north of 650 LOPD patients in total. And we highlighted also separately all those 10, the five where we recently had some great success from a pricing and reimbursement standpoint. And those are Italy, the Netherlands, Switzerland, Sweden and the Czech Republic. We also share that those countries represent 350 plus of the 650 that I just mentioned earlier. This gives you a little bit of relative importance of those markets. Of the five, clearly, based on the comments Brad just made about the Netherlands, this is one of the largest markets in Europe. We estimate that there’s about 125 patients, adults with LOPD being treated in the Netherlands.

Italy is also sizable one. Now, while the Dutch market is very concentrated. The Italian market is on the contrary, fairly fragmented. And while we have already reimbursement at a national level, we are in the midst of regional negotiations and those are going very well. We have now, I think, more than five that have already provided the green light for regional reimbursement in Italy. So, we’re progressing fast. We indicated that we would expect the launch in these five new markets where we obtain access to gradually increase over the course of the first half of 2025. That also means we’ve got another five markets to be launching and probably more towards the second half of this year. Of those will include, hopefully Japan, with an approval anticipated in the second half and launch probably closer to around the fourth quarter of this year.

So that might be one of the last new launch countries, Japan. I did highlight that we recently got approval in Australia, I mentioned that we are expecting approval this year in Canada. Both Australia and Canada, due to the reimbursement process, will likely be launching in 2026 and not 2025. So, again, although the regulatory approvals will be in ’25, the actual launches in Canada and Australia will take place in ’26.

Ellie Merle: Great.

Operator: Thank you. Next question coming from the line of Dennis Ding with Jefferies. Your line is now open.

Dennis Ding: Hi, good morning. Thanks for taking our questions. I just had one specifically on FX. Can you elaborate a little bit more on FX and where do you see that going this year, especially with this whole macro narrative around interest rates being higher for longer? Does Amicus have any hedging programs designed to mitigate FX volatility and maybe also comment how impactful those were historically? Thank you.

Bradley Campbell: Thanks, Dennis. I will say we will hesitate to speculate forward-looking FX given, as you said, all the interesting macroeconomic factors going on. But Simon, maybe talk a little bit more or remind Dennis and the audience on what’s happened with FX so far, and then answer a specific question around, are there opportunities to mitigate against FX?

Simon Harford: Yeah. Thanks for the question, Dennis. In terms of FX, for a company of our size, we have not traditionally hedged FX exposure primarily because, frankly, we’re not experts at predicting where FX will go, as Bradley has sort of said. So, it can be a positive, it can be a negative. And obviously with 60% of our revenues based outside of the US, there is some exposure to that in both directions. I would say, in terms of thinking about rates currently, as I said in my call text, basically a one percentage point move in the dollar up or down essentially is roughly a $4 million revenue impact. But that can be a positive or negative. We highlight it simply and purely at this point in time because given where we are with some of the discussions that are going on geopolitically as well as I think you referenced sort of more sticky inflation, it’s possible that some of those actions could impact exchange rates one way or the other.

As I say, we’re not really predicting at this point in time, but that we just wanted you to understand what the impact is up or down.

Dennis Ding: Perfect. Thank you.

Operator: Thank you. The next question coming from the line of Joe Schwartz with Leerink Partners. Your line is now open.

Joe Schwartz: Great. Thanks very much for taking my question. I was wondering if you could update us on your progress towards establishing second source manufacturing for Pom-Op. And is there any risk or exposure regarding tariffs in the importation of Pom-Op from China currently?

Bradley Campbell: Yeah. Thanks, Joe. Really appreciate it. Yeah. So, making great progress on the second site of manufacturing in Dundalk, Ireland with WuXi. Have had successful PPQ batches, a successful European inspection there, and we’re on track for commercial product to come into the supply chain in Europe probably in the back half of this year, in the US the following year. So right in line with what our sort of plan was from a global supply perspective. In terms of tariff exposure, very little exposure this year from any potential tariffs and likewise very little exposure next year. We’ve done a great job from supply chain perspective ensuring that we are sort of optimizing where the drug product and finished goods sat in anticipation of potential changes.

So, you should expect very little impact and all of our guidance includes an anticipation of those tariffs staying in place. Of course, we’re doing everything we can to see if there are ways we can mitigate against that. But for now, you shouldn’t expect any material impact on our financials.

Joe Schwartz: Excellent. Thank you.

Bradley Campbell: Yeah. Thanks, Joe.

Operator: Thank you. The next question coming from the line of Kristen Kluska with Cantor Fitzgerald. Your line is now open.

Kristen Kluska: Hi. Good morning, everybody. You talked about the proportion of patients that may be considering switching to Pom-Op from Nexviazym based on being on therapy for up to two years and some of the effects starting to wear off. But I wanted to ask a on the flip side of that, for those patients that were treated with Pom-Op and perhaps before that other option, are you seeing something similar, or are you seeing that physicians want to keep their patients on Pom-Op for longer as the effects are still persistent?

Bradley Campbell: Sure. Thanks, Kristen for the question. I’ll just say the top line, we’re seeing well over 90% compliance and adherence with Pombiliti and Opfolda, which again has been a great strength of Galafold and MF kind of the levels that we would anticipate for Pom-Op going forward. But maybe Jeff, just talk about you remind — Kristen and the audience around sort of how long some Pombiliti and Opfolda patients have been on therapy from our clinical studies and also just some of the opportunities to publish on those data as we go forward.

JeffreyCastelli: Yeah. Thanks Brad. And thanks Kristen for the question. So, we have seen now, I guess, published out to four years, we’ve shown data from our trials and really that mean improvement that we’ve seen on many parameters is sustained over that time so far. I think one thing that is really an important dynamic that is out there is for many years kind of a stability or a slow decline was viewed as sort of the goal in Pompe treatment. And through our PROPEL study and other studies, a lot of what we highlight at WORLD, we have shown that when patients switch to Pom-Op, there are substantial number that actually can regain some function after switching. And that’s an important sort of education, I think, for the Pompe community and the treaters that thinking about that stability and only waiting to switch after patients decline might not be what’s best for a patient.

It might be better to switch earlier and have that person regain some function, possibly, or the opportunity to regain some function. So, that’s important for us to remind folks of that dynamic early on the switching. But as Brad mentioned, what we’ve seen both from trials and so far from a commercial perspective, we’ve seen really good durability and compliance and adherence once patients go on Pom-Op.

Bradley Campbell: Thanks, Jeff. Thanks, Kristen.

Operator: Thank you. Next question coming from the line of Malcolm Kuno with JPMorgan. Your line is now open.

Malcolm Kuno: Hi, thank you for taking the question. For the EU countries coming online during the first half of 2025, with regard to the specifically the EAP patients, how many should we be expecting to transition to commercial therapy?

Bradley Campbell: Yeah. Great question, Sebastien, can you remind us on kind of the remaining clinical trial and expanded access patients in those markets?

Sebastien Martel: Yeah. Happy to do so. So, of the 10 countries where we intend to launch this year, we’re talking about roughly 30 patients that are on clinical studies that would then be switched to commercial treatments for the course of the year, pre zero. And that’s in the late-onset population. We do, of course, have a fairly large number of pediatric patients who are involved in our clinical studies. Some are also on expanded access. And as we get closer to finalizing those studies and pursuing label expansion, we’ll also provide similar color into how many patients in that cohort we can expect to switch over to commercial. But for now, we’re focused, of course, on the late-onset population.

Malcolm Kuno: Great. Thank you.

Operator: Thank you. Next question coming from the line of Salveen Richter with Goldman Sachs. Your line is now open.

Salveen Richter: Thank you for taking my question. [Indiscernible]. While you are executing commercially and moving to profitability, could you speak to your strategy for future growth via R&D?

Bradley Campbell: Yeah, thanks for the question. I would really orient you to two opportunities there. The first is, as we’ve said, we think we have a global commercial infrastructure that is highly leverageable. And late-stage development infrastructure. And so, we are looking for ways to build upon that portfolio in a stepwise fashion and bring in additional assets over time. We think that’s a real opportunity. But we do have both our internal, very, very early-stage discovery efforts. And I think over the next kind of 12 to 24 months, I’d like to see an opportunity as we have more room in the P&L to potentially move some of those technologies forward. And that’s primarily in the Fabry and Pompe space. And then likewise, I think we continue to look at all of the early technologies in Fabry and Pompe and again, kind of over the next 12 to 24 months as we continue to build a strong financial profile, I’d like to see us build out our early discovery and development programs and maintain our leadership position in Fabry and Pompe.

So, I think those two areas of focus will help us over the next three to five years evolve into a fully integrated biotechnology company and again, one of, we hope, the leading rare disease focused biotech companies.

Operator: Thank you. The next question coming from the line of Gil Blum with Needham & Company. Your line is now open.

Gil Blum: Good morning, everyone and thanks for the updates. Maybe a question on the AI aspect here. So, what regulatory or logistical burden, if any, do you anticipate to be required to rollout something like OM1? Thanks.

Bradley Campbell: Yeah. It’s a great question. Right now, this is very much driven by, I think, two factors. Well, maybe three factors. Of course, the first is proving the technology. And that’s part of why we’re so excited to go through this project with University of Pennsylvania and with OM1. If we can prove that in fact this leads to better diagnosis of Fabry patients, we think it could be very beneficial for the medical community and the patient community out there. I think the second two factors, frankly, are right now this is relying on electronic health records. And so, within the United States as an example, there are a fair number, maybe a dozen to two dozen really large systems that have end-to-end electronic health records.

And that’s an important part of the opportunity here. If you’re in a distal node of the healthcare system and you don’t have EHR, it’ll be very difficult to apply this kind of algorithm in a sustainable way. And then the third piece, frankly is this is very much a partnership with physicians. And so, the idea here is not that Amicus is going to commercialize some new AI diagnostic product, but rather help provide this tool to Fabry physicians who are interested in proving the diagnosis within their population. So, I think those three things are really what will help us deploy this within the United States. And then as Jeff mentioned, we are doing some similar work, maybe coming ahead from a slightly different perspective in the UK and we hope to bring that process into other markets as well.

So, I think you’ll see us kind of come at it from two different angles, Gil.

Gil Blum: Thanks.

JeffreyCastelli: One of the great things as a reminder for Fabry is, it’s an X-linked dominant disease. So, as you find a patient in a health system through this type of approach, you can make sure that there’s good family counseling and kind of screening of family members. And typically you find three to five additional family members that might live anywhere in the United States, not just in the healthcare system being screened. So, it’s really highly leverageable. As you theoretically could roll this out through collaboration to 5, 10 different large healthcare systems. You could really make a big impact on finding people across the country in those systems and their family members living elsewhere.

Operator: Thank you. And the next question coming from the line of Jeff Hung with Morgan Stanley. Your line is now open.

Jeff Hung: Thanks for taking my question. Maybe a follow up on the AI collaboration with OM1 and Penn. Have any of the high potential patients begun to be seen by physicians and informally diagnosed with Fabry? And I think you’ve said that it’ll take about six months to do the testing phase. I was just curious if you’ll provide a formal update when this phase is completed and the outcomes of that, whether in terms of the families that additional patients that you guys identify. Thanks.

Bradley Campbell: Yeah. We would love to publish on and share the outcome of the research here and so look for opportunities for us to do that over the kind of the back half of the year. What we’ve said so far is that we have completed the process of identifying the most high-risk patients for having undiagnosed Fabry within that system. And the physician is now starting to reach out to those individuals to offer them a chance to come in for confirmatory testing. So that’s kind of the phase we’re at right now, and we’re very eager to see the outcome and then share the results as they come out.

Jeff Hung: Thanks.

Operator: Thank you. Next question coming from the line of Ritu Baral with TD Cowen. Your line is now open.

JoshuaFleishman: Hi. This is Joshua Fleishman on the line for Ritu. Thanks for taking the question. How has the commercial competitive dynamic evolved for Pom-Op? Our team attended WORLD and we noticed that Sanofi and Genzyme are doing less with Nexviazym. Is this something you guys have noticed in the field? Also, can you please give us an update on the LOPD label expansion and enrollment and timing for the IOPD study? And lastly, what technologies or features are you looking at for business development candidates? Thank you.

Bradley Campbell: So, Josh, you’re taking up the mantle of your colleague Ritu and asking one question with multiple parts. So, I appreciate that. So, I think we had the sort of competitive dynamic out there. We had the last one was BD and then the middle one was kind of the label expansion opportunities. So, I’ll take maybe the first one. I’ll let Sebastien again kind of reiterate what I shared on the BD side of things, if we’re focused on anything technologically or from a disease perspective. And then I’ll let Jeff talk a little bit about the regulatory piece. So, from competitive dynamic perspective, yeah, we also noticed perhaps a slightly lesser presence from Sanofi at the World Congress. I don’t want to speak for them.

What I will say is we were — as Jeff said, we were just super excited about really having a chance to across both of our products, Galafold and Pombiliti and Opfolda, share new data, have conversations with physicians, focus on diagnosing new patients, focus on the dynamics and the opportunities and drivers of switching to Pombiliti and Opfolda. Some real-world evidence starting to come out and I hope more and more of that will come. So, I’ll let Sanofi speak for themselves. But from our perspective, we thought that the reception for our team for the questions we were asking, for the data we were providing, the interaction with physicians was just super, super high energy. And we were pleased to see the note that you guys put out reflecting some of that.

Maybe just in order, Jeff, talk a little bit about the label expansion opportunities for Pom-Op and then Seb just hit the highlights and kind of strategically, what are we focused on from a business development perspective?

JeffreyCastelli: Yeah. Thanks, Brad. And thanks Josh for the question. So, first, starting with the late-onset Pompe disease and the pediatrics, so it’s really broken into two cohorts, the 12 to 17-year-old kind of adolescent patients and then the sort of 1 to 12-year-old earlier aged LOPD patients. So, for the adolescent group, we’ve completed enrolling that group. They’re finishing up their sort of year of follow up. We’ll be submitting that to FDA this year and we would look to have as early as next year, kind of official labeling into that group. For the 1 to 12-year-old LOPD, we’re making great progress on enrolling that and are looking to have our last patient enrolled this year and then obviously your follow up. So you’d probably be looking at the year after next for them to be officially added into labels.

And then on IOPD, that’s one cohort of 0 to 17 year olds, either experienced or naïve. In that group, we’re making good progress in enrollment. Those patients are much more rare, so it’s taken a little bit longer to enroll. So, we’re probably looking to finish enrolling that by the end of next year. And then obviously the amount of time for treatment and labeling. The nice thing with the late-onset group, the first two I talked about, is we do have alignment with agencies for extrapolation of efficacy into those patients. So, really, it’s just sort of safety and PK in that group. So, making good progress, looking for the first labeling in the adolescent LOPD, then the kind of younger LOPD and then IOPD to follow. Last thing I’d quickly add, we did note at WORLD, what we’re seeing, especially in the US with newborn screening, is a lot of these kids with what are really late-onset Pompe disease mutations are now being followed and they’re seeing symptoms much earlier.

It was kind of thought before that you wouldn’t see symptoms until 2030. And we’re actually seeing a substantial number of those kids being treated. So, for us, getting labeling down into that group is going to be a really important opportunity both to offer what we think is a great treatment to those kids and also even now, more and more from a market opportunity, that group is going to be really important. Seb, over to you for the rest of the question.

Sebastien Martel: Yeah. Thank you, Jeff. Thanks, Josh, for the question. I think we really highlighted today that overall the business is in great shape. We’ve got two growing medicines with Galafold that continues to deliver and Pom-Op, which continues to be rolled out with another 10 markets today. So that will drive sales of the existing business in the double-digit range for the foreseeable future. You also heard from Simon that our growth in OpEx is measured or limited. And so that also gives us a lot of confidence in our operating leverage and the growth that we’ll see in our net income and cash flows over the next years to come. So, we now at a stage where we feel we could even potentially accelerate this top and bottom line growth by leveraging the infrastructure that we’ve developed.

So, we were you know we’re carefully looking at opportunities within adjacent spaces. We are more focused on late-stage assets and near commercial or recent launched opportunities and a lot of those have to do with in licensing. We happen to be in a global biotech market where you’ve got a fair number of small US biotech companies who don’t necessarily have the ability to commercialize their products outside of so. Those lifechanging opportunities at times may come up from regional rights, and again, I think we’ve built a very solid global leverageable infrastructure that can be put to good use to further accelerate both top and bottom line.

Bradley Campbell: Great. Thanks, Sebastien. Thanks all for the questions. And Andrew anything left in the queue?

Andrew Faughnan: Nope. Operator, we can end the call. Thanks all.

End of Q&A:

Bradley Campbell: Great. Thanks everybody for listening and have a great day.

Operator: Thank you. That was your last question. Ladies and gentlemen, this concludes today’s conference call. You may now disconnect. Have a great day.