Amicus Therapeutics, Inc.

Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics Second Quarter 2024 Financial Results Conference Call and Webcast. At this time, all participants are in a listen-only mode. Later, we'll conduct a question-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 Fonin, Vice President of Investor Relations. You may begin.

Thank you. Good morning, and thank you for joining our conference call to discuss Amicus Therapeutics second quarter 2024 financial results and corporate highlights. Leading today's call, we have Bradley Campbell, President and Chief Executive Officer, Sebastian Martel, Chief Business Officer, Dr. Jeff Costelli, Chief Development Officer, and Simon Harford, Chief Financial Officer. Joining for Q&A is Dr. Mitchell Goleman, Chief Medical Officer, and Ellen Rosenberg, Chief Legal Officer. As referenced on slide two, we may make forward-looking statements within this meeting of the Private Security 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 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 dates 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 dates 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 factor sections of our annual report on Form 10-K for the year ended December 31st, 2023, and the quarterly report on Form 10-Q for the quarter ended June 30th, 2024, to be filed with the Securities and Exchange Commission today. At this time, it's my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer.

Bradley? Great. Thank you, Andrew, and welcome everyone to our second quarter 2024 conference call. I'm pleased to highlight what has been a very successful first half of the year across our global business and particularly an incredible quarter. In this time, we have continued to build on our top line revenue growth momentum to put us well on our way to our first full year of non-GAAP profitability, while also advancing our mission of bringing hope to individuals and families affected by rare diseases. As we did in this morning's press release, let me highlight several key points. First, we continued our excellent commercial execution and delivered total revenue of 127 million in the quarter, representing 34% growth year over year or 36% on a constant currency basis. This strong performance has led us to increase our total revenue guidance for the full year to 26 to 31% from 25 to 30% previously. At the product level, Gallifold continues its strong performance with $111 million in global revenue in the quarter, which represents 19% growth from last year on a constant currency basis. In the first half of the year, operational growth was 17% year-over-year at constant exchange rates, coming in at the high end of our guidance for the year. We continued to observe strong trends across our key performance indicators and all key geographies in the second quarter, including continued demand through new patient starts, both from switch and naive populations in all of our leading markets, and sustained patient compliance and adherence rates of over 90%. All of this is against the backdrop of significant growth in diagnosed and treated patients that we've highlighted previously. Eight years now after our first commercial launch, it's remarkable to see what an impact this medicine is having on people living with Fabry disease around the world. And we continue to see Gallifold serving as the foundation of our business for the next decade and beyond. Based on the sustained performance, we are increasing our full-year 2024 revenue growth guidance range for the second time. We started the year with a growth range of 11% to 16%. In May, we raised it to 13% to 17%, and now we're projecting 14% to 18%. Second, let me highlight the continued strong global commercial launch of Pompility and Outfolda, our novel therapy for late-onset Pompe disease. Pompility and Upholda has been and will continue to be a huge growth driver for us this year. We've already made great progress against our key performance indicators, which continue to demonstrate the strength of this launch. First and foremost, our number one focus for the year is to maximize the number of patients on therapy by year end. It's great to report that the rate of new commercial patients coming on Pompility and Upholda in 2024 continues to progress exceptionally well. In the second quarter, we saw the largest number of new commercial patients meaning patients who were not in our clinical studies. And as of the end of July, we had 186 patients who had been treated or scheduled for treatment. We are incredibly pleased with the demand globally from patients and physicians of this new therapy and consistently hear inspiring anecdotes from healthcare professionals around the world on how their patients are responding to Pondability and Upholda, which will continue to fuel the momentum throughout the year and beyond. Sebastian will provide more details in a moment, but the switch dynamics in the U.S., Europe, and the U.K. continue to look strong, and we're seeing great uptake in naive patients and markets outside the U.S. as well. We're also making significant progress on reimbursement front globally, and this includes moving patients more quickly through the insurance process in the U.S. as we've anticipated. Throughout the remainder of the year, we'll focus on increasing patient access as we gain reimbursement and launch in additional countries throughout Europe. On the regulatory front, we're pleased to announce that in July, the Swiss Medic approved Pompility and Upholda for adults living with late-onset Pompe disease in Switzerland. For the full year 2024, we're well on track to deliver our guidance of $62 to $57 million in global Pompility and Upholda sales, which will be a significant contributor to our growth and set us on a great course to achieve our ambition for POMOP to become the new standard of care treatment in this devastating disease. We're incredibly pleased to be providing a real choice for patients and challenging therapeutic expectations for both physicians and people living with Pompe disease. And finally, as we continue our excellent commercial execution across both therapies and prudently manage our resources, we are excited to share that Amicus was profitable on a non-GAAP basis in the second quarter, as well as the first half of the year. We are confident we'll see this number increase as we look to achieve our full year non-GAAP profitability in 2024. Ahead on slide four, as we laid out at the beginning of the year, we're focused on achieving our four key strategic priorities for 2024, including first, sustaining double-digit Gallifold revenue growth. And again, on the back of strong sales growth so far, we've raised the expected annual growth rate of Gallifold to 14% to 18%. Successfully executing on multiple commercial launches of Pompility and Opfolda, advancing our ongoing studies to support our medical and scientific leadership in Fabry and Pompe disease, and maintaining a strong financial position as we carefully manage our expenses and investments to achieve non-GAAP profitability for the full year. With that highlight, let me now hand the call over to Sebastian, who'll go through our commercial performance in more detail. Sebastian?

Thank you, Bradley, and good morning to everyone on the call. As always, I'll start by providing you with more details on our GAAP full performance for the quarter. On slide six, for the second quarter of 2024, GalaFold reported revenue reached $111 million, driven by strong patient demand, particularly from our leading markets. We ended the second quarter with more than 60% of the global market share for treated family patients with amenable mutations. And the good news is that there are still many more potential patients eligible for our therapy. As Bradley highlighted, given the continued strong performance of GalaFold throughout the second quarter, raising again our full year 2024 revenue growth guidance range to now 14 to 18%. Turning to slide seven, our results in the second quarter highlight the strengths 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 19% over the same period in 2023 at constant exchange rates. Our leading markets, such as the UK, The U.S., top new countries, and Japan remain the biggest drivers of patient demand and gives great confidence in the growth this product has over the long term. The U.S. in particular saw impressive patient demand, the highest number of net new patients seen in over five years, and we expect this trend to continue for the full year. Within the global mix, which is about 42% switch and 58% naive, we're now seeing stronger uptake in naive populations. We continue to achieve high market shares in countries where we've been approved the longest. There's plenty of opportunity to continue to switch patients over to Gallifold and to keep growing the market as we penetrate the diagnosed, untreated, 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 Gallifold predominantly stay on Gallifold. We're very pleased to see that prescribers continue to position GalaFold as the treatment of choice for amenable Fabry patients. This leadership position is supported by our continuous investment in medical education and evidence generation. I'm very pleased to recognize the first publication of the results from our own Fabry disease registry, the Follow Me registry, in July. These results were published in the Journal of Inherited Metabolic Disease and constitute a really important milestone for Amicus. as we continue to generate positive data for GalaFold. Data from the study aligns very well with previous observations from clinical trials and extends the available data supporting the real-world multi-system benefits of GalaFold. This publication, along with our ongoing medical education at Congress, is an important part of the story of this oral precision medicine and helps support the long-term growth potential we envision GalaFold will have in this growing public market. On slide eight, We know that there's a significant patient demand for GalaFord and that the segment of the global Fabry market made of patients with a medical mutation 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 drivers. First, the Fabry market is growing robustly with a significant portion of growth coming from finding new patients and reaching the diagnosed and treated population. As we mentioned previously, at the end of 2023, there were more than 2,400 individuals on GalaFold, and about 1,400 of those were individuals who were naive to any treatment before GalaFold. And those numbers obviously continue to grow this year, and we'll be pleased to report an update at our year-end results. We've seen many new patients go into treatment through newborn screening, family screening, and we continue to increase patient identification capabilities with ongoing medical education and support of novel screening initiatives. Fabry remains, unfortunately, one of the most under-diagnosed rare diseases, so the more patients that can be identified, the more patients may benefit from Gaiafol. We're also seeing many diagnosed untreated patients transition to treatment as the need for earlier treatments, especially in females, becomes better appreciated. The other piece is continuing to drive Gaiafol's market share of treated amenable patients through continued commercial execution. As noted, Galapagos currently has more than 60% of the global amenable market. What we're seeing in our most mature markets is it can reach up to 85-90% of market share. So we know that there's the potential to reach those levels in the global market share as well. And again, all of these efforts are supported by solid compliance and adherence rates through physician and patient education and support programs. Additionally, we'll continue to make progress on expanding GalaFold into new markets and extending the labels. There are still some markets in Latin America, 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 drug exclusivity in the US and Europe. And in addition to our now 61 orange book listed patents, 45 of which provide protection into 2038 and beyond, including 14 composition of matter patterns. This provides us the opportunity to continue 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 with our strong IP protection, GalaFold is a long-run way well into the next decade. Turning now to Pompe disease on slide 10, we outline our global launch progress with Pompility and Upholda. For the second quarter of 2024, Pompility and Upholda reported revenue reached $16 million. This represents an increase of 44% compared to the first quarter of 2024 and provides a strong foundation for the remainder of the year. In the US, Q2 benefited from the remaining clinical trial patients transitioning to commercial treatments, in addition to patients switching from other therapies. We continue to see a majority of patients switching from Nexviazyme, about 68%, and the remaining from Lumizyme. This means we're switching patients proportionally from both products in the US. We're also seeing a broadening and deepening of our prescriptions, with more sites coming online and multiple new prescriptions from physicians coming in at accelerated and increased rates of a Q1. Outside of the US, we're seeing patients from all three segments, some switching from myozyme, some from Nexviadime at a proportional rate to the respective market shares, and some from the naive populations. That's exactly what we want to be seeing at this stage in the launch. A few updates on the launch in Europe. We're pleased to announce that Switzerland's Swiss Medic as a proof for the long-term enzyme replacement therapy and enzyme stabilizer for adults with LOPD, another key regulatory authority who recognizes the benefits of this therapy. In Germany, we have successfully finalized key negotiations with the National Association of Statutory Health Funds, and we're very pleased with the outcome, and it continues to reflect the value health technology assessments are seeing with this therapy. The price acknowledges the added benefit of Pombility plus Opolda for LOPD patients and will be closely aligned with the price we set at launch. Additionally, we anticipate this to be an important reference point for future pricing and reimbursement discussions. In Spain, our newest launch country, we've added a significant number of patients and new prescribing accounts, all within the country's first quarter of launch. We remain very pleased with our take of Pombility and Opolda in the UK, where we've captured greater than a third of the market share within the region. With the benefit of EAMS, Pompiditi and Upholda have actually been in the market for two years in the UK, and we believe that the current market share is indicative of how this product can perform over two-year periods, which is a great example of its potential demand and uptake. Given Pompiditi and Upholda's solid commercial execution thus far, the first half of 2024 We're well on our way to deliver our full-year revenue guidance of $62 to $67 million for Pompidou Tienoprola. Moving to slide 11, very pleased with the launch momentum for the first half of the year. As Bradley mentioned earlier, there are about 196 patients that have been treated or are scheduled to be treated at the end of July. That's about 174 on therapy and the remaining 12 were scheduled. We remain very pleased with the ongoing demand for this therapy, as the rate of new commercial patients coming onto POMBILITY and APOLDA continues to increase across all three markets. Q2 in particular was a very strong quarter, having seen the largest number of new demand patients being prescribed POMBILITY and APOLDA. These are individuals not from clinical trials choosing to come onto commercial therapy. This is important that it further supports our thesis that launch momentum will continue to build throughout the year, as we move more quickly through the prescription to treatment process in the US and as we launch in new countries in Europe. Our launch has leveraged our highly experienced cross-functional teams and we've had great outreach with key opinion leaders. We're seeing an increase in depth and breadth of prescribers across all pre-markets. In Q2 alone, the global number of prescribing accounts increased by 50%. All core treating centers have been engaged And they've provided very positive feedback, feedback from both HCPs and other stakeholders as to our business approach, our support, and our 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 Pompility and Upholder. In the U.S., the largest payers have already put Pompility and Upholder onto their respective formularies. And we have also seen strong acceptance by Medicare and Medicaid. The overall time from prescription to infusion is now down to around 65 days, with payer approvals happening in around 30 days. And the last few commercial patients have actually come in significantly quicker. We believe this will continue to improve. Today, we're launching Germany, the UK, US, Australia, Spain, but we remain in active pricing and reimbursement discussions with additional major European markets, as we focus on securing broad patient access throughout the European market. Overall, we've had a very strong first half and we're very pleased with the building momentum on patient demand. Throughout the second half 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 COMBILITY and OPFOLDA across the first wave of countries, the strength of our clinical data, the depth of our experience and talent, we have at Amicus gives us great confidence in our ability to make a real difference for people living with Pompe disease. We believe Amicus is in a great position with our second commercial launch. And with that, I will hand the call over to Jeff Castelli, our chief development officer, to discuss the ongoing clinical study and regulatory timelines.

Jeff. Thank you, Sebastian, and good morning, everyone. On slide 12, we outline how we continue to build the body of evidence for Pompility and Op Fulda through our ongoing clinical studies, as well as through our amicus Pompe registry, as we also continue to execute on expanding commercial access through reimbursement dossiers and regulatory submissions. As we enter this second phase of launch, In addition to the various reimbursement dossiers that we have or are in the process of submitting, we also have multiple ongoing or planned regulatory submissions for marketing approval in new geographies throughout the year. We've just mentioned the approval in Switzerland. Additionally, we have our regulatory dossiers being reviewed in Australia and Canada, and we're working towards a submission here in Japan before the end of the year. For the younger Pompeii community, We continue to enroll the ongoing open-label ZIP study for children living with late-onset Pompe disease and the open-label Rosella study for children living with infantile-onset Pompe disease. We see this as an important opportunity to support label expansions into these patient segments in the years ahead and, very importantly, to address the significant unmet needs for these children. Through ongoing clinical studies and the amicus Pompe registry, We continue to generate evidence on the differentiated mechanism of action and on the long-term impact of palmbility and opfota across endpoints and patient populations. Our medical conference presence and publications continue to be an important part of our education efforts. Finally, as highlighted in the pipeline slide in the appendix, for our earlier stage pipeline, we continue to focus on novel approaches to next-generation therapies in Fabry and Pompe diseases. 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. Simon?

Thank you, Jeff.

Our financial overview begins on slide 14 with our income statement for the second quarter ending June 30th, 2024. For Q2, we achieved total revenue of $127 million which is a 34% increase over the same period in 2023. At constant exchange rates, revenue also grew 36%. The global geographic breakdown of total revenue during the quarter consisted of $77 million or 60% of revenue generated outside the United States and the remaining $50 million or 40% coming from within the U.S. Cost of goods sold as a percentage of net sales was 9% in Q2 2024, as compared to 10% for the prior year period staying relatively flat. Total gap operating expenses decreased to $100 million for the second quarter 2024, as compared to $104 million in the same period last year, a decrease of 4%. On a non-GAAP basis, total operating expenses decreased to $82 million for the second quarter of this year, as compared to $84 million in the same period last year, a decrease of 2%. We define non-GAAP operating expenses, research and development, and SG&A expenses, excluding stock-based compensation, loss on impairment of assets, changes in fair value of contingent consideration, restructuring charges, and depreciation and amortization. On a gap basis, net loss for the second quarter of 2024 reduced to $16 million or $0.05 per share compared to a net loss of $43 million or $0.15 per share for the second quarter of 2023. In Q2, non-GAAP net income was $18 million, or 6 cents per share, compared to a loss last year in the same period of $20 million, or 7 cents per share. Cash, cash equivalents, and marketable securities were $260 million at June 30, 2024, compared to $286 million at December 31, 2023. Turning now to slide 15, we are raising our full year 2024 total revenue guidance range to 26 to 31%, up from 25 to 30%. This is driven by the increase of our full year 2024 Garlafold revenue growth guidance, which started the year at 11 to 16%, was most recently 13% to 17%, and now is 14% to 18% at constant exchange rates. In addition, we are reiterating the guidance of $62 to $67 million for probability and off-folder sales for the full year 2024. Our full year 2024 non-GAAP operating expense guidance has been narrowed from $345 to $365 million to $345 to $360 million, or a five-cent reduction at the top end. With our commitment to full-year non-GAAP profitability during the first full year of launch for Pombility and Opfolder, we are keeping operating expense growth in low single digits year over year at the midpoint of guidance. As a reminder, we continue to have R&D commitments, including registry studies in both Fabry and Pompeii, the ongoing Pompeii Phase III study in countries which aren't yet reimbursed, as well as next-generation manufacturing for Pombility. In the second quarter of 2024, non-GAAP profitability was 18.5 million, and for the first half of 2024, $13.9 million. With our total revenue guidance of 26% to 31% growth, we remain comfortably on track for 2024 to be our first full year of non-GAAP profitability as profitability continues to accelerate in the second half of the year. And with that, let me turn the call back over to Bradley for our closing remarks. Bradley.

Thank you, Simon, Jeff, and Sebastian. As you can all see, we've been highly focused this year on our commercial execution, continuing to strengthen our financial profile, and ultimately delivering value for our shareholders. Our first half performance has laid the groundwork for us to continue to achieve our goals and fulfill our mission for delivering life-changing therapies. And with that, operator, we can now open the call to questions.

Yes. Ladies and gentlemen, if you have a question, please press star one one on your touch tone telephone. At this time, we request that you only ask one question. If you have additional questions, please enter back into the queue. Thank you. Your first question comes from, just one moment please. This question comes to the line of Tazeen Ahmad with B of A Securities. Your line is now open.

Hi, guys. Thanks for taking my questions. Good morning. Maybe, Brad, I just wanted to get a sense from you about how we should be thinking about the cadence of the Europe launch versus how the U.S. launch is going. The label languages are slightly different. And so as we gain traction in the U.S., how should we be thinking about how that could or could not be mirroring what you're seeing in Europe? Thanks.

Yeah, thanks, Suzanne. Thanks for the question. So, as you mentioned, a couple things. So, first of all, I think, you know, as you saw from the numbers today, continuing to see great progress in both markets. I think you have, you know, two different dynamics going on. In the U.S., it's the largest single market. And so, you know, the rate of new patients will continue to be strong as we go throughout the year. However, in Europe, we're adding new countries as we go. You know, we launched in Spain. We just got approval in Switzerland. We're working on other reimbursements. So, I think over the course of the year, the balance of the new patients will probably start to favor the United States, but that's just a matter of size. But overall, I think both markets are progressing extremely well. In terms of the label, as you said, and as I kind of provided on the call, we and Sebastian provided this detail as well. In Europe, we're seeing switching patients from both Myozyme and Nexviadime, as well as new patients, which are on the label there. In the U.S., we're seeing predominantly switches from Nexvizyme and some switches from Vizyme, as that's the much smaller portion of the population. So the key performance indicators we're watching are going really well, and we're excited to continue to see the momentum.

Thank you.

Your next question comes from Eliana Merle with UBS. Your line is now open.

Hey, guys. Thanks so much for taking the question. In terms of some of the dynamics in the U.S., I guess, of the patients that are switching from NexBioZyme, I guess, what are you seeing just in terms of trends of the types of patients that are switching? And in particular, I guess, what are you seeing in terms of, like, the patient average length on NexBioZyme prior to switching to palm-off things?

Yeah, thanks. I think essentially we're seeing what we had expected to see, which is the majority of patients switching from Nexviazine had been on treatment in that kind of year to two years. And that's, you know, a dynamic that we've described before. The good news is, of course, you know, there's a huge bolus of patients that are kind of rolling through that year to two years on therapy and you know, over the course of this year and into next year. And so I think, you know, we've got a large bolus of patients that we can target. We do see some patients who have switched earlier in their journey. And I would say that probably comes more from word of mouth or from knowing other patients in the community who had a positive experience with Pompili-Napfolda. And I think that's another dynamic, too, that we'll want to continue to see, which is you know, as we establish this as an important new therapy, as more physicians and more patients get experience, and hopefully those experiences will be positive, I think that creates, you know, some demand to switch earlier when they realize, you know, what Palmbelly and Upholder can do for them.

Great, thanks. Thank you.

Your next question comes to the line of Anupam Rama with JPM. Your line is now open.

Hey, guys. Thanks so much for taking the question and congrats on all the progress here. Just on the Gallipol guidance increase, should we be thinking about any type of regional variation of where growth is coming from or region or regions that are leading to this guidance increase? Thanks so much.

Maybe I'll start at a high level and then ask Sebastian to add a little color there. So, you know, Anupam, honestly, we're seeing great growth in all of our key markets, which is, you know, what you want to be seeing. But Sebastian, maybe provide a little bit of color on some of the unique elements of the U.S. and anything else that you think is relevant there.

Yeah, thanks, Brad. So, Anupam, we're seeing very strong demand for naive patients, muti diagnosed patients in the U.S. and have seen that you know, for a number of quarters now. That's actually why we've now raised, you know, guidance twice this year on GalaFold. So, you know, a growing proportion of newly diagnosed patients really are put on GalaFold as the very first line of treatment if you have amenable mutations. The number of PRS we've recorded in the first half of the year, as I said earlier, is close to the highest we've seen in the last five years. So strong, very strong performance in the U.S. We continue to see the shift that we've seen, you know, for ever since launch, actually, that a growing proportion of female with Fabry disease are also being treated. And the tendency of patients who have been diagnosed moving to treatment earlier than they may have in the past. In Europe, we're very pleased to see a bit of a similar pattern with the majority of the growth coming from naive patients. And we're seeing that in our largest markets in the UK. We're seeing great performance in Japan as well. We actually think that we have more growth upside in Japan, simply speaking. Because the Japanese business to us is our fourth largest. If you look at the whole public market, Japan is actually the second largest market. So there's no reason why Japan couldn't at some point in time become our second largest market as well. So these are sort of the key highlights on regional performance.

Thanks so much for taking our question.

Thank you.

Your next question comes from Joseph Schwartz with Lyric. Your line is now open.

Hi, all. This is Will on for Joe. Thanks for taking our question this morning and congrats on the progress this quarter. A question on Palmol. Based on the metrics for patients treated or scheduled to be treated, it seems like you've added roughly the same number of patients in the second quarter as compared to the fourth quarter. Is this within expectations and how should we think about the inflection point in the back half of the year as other geographies come online in the EU? Thank you.

Yeah, thanks for the question. I think one of the things we talked about that Sebastian highlighted is the rate of new patients this year continues to be much higher than it was last year, and that's exactly what we expected. In terms of new patient ads, I think we'll continue to build momentum as we go towards the back half of the year, especially as we open up new countries. That being said, from a revenue perspective, especially because a lot of those reimbursement and launches will be in the fourth quarter, the rate of new revenue won't change very much. But obviously next year, it'll be really important. So that's why we focus on sort of maximizing the number of patients on therapy by the end of the year, because that maximizes the run rate going into next year.

Thank you.

Your next question comes from the line of Ritu Barrel with TD Cowan. Your line is now open.

Good morning, guys. Thanks for taking the question. Congratulations on the metrics of this quarter. From our tracking survey, our pump-up tracking survey that we ran recently, we got some input and some good flavor on the competitive dynamics from Genzyme, which seemed to be quite considerable. And we're hearing that at least the Nexviazyme team over there had some very interesting messaging about Nexviazyme superiority over MiZyme, MuZyme that seemed to be resonating with some of the doctors that we surveyed. can you talk to i mean if that's the palm up counter detail can you talk to your counter counter detail on what's going on messaging wise on what defines a decliner and how the two drugs sort of stack up against each other in the field and then i've got a follow-up on insurance thanks thanks for two maybe i'll start and i'll have jeff add some color you know i would just

I won't speak to how they're detailing. But what I would say is that, you know, we're the only product that has shown in a controlled phase of the phase three and improvements in both six minute walk and forced vital capacity versus an active comparator. And for me, the most important thing here is the efficacy of the product. And I think that's a very important part of our, our label. And in fact, You may remember our promotional materials, which is pretty incredible. We can effectively say improvement is possible with this therapy. And I think that's a resonating message that we're very confident in. And I think that describes why we've had such a great launch so far. But Jeff, maybe talk a little bit more about the kinds of things that physicians are focusing on and maybe the importance of some of the other data points that they're following.

Yeah, thanks, Brad, and thanks, too, for the questions. Brad, I think you hit on the main point, which is, from an amicus perspective, we obviously are still educating people on the data from our phase three, which was largely in ERT-experienced patients, randomized, blinded, where we showed, you know, in that large group of switch patients, you know, improvements on six-minute walk FEC and the key endpoints, and it would be presented across all the endpoints in that trial. We see patients, when switching, have improvements across numerous aspects of muscle strength, quality of life, breathing, et cetera. So, you know, we're still really educating everyone about that data. Obviously, that data is, you know, one of the highest levels of evidence that you can have. And then, you know, there's still continuing education around mechanism of action and the unique differences in what we think we've built here with Pompility Now Folder. You know, moving forward, as I talked about briefly in the transcript, we are really invested in real-world evidence and the registry and looking to see how people are doing when they're on POMOP across all sorts of parameters, whether that's naive patients outside the U.S., people switching from Nix-Biozyme, people switching from Lumizyme, and we'll continue to report out that data, importantly, from our registry and other areas. And we're really excited from everything we're hearing anecdotally about the patient-physician response to POMABILITY-UP-FOLDA. But, yeah, certainly there's different messages out there, but we're really pleased with where we are today and where we're going in the future.

Great. And some of the survey focused on the reimbursement landscape, and there seems to be sort of continuing griping from some of the respondents about insurance coverage. Not that it's terrible, but we've heard anecdotes of not getting the op-folder component approved. Can you speak to how that has been going now that you got a full quarter's worth of your new J-code? Has this all mostly been resolved?

Yeah, thanks, Ritu. You know, it's funny. One thing we would remind everybody, I think when the first prescription happens, and in all of these therapies, frankly, the physician or their staff have to go through the pre-approval process. And there are two products here. But I would say that we haven't seen any patients be denied coverage for either the ERT or the small molecule. And we share the trends. We're seeing things proceed exactly as we'd hoped, which is shortening the time from prescription to infusion. We're now down to 65 days. And then shortening the insurance time too, which is now down to 30 days. So I'm sure that the very first time that the staff goes through any new, you know, therapy, you know, they have to get used to the paperwork, et cetera. And I'm sure that's what you're seeing in some of your surveys. But everything we're seeing and the facts are that we're getting patients through the system and we're getting them through much more quickly than we did at the start of the process, which is what we want to see. And, yeah, I'm sure the coding piece helps to some extent there as well.

Great. Thanks. Thank you.

Your next question comes to the line of Jeffrey Hung with Morgan Stanley.

Hi, this is Michael. Hi, this is Michael Riad. I'm for Jeff Hung. Thank you for taking our questions and congrats on the progress on all fronts. For Gallifold, given the growth you had referenced and diagnosed and treated patients with Fabry, how much more room do you think there is left for new patients to add? Just like curious as to why you saw a stronger uptake in naive patients versus switch in 2Q. Thank you.

Yeah, I'll let Jeff maybe talk a little bit more about that. But the reality is the overall market just continues to grow, and that's fueled by, you know, I think improving diagnosis through the kinds of things that Sebastian talked about. But, Jeff, maybe remind us the sort of change in market size from where we started the launch to today and then, you know, kind of what has changed in the diagnostic landscape that we think it's fueling us.

Yeah, thanks, Brian. Thanks for the question. As Brad said, it was about 10,000 patients when we launched Gallifold seven or eight years ago. It's now over 18,000 patients diagnosed. And when you look at all the numbers out there from various screening programs, whether it's newborn screening across different countries or at-risk screening of patients that likely have febre, it's clear that there are many, many more people and families living with febre that are undiagnosed today than the 18,000 that are diagnosed. So The good news is there's a lot of tailwinds on diagnosis. Medical education continues to improve so physicians know when to suspect Fabry. There's a lot more access to screening paradigms, low-cost genetic testing, a lot more education about when you diagnose a Fabry patient, if it's a late-onset male or female, about the burden of treatment and the need to treat earlier. And those are all things that Amicus, along with the other companies in the space and physicians, have really been doing from a medical education perspective. Lots of exciting developments on the kind of medical record use of AI potential to screen for people that might be suffering with that very unknowingly. Um, so, you know, as we look moving forward, we think there's going to be lots and lots of people being diagnosed. Many of them will have amenable mutations. That's something we've learned here too, that we seem to see more, a higher percentage of amenable patients and the new people being diagnosed than historically. Largely because late-onset patients are harder to diagnose. Late-onset patients tend to have medical mutations. And more and more, Galliford is a standard of care for people with this mutation. So lots of positive forces all coming together, I think, that are driving what we're seeing. And particularly in the U.S., the last thing I'll add is, you know, there is newborn screening going on in five or six states. And when they find the newborn, often that is the index patient in a family. And then there's ability to screen the families for the other three to five members that also have February that are adults and likely suffering. So lots of great tailwinds for the community in terms of finding new patients.

And I would add that, you know, everything that Jeff said is actually, you know, highlighted in the growth rate that we see for the quarter, not just for ourselves. So we were, again, the fastest growing brand for February with 19% growth. And when we look at the performance of Fibrozyme and Replaga, so the two ERTs, we estimate that the overall Fabry market growth rate from a dollar standpoint was north of 12% in the second quarter. So everything that, again, Jeff mentioned contributes to that overall healthy Fabry market growth.

Thanks so much. Appreciate all the context.

Thank you. Your next question comes to the line of Daigon Ha with Stiefel. Your line is now open.

Hey, good morning, guys. Thanks for squeezing me in here. Maybe going back to, I guess, similar to Ritu's question, you know, our channel checks also indicate that there is a lot of enthusiasm to switch over to POMOP. But I guess what's interesting is, you know, a lot of these physicians say sort of the switching impetus is dependent on progression of disease or nexiazyme not showing any meaningful benefit. Yet those same physicians also talk about how the muscle assessment or other functional assessment frequency hasn't really changed since Nexiazyme launch or POMOP launch. So kind of curious, is that part of your marketing slash commercialization strategy to maybe induce more of these assessments so that any kind of slowing of efficacy or progression of disease can be picked up quicker and therefore drive more switch? Thanks so much.

Thanks, Dagon. Yeah, you know, you're hitting a very important issue, which is this is really the first time physicians have had a real choice between products. And frankly, now they have two products that they're looking at. And so it is an element of changing expectations for therapy. You know, we focus on that actually improvement is possible, you know, maybe for the first time. So, yeah, it's very much an educational effort and it's very much Again, as patients and physicians get experience with the product, I think it will, you know, encourage them to look more closely at, you know, not just the primary measure, six-minute walk and core spinal capacity, but the other measures that may be changing subtly over time. And if we can change the expectation of those physicians and patients of what they're getting from their therapy, I think that very much favors Pompility Not Folder.

Thank you.

Hey, Brad.

One other thing I'd add real quickly there. It's definitely something we're hearing from all the physicians about now kind of the need for more standardization about how often they're monitoring their patients, what parameters they're able to measure in a given clinical visit. So that's something that amicus, I think, you know, the community is all now having to work together on as we have multiple treatments available and patients really need to be armed better with all the information about making informed treatment decisions. The other side of it from an amicus perspective is we're out there reminding people about the data that we saw, you know, in people that switched from ERT to palm up that those patients, many of them saw improvements across different parameters. So in some way, you know, stable is not necessarily you know, the best outcome, that there is potentially an opportunity to regain some function. So that's something that we're reminding people from the data we've seen.

Thank you. Your next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open.

Hi. Thank you so much for taking my question. This is Srinath Rao for Salveen. So do you see any trends that suggest that physicians are maybe preferring to switch patients from myozyme to Nexmyozyme and evaluating them on that before going to Pumbility in both ERT-experienced patients in the US as well as naive patients in Europe? And just a quick second part, you mentioned that you're now down to a 65-day lag between prescriptions to infusions. what is your best estimate around when you get to that 30 to 45-day target that you had mentioned early on?

Yeah, thanks for the questions. I think for the first one, no. I think the dynamic is really that in the U.S., as an example, Nexvizime was approved far earlier than us, so the majority of patients were already switched over, although there are some remaining patients from Mizime. And then outside the U.S., it's much more of a mixed circumstance. Excuse me. So what we've seen is that we're taking switch patients from kind of each segment equally. And I think that reflects that we're making very good headway with the launch and that their physicians aren't preferencing switching to Nexviazine first. I think it's just a reflection that we weren't available before. Excuse me. And then in the second case, as relates to the time to infusion from prescription, Our goal is really by the end of this year, we should be down to that 30 to 45 days. That's kind of the journey we were on with Gallifold. By the end of the first full year of launch, we were down to sort of 30 plus days. The one difference here, the reason why we sort of say 30 to 45 days is, you know, these patients come in every other week for an infusion. So you probably have a two week kind of infusion window as well. But yeah, we're looking to do that by the end of this year.

Thank you.

Your next question comes from the line of Kristen Kluska with Cantor Fitzgerald. Your line is now open.

Hi, this is Rick Miller on for Kristen. Thanks for taking our question. Just one from us. For POMBILITY plus OPFOLDA, can you comment on the prescriber mix you're seeing? Does this break down across larger academic centers versus community settings? And are there any other interesting trends that you're seeing on that front? Thanks.

Yeah, great question. I think Sebastian highlighted one of the most important metrics, which is the number of prescribers globally has increased by 50%, and that's really important. We want to see continued breadth, i.e. new prescribers. We also want to see continued depth, which we're seeing as well, which is prescribers adding their second or third or fourth prescription. So both of those dynamics have been really strong. To your question in terms of where are they coming from, Again, I think it depends on the market. So a market like the UK, which is very concentrated, all of the key centers are prescribing. In markets like Germany and the US, you do have a top prescriber base, and we're seeing great penetration into those. But you also have sort of, you know, just because of the size of the geography and the more distribution of physicians, And now we're starting to see more and more, I would say, distal physicians that are prescribing as well. And so those are dynamics we'll continue to speak to.

And so far, we're seeing great uptake in both of those segments.

Thank you. That was your last question.

This concludes today's conference. Have a great day.