Amicus Therapeutics, Inc. Price & Performance (FOLD)

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 this cautionary statement and we undertake no obligation to revise or update this presentation and conference call to reflect results or circumstances after the date hereof. For a full discussion of our 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 of our annual report on Form 10 ks for the year ended 12/31/2024, to be filed with the Securities and Exchange Commission today.

At this time, is my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer, [indiscernible] Great. Thank you, Andrew, and welcome everyone 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 and global rare disease capabilities, we have 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 our about 2024 on Slide four. First, we continued our excellent commercial execution and delivered total revenue of $528,000,000 for the full year, representing 32% growth year over year or 33% 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 twenty twenty four, there were more than two thousand seven hundred people living with Fabry disease taking Galafold.

For the full year, Galafold revenue was $458,000,000 which represents 18% growth year on year or 19% at constant 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 ten thousand people worldwide living with Fabry disease who had been diagnosed. About five thousand of them were treated at the time, and about five thousand were untreated. Fast forward to 2024 and there are now eighteen thousand patients globally diagnosed with Fabry disease, treated market alone has more than doubled to twelve thousand people globally on some form of treatment for Fabry. While the untreated market has also grown now to six thousand 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 January 2037, This is a huge milestone that represents a major step forward in ensuring Amicus can continue to support the fabric 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, we with projected revenue growth of 10% to 15% at constant exchange rates. We are extremely pleased by the meaningful impact this meta [indiscernible] in countries around the world. And we believe that we have a very clear path to surpassing $1,000,000,000 in product sales from Galafold before the end of its lifecycle. Second, let me highlight the continued strong global commercial launch of PONBILETE and APFOLDA, our novel therapy for LADOS and Pompe disease. Tomoth, 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, PONBILITY and AFFOlder revenue was over $70,000,000 globally. As we've mentioned, our number one focus for the year was to maximize the number of patients And as we shared earlier in January at the JPMorgan Conference, there were two twenty people living with late onset Pompe disease who had been treated or scheduled for treatment with commercial product at the end of twenty twenty four. With 25 new prescriptions in Q4 alone. We are pleased with the global demand for this new therapy and consistently hear an inspiring feedback from healthcare professionals around the world on how their patients are responding to PONBILILET and OPOLDA most recently at the World LBN 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 U. S, Europe and The U. K, 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 thirty days as 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 Palmaq, 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 twenty twenty four or early twenty twenty five and now most recently The Netherlands, an extremely important market for Pompe disease Sebastien 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% Pumbiliy net 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 Pumbiliy naphtha 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. [indiscernible] Finally, as we continue our excellent commercial execution across both therapies, we are focused on delivering significant long term revenue growth anticipate surpassing $1,000,000,000 in total sales in 2028. Amicus achieved well over $500,000,000 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 organization can allow us to continue delivering strong revenue growth in the years 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, continue delivering total revenue growth of 17% to 24% at constant exchange rates, That includes double digit 10% to 15% in constant exchange rates, As I mentioned previously, PONBility and Upholder 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 twenty twenty five.

With that preview, now let me hand it over to Sebastian Martel, who to further highlight our commercial performance. [indiscernible] Thank you, Bradley, and good morning to everyone on the call. Start by providing you with more details on our Gannav full performance for the year. On Slide seven for the full year 2024, Gallipol reported revenue reached $458,100,000 driven by strong patient demand, particularly from our leading markets. In 2024, we delivered Ganapol 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 choice for Fabry patients with amenable volumes. The great news is there's still many more potential patients eligible for our therapy. Our results in the full year highlight the strength of our commercial effort. The demand for GASL globally continues to be strong with patients added in all major We're very pleased to share that in 2024, despite being on the market for eight years, Gannafold grew at the largest rate of new patient demand Our leading markets such as The U. S, The UK, South New Countries and Japan remain the biggest drivers of patient demand.

In fact, in 2024, this was the highest year for U. S. Growth patient subs in launch. This growing demand gives us great confidence in this therapy's outlook over the long term.

Within the global mix, which is about 60% naive and forty percent switch, seeing stronger uptake in naive populations.

So we continue to achieve high market share in countries where we've been approved the longest There's still plenty of opportunity to continue to switch patients over to Galafold To keep growing the market as we penetrate the diagnosed untreated and newly diagnosed segments.

We know that there's significant patient demand for Galapol 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 a medical to potentially reach up to $1,000,000,000 in annual revenue by the end of the decade. For the full year 2025, company currently forecasts revenue growth of Galafold of 10% to 15% growth on a constant currency basis. We anticipate sustained growth in 2025 and beyond to be driven by several key drivers. First, the fabric market is growing robustly with a significant portion of growth coming from finding new patients and reaching the diagnosed and treated population. Second, we continue to make progress on expanding Datapol into new markets and expanding the labels. Third, we're also seeing many diagnosed untreated patients transition to treatment as the need for earlier treatments, especially in females, becomes better appreciated. Fourth, the other piece of continued the other piece is continuing to drive Gatwo's market share of treated amenable patients who continue commercial execution. As I said earlier, Galapo currently has more than 65% of the global Amenable market We're seeing in our most mature markets that we can reach up to 85%, 90% of [indiscernible] 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 but continue to exceed 90%, reiterating our belief that those patients who go on Galafold presently stay on Galafold. Finally, as I mentioned in past calls, due to a variety of factors including uneven ordering patterns and FX operations 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 U. S. 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 is a long runway well into the next decade and Cleopamp to surpassing $1,000,000,000 in revenue in the next twelve years. Let me briefly turn the call over to Jeff Castellis to provide you with an update on some of the initiatives we're currently supporting to improve diagnosis, [indiscernible] Thank you, Sebastian, 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 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 going on to treatment through new board 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 records. And through that process, we've identified the top 100 people in the system with a significantly increased suspicion of having undiagnosed Fabry.

Individuals identified are in the process of being offered a diagnostic workup and genetic testing to determine if they have Fabry 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 has revealed that eighty five percent of the people diagnosed with Zimbra 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 fibroid disease, otherwise would not have been diagnosed and focused outreach efforts are underway. Fabryta remains one of the most under diagnosed rare genetic diseases, 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 Sebastian to continue reviewing the 2024 performance of Pumbili and OpFolta. [indiscernible] Sebastian, I believe you're muted. Thank you, Jeff. So now let's turn to Slide 11, and we outline here our global launch progress with Pumbiliotilda. We had a very successful first year of launch in The U. S. Germany, Austria, Spain and The UK.

Using this therapy. For the full year 2024, Pompidide and Opdivo reported revenue reached $70,200,000 line with our latest guidance range. This is really strong growth coming off the base of roughly $12,000,000 in 2023. When looking at the geographic mix of revenue, over the course of the year, observed 57% of sales and 43% within The U. S. That's the global average for all Pompe sales We expect that number to move closer to a fifty-fifty split over the course of this year with The U. S. Being the largest market in terms of LMT patients, and the highest price points but also at the same time launching in up to 10 countries this year. Moving on to Slide 12, [indiscernible] As Brandy mentioned earlier, our focus for the year was to maximize number of patients therapy by year end. We ended 2024 with about two twenty patients treated or scheduled for treatment in five countries. About two zero nine patients have been treated. And also about twenty five new prescriptions added in Q4. And as we stated before, all eligible clinical trial patients A launch market have been converted to commercial therapy by the end of the first half of twenty twenty four.

Our launch has leveraged our highly experienced cross functional teams seeing an increase in the depth and breadth of prescribers across all five markets indicating to us that physicians are having positive experiences with a therapy and are gaining greater confidence in using 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 Prometic Care Ophelia. And we're very pleased to say that the overall time to U. S. Insurance process has dropped to less than thirty days. This was exactly where we had hoped to get it. In The U. S, we continue to see a majority of patients switching from your time. About sixty eight percent. And the remaining from LuminAd. This means we're switching patients proportionately from both products We continue to see a broadening and deepening of prescriptions with more sites coming online. [indiscernible] new prescriptions from physicians. Outside of The U. S, we're seeing patients from all three segments some switching from MYOBYNE, and from Natradyme a proportional rate to the respective market shares and some from the naive population.

On Slide 13, we're expecting Pombilipe and Opoda 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 U. S. About forty percent of NexiaZan patients will be coming up to the two year mark [indiscernible] [indiscernible] 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 three study. Second, we're also going to keep increasing the depth and breadth of prescribers Third, 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 three extension studies, which continues to be an important part of the conversation with physicians. We're 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 therapies.

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 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 growth for Combilitian of Fulga over the course of this year. Today, we're launching The U. S, Germany, Austria, Spain and The UK. As mentioned, in January, we received pricing and reimbursement in Italy 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 which the disease was actually discovered And one that has a very high prevalence of Pompilipe in Europe. As a result, The Netherlands is a highly regarded research hub with a globally renowned center of excellence and respected [indiscernible] In Sweden, Pembolitinoporga 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 stopped anticipated to occur the first quarter of this year. We expect the first commercial patients from all of these respective countries to be in treatment in the first half of twenty twenty five. In addition, we have regulatory dossier under review with anticipated approvals in Canada, and Japan as Bradley highlighted, OMVILITIANONPORATE was recently approved in Australia. [indiscernible] We continue to be focused on securing broad patient access broad EU and we anticipate launching an to 10 new countries in 2025. Including the five that that represents around six fifty LOBD patients aged 18 and older. This will be key to driving commercial uptake in these countries this year. So overall, we're very pleased with the ongoing launch, the strength of our clinical data that 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 And with that, let me hand the call over back to Jeff to highlight our ongoing clinical studies Thank you, Sebastian. On Slide 15, we outline how we are continuing to grow the body of evidence for Pompeility and OpFolte, 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 Rosella 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 in the Amicus Pompe registry, we continue to generate evidence on the differentiated mechanism of action and on the long term impact of PALMAP across endpoints and across patient populations. Medical conference presence and scientific publications continue to be an important part of our including an exceptionally strong presence at the World Symposium earlier this month. Moving on to Slide 16, we once again had a very significant presence at the World Conference twenty 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. 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 fibrata 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 additional data generated from real world evidence supporting the use of Pembility Napfola 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 Palm Building Upfoda. And overall, we were highly encouraged by the engagement we received and look forward 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?

Thank you, Jeff. Our financial overview begins on Slide 18.

With our income statement for the full year ending 12/31/2024.

For the full year, we achieved total revenue of $528,000,000 dollars 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 $322,000,000 or 661% of revenue generated outside The United States and the remaining $2.00 $6,000,000 or 39% coming from within The U. S. Cost of goods sold as a percentage of net sales was 10% for full year 2024 as compared to 9.3% for the prior year period. Total GAAP operating expenses increased to $450,000,000 in 2024 as compared to $439,000,000 in 2023. An increase of 3%. On a non GAAP basis, total operating expenses increased to $348,000,000 in 2024 as compared to $342,000,000 in the prior year.

An increase of 2%. We define non GAAP operating expense as research and development and SG and 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 $56,000,000 or $18 per share compared to a net loss of $152,000,000 or $0.51 per share in 2023. In 2024, non GAAP net income was $74,000,000 or a profit of $0.24 per share, compared to a non GAAP net loss of $39,000,000 or a loss of $0.13 per share in 2023. Cash, cash equivalents and marketable securities were $250,000,000 at December 31, 2024 compared to $286,000,000 dollars at 12/31/2023. As highlighted on Slides nineteen and twenty, we are reiterating our full year financial guidance for 2025 as follows: total revenue growth guidance of 17% to 24% 10% to 15%, and PONBILITY and OPFOLDER 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 rep 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 operating expense guidance of $350,000,000 to $370,000,000 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 Pumbiliy and OpFolder, we kept our operating expense growth in low single digits year over year at the midpoint of guidance. As a reminder, we continue to have R and D commitments including registry studies in both Fabry and Pompe, the ongoing Pompe Phase III study in countries not yet reimbursed as well as next generation MANA As previously noted, we anticipate 2025 be a hybrid year for Fondbility and OcFolder COGS. As we expect to work through the previously expensed inventory during the first half of twenty twenty five, Total gross margins for the full year 2024 were approximately 90%. Again, we expect gross margins in the mid-eighty percent range for this year as we begin to recognize Pumbilioti OpFolder COGS through the P and L. Given the proportion of Amica sales generated outside The U. S, 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 U. S. Dollar exchange rates of plus or minus 1% compared to year end 2024 rates could lead to a $4,000,000 approximately move in total reported revenues in 2025. And with that, let me turn the call back over to Bradley for our closing remarks. Great. Thank you, Simon, Jeff and Sebastian.

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 that over time will lead us to be become one of the leading rare disease biotechnology companies we have laid a solid foundation for Amicus Amicus [indiscernible] and for many years to come. With that operator, we can now open the call to questions. If you have any additional questions, Your first question comes from the line of Tazeen much of America Securities. Your line is now open. Hi, guys. Good morning. Thanks for taking my question. I wanted to ask about PalmaP. 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 fantasy ERTs before moving patients over to Amicus because we've done checks which indicate there is excitement about The third option being available for patients who have unmet need, But there's also been talk about keeping patients on the first two gen drugs as long as possible. So I wanted to get a sense of what you're hearing from your field Thanks.

Sure. Thanks, Tazeen. Appreciate the question. Totally agree.

We continue to hear great excitement for the prospects of Pumbili de Alfalda And I think Sebastian highlighted the great uptake that we've seen and 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 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 U. S. Situation where we estimate now up to forty percent of patients who have switched to NexvioZYZYM 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 their going to look for new answers. And as we came into this market, we did share some market research that suggested that twenty five percent of all patients are in some sort of decline phase. Phase on a previous medicine. I think those are the sort of clear target opportunities. But about fifty percent maybe 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 trends 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 Thank you. The next question coming from the line of Elyse Murli with UBS. Your line is now open. Hey guys. Thanks so much for taking the question. You mentioned that there's a high prevalence of Pompeii 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 Palm Off and your expectations there, particularly as we think about the quarterly cadence of revenues throughout the year?

Sure. I'll have Sebastian comment on most of that. I will say just as a reminder Pompe disease, was first described by a Dutch physician, Doctor. 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 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 Pumbiliacaftsulta 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 to Pumbiliapolva sort of towards the end of Q1 in or into early Q2, but it will be an important driver for us this year. With that further detail, Sebastian, do you want to talk a little bit more around some of the other dynamics that Ellie asked about? [indiscernible] Thanks, Brad, and happy to do so, Elyse.

So So I mentioned that we're targeting up to 10 new countries in 2025. All in all, these 10 markets could represent not of six fifty LOPD patients in total And we highlighted also separately of Luzstan 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 shared that those countries represent three fifty plus of the six fifty that I just mentioned earlier. But this gives you a little bit of a relative importance of those markets Of the five, clearly based on the comments Brad just made about the new events, this is one of the largest markets in [indiscernible] We estimate that there's about one hundred and twenty five patients adults with LOPDs being treated in in The Netherlands. Italy is also a sizable one. [indiscernible] the Dutch market is very concentrated, Italian market is on the contrary fairly fragmented. And while we have already reimbursement at a national level, we are in the midst 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 needs to be.

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 of the first half of twenty twenty five. 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 approval anticipated in the second half and a 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 a approval in Australia, 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 approval will be in 2025, the actual launches in Canada and Australia will take place in '26 Great.

Thanks. Thank you. Next question coming from the line of Dennis Ding with Jeff Your line is now open.

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 AMOCA 70 hedging programs designed to mitigate FX volatility and maybe also comment how impactful those were historic?

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 remind Dennis and the audience on what's happened with FX so far and then answer a specific question Yes. Thanks for the question. Dennis.

In terms of FX, 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 a negative. And obviously, with 60% of our revenues based outside of The U. S, 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, it's roughly a $4,000,000 revenue impact That can be a positive or negative. We highlighted 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. Perfect. Thank you.

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

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 PAMAUP? And is there any risk or exposure regarding tariffs and the importation of palm up Currently, Yes. Thanks, Joe. Really appreciate it. Yes. 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, The U. S. 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 a supply chain perspective ensuring that we are [indiscernible] where the drug product and finished goods sat 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.

Excellent. Thank you.

Yes. Thank you. The next question coming from the line of Kristen Kliska with Cantor Fitzgerald. Your line is now open. Hi, good morning everybody. You talked about the proportion of patients that may be considering switching to Palma from NextViazyme based on being on therapy for up to two years and some of the effects starting to wear off. But I wanted to ask on the flip side of that. For those patients that were treated with PalmaP and perhaps before that other option, are you seeing something similar or are you seeing that physicians want to keep their patients on POM up for longer as the effects are still persistent?

Sure. Thanks, Kristen, for the question. I'll just say at a top line, we're seeing well over 90% compliance and adherence with Pumbiliap Folda which again has been a great strength of Galafold and that's kind of levels that we would anticipate for PalmaP going forward. But maybe Jeff just talk about you remind Kristen and the audience around sort of how long some PONVILLA have full the 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.

Yes. Thanks, Brian, and thanks, Kristen, for the question. So We have seen now, I guess, published out of 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 And through our PROPEL study and other studies, a lot of what we highlight at World We have shown that when patients switch, to PalmaP, 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 on the switching But as Brad mentioned, what we've seen both from trials and so far from a commercial we've seen really good durability and compliance and adherence once patient Thanks, Jack.

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

Hi. Thank you for taking the question. For the EU cut coming online during the first half 2025.

With regard to the specifically the EA EAP patients, how many should we be expecting to transition to commercial therapy?

Yes, great question. Sebastian, can you remind us on kind of the remaining clinical trial and expanded access patients in those markets?

Yes, happy to do so. 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 then be switched to commercial treatments. For the course of the year. Three-zero.

And And that's in the late onset population. We do, of course, have a fairly large number of pediatric patients who are involved 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 focusing of course on the late onset population.

Great. Thank you.

Thank you. Next question coming from the line of Solvian Richter with Goldman Sachs. Your line is now open. [indiscernible] Why do you want executing commercially and moving to Could you please give your strategy for future growth via R and D?

Yes. 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. Late stage development infrastructure. And so we are looking for ways to 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 twelve to twenty four months, I'd like to see an opportunity we have more room in the P and 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 Fab brand Pompe. And again, kind of over the next twelve to twenty four months as we continue to build the 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 we hope the leading rare disease focused biotech companies.

Thank you. The next question coming from the line of Gilbourne with Nedam and Company. Your line is now open.

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 roll out something like OM1 Thanks.

Yes, it's a great question. Right now, this is very much driven by, I think, two fact or 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 this project with University of Pennsylvania and with OM1. If we can prove that in fact leads to better diagnosis of febrile, 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 [indiscernible] large systems that have end to end electronic health records. And that's an important part of of the opportunity here. If you're in a distal node of the healthcare system and you don't have EHR, it will 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 U. K. And we hope to bring that that process into other markets as well. So I think you'll see kind of come at it from two different angles, Gil.

One of the great things as a reminder for Fabre is it's an excellent 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 theoretically can roll this out through collaboration to five, ten 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.

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

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 been formally diagnosed with Fabry? And I think you 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 you know the outcomes of that weather in terms of like families that additional patients that you guys identify?

Yes. We would love to publish on and share the outcome 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 a diagnosed 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 confirm arctuate 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 up.

Thanks.

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

Hi. This is Joshua Fleishman on the line for Ritu. Thanks for taking the question.

How has the commercial competitive dynamic evolved for PalmaP Our team attended WORL and we noticed that Sanofi and Genzyme were doing less with NexisviaZYme this something you guys have noticed in the field?

Also, can you please give us an update on the LOPD label expansion and enrollment in timing for the IOPD study? And lastly, what technologies are features are you looking at for business development candidates? [indiscernible] you're taking up the mantle of your colleague Ritu and asking one question multiple parts. So I appreciate that. So I think we had the sort of competitive dynamic out [indiscernible] opportunities. So I'll take maybe the first one. I'll let Sebastian again kind of reiterate what I shared on the BD side of things. What we're 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 Amicus competitive dynamic perspective, 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 Pumbiliab Pumbiliab Pumbiliab Pumbiliab Pumbiliab Pumbiliab Pumbiliab Pumbiliab Pumbiliab, share new data, have conversations with physicians, focus on diagnosing new patients, focus on the dynamics and the opportunities and drivers of of switching to Pumbiliya FUDA some real world evidence starting to come out and I hope more and more of that will come.

So I'll let Tanafi 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 a pump up and then Seb, just hit the highlights and kind of strategically what are we focused on from a business development perspective?

Yes. Thanks, Brad, and thanks Josh for the question.

So first starting with the late onset Pompe disease in 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 one 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 one to twelve year old LOPD, we're making great progress on enrolling that 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 and then it'd be officially added into labels. And then on IOPD, that's one cohort of 17 year olds either experienced or naive. That group, [indiscernible] 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. [indiscernible] making good progress, looking for the first labeling in the adolescent LOPD, then the kind of younger LOP and then IOPD to follow.

Thing I'd quickly add, we did note at World what we're seeing especially in The U. S. 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 till 02/1930. We're actually seeing a substantial number of those kids being treated. So for us getting labeling done 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. Sub, over to you for the rest of the question.

Yes. Thank you, Jeff. Thanks, Josh, for the question. I think we've really highlighted today that Overall, the business is in great shape. We've got two growing medicines with Gafald that continues to deliver and pump up 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 now at a state where we feel we could even potentially accelerate this top and bottom line growth by leveraging the infrastructure that infrastructure that we've that we've developed. So we were carefully looking at opportunities within adjacent spaces. We are more focused on late stage assets and near commercial recently launched opportunities And a lot of those have to do with in licensing. We We happen to be in a global biotech market where you've got a fair number of small U. S. Biotech companies who don't necessarily have the ability to commercialize their products outside of The U. S. So [indiscernible] 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 both top and bottom line. Great. Thanks, Sebastian.

Thanks all for the questions and Andrew, anything left in the queue?

No problem. We can end the call. Thanks all.

Great. Thanks everybody for listening and have a great day.

Thank you. Our last question Ladies and gentlemen, this concludes today's conference call. You may now disconnect. Have a great day.