Good morning ladies and gentlemen and welcome to the Amicus Therapeutics' Full Year 2023 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.

Great. Thank you, Didi. Good morning. Thank you for everyone. Thank you for joining our conference call to discuss Amicus Therapeutics' full year 2023 financial results and corporate highlights. Leading today's call we have Bradley Campbell, President and Chief Executive Officer; Sebastien Martel, Chief Business Officer; Simon Harford, Chief Financial Officer; and Dr. Jeff Castelli, Chief Development Officer. Joining for Q&A is Dr. Mitchell Goldman, Chief Medical Officer; and Ellen Rosenberg, Chief Legal Officer. As referenced on Slide 2, 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 this 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 of our annual report on Form 10-K for the year ended December 31st, 2023 to be filed today with the Securities and Exchange Commission. At this time, it's my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer.

Great. Thanks Andrew and welcome everybody to our full year 2023 conference call. This year, our call falls a day before Rare Disease Day, so before I dive into our results, I just wanted to take a minute to acknowledge this important day for the rare disease community. This year's theme is achieving true health equity for the nearly 300 million people around the world living with a rare condition. Since our inception, Amicus has been dedicated to serving the needs of those in the rare disease community in extraordinary ways and we are committed to advocating for patient communities and fighting on behalf of those whose voices have not been heard. Rare Disease Day serves as a global call to action to collectively work towards equity and social opportunity, healthcare, and perhaps most importantly, access to medicines for people living with rare diseases. So, I just ask that all of you join me in commemorating this important day for the global rare disease community. So, with that, let me shift into our financial results and outlook and I'm very pleased to highlight what tremendous progress we made across our global business last year and into the start of 2024. As you saw in this morning's press release, I'll highlight several key points before I turn it over to the team to go through more detail. So, first Galafold continues its strong performance and it remains the cornerstone of our success. We are very pleased with the continued uptake of Galafold globally. We now have over 2,400 people living with Fabry disease who take Galafold or were taking Galafold at the end of 2023. For the full year, that translated to Galafold revenue of $388 million globally, representing 18% growth year-over-year, outperforming our expectations and our initial guidance for the year. Throughout 2023, we continue to observe strong trends across our key performance indicators in all of our key geographies including continued demand through new patient starts from both switch and naive populations in all of our leading markets. We saw steady growth of in-person visits between our field team and Fabry treaters and we've continued to see sustained patient compliance and adherence rates of over 90%. Growth in 2023 was driven primarily by patient demand from net new patient starts, continuing to switch patients in our newer launch markets, and continued penetration into the diagnosed and untreated population, which we expect to continue to be a major driver of growth in 2024 and beyond as the Fabry market continues to see improved diagnosis and medical education in finding patients. Just to put that in perspective for a minute. As a reminder, just over eight years ago, we estimated there were 5,000 treated Fabry patients and 5,000 patients who are diagnosed with untreated. Today, there are more than 11,000 treated patients. So, the treated market has more than doubled in that time, while the untreated market has also increased to almost 6,000 patients. These underlying market dynamics will provide the opportunity to grow Galafold for many years to come, including in 2024, when we expect another great year with 11% to 16% projected growth at constant exchange rates. Second, the global commercial launch of Pombiliti and Opfolda is underway and is off to a great start in the three largest Pompe markets. Our teams have made significant progress in the initial commercial launch in Germany, the UK and the US, and we remain incredibly pleased with the launch so far. Seven weeks ago at JPMorgan, we shared that 120 patients were on treatment or scheduled for treatment, including 15 new commercial patients. And as we said at the conference, we're not going to give mid-quarter updates, but I can share more color on how incredibly pleased we are with the continued patient and physician demand for this new therapy. The key performance indicators that we talked about last time continue to improve and continue to give us confidence in the strength of this launch. Specifically, the rate of new commercial patients coming on to Pombiliti and Opfolda continues to increase in all three markets, as we progress through the early weeks of the year. We anticipate launches in additional countries will add to that growth through the latter part of the year. And importantly, for our new commercial patients, we continue to see prescriptions proportionally coming from Nexviazyme and Lumizyme, as well as naive patients in ex-US markets. So that means in the US, the majority of new patients are switching off of Nexviazyme and coming on to Pombiliti and Opfolda, whereas in Europe, where Lumizyme has the majority market share, most of our switch patients are coming from that therapy, and we're seeing an increasing number of naive patients as well, so all the patient segments are performing as we would expect. In a moment, Sébastien will provide further color on the ongoing launch of these key performance indicators, but overall, we're very pleased by the launch and the great momentum we're seeing across each of our markets. Throughout 2024, we'll continue to focus on increasing patient access by expanding into additional European countries, as we navigate the country-by-country pricing and reimbursement process and focus on additional regulatory submissions as well. We are incredibly pleased to be providing a real choice for patients and challenging therapeutic options for both physicians and people living with Pompe disease. Third, Amicus has maintained an incredibly strong financial position as we continue to execute on the expansion of Galafold and advance the global launch of Pombiliti and Opfolda. We are pleased to share today that as we promised, we delivered our first quarter of non-GAAP profitability in the fourth quarter of 2023. This is obviously a significant milestone as we now look to deliver our first full year of non-GAAP profitability in 2024, supported for the first time by well over $0.5 billion in combined product sales, as well as prudent expense management to achieve significant milestones in the evolution of Amicus as a biotechnology company in the rare disease space. Our key strategic priorities for 2024 are laid out in slide four. As we laid out last month, we are focused on achieving our key strategic priorities for 2024, including: number one, again, sustaining that double-digit Galafold revenue growth of 11% to 16% at constant exchange rates, continuing our successful launch of Pombiliti and Opfolda, and executing multiple successful new commercial launches throughout the year, advancing our ongoing studies to support our medical and scientific leadership in Fabry and Pompe disease, and finally, maintaining our strong financial position as we carefully manage our expenses and investments in order to achieve a full year of non-GAAP profitability. With that, let me now hand the call over to Sébastien, who can give further highlights on our commercial performance.

Thank you, Bradley. Good morning or good afternoon to everyone on the call. I'll start by providing you with more details on our Galafold performance for the year. On slide 6, for the full year 2023, Galafold reported revenue reached $387.8 million. Galafold growth in 2023 was primarily driven by strong patient demand, particularly from our leading markets. Turning to slide 7. Our results in the full year highlight the strength of our global commercial efforts. The demand for Galafold globally continues to be strong with patients added in all major markets, delivering operational growth of 18% over the same period in 2022 or 17% at constant exchange rates. We finished the year strongly, with fourth quarter 2023, Galafold reported revenue of $106.6 million, up 21% or 19% at CER. We're pleased to share that 2023 was the strongest year for net new Galafold patients since 2019. Our leading markets such as the UK, the US, EU 5 countries and Japan remain the biggest drivers of patient demand and gives great confidence in the growth this product has over the long run. As Bradley mentioned, we ended the year with more than 2,400 patients on Galafold, which is roughly over half of the global market share of treated amenable patients. Galafold has captured 60% to 65% of the global market share of treated amenable patients. But the good news is there are still many more patients to put on therapy. Within the global mix, which is about 43% switch and 57% naïve, 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 keep on growing the market as we penetrate into the diagnosed and treated and newly diagnosed segments. 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 for them to please stay on Galafold. As mentioned on past calls, due to a variety of contributing uneven ordering patterns and FX fluctuations, the rate of growth within the year is typically nonlinear. Additionally, we've historically seen Q1 revenues come in slightly below prior Q4 due to the timing of orders and the reauthorization process in the U.S. and we expect that to continue into 2024. So within the table, on the right hand side of the slide, we've provided a five-year historical snapshot of the percentage of Galafold sales, and after each quarter during a given year. Interestingly, the average of quarterly sales distribution over the last five years corresponds precisely to what we achieved for the full year 2023. We would expect a similar trend to occur this year. So, as an example, we expect Q1 sales of the current year to be around 22% of full year sales for Galafold. On Slide 8, we know that there's a significant patient demand for Galafold and the segment of growth of the global Fabry market made up of patients with amenable mutations has the potential to reach up to $1 billion in annual revenue by the end of the decade. We anticipate sustained growth in 2024 and beyond to be driven by several key growth drivers. First, continuing to increase patient identification through ongoing medical education, screening and improved diagnosis. As you know, Fabry is one of the most underdiagnosed rare diseases. So the more patients are identified, the more patients can be eligible for Galafold. Second, the other piece is continuing to drive Galafold's market share of treated amenable patients through continued commercial execution. As noted, Galafold currently has 60% to 65% of the global amenable market. What we're seeing in our most mature market is that we can reach up to about 85% or 90% of market share. So we know that there's potential to reach new levels in the global market share as well. Importantly, as Bradley highlighted earlier, this is a robustly growing Fabry market with a significant portion of growth coming from finding new patients and penetrating into the newly diagnosed and untreated populations. Just within the 2,400 patients on Galafold at the end of 2023, about 1,400 of these individuals were naive to any treatments before coming on Galafold. We've been successful in finding new patients through newborn screening and other diagnostic initiatives, as well as artificial intelligence through our partnership with OM1. And again, all of these efforts are supported by solid compliance and adherence rates from physicians and patient education and support programs. We'll continue to make progress on expanding Galafold into new markets and extending the labels. There are still some markets in that time, some in the Middle East and Asia Pacific regions where Galafold is either newly reimbursed, or we expect reimbursement. Also important to note here, we have orphan exclusivity in the US and Europe in addition to our 57 orange-book patents, 41 of which provide protection into 2038 and beyond, including 11 composition of matter patents. This provides us with the opportunity to provide access to Galafold globally for a long time to come. We intend to continue to protect and enforce our broad intellectual property rights. Looking ahead, we expect steady double-digit growth for Galafold throughout 2024 and we remain confident that our strong IP protection will provide Galafold a long runway well into the next decade. Turning now on to Pompe Disease on Slide 10. We outline our global launch progress with Pombiliti and Opfolda. So for the full year 2023, Pombiliti and Opfolda reported revenue reached $11.6 million for the full year and $8.5 million for the fourth quarter. At the beginning of the year, 2024, 120 patients were on treatment or scheduled for treatment, of which approximately 105 were from our clinical trial and early access programs, and 15 from competitor ERTs or naive to treatment. We've been pleased with the continued demand for this new therapy. As Bradley said, and as anticipated, I would say, the rate of new commercial patients coming onto Pombiliti and Opfolda continues to increase across all three markets. In the US, we continue to see a majority of patients switching from Myozyme, roughly about 75% of the switches we've seen, and the remaining 25% coming from Lumizyme. This means we're switching patients proportionally from both products. Outside of the U.S., we're seeing patients switching from all three segments, from Myozyme, Nexviazyme and naive population, at a proportional rate, exactly what we want to be seeing at this stage. Our launch has leveraged our highly experienced cross-functional teams, and we've had great outreach with KOLs. We're seeing an increase in depth, as well as breadth of prescribers, across all three markets and in particular, see a growing number of prescribers who are not part of our clinical studies or expanded access programs. All core treating centers have been engaged with, and we have had very positive feedback from HCPs and other stakeholders as to our business approach, support and patient focus. Finally, we find an important metric to track is our progress with access and reimbursement. We have a highly experienced team who are engaging in positive conversations with payers to demonstrate the value of Pombiliti and Opfolda. In the US, and with the start of the new year, many of the large payers have already put Pombiliti and Opfolda onto their respective formularies, and we've also seen strong acceptance by Medicare and Medicaid as well. Today, we're launched in Germany, the UK, the US, and Austria. We're also in active pricing and reimbursement discussions with additional major European markets as we focus on securing broad patient access throughout the EU. More than 10 reimbursement dossiers have been submitted. Overall, we're starting off the year strong, and we're very pleased with the building momentum on patient demand. Over the course of 2024, our focus will be on maximizing the number of patients on therapy by year-end. So, in summary, we're very pleased with the launches of Pombiliti and Opfolda across all the first wave of countries, the strengths of our clinical data, the depth of experience and talent we have at Amicus gives us great confidence in our ability to make a real difference to people living with Pompe disease. We believe Amicus is in a great position for our second successful launch. And with that, I will hand the call over to Jeff Castelli, our Chief Development Officer, to discuss the ongoing clinical studies as well as regulatory timelines.

Thank you, Sébastien, and good morning, everyone. On Slide 11, we remind everyone that we continue to build the body of evidence for Pombiliti and Opfolda through our ongoing clinical studies as we also continue to execute on expanding commercial access through regulatory submissions. As we enter the second phase of launch, in addition to the various reimbursement dossiers that we have or that we are in the process of submitting, we also have multiple ongoing or planned regulatory submissions for marking and approval in new geographies throughout this year. 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 RZELA study for children living with infantile-onset Pompe. We see this as an important opportunity to support label expansions into these patient segments and provide access to these kids much in need in the years ahead. Through ongoing clinical studies and the Amicus Pompe registry, we expect to continue generating evidence on our differentiated mechanism of action and long-term data supporting the impact of Pombiliti and Opfolda across endpoints and patient populations. I am very excited to announce that we have actually now begun enrolling patients into the Amicus Pompe registry globally. And here in February, we once again had a very engaging conference and a significant presence at the 20th Annual World Symposium that was held in San Diego. Amicus had 11 posters and an oral presentation highlighting our continued work across Fabry and Pompe disease. Of note, Amicus was honored with the WORLDSymposium 2024 New Treatment Award for Pombiliti and Opfolda, which recognizes companies that have made important achievements in advancing treatments for lysosomal diseases and have obtained regulatory approval. It's an honor to achieve an award based on our scientific innovation, but even more importantly the meaningful difference we can make in the lives of so many people living with these rare diseases. Finally, as highlighted in the pipeline slide in the appendix for our earlier stage pipeline, we continue to focus on novel approaches for Fabry and Pompe including delivery of our engineered GLA and GAA transgenes and the next-generation Fabry-Chaperone. With that, I would like to now turn the call over to Simon Harford, our Chief Financial Officer to review our financial results, guidance and outlook.

Thank you, Jeff. Our financial overview begins on slide 13 with our income statement for the full year ending December 31, 2023. We had a very successful year, achieving total revenue of $399 million, which is a 21% increase over the same period in 2022. At constant exchange rates, revenue grew strongly by 20%. A global geographic breakdown of total revenue for 2023 consisted of $250 million or 63% of revenue generated outside the United States and the remaining $147 million or 37% coming from within the US. Cost of goods sold as a percentage of net sales was 9.3% for the full year 2023 as compared to 11.7% for the prior year period. Total GAAP operating expenses decreased to $439 million in 2023 as compared to $503 million in 2022, a decrease of 13%. On a non-GAAP basis, total operating expenses decreased to $342 million for 2023 as compared to $413 million in the prior period, a decrease of 17%. 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 and depreciation. Net loss for the full year 2023 reduced to $152 million or $0.51 per share, including a $14 million or $0.05 per share expense related to the extinguishment of prior debt following our Blackstone refinancing that compared to a net loss of $237 million or $0.82 per share for 2022. In the fourth quarter as Bradley mentioned, we achieved our goal of non-GAAP profitability, which was $2.6 million. Cash, cash equivalents and marketable securities were $286 million as of December 31, 2023 and that compared with $294 million at the end of 2022. Turning now to slide 14. I'm pleased to share our full year Galafold revenue growth guidance of 11% to 16% at constant exchange rates. Our full year 2023 non-GAAP operating expense guidance is $345 million to $365 million. We are pleased to share that amidst a launch year, we have kept operating expense growth minimal. As a reminder, we continue 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 for Pombiliti. There is very minimal investment in preclinical activities, which we expect to continue in 2024. Following the achievement of non-GAAP profitability in Q4 of 2023, we anticipate to achieve non-GAAP profitability for the full year of 2024 driven by our first year of well-over $0.5 billion in combined revenue and continued prudent expense management. As we think about profitability throughout the year, we anticipate a similar non-GAAP profit in Q1 2024 as we saw in Q4 2023, and non-GAAP profit is expected to build sequentially quarter-over-quarter after that. And with that, let me turn the call back over to Bradley for our closing remarks.

Great. Thanks Simon, Jeff, Sébastien, as well a huge thanks to all of our employees around the world, who I know continue to work tirelessly for people living with rare diseases. Looking at 2024, we will continue to drive significant top-line revenue growth supported by sustained double-digit Galafold performance and the successful ongoing global commercial launch, which puts us on track for our first full year of non-GAAP profitability. As I said in my opening comments, Amicus is at a major inflection point. We are strongly positioned to continue to advance our mission of delivering groundbreaking new medicines to thousands of people living with rare diseases around the world and creating value for our shareholders. With that, operator, we can now open up the call to questions.

Thank you. Our first question comes from Anupam Rama of JPMorgan.

Hi. Thank you for taking the question. This is actually Malcolm Kuno on for Anupam. So, in the US with regard to pump pay, are you seeing switches from patients that are clearly progressing or patients who are stable but just not gaining a benefit from their current treatment?

Yes, great question. I think the answer is a little bit of both. So, you know we know that some patients we've heard, I should say that some patients who were new commercial patients not in clinical studies, have heard by word of mouth or through relatives, who might be participating in those studies about how well they thought that those patients stayed in the study. And so those patients, I think were eager to start Pombiliti and Opfolda kind of regardless of their own status. And then, I know that others, I'm sure were in a declining phase, and therefore wanted to switch with the hopes of seeing different outcomes, which of course, as per the label where we have the drug is indicated for patients who are not improving on current therapies. So, I think we're seeing healthy dynamics from both of those segments.

Great. Thanks, Brad.

Thank you. One moment for our next question. And our next question comes from Ritu Baral of TD Cowen.

Good morning, guys. Thanks for taking the question. To drill down a little further on that Brad and Sebastien, how are you guys seeing clinicians in the field define the decliners and the two symposiums that world, both yours and your competitors, having spent a lot of time on defining decliners, defining stable. What do you see in your conversations during the conference on the tools that clinicians are using to define that in their own head? Have you done any market research on segmentation of the population into sort of that definition of decliner that definition of stable as you see it now?

Sure. Yes. Great question, Ritu. Thanks very much. I'm going to let Jeff talk to the first part of your question, which is sort of what are the tools and end markers that clinicians might use to follow or determine whether a patient is stable or declining. I would remind you though that the indication statement is for patients not improving on therapy, which means that either stable or declining patients are eligible for us from a market research perspective. But the work that we did leading into the launch suggested that about 50% of patients would historically be defined as stable. Although, I think Jeff will talk us through why in fact they may be suddenly declining as well. About a quarter of patients are clearly declining, and about a quarter of patients are likely in some sort of improvement phase, which is what we would expect based on historical data. But Jeff maybe talk through how physicians the obvious ways that they would look for declining patients and then maybe the not so obvious more subtle but equally important ways that patients may be declining.

Yes. Thanks, Brad. And thank you for the question Ritu. So first of all, just in terms of the follow-up typically the cadence for Pompe patients is about every six months. They come in and visit with their primary treating physician and care team. They do measure the quantitative endpoints you know on motor function, respiratory function that are cited in the trials, things like six minute walk distance, forced vital capacity, other measures of motor function and respiratory parameters. So what we see is that a lot of what they do is really more qualitative in terms of some of the formal questionnaires, but really just asking the patient how are they doing during activities of daily living. And then of course they also do look at biomarkers depending on the site they may put more or less importance on the biomarkers. So it's very much a holistic assessment of different parameters. And what we're learning is that actually does differ across sites and across countries. And one of the things that we're looking to do is trying to help in the community of physicians look at trying to standardize some of those assessments more moving forward? So in terms of, as Brad mentioned, you know it's as we look in the US, for example it's about 25% we would estimate improving, 25% clearly worsening. And then that 50% in the middle overseeing as physicians now have more treatment options and are really digging into how patients are doing. I tried to say who is declining, who is stable, who is improving. We're starting to hear that many of those patients that they might have perceived as stable, as they do that deeper holistic assessment of they're finding out that while six minute walk or forced vital capacity might be generally stable, that patients reporting having a much harder time climbing stairs or going out and doing tours or their fatigue when they're sleeping. So we do think a significant chunk of that 50% sort of stable middle patient segment is actually declining when physicians start to dig in more holistically. So it's definitely an evolving space in terms of how physicians monitor patients especially related to switching, there's been a lot of different symposium and meetings on this topic. So it's something that we'll certainly keep an eye on. But as I said, it's really this holistic approach. It's not one or two parameters that they used to define sort of status and when patients might switch and how they do after switch?

Thanks Jeff. I would think that's really the exciting opportunity. Ritu is for us to challenge the expectations of therapy. Now that as Jeff said we have more choices for physicians and patients.

Great. Thanks.

Thank you. One moment for our next question. And our next question comes from Dae Gon Ha of Stifel.

Good morning, guys. Thanks for taking our question on Pompe, if you can just remind us on the 15 that were new and not part of the expanded access or clinical trial. Did you guys ever break that down in terms of geographies? And I guess what I'm thinking about is 2024 how we should think about the cadence of patient onboarding given that you have these multiple launches going on?

Yes, thanks, Dae Gon. What we had said at the JPMorgan, which will remind you here, is those patients came roughly equally from each of the launch countries. Remember, we launched in Germany and the UK first and then the US later in the year. So we thought that was very positive. The other thing we saw, which we highlighted in the call here, is in each of those markets we're pulling and this trend continues. We're pulling kind of proportionately from the patients who are treated on the various medications. So in the US, as Sebastian highlighted, the majority of our patients are coming from Nexviazyme; that makes sense because the majority of patients in the US are not treated with Nexviazyme. And then in Europe we're pulling from both Lumizyme as well as Nexviazyme and increasingly in naive patients, which is an important segment there as well. And then to your last point, I think the color we provided here is that we're seeing the rate of new patient starts increasing at an increasing rate. So the first two months of the year and then a faster net new patient acquisition versus the months over the course of launch last year so all of those things for us point to continued building momentum and gives us great confidence in the launch.

But any visibility on ex-US versus US kind of the cadence of growth that you anticipate this year?

Yes. I think you'll see just because the US is such a larger market you'll start to see more patients coming on in the United States. I think that's just a volume point. And I think typically what we'll see is that will carry us through the various markets. The bigger markets have more patients to bring on and you'll start to see that play out.

Excellent. Thank you very much.

Thank you. One moment for our next question. And our next question comes from Joseph Schwartz, Leerink Partners.

Thanks so much and congrats on the progress. It's interesting that you're getting more switches from Nexviazyme and Lumizyme. So I was wondering, if you could talk about why that might be? Maybe give us some color in terms of the proportion of each of those sub-segments that you think might be deemed to not be improving. And yeah, just give us any color in terms of that dynamic that would be helpful. Thank you.

Thank you, Joe. A key question that many had was whether patients in markets where Nexviazyme has been established for a longer time would be too loyal, making it difficult to enter those markets. Although it's still early to draw definitive conclusions, our observations suggest otherwise. Most of the patients in the United States, as we have mentioned, are now coming from Nexviazyme, a trend that has continued into this year. Physicians and patients seem to be more concerned with their health outcomes, rather than simply which medication they are using. If a patient is stable or starting to decline, they may seek better results. Having options allows us to address those outcomes. It’s not primarily about which drug a patient is on; it’s more about their overall health and their expectations for treatment. We are eager to meet those expectations and, as Jeff pointed out, encourage physicians and patients to evaluate their current treatment more critically. So far in the U.S., most new patients are transitioning from Nexviazyme, though we are also seeing some coming from Lumizyme. Internationally, even though the market is still largely Lumizyme, we are seeing a significant number of switches from Lumizyme, along with patients transitioning from Nexviazyme and new patients as well. We believe that these dynamics are positive and will persist.

Great. Just to follow-up if I could. Does it indicate or could it indicate at all that patients on that Nexviazyme patients are essentially self-selecting to be more severe and there might be more people on Lumizyme in the United States that are satisfied and they might be harder to switch?

I don't think that's necessarily the case. I think it's likely that patients who have just started a medication, i.e. Lumizyme or Nexviazyme are going to be at a, how am I doing mode for a period of time. And that's that kind of 25% of the segment that we talked about when we did the market research, and I think physicians said about 25% of the patients are in an improving phase. I don't think patients or physicians would necessarily look to switch those patients initially. It's really more of those stable or declining patients where we have a real opportunity. And again, we estimate that's about 75% of market.

Very helpful. Thank you.

Thanks, Jeff.

Thank you. One moment for our next question. And our next question comes from Ellie Merle of UBS.

Hey guys, congrats on the progress. And thanks for taking the question. Just if you could talk a little bit more income pay in terms of the numbers of centers or physicians that you're targeting as the key prescriber base here? And I guess what proportion of these have already written a script for the possibility of full data, like you mentioned that you're seeing increasing starts at an increasing rate. Are you seeing something similar in terms of the specific new physicians? Or is it a deepening of prescriptions from those sites that were already prescribing or involved in the clinical trials?

Yeah. Great question, Ellie. So as Sebastian mentioned on the call we're seeing both increasing breadth and depth. So it's kind of both of what you asked. So the physicians who have already been writing prescriptions are continuing to write prescriptions. But then we're seeing expanding numbers of centers, in particular in the US and Germany that weren't involved in the clinical trials who are now starting to write prescriptions as well, so both of those segments are improving. I would note in the UK, all of the centers participated in the AIMS program or the Clinical Trial Program. And so they all have were already writing prescriptions and continued to do so. So I think yes, really healthy dynamic so far.

And then just of the 120 patients that you mentioned at JPMorgan I guess any color on what proportion of these are already reimbursed?

Yeah, the majority of them are already reimbursed. And I would say that as a reminder it takes about 90 days to go from prescription to commercial infusion at this point in time. So that means the people who got their prescriptions in December and January may still be in that process. But of course, as we highlighted in the call, we're continuing to add more patients into the funnel which is great. And the other thing we're seeing is that the newer commercial patients are going through the process more quickly as we continue to see possibility unfold to add to more and more formularies in the United States. And so we could we would continue to expect that number to come down as we progress through the launch. That was the same trend we saw as you might remember with Galafold as well, where it sort of started in that 90-day range. And then over time, it winnowed down to where we sit today which is around 30 days.

Great. Thanks so much.

Thank you. One moment for our next question. And the next question comes from Jeff Hung of Morgan Stanley.

Thanks for taking my question. I mean, you talked about the seasonal patterns you've seen in the past with Galafold going from Q4 to Q1. How should we think about the potential seasonal trends for Pombiliti and Opfolda? I know would you expect them to move similarly? Or do you think that maybe it doesn't apply as much this year given that the launch is still fairly early?

Yeah, good question. I think probably the answer is too soon to tell. I think in a launch year, you would expect to continue to build momentum throughout the year, which is I think a natural phenomenon as you get more and more physicians and patients with experience as we add countries over the course of the year. And so I guess, the answer is too early to tell, as we are able to provide color there going forward. Of course, we'll share that with you. But I think in general you could just expect momentum to build throughout the year given it's a larger.

Thank you.

Thank you. One moment for our next question. And our next question comes from Kristen Kluska of Cantor Fitzgerald.

Hi, good morning, everybody. The patient diagnosis growth has been really impressive. Fabry growing 70% from 2015 to 2023. So, since part of this growth came from new therapies on the market including your own. Curious how you're thinking about some of the growth we might see in the postpaid market numbers with the recent launches?

Thank you, Kristen. It’s a trend we often observe where increased involvement from more companies and the availability of additional therapeutic options lead to a heightened emphasis on diagnosis and treatment. Therefore, I wouldn't be surprised if this is contributing to growth. However, I would like to note that while Pompe is not as underdiagnosed as Fabry, we have seen substantial evidence over the past decade indicating that its prevalence is actually higher than initially reported in the literature. Jeff, could you elaborate on the data from newborn and high-risk screenings that supports the idea that Pompe should benefit from increased diagnosis moving forward?

Yeah. Thanks, Brad, and thanks for the question Kristen. There's a few dynamics leading to better diagnosis across rare diseases. One is doing better education of physicians and other importantly is a better diagnostic tools and low-cost genetic testing there. Also our newborn screening initiatives in many countries importantly in the US. So I think a lot of that is similar in Fabry and Pompe for Fabry. The extra benefit is the fact it's an X-linked dominant disease and you find one patient and then you can screen the whole family. Pompe is more of a recessive disease. So you need to find each patient independently of themselves or siblings but you know the Pompe similar to Fabry. When you look classically it was thought to be one in 40,000 more than 50,000 screening studies, both newborn as well as looking at people just with elevated CK levels, or limb-girdle muscular dystrophy weakness type symptoms. Many of them have Pompe and the Apex actual estimate of Pompe is more like one in 15,000. So two to three times more common than what has been thought. So a lot of patients still left to be diagnosed in Pompe a lot of the same underlying factors that are helping us diagnose more patients. I think Fabry is just sort of a little bit ramped up, because of that X-linked factor, but we do expect significant underlying growth of new patients, coming onto therapy being diagnosed and definitely having multiple companies helping with some of that diagnostic initiatives in education will certainly help drive that as well.

Thank you.

Thank you. One moment for our next question. And our next question comes from Salveen Richter of Goldman Sachs.

Hi this is for Shrinachal on for Salveen. Thank you for taking our question. You mentioned in the slides that your focus in 2024 is to maximize the number of patients on therapy for Pombiliti and Opfolda, is there a target number that you have in mind in this aspect and on payer coverage particularly for Medicare and Medicaid? Or when do you expect to see publish Pombiliti and Opfolda there. Thank you.

I'm sorry I just missed the first part of the question. I got the second one, can you repeat that?

Sure. In the first part I asked given that your focus is to maximize the number of patients on therapy for Pombiliti and Opfolda. Is there a target number that you have in mind that you want to achieve by the end of 2024?

Great question. As I think we've said before, we can't give guidance at this point just given the fact that it's a launch year but of course, we have our own internal targets. But I think at this point, we're still in the early part of the launch. So it wouldn't be prudent to give guidance yet, as soon as we have more color. And I'm sure going into next year, we'll be able to provide I think more clarity and more guidance on revenue in particular and we will continue from a quarterly basis to report patients on therapy as we have done. And I'll give you a flavor for the ramp As it relates to your second question. Yes, good news is as Sébastien mentioned in addition to being adding to a number of major payer formularies in that process will continue to increase and over the first few weeks of the year, we have already seen a number of patients accepted through both Medicare and Medicaid. So both government patients and private insurance patients are being accepted and getting through the process.

Thank you.

Thank you. One moment for our next question. And our next question comes from Gil Blum, Needham.

Hi. This is Ethan on for Gil. Thank you for taking our question. Moving to Fabry for a second. How important do you think your partnership with OM1 and the recent advances in AI and machine learning in general are to identifying more patients and further driving market penetration for Galafold? Thank you.

Yes, great question. I'll start but then Jeff can give more color on that collaboration. I think that machine learning will have a major impact on diagnosing, all different sorts of patients. We're already starting to see some of that. And but I'm really excited to see the outcome of that out of that partnership, and in particular in Fabry. But again, I think that will be an industry-wide and hopefully disease-wide phenomenon. But Jeff maybe, give a little bit of color on what we're doing with OM1 the partnership and what the intent is there?

Yes. Thanks for the question. So really the approach with OM1 and other similar AI electronic medical record initiatives is to create sort of a medical record fingerprint of Fabry disease so that you know all of the healthcare records or people that have given consent within a health system can have their medical records and symptoms scanned by the AI, and you basically flag a bunch of people that may well have Fabry disease and don't know it. And then testing could be offered through different programs to those patients on. We're very excited that we published on the development of the outgrowth algorithm in Fabry; it looks like it can do a very good job. And we're actually just on the cusp here of testing it in a very large academic center here in the States. And by mid-year, we should know how well that did. And we actually could see how many people are opting into potentially getting tested through the health provider. So that in February in particular, we're really excited about this because with being an X-linked disease when you find patients within a certain health care system potentially, with this type of approach, you could then also help that family find people living around the country or around the globe. You don't have to kind of screen every single health care system. We are going to certainly look to see if it's successful and valuable to see if that could be used in other systems as well. And this is not only for Fabry, there's actually been similar programs and initiatives done already for other diseases like Pompe and that has shown a similar approach works there as well.

Thank you.

Thank you. That was your last question. This concludes today's conference call and have a great day.