Amicus Therapeutics, Inc.

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 -and-answer session, and instructions will follow at that time. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Fonan, Vice President of Investor Relations. You may begin.

Great. Thank you, Deedee. Good morning. 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, Sebastian 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 two, we might make forward-looking statements within the meaning of the Private Security for Legation 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 that 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 31, 2023 to be filed today with the Securities and Exchange Commission. At this time, it is my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer. Bradley?

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 want 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, health care, 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 just shift into our financial results and outlook, and I am very pleased to highlight what tremendous progress we made across our global business last year, and to 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, Gallifold continues its strong performance, and it remains the cornerstone of our success. We are very pleased with the continued uptake of Gallifold globally. We now have over 2,400 people living with Fabri disease who take Gallifold or were taking Gallifold at the end of 2023. For the full year, that translated to Gallifold 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 Fabri treaters, and we continue to see sustained patient compliance and adherence rates of over 90%. Growth in 2023 was driven primarily by patient demand from that 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 Fabri market continues to see improved diagnosis and medical education and 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 Fabri patients and 5,000 patients who were diagnosed but 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 Gallifold for many, 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 Pombilie and Apfolda is underway, and it's off to a great start in the three largest Pompeii 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, 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 onto Pombilie and Apfolda 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 Nexvizime and Lumizime, as well as naive patients in XUS markets. So that means in the US, the majority of new patients are switching off of Nexvizime and coming onto Pombilie and Apfolda, whereas in Europe, where Lumizime 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, Sebastian will provide further color in 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, Anikus has maintained an incredibly strong financial position as we continue to execute on the expansion of Gallifold and advance the global launch of Pombilie and Apfolda.

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 half a billion combined product sales as well as prudent expense management. Two really significant milestones in the evolution of Anikus as a biotechnology company in the rare disease space. Our key strategic priorities for 2024 are laid out in the slide here for as we laid out last month, we're focused on achieving our key strategic priorities for 2024, including Number one, again, sustaining that double digit Gallifold revenue growth of 11 to 16% in constant exchange rates, continuing our successful launch of Pombilie and Apfolda and executing multiple successful new commercial launches throughout the year, advancing our ongoing studies to support our medical and scientific leadership in Fabri 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 Sebastian who can give further highlights on our commercial performance. Sebastian.

Thank you, Bradley. Good morning or good afternoon to everyone on the call. I'll start by providing you with more detail on our Gallifold performance for the year. On slide six for the full year 2023, Gallifold reported revenue reached $387.8 million. Gallifold growth in 2023 was primarily driven by strong patient demand, particularly from our leading markets. Turning to slide seven, our results in the full year highlight the strengths of our global commercial efforts. The demand for Gallifold 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 Foursquater 2023, Gallifold reported revenue of $106.6 million, up 21% or 19% at TER. We're pleased to share that 2023 was the strongest year for net new Gallifold patients since 2019. Our leading markets such as the UK, the US, EU5 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 Brad mentioned, we ended the year with more than 2,400 patients from Gallifold, which is roughly over half of the global market share of treated and medical patients. Gallifold has captured 60 to 65% of the global market share of treated and medical patients. The good news is there are still many more patients to put onto therapy. Within the global mix, which is about 43% switch and 57% naive, 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 Gallifold and keep on growing the market as we penetrate into the dynode untreated and newly dynode 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 Gallifold predominantly stay on Gallifold. As mentioned on past calls due to a variety of interviewing and even ordering patterns and effect fluctuations, the rate of growth within the year is typically non-linear. 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 US. 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 Gallifold sales that occur each quarter during a given year. Interestingly, the average of quarterly sales over the last five years corresponds precisely to what we achieve 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 Gallifold. On slide eight, we know that there's a significant patient demand for Gallifold and that the segment of the global fabric market made of patients with amenable mutation has the potential to reach up to a billion dollars 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, Fabria is one of most underdiagnosed rare diseases, so the more patients are identified, the more patients can be eligible for Gallifold. Second, the other piece is continuing to drive Gallifold's market share of treating patients through continued commercial execution. As noted, Gallifold currently has 60 to 65% of the global amenable market. But 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 a potential to reach those levels in the global market share as well. Importantly, as Bradley highlighted earlier, this is a robustly growing fabric market with a significant portion of growth coming from finding new patients and penetrating into the diagnosed untreated population. Just within the 2,400 patients on Gallifold at the end of 2023, about 1,400 of those individuals were naive to any treatment before coming on Gallifold. 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 through physicians and patient education and support programs. We'll continue to make progress on expanding Gallifold onto new markets and extended the labels. There are still some markets in the time, some in the Middle East and Asia Pacific regions where Gallifold is either newly reimbursed or we expect reimbursement. Also important to note here, we have often exclusivity in the US and Europe in addition to our 57 orange book listed patents, 41 of which provide protection into 2038 and beyond, including 11 composition of batter patents. This provides us with the opportunity to provide access to Gallifold 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-g growth for Gallifold throughout 2024 and we remain confident that our strong IP protection will provide Gallifold a long runway well into the next decade. Turning now onto Pompei d'Isil on slide 10, we outline our global launch progress with Pompiletien Opolda. So full year 2023, Pompiletien Opolda 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 Brad said and as anticipated, I would say the rate of new commercial patients coming onto Pompiletien Opolda continues to across all three markets. In the US, we continue to see a majority of patients switching from Nexia Zyme, 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 US, we're seeing patients switching from all three segments, from Myozine, Nexia Zyme, and the naive population at a proportional rate, exactly what we want to be seeing at this stage. Our launches leverage 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 were 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 Opolda. In the US and with the start of the new year, many of the large payers have already put Pombiliti and Opolda onto their respective formularies and we've also seen strong acceptance by Medicare 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 Opolda 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 Cattelli, our Chief Development Officer, to discuss the ongoing clinical studies as well as regulatory timelines. Jeff?

Jeff Cattelli, Chief Development Officer, Amicus Thank you, Sebastian, and good morning, everyone. On slide 11, we remind everyone that we continue to build the body of evidence for Pombiliti and Opolda 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 regulatory submissions for marketing 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 Rosella 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 Opolda 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 Fabri and Pompe disease. Of note, Amicus was honored with the World Symposium 2024 New Treatment Award for Pombiliti and Opolda, 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 Fabri and Pompe, including delivery of our engineered GLA and GAA transgenes and the next generation Fabri-Chaperon. With that, I would now like 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 13 with our income statement for the full year ending December 31, 2023. We had a very successful full 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, 20%. The 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 .3% for the full year 2023 as compared to .7% for the prior year period. Total gap operating expenses decreased to $439 million in 2023 as compared to $503 million in 2022, a decrease of 13%. On a non-GAP 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-GAP 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 51 cents per share, including a $14 million or 5 cents per share expense related to the extinguishment of prior debt following our Blackstone refinancing. That compared to a net loss of $237 million or 82 cents per share for 2022. In the fourth quarter, as Bradley mentioned, we achieved our goal of non-GAP 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 Garlefeld revenue growth guidance of 11 to 16% at constant exchange rates. Our full year 2023 non-GAP operating expense guidance is $345 to $365 million. We are pleased to share that amidst the 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 Pompeii, the ongoing Pompeii phase three study in countries not yet reimbursed, as well as next-generational manufacturing for Pombility. There is very minimal investment in preclinical activities, which we expect to continue in 2024. Following the achievement of non-GAP profitability in Q4 of 2023, we anticipate to achieve non-GAP profitability for the full year of 2024, driven by our first year of well over $500 million in combined revenue, as well as continued prudent expense management. As we think about profitability throughout the year, we anticipate a similar non-GAP profit in Q1 of 2024 as we saw in Q4 of 2023. Non-GAP profit is expected to build sequentially quarter over quarter after that. With that, let me turn the call back over to Bradley for our closing remarks.

Bradley Berge-Kroft Great. Thanks, Simon, Jeff, Sebastian, 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. Look, in 2024, we will continue to drive significant top-line revenue growth, supported by sustained double-digit Gallifold performance and successful ongoing global commercial launch of Pombility and Opfolda, which puts us on track for our first full year of non-GAP profitability. As I said in my opening comments, Amicus is at a 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.

Operator Thank you. Ladies and gentlemen, if you have a question, please press star 1-1 on your touchtone telephone. At this time, we request that you only ask one question. If you have any additional questions, please enter back into the queue. Thank you. One moment

for our first question. And our first question comes from

Anupam Rama of JPMorgan.

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

Yeah, 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, heard by word of mouth or through relatives who might be participating in those studies about how well they thought that those patients did in the study. And so those patients, I think, were eager to start pumbillia and apholda 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 is per the label where we, the drug is indicated for patients who are not improving on current therapy. 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 Retubarrell of TD

Kallen.

Good morning, guys. Thanks for taking the question. To drill down a little further on that, Brad and Sebastian, how are you guys seeing clinicians in the field define the decline you know, the two symposiums at World, both yours and your competitors, I think, 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? And 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.

Yeah, great question, Rutu. 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 the 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, the work that we did leading into the launch suggests 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 subtly 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.

Yeah, thanks, Brian, and thank you for the question, Rutu. So first of all, just in terms of follow-up, typically the cadence for Pompeii patients is about every six months they come in visit with their primary treating physician and care team. They do measure the quantitative endpoints on motor function, respiratory function that are studied in the trials, things like six-minute autism, sports vital capacity, other measures of motor function, respiratory parameters. 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 the patient. And then they 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 it actually does differ across sites and across countries. And one of the things that we're looking to do is trying to help the community of physicians look to try to standardize some of those assessments more moving forward. So in terms of, as Brad mentioned, 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, what we're seeing as physicians now have more treatment options and are really digging into how patients are doing to try 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 do that deeper holistic assessment. They're finding out that while six minute walk or four-spinal capacity might be generally stable and the patient's reporting having a much harder time climbing stairs or going out on doing chores 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 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 use to define sort of status and when patients might switch and how they do after switch.

Thanks, Jeff. I think that's really the exciting opportunity or two 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 Digan Ha of Stiefel.

Good morning, guys. Thanks for taking our question. On Pompeii, 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 them 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. Thanks so much.

Yeah, thanks, Digan. What we had said at the JP Morgan, which we'll 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 proportionally 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 Nexviizime. That makes sense because the majority of patients in the US are now treated with Nexviizime. And then in Europe, we're pulling from both Lumizime as well as Nexviizime and increasingly 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 patients starts increasing at an increasing rate. So the first two months of the year have been a faster net new patient acquisition versus the months over the course of the launch last year. So all of those things for us point to continued building momentum and give great confidence in the launch.

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

Yeah, 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 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, Learing Partners.

Thanks so much and congrats on the progress. It's interesting that you're getting more switches from Nexviizime than Lumizime. So I was wondering if you could talk about why that might be and maybe give us some color in terms of the proportion of each of those subsegments 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.

Yeah, thanks, Joe. I think, you know, one of the big questions that everybody had was, boy, in the markets where Nexviizime has been launched the longest, well, maybe those patients are going to be too sticky and you'll have a really hard time penetrating into those markets. I think what we've seen, you know, it's still early days, but what we've seen is no. And in fact, we're, as we said, the majority of the patients in the United States and that has continued into this year are coming from Nexviizime. So I think what really is is, you know, physicians and patients are focused much more on how they're doing, as Jeff described, versus what medication they're on. And so if a patient is stable or declining, they may be looking for better outcomes. And with choice, you have a chance to challenge those outcomes. So I don't think that it's a question of, you know, which drug am I on? I think it's a question of how am I doing? And what are my expectations for therapy? And that's where we're really excited to really challenge those expectations. And as Jeff said, drive that question for physicians and patients to think a lot more carefully about how they're performing on their current medication. So that's why I think we've seen, you know, so far in the U.S., again, with a majority of patients on Nexviizime, we're switching, you know, the majority of our new patients are switching from Nexviizime, although we are getting some Lumizime patients as well. And then outside the U.S., where it's still a majority Lumizime market, we're getting a majority of switches from Lumizime, although we are getting Nexviizime patients and we're getting naive patients as well. So we think all those dynamics are really healthy and we'll continue.

Brad, just to follow up, if I could, does it indicate or could it indicate at all that patients, that Nexviizime patients are essentially, you know, self-selecting to be more severe and there might be more people on Lumizime 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, you know, just started a medication, i.e. Lumizime or Nexviizime, are going to be in a, you know, 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. You know, I think 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 the stable or declining patients where we have a real opportunity and again we estimate that's about 75% of the market.

Very helpful. Thank you.

Thanks,

Joe.

Thank

you. One

moment for our next question. And our next question comes from Ellie

Murrell of UBS.

Hey guys, congrats on all the progress and thanks for taking the question. Just if you could tell us a little bit more in Pompeii in terms of the numbers of centers or positions that you're targeting as the key prescriber base here. And I guess what proportion of these have already written a script for Pumbility Opsolda. Like you mentioned that you're seeing increasing starts at an increasing rate. Are you seeing something similar in terms of the, you know, specific new positions or is it, you know, deepening of prescriptions from those sites that were already prescribing or involved in the clinical trials? Thanks.

Yeah, great question, Ellie. So as Samashin mentioned on the call, we're seeing both increasing breadth and depth. So it's 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 EAMS program or the clinical trial program. And so they all have, were already writing prescriptions and continue to do so. So I think really healthy, you know, dynamics so far.

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

Yeah, majority of them are already reimbursed. 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 pump ability up fold to add it to more and more formularies in the United States. And so 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 Gallifold as well, where it sort of started in that 90 day range. And then over time, windowed down to where we sit today, which is around 30 days.

Great. Thanks so much. Thank you. One moment for our next question.

And our next question comes from Jeff

Hung of Morgan Stanley.

Thanks for taking my question. You talked about the seasonal patterns you've seen in the past with Gallifold going from Q4 to Q1. How should we think about the potential seasonal trends for pump ability and up fold? 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? Thanks.

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. 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 launch year.

Thank you.

Thank you. One moment for

our next question. Our next question comes from

Kristen Kluska of Cantor Fitzgerald.

Hi. Good morning, everybody. The patient diagnosis growth has been really impressive in FABRE 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 Pompeii market numbers with the recent launches?

Yeah, thanks, Kristen. I think it's a phenomenon you typically see, right, which is when more companies are involved, when more therapeutic options are out there, I think you do tend to see an increased focus in diagnosis and treatment. So I wouldn't at all be surprised if that's part of the driver of growth. Although we would also remark, and maybe, Jeff, you can share some of the details here. While not quite as underdiagnosed as FABRE is believed to be, we, in the last sort of 10 years, have seen significant evidence that, in fact, Pompeii is significantly more prevalent than what was originally reported in the literature. So maybe, Jeff, talk a little bit about kind of the data from newborn screening and from high-risk screening that would lead us to believe that Pompeii should also benefit from increased diagnosis over time.

Yeah, thanks, Brian. Thanks for the question, Kristen. You know, there's a few dynamics that are importantly leading to better diagnosis for the disease. One is, you know, better education of physicians. Another importantly is, you know, better diagnostic tools and low-cost genetic testing. There also are newborn screening initiatives in many countries, importantly in the U.S. So I think a lot of that is similar in FABRE and Pompeii. You know, for FABRE, the extra benefit is the fact it's an excellent dominant disease and you find one patient and then you can screen the whole family. Pompeii is more of a recessive disease, so you need to find each patient independently of themselves or siblings. But, you know, Pompeii, similar to FABRE, when you look classically, it was thought to be 1 in 40,000, 1 in 50,000. You know, screening studies, both newborn as well as looking at people just with elevated CK levels or limb cortomuscular dystrophy weakness-type symptoms, many of them have Pompeii and the actual estimate of Pompeii is more like 1 in 15,000. So two to three times more common than what has been thought. So a lot of patients still have to be diagnosed in Pompeii. A lot of the same underlying factors that are helping us diagnose more patients. I think FABRE is just sort of a little bit ramped up, you know, because of that X-linked factor. But we do expect significant underlying growth of new patients coming on to therapy, being diagnosed, and definitely having multiple companies helping with some of that, you know, diagnostic initiatives and 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 Golden Facts.

Hi, this is Srinath Rao for Salveen. Thank you for taking our question. You mentioned in the slide that your focus in 2024 is to maximize the number of patients on therapy, affordability, and up-folder. Is there a target number that you have in mind in this aspect? And on fair coverage, particularly for Medicare and Medicaid, when do you expect to see coverage, affordability, and up-folder there? Thank you.

And I'm sorry, I just missed the first part of the question. I caught the second one. Can you repeat that?

Sure. The first part I meant, given that your focus in 2024 is to maximize the number of patients on therapy and affordability and up-folder, 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 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 relates to your second question, yeah, good news is, as Sebastian mentioned, in addition to being adding to a number of major payer formularies, and that process will continue to increase over the first few weeks of the year here, we have already seen a number of patients accepted through both Medicare and Medicaid. And 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 of

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 Gallupold? Thank you.

Yeah, 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, but I'm really excited to see the outcome of that partnership, in particular Fabry. But again, I think that'll 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.

Yeah, thanks for the question. So really the approach with OM1 and other, you know, 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 kind of scanned by the AI and you basically flag a bunch of people that very well have Fabry disease and don't know it. And then, you know, testing could be offered through different programs to those patients. We're very excited with, you know, we published on the development of the 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 their health provider. So that's, in Fabry in particular, we're really excited about this because, you know, with being an excellent disease, when you find patients within a certain healthcare 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 healthcare system. We are going to certainly look to see if it's successful and valuable, to see if that could be used, you know, in other systems as well. And, you know, this is not only for Fabry, there's actually been similar programs and initiatives done already for other diseases like Pompeii that have shown a similar approach work there as well. Thank you.

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