Amicus Therapeutics, Inc.

Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics second quarter 2023 financial results conference call-in webcast. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instructions will follow at that time. As a reminder, this conference 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, Tana. Good morning. Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics second quarter 2023 financial results and corporate highlights. Leading today's call, we have Bradley Campbell, President and Chief Executive Officer, Daphne Creamy, Chief Financial Officer, Sebastian Martel, Chief Business Officer, and Dr. Jeff Costelli, 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 may make forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business as well as our plans and prospects. Our forward-looking statements should not be regarded as representation by us that any of our plans would 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. We are cautioned not to place undue reliance on any forward-looking statements which speak only to the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, and we undertake no obligation to revise or update this presentation and conference call to reflect events or circumstances after the date hereof. For a full discussion of such forward-looking statements and the risks and uncertainties that may impact them, we refer you to the forward-looking statements and risk factors section of our annual report on Form 10-K for the year ended December 31st, 2022, and the quarterly report on Form 10-Q for the quarter ended June 30th, 2023, to be filed later today with the Securities and Exchange Commission. At this time, it's my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer. Bradley?

Great. Thank you, Andrew, and welcome everybody to our second quarter 2023 conference call. I'm very pleased to highlight what has been an incredibly successful first half of the year across our global business. As we did in this morning's press release, let me highlight several key points. First, Gallifold continues its strong performance and remains the cornerstone of our success. We remain very pleased with the commercial uptake of Gallifold globally, with $180 million in revenue for the first half of 2023. This represents 16% growth from last year on a constant currency basis, and the second quarter operational growth was 17% year over year at constant exchange rates. We continue to observe strong trends across our key performance indicators in all key geographies in the second quarter. This includes increasing demand through new patient starts from both the switch and naive populations, steady growth of in-person visits between our field team and Fabrate treaters around the world, and sustained patient compliance and adherence rates of over 90%. Growth in the second quarter was driven primarily by patient demand, and as Sebastian will highlight in a moment, we saw new patients starting on Gallifold globally throughout the second quarter at rates we haven't seen since the first few years of launch. Based on Gallifold's strong first half performance, We're pleased to be raising our full year 2023 revenue growth guidance range to 14 to 18% at constant change rates. Second, we continue to make great progress on our global regulatory filings and have now commenced the commercial launch for Pompbility and Opfolda, our novel two-component therapy for Pompe disease. Following the EC approval of Opfolda in June, the commercial launch is well underway in Germany. Our team is in the process of switching over individuals from clinical studies and expanded access programs to commercial supply. And we're pleased to share that the first patients have now been dosed with commercial products, with multiple additional patients having been scheduled to start their infusion in the coming days and weeks. Importantly, we're well on track to transition to 20 clinical trial and expanded access patients within our 90-day target. Outside of Germany, we're focused on broader patient access across Europe as we navigate the country-by-country pricing and reimbursing process. In the U.S., we've been pleased to see an increased level of engagement from the agency in recent weeks and are confident now we're on track for an FDA approval in Q3. And finally, the U.K. regulatory process for APGA was initiated in December of last year, and we have just received word this morning that the MHRA has approved Opfolda. As a reminder, MHRA previously approved Pombility and both have received orphan designation. We now expect the NICE final assessment document to come in the next few days, at which point it will take about 30 days for the NHS to provide funding to local centers to begin commercial infusions. With our international launch commenced and poised for regulatory approval in the US and additional key markets on the horizon, we look forward to providing a real choice and challenging therapeutic expectations for both physicians and the people living with Pompe disease around the world. Finally, Anikus has maintained a strong financial position as we continue to execute on the global expansion of Galfold and begin the global launch of Pompbility and Upholda. Importantly, based on the latest assumptions on approvals and launch of Pompbility and Upholda, combined with the strong growth we've seen in Galfold in the first half of the year, we are on track to achieve our target of non-GAAP profitability in the second half this year. Ahead on slide four, we're making great progress across our key strategic priorities for 2023, including sustaining double-digit Gallifold growth, now at an anticipated growth rate of 14% to 18% at constant exchange rates, securing regulatory approvals of ATGA by the FDA, EMA, and MHRA, and executing successful launches in those key markets. continuing to judiciously invest in the advancement of our best-in-class next-generation Fabre and Pompe genetic medicines and capabilities, as well as our next-generation chaperone for Fabre disease, and as always, maintaining a strong financial position as we carefully manage our expenses and investments on our path to non-GAAP profitability. With that overview, let me now hand the call over to Sebastian Martel, our Chief Business Officer, to further highlight our commercial performance.

Sebastian? Thank you, Bradley, and good morning to everyone on the call. I'll start by providing you with more detail on our Gallifold performance for the quarter. On slide six, for the second quarter of 2023, Gallifold reported revenue reached $94.3 million, driven by strong patient accruals, particularly in the U.S., but also in key European markets and Japan. Geographic breakdown of revenue during the quarter consisted of $57 million, or 61% of revenue, generated outside of the U.S. and the remaining $37 million, or 39%, coming from within the US. We're very pleased to see continued patient growth in countries across our leading markets. Turning on to slide seven, our results in the first half of the year highlighted the strength of our global commercial efforts. The demand for GalaFold globally continues to be strong, with patients added in all major markets, delivering operational growth rate of 16% over the same period in 2022 at constant exchange rates. From a year-over-year perspective, the negative impact from foreign currencies was 3% in the period, and as a result, GalaFold reported revenue growth was 13%. GalaFold continues to be the fastest-growing treatment for Fabry disease globally, and I'm pleased to report that our monthly net new patient trends continued to increase in Q2. And if you look at the growth in net patients on GalaFold globally, we've seen significant net patient gains on GalaFold at the end of the second quarter. Throughout the first half of 2023, the number of patients coming onto GalaFold has actually exceeded internal expectations, and we're therefore raising our full year 2023 revenue growth guidance to 14% to 18% growth at constant exchange rate. We ended the second quarter with about 60% of the global market share of treated amenable patients. And within the global mix, we're seeing stronger uptake in naive populations. And while we're achieving high market shares in countries where we've been approved the longest, there's also plenty of opportunity to continue to switch patients over to GalaFold and continue to grow the market as we penetrate into the diagnosed and treated and newly diagnosed segments. All of that is underpinned by impressive compliance and adherence rates, that continue to exceed 90%, reiterating our belief that those patients who go on GalaFold predominantly stay on GalaFold. As mentioned on past calls, due to a variety of factors, including uneven ordering patterns and effects fluctuations, the rate of growth within the year is typically nonlinear. We expect that to continue throughout 2023. And to support quarterly forecasting, we provide a table showing distribution of GalaFold revenue by quarter in the past five years in the appendix section of our IR presentation. On slide eight, we know that there's significant patient demand for GalaFault and that the segment of the global salary market made of those amenable mutations has the potential to surpass a billion dollar in annual revenue in around five years. We anticipate sustained growth throughout 2023 to be driven by several key growth drivers. First, continuing to penetrate into the existing markets further uptake into the diagnosed and treated population, and expanding into new geographies and label extensions. All of these efforts are supported by positive reimbursement and access mechanisms around the world. I'm pleased to share that we continue to make progress on expanding GalaFold into new markets and extending the labels. Just to name a few examples, we recently received reimbursement in Taiwan for individuals over the age of 16-year-olds. The Fabry market within Taiwan is quite sizable, with over 350 individuals diagnosed with Fabry disease. Of note, GalaFold was designated the first inline therapy for all amenable patients living with Fabry disease in Taiwan. Additionally, we've submitted the marketing authorization application in New Zealand, and we've entered into pricing and reimbursement negotiations for GalaFold in Turkey. In the longer term, we continue to see significant growth in the Fabry market globally, driven by diagnosing patients through a variety of measures, including high-risk screening, newborn screening, and other diagnostic initiatives, which we continue to support and invest in as well. With that, let me now hand the call over to Dr. Jeff Castelli, our Chief Development Officer, to highlight the regulatory updates on our ATDA program.

Jeff? Thank you, Sebastian, and good morning, everyone. Starting on slide 10, we remind everyone that late-onset Pompe is a severe and fatal neuromuscular disease and one of the most prevalent lysosomal disorders. Within LOPD, individuals may experience impaired motor function and respiratory difficulties as the disease progresses, with these potentially debilitating symptoms tending to become more serious and problematic over time, and often respiratory failure being the major cause of mortality in LOPD. Multiple publications and natural history studies continue to show that the initial benefits of treatment are often followed by continued long-term decline for many individuals. We recognize that Pompe disease continues to pose a range of health challenges for people affected by the disease, and having therapeutic options is crucial. Moving on to slide 11, we briefly outline the current regulatory status of ATGA by key markets. First, as noted in June, POMBILITY and APFOLDA, both were approved in the EU and the commercial launch is underway, as Sebastian will detail in more in the next section. And in the U.S., as Bradley noted, we're pleased to see the increased level of engagement from the agency in recent weeks and remain confident we are on track for approval in the third quarter for both components of ATGA. And finally, just this morning, we were very excited to receive the final full approval and orphan designations for both Pombility and Upholda by MHRA, and now the team can begin launching this important new therapy for people living in the UK with Pompe disease leveraging that positive reimbursement appraisal from NICE. Moving on to slide 12, we remind everyone of our ongoing clinical studies and multiple mechanisms of expanded access that support much of the early demand for ATGA. For the younger Pompe community, we continue to enroll the ongoing open label ZIP study in children up to 18 years of age living with LOPD. and have begun enrolling the open label Rosella study for children living with infantile onset Pompe disease. We have multiple expanded access programs in place in countries where we are not yet approved, and interest and momentum for ATGA continues to grow, and we're pleased to be able to provide access to those who are eligible through those programs. As a reminder, at the time of our first approvals, which was first in the EU during that last week of June, There were approximately 200 patients worldwide being treated with ATGA across the clinical extension studies and expanded access programs. And importantly, experience with ATGA is quite broad, with approximately 75 centers participating in trials in various access programs around the world. Finally, as highlighted in the pipeline slide in the appendix, for our earlier stage pipeline, we continue to focus on novel approaches for Fabry and Pompey, including gene therapies to deliver our engineered GLA and GE transgenes, and the Next Generation February chaperone program. With that, I'll turn the call back over to Sebastian to discuss the early commercial launch progress of POMBILITY and UFOLDA. Sebastian?

Thank you, Jeff. On slide 13, we outlined the initial launch progress and market opportunity for POMBILITY and UFOLDA in the EU. Pompility Plus Upfolder is approved as the first and only two-component therapy available in the EU for the treatment of adults living with late-onset pompidities. We're very pleased with the strong indication for Pompility Plus Upfolder, which addresses all adults living with LOPD. The EU market represents a sizable opportunity of $450 million plus and is a key market to support these early stages of global launch. Within Europe, there are currently around 1,300 patients estimated to be on treatment, and of that 1,300, currently 60 patients are being treated with POMBILITY plus Opfolda, and around 20 of those in Germany and Austria. As of today, we are launched in Germany with progress being made on all fronts, and we're seeing the start of a very strong uptake. Importantly, in Germany, the Federal Joint Committee, or GBA, has classified POMBILITY as a new active substance. As a result, Pompility will undergo a benefit assessment under the AMNOT process with a free pricing period, after which there will be negotiations on the final reimbursed price. Based on feedback from key treaters through our clinical development, access, and medical affairs, we're very pleased with the progress made towards transitioning patients over to commercial supply. We've been successful in engaging with the top prescribers in Germany within the first 30 days, We've also been very pleased with the positive feedback from the expanded access program, CUP, from both a physician and patient perspective. As Bradley mentioned, the first patients have been recently moved to commercial supply and more are scheduled in the coming weeks. So we're well underway to achieving our goal of converting all of the 20 or so expanded access patients and clinical trial extension patients within the first 90 days of launch. On slide 14, as you know, we've been preparing for the commercial launch of Pompility Plus a Folder, and are both excited and confident that through our world-class commercial and medical organizations, we're in a very strong position for a second successful launch at Amicus. In these early days, we're leveraging this experienced team to transition the first group of clinical trial and expanded access program patients in the EU onto commercial supplies. Given the significant overlap of treatment centers, hospitals, and physicians between Fabry and Pompe disease, we have the existing relationships with KOL and the commercial infrastructure necessary to support a seamless transition. As of today, we've had the first patients infused, and multiple additional patients are scheduled to start their infusions. Within these early days, 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 interactions with payers to demonstrate the value of Pompility Plus Up Folder. Today, we're launching in Germany, but we're also in active pricing and reimbursement discussions with additional European countries as we focus on securing broad patient access to the EU. We're working in partnership with physicians to ensure they have all the information they need on Pompility Plus Up Folder for their patients, and believe this two component therapy is poised to have a significant commercial opportunity in the EU and additional markets as they come online. As Jeff indicated from the late breaking news, we're thrilled with today's approval of MHRI approval for a folder. We also were granted often designation for a folder like we did with Pompility in the UK. Market opportunity within the UK includes more than 200 people with Pompe disease Estimated to be on treatment. 45 of these 200 individuals are already on POMBILITY plus a folder, and that's a remarkable number. Either through a clinical trial or through the Early Access Medicine Scheme. As we've mentioned previously, all leading centers across the UK have requested access to POMBILITY plus a folder through IMSS. Now that approval has been granted, our team anticipates the transition of all patients in the UK onto commercial products within 90 days. And importantly, that transition will be supported by the very positive NICE recommendation for reimbursement of POMBILITY Plus a Folder within the NHS, which is an achievement we are incredibly proud of. As stated in the guidance, NICE concluded that the cost effectiveness estimates for POMBILITY Plus a Folder showed a positive net health benefit and therefore has recommended Pompility Plus or Folda for adults with LOPD as first line and later lines of therapy. With that, I'd like to now turn the call over to Daphne Quimmy, our Chief Financial Officer, to review our financial results, guidance, and outlook. Daphne?

Thank you, Sebastian, and good morning or afternoon, everyone. Our financial overview begins on slide 16 with our income statement for the second quarter ending June 30, 2023. For the second quarter, we achieved total revenue of $94.5 million, which is a 17% increase over the same prior year period in 2022. This includes year-over-year operational revenue growth measured at constant currency exchange rates of 17% and a negligible currency impact at 0%. Cost of goods sold as a percentage of net sales was 9.6% as compared to 10.2% for the prior year period. Total GAAP operating expenses decreased to 104.2 million for the second quarter of 2023 as compared to 133.1 million in the second quarter of 2022. On a non-GAAP basis, total operating expenses decreased to 84 million for the second quarter of 2023 as compared to $119.2 million in the second quarter of 2022, primarily reflecting decreased program spend. We define non-GAAP operating expenses as research and development and SG&A expenses, excluding share-based compensation expense, loss on impairment of assets, changes in fair value of contingent consideration, and depreciation. Within other expenses in the income statement in the second quarter, we recorded approximately $11 million in unrealized foreign exchange losses. This compares to a $7 million gain in the second quarter of 2022. We are currently taking steps to mitigate our future exposure. Net loss for the second quarter of 2023 was 43.2 million, or 15 cents per share, as compared to a net loss of 62.2 million or 21 cents per share for the prior year period. Driven by the revenue growth of Gallifold and careful expense management, we continue to make progress towards our path to non-GAAP profitability in the second half of this year. As of June 30, 2023, we had approximately 287 million shares outstanding. Turning now to slide 17, with a focus on achieving non-GAAP profitability, I am pleased to share that we have revised both our revenue and operating expense guidance for the year. We are raising full-year Gallifold revenue growth guidance to 14 to 18% at constant exchange rates driven by patient demand. We are also reducing our full-year 2023 non-GAAP operating expense guidance to $330 million to $350 million. The decrease in operating expense for 2023 as compared to 2022 will be achieved by continuing to drive efficiencies and prudent expense management, offset by continued investment in Gallifols, ATGIA clinical studies, non-recurring costs for manufacturing, as well as global launch activities. We anticipate operating expenses to be nonlinear this year due to these pre-launch and launch expenses. We also expect to see a larger portion of our operating expenses allocated to G&A this year. as we align our resources to support the launch of ATGAA and the continued growth of Gallifol. Cash, cash equivalents, and marketable securities were $265.6 million as of June 30, 2023, compared to $293.6 million as of December 31, 2022. And with that, let me turn the call back over to Bradley for our closing remarks.

Great. Thanks, Daphne, Jeff, Sebastian. As you can see, we've been relentlessly focused on execution across our global business, and we look forward to embarking on this next phase of Amicus as a company with two commercial therapies. Thank you to all of our employees who have enabled us to achieve these recent corporate milestones and who are always committed to our patient-focused mission of delivering life-changing therapies to people in need. Before I hand the call over to Q&A, as you may have also seen in this morning's filing, after 15 incredible years at Amicus, Daphne, our longtime chief financial officer, leader, and friend, has decided to retire. She'll remain in her current role as CFO until we appoint her successor, at which point she'll remain on with Amicus through the end of the year in order to support a smooth transition. A search is underway, and we've already identified a number of highly qualified candidates. I also just want to add that I'm personally grateful to Daphne for your years of exemplary service here at Amicus, and in particular for helping lead us on our course to achieve non-GAAP profitability later this year. On behalf of the Amicus board of directors and the entire executive team, I'd like to take this opportunity to formally thank you. You've been a significant part of the growth at Amicus and instrumental in guiding us to the sound financial position we're in today. With that, operator, we can now open up the call to questions.

Certainly. Ladies and gentlemen, if you do have a question, please press star one one 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.

And one moment for our first question. And our first question comes from Tazeen Ahmad.

of Bank of America. Your line is open.

Hi, guys. Good morning, and thanks for taking my question. Brad, I just wanted to clarify on the timeline that you've stated forward for GAA is still expecting approval in 3Q. Do you get a sense that the responses that you gave FDA post the WUSHI inspection facility have been sufficient for the agency? If not, what do you think are the remaining gating factors regarding questions around the facility in order to get approval? Thanks.

Thanks, Nazeen. Yeah, great question. Just as a reminder, we were very pleased with the outcome of the pre-approval inspection at WUSHI. We do feel like our responses were all adequate, and the color we provided in the call here today I think is important, which is in the last few weeks we've seen an increased level of engagement from the agency, and so that gives us great confidence that we're on track for QPA approval.

One moment for our next question. And our next question will come from Anupam Rama of JMP.

Your line is open.

Hey, guys. Thanks so much for taking the question. Congrats on the progress. And, Daphne, I'll miss you at the conference this coming year. On the Gallup Hold Guidance increase, Maybe from a regional perspective, where is that coming from? Is it coming from deeper penetration in core countries or progress in some of the new emerging countries?

Yeah, I'm happy to have Sebastian add a little bit of color, but honestly, Anupam, it's coming from all of those things. So most importantly, what we're seeing is across all of our key geographies, as we mentioned on the call, rates of net new patients starts at levels that we haven't seen since the first couple of years of launch. And so clearly demand for this product is growing. But Sebastian, maybe touch on a few of the different growth drivers that Anupam highlighted and give a little bit more color there.

Yeah, I just add, you know, for example, in the US alone, remember we launched in 2018. The current rate of net new patients that we've seen in the second quarter is as strong as what we saw in 2019. So we're really in a post-COVID world as we speak, and we're seeing strong patient accruals. This is also the case in Europe. And remember, in Europe, we were launched a couple of years earlier. So, our penetration rate within the amenable population is, you know, slightly greater. And yet, we're seeing very strong demand. A lot of naive patients actually go on Ganafold when they're diagnosed. So, we've essentially established Ganafold as the, you know, new first in line treatment for Fabry patients with amenable mutations in those markets.

Yeah, maybe other things I'd highlight. Sorry, I didn't mean to cut you off. I was just going to say the other thing I'd highlight is, and Sebastian mentioned on the call, not only are we seeing great penetration rates, we're opening up new geographies. So we have some important countries coming on board this year. It's also in the backdrop of a very healthy and growing fabric market. So diagnosis continues to be strong. And as we find those patients, as a reminder, typically you find one undiagnosed Fabry patient or newly diagnosed Fabry patient. And because it's an X-linked disease, that typically leads to four to five additional family members who are diagnosed. So in addition to, I think, executing incredibly well, which we've continued to do, we're also seeing just a healthy growth of market. And as Sebastian highlighted, we're actually the fastest growing of the Fabry treatments for patients with the mental mutations.

Thanks for taking our questions.

One moment for our next question. Our next question will come from Ritu Barau of TD Cohen. Your line's open.

Good morning, guys. Thanks for taking the question. I want to go back to the WUSHI inspection and follow up on Tuzine's question. Brad, can you give any additional detail on the points of the increased level of engagement that the agency has had just wrapping all of this up? Do you think that there's any possibility of requiring a re-inspection, or do you feel that the outstanding items are addressable over, you know, written or verbal interactions? Any additional detail would be helpful.

Yes, thanks, Zee. No, we do not believe that there will be any additional inspections needed at WUSHI. We are very confident and we're very pleased with the outcome of the inspection. And again, just based on the kind of level of re-engagement we've seen, the increased level of engagement we've seen in the last couple of weeks, it feels to us, as you said, that they're wrapping things up and we feel like we're getting close to an approval here, as we suggested, on track for Q3. So we're really excited. The team is ready. We're really pleased to see the UK news this morning. So I think the momentum is building and really eager to see the remaining months of the year play out.

Got it. If I can squeeze one more in about how much supply do banks, how much supply from the open label are German and UK patients sort of sitting with before they start on the path to commercial conversion?

Yeah, we have, our target is about two years of go forward supply. Remember we've made quite a bit of it.

I'm sorry. I meant, I meant like how much supply clinic, um, how much drug supply do they have sitting at home from the open label?

Right. Right. Got it. Sorry. Thanks for the clarity. Yeah. The good news is, um, unlike Gallifold where, you know, you would typically, because it, it was, you know, long shelf life, et cetera, you know, you could, you could be sitting in kind of three months of supply of Gallifold as we were winding down the clinical studies and transitioning over to, to commercial in this case, it's a much tighter, um, uh, supply situation. And the clinical operations team at Amicus, who of course has already done this once before with Gallifold, works very closely with the medical affairs team, with the sites themselves. And so it's a really fine and precise level of supply. And that's what allows us to very carefully manage and have that goal of 90-day transition. And in Germany, so far, as I've said, you know, even in the first, you know, kind of 30 days of launch now, we are making those transitions. And we're confident we'll be able to execute that within the first 90 days. And I think likewise in the U.K. and then the U.S. when we see the approval.

Great. Thanks.

Yep.

One moment for our next question. And our next question will be coming from Ellie Merle of UBS. Your line is open.

Hey guys, thanks so much for taking the questions. Just if you could provide us a little bit more color on how you're thinking about new patient starts in Germany and the UK beyond the patients that are on expanded access. So maybe just of the 200, I think you said Pompe patients total in the UK, and I think you said 45 were already on ATGAA. How should we think about the other 150 patients and maybe what proportion might be on Nexiazyme already and just the timelines for when you expect the nice reimbursement to kick in from a revenue perspective. And then in Germany, I know you mentioned you have 20 patients already on ATGIA, but just if you could give us a sense of maybe how many Pompe patients there are in Germany and how you think about the landscape there relative to next year's items. Thanks.

Sure. I'll take some of those and then I'll ask Sebastian to add some color as well. That was a cleverly worded one question, multi-question prompt, but happy to address all of those. So first of all, yeah, the first priority, as we've said, in each of those markets, because we have such a large bolus of patients, is to convert the expanded access and clinical trial patients. But of course, in parallel, we're also working to start to begin bringing on new patients as well. We should be able to provide more color on that in the November call, but again, we're first priority low-hanging fruit patients on APGA already, and then in parallel start to bring on new patient starts as well. And then maybe Sebastian, just give the color that we know based on, you know, publicly available information, what progress has been with Nexzyme in those two markets and a sense for how large the German market is outside the 20 patients already on APGA.

Yes, thanks, Bradley. So I can share with you the breakdown between Nexiazyme and Myozyme across Europe. It's virtually 80-20 or 77%, 23% to be precise. So the vast majority of patients are still on Myozyme. Again, 77% across Europe and 23% for Nexiazyme. If you look at the the UK numbers, you know, you have them, you just quoted them early. So 200 patients total, 45, which is probably the largest number of patients we have in, you know, in a country on clinical trial plus early access. And so as Brad mentioned, you know, we think that Given the fact that the six key centers have all had experience with Pumbility and Opfolda, they will have patients transition from either clinical study or IMSS. They have experience, they've used the product before. They have obviously the feedback also from patients who have been on it. So we think that the uptake and our ability to convert commercial patients from Myozyme or Nexiazyme is high in this market. In Germany, the market is a lot more fragmented than the UK. The number of patients is also higher, somewhere between 300 and 350 total patients. We did mention here that we've got around 20 in Germany and Austria. So those, you know, will be, you know, the first patients onto commercial product. But as I mentioned, our team, you know, has been visiting top prescribers in Germany for a number of weeks now and established, you know, those contacts and will be working with those physicians to convert and switch patients from their existing treatment onto Pompility Plus or Folda over the next weeks and months.

And I think you had maybe one more question, Ellie, on the reimbursement process in the UK. So as I mentioned in the call, once you have MHRA approval, what's remarkable here is we've already had the initial recommendation for reimbursement by NICE, which we think is one of the fastest ever to get to that answer prior to MHRA approval. The process from here should take a few days to a week to get to the final approval. Patrick T. O' appraisal document by NICE. The draft is already posted, so that should come here relatively shortly. And then it takes around 30 days for NHS to provide funding to the local centers. And that's when we'll start actually converting those expanded access and clinical trial patients. But in the meantime, with the approval, our sales team can go out into the field, visit the physicians. And again, along with the medical affairs and clinical operations team can begin scheduling those infusions ahead of time. So effectively launch is underway and we're waiting about 30 days for that reimbursement process to kick in at the local centers.

Great. Thanks. Really helpful.

Thanks, Alex.

One moment for our next question. And our next question will be coming from Joseph Schwartz of Lee Ring Partners. Your line's open.

Great. Thanks very much for the update. I was wondering beyond the EAP conversion of those patients to commercial status, how should we be thinking about the cadence of uptake for ATGAA? And what metrics will you be providing us in order to gauge your progress with that? And are there any analogs that you can think of that might be helpful for us when envisioning the launch curve And then can you remind us of your most recent thoughts around pricing and how this relates to the current price of Sanofi's products? Thank you.

Yeah, thanks, Joe. All good questions. So as relates, I'll start with the last one first. As a reminder, our pricing philosophy is parity or modest discounts to standard of care. And we have shown with Gallifold that that is an incredibly successful strategy. We went through the pricing and reimbursement process with Gallifold much faster than industry average. And I think it's because the healthcare systems are recognizing that we're bringing significant value but we're pricing at roughly parity, which takes the pricing decision off the table and focuses on the value of the product. And what we saw is that way you can maximize access to therapy and maximize the number of patients on therapy as quickly as possible versus taking time to negotiate for some extra dollars on the price. And I think the nice appraisal that we saw here, which again, I think is one of the fastest ever in our industry, is a great reflection of that value that the payers are seeing. So we're confident that strategy will be very successful here, and we'll roll that out as we go through the process in Europe and the U.S. and other markets. On the first one, in terms of key performance indicators that we'll share, I think what you heard on the call today is some of the qualitative things we'll talk about in terms of getting out to see the key centers, in terms of having patients start at infusions and convert from clinical trial to commercial products. We haven't given any forward-looking guidance for this year just because it's such a stub year, but I think you'll hear on the November call that we'll provide an update on the number of commercial patients on drugs, so that'll be a nice milestone to wait for. In terms of analogs, it's so unusual to have a second-generation product launched into the rare disease space. I don't know if there are great analogs. The one thing I would point to, though, is kind of a thought experiment, perhaps, is remember, we qualified for that EAMS program in the UK about a year ago. And within a first year, remember that you can't promote on that product. It's simply offering it and it's purely demand driven. And we were able to get to a 15 to 20 percent market share. through that program alone, again, with no promotion. So for me, that gives you a great perspective on, you know, imagine what we can do once we're out there promoting the product. So we'll do our best to give good color on how the launch is going, and hopefully that gives you a flavor of how we can talk to that over the coming, you know, days and weeks. And again, November, I think, will be a really important update there. Thank you.

One moment for our next question. And our next question will be coming from Dagon Ha of Stifel.

Your line is open.

Hey, good morning, guys. Thanks for taking that question. One clarification, the slide says first patients, as in plural, has been infused with LOPD, I guess ATGA product. Just wanted to clarify that it was more than one. And then my actual question was the physician feedback and engagement in What are you guys hearing in terms of the lineup that physicians will take once ATGA becomes available as a third line? I mean, does it get kind of placed at a third line, or do you see it being used sort of in between myozyme, Nexviazyme, or Nexviazyme onto ATGA? Any color on that would be helpful. Thanks.

Yeah, thanks. So first and foremost, the feedback we've received has been incredibly positive from physicians, and we're hearing through them that the experience from patients has also been very positive. So we feel like everything is going really well. Yes, to clarify your first question, it is multiple patients have been converted, which is great, and multiple patients have been scheduled for their infusions. And we're working to schedule the remaining conversions within that 90-day target. So really, really good progress as we've gotten started here. And then, sorry, remind me the second part of your question. Oh, in terms of positioning. Yeah, so reminder in Europe, the indication statement is for all patients, late-onset Pompe disease patients. And so we'll position this, and we think this will be a great treatment option for all of those patients. Remember, though, that the vast, vast majority of the market opportunity here is patients currently on myosin. And so, you know, you should see, just like we saw with Gallifold, you should see the vast majority of growth in all of our markets coming from, you know, patients who we switch from myosin to. or NexVizine, frankly, to APGA. And I think that's an important point, right, which is the indication is for all patients with LOPD in Europe who are on label, and that means that we can target any patient on therapy or, frankly, any new patient that's diagnosed or has already been diagnosed.

And just to add to what you were saying, Brad, I think to give a little bit of color on the global opportunity from a patient standpoint. There are 3,500 to 4,000 patients being treated worldwide for Pompe disease today. We estimate that depending on the year, you've got somewhere between 100 to 200 naive patients put on treatment every year. So the commercial opportunity as of this point is really looking to switch patients, whether they are on myozyme or whether they are on nexiozyme. This is the main patient group that we're going to go after.

And the last thing I'll say there is remember, You know, the real promise of this medicine is that we're the only product in a well-controlled clinical study that shows that patients who are on an existing ERT can switch to ATGA and see improvement in six-minute walk and forced vital capacity. So we think that's a truly differentiated component of this therapy, and we're just so pleased and eager to get this out to as many patients as possible, as quickly as possible.

Great. Thanks for the caller. And Daphne, thanks so much for your service.

One moment for our next question.

And our next question will be coming from Jeff Hung of Morgan Stanley. Jeff, your line is open.

Congratulations on the MHRA approval of Upholda and congrats to Daphne on her upcoming retirement. You've reduced expenses to support your path to non-GAAP profitability. Can you just talk about the importance of that relative to further bolstering your pipeline and advancing your next-gen pipeline programs? Thanks.

Yeah, so the vast majority of our expenses go towards both the ongoing clinical studies to support the post-marketing commitments and remaining clinical studies extensions in Pompe disease, also manufacturing until recently when now we have commercial products, so that ends up showing up in cost of goods. But that's the vast majority, and then, of course, the G&A that goes along with that. We do have some modest spend towards the pipeline. And we are making, I think, good progress there. I think you should expect to hear us talk more about the pipeline as we come into next year. But you should know that this laser focus on non-GAAP profitability does include a modest amount of investment in the pipeline. That's an important part of the future of Anarchist. And again, we'll talk more about that, you know, probably coming into next year. Thank you.

One moment for our next question.

And our next question will be coming from Salveen Richter of Goldman Sachs. Your line is open.

Hi, this is Srinath Rao for Salveen. Thank you for taking our question. First on Gallifold, in your view, how much of the growth that you need to get to your prior guidance of 1 billion peak sales for Gallifold will be driven by new patient diagnoses like genetic screening, etc.? ? versus the naive patients or already diagnosed and switched patients. And on ADGA, if you could provide some more color on the reimbursement process in Germany. Thank you.

Yeah, so a couple of points there. So if you think about just the market today for Fabry, the global market, you've got a little over $2 billion in global sales. And You know, here we are sitting at, you know, with guidance of kind of 375 to 388 million. If you assume a third to half of the patients on drugs today have a minimal mutation, then, you know, you've got another maybe doubling of the current revenue base just by existing diagnosed and treated patients today. So lots of opportunity to continue to switch patients, which is great. Some of that comes through market expansion and some of that comes through execution in our existing markets. We also know if you look kind of globally, that sort of over $2 billion in global sales represents about 11,000 treated patients. And we believe there's roughly another 5,000 or 6,000 diagnosed untreated patients. And so again, if you take that kind of third to a half number, that's, you know, an additional call it 3000 or so, uh, diagnosed untreated patients who have a mental mutation. So another significant chunk of existing patients today, I think that gets you sort of well towards that, that. Peak market opportunity that we've talked about, but then as Sebastian and Jeff have highlighted in previous calls, we're seeing significant growth in the underlying diagnosis, maybe 10% or so a year. And so you put all those together, and I think it's easy to see a way towards a billion-dollar product opportunity here. And then you had asked a little bit about Germany. Maybe, Sebastian, do you want to talk to the dynamics in Germany again?

Yeah. Thanks, Bradley. So as I mentioned, in Germany, the GBA has classified mobility as a new active substance. We're very pleased with that. And as a result of that designation, Pompility will undergo benefit assessment under the MNOC process. We have, you know, a six-month free pricing period, and after that, there'll be negotiations on a final reimbursed price. So, you should expect to see an agreed upon published price sometimes around Q3 of 2024. We think we've set, you know, a competitive price for the combination of Pompility plus Opfolda versus other Pompe therapies available in the German market. And the price is, again, very much in line with the pricing policy that Bradley mentioned earlier on.

One moment for our next question.

And our next question will be coming from Krista Kluska of Cantor Fitzgerald. Your line is open.

Hi, good morning, and congrats on the additional approval this morning and also sending my best to Daphne. I know it's early days in Europe, but can you talk about what have been the biggest selling points in terms of generating interest over other therapies now that you have an approval in place beyond the prep work? So, for example, is it the mechanism, the full data set across the different patient populations, the open label, a certain endpoint that they're focusing on, or is it really just a combination of this? Thank you.

I'll hit the top. Sorry about that. I'll hit the top line and then maybe Jeff talk about the broader data that we've showed in previous calls. So, you know, from a label perspective, clearly the most important two data points are the six-minute walk test and the forced vital capacity, which As I mentioned before, we've shown significant differentiation. We're the only therapy that's shown improvement in those measures in patients who switch from existing ERT to ATGA. So I think that's a really powerful story and one that physicians will clearly focus on. But I do think another important part of this is the really broad data set that we've published now in various places. It won't necessarily show up in the label, but as we continue our medical education strategy, we'll be able to share those. So maybe, Jeff, talk about what we've already published across those other endpoints and any other call you might want to provide.

Yeah, thanks, Brad, and thanks, Krista, for the question. So, you know, as Brad noted, you know, the key there is showing the improvement on six-minute walk and FDC and the switch patients in a controlled trial. But, you know, it's really that consistency across endpoints. You know, we've shown some of that previously at a high level. We're going to continue to really focus on that here in upcoming conferences just to show, you know, the range of improvements that we're seeing across endpoints for these patients. And I'd say the other thing is the emerging durability data as well. You know, we've now shown out to four years from our phase one, two, that the initial improvements observed across naive patients, which patients in those trials have been maintained long term. So we think that that's going to be a continued focus of physicians and a strength so far of what we've seen with ATGA. You know, really strong core of data. I think the MOA is also something that, you know, gives people a reason to believe in some of those clinical observations that there is a very differentiated MOA. And that's also something that I think we're going to continue to, you know, provide publications and more information there as we continue to learn about the MOA.

And one moment for our next question. And our next question will be coming from Ethan Markowski of Needham & Company. Your line is open.

Good morning, and thanks for taking our question. Just a quick one on the current SG&A spend. So you're currently relying somewhat on the existing sales force for Gallifold, but we've definitely seen an uptick in SG&A. Just to give us an idea, now that you're rolling out, of HomeLady and looking at a U.S. launch, how much more of the SG&A spend increases we expect in the near term? Thank you.

Daphne, I'll let you talk to the accounting treatment that I think is describing a lot of that change. From an infrastructure perspective, what we've said before is we literally have hired less than a dozen employees globally to support the launch of ATJ. That includes some Amicus Assist, which is our case management hub in the United States, some patient education liaisons, some direct marketing and medical affairs people, but hugely leverageable existing commercial infrastructure. But maybe, Daphne, talk to the trends that the question was speaking to.

Yeah, sure. So I would remind everyone, in prior years, we had a portion of the support for both GalaFold and now ATGAA in the research and development line. But now as we are aligning resources to support two commercial products, some of that spend is now shifting from the R&D line to the SG&A line. So it is a bit of a – it's a classification issue when you look at current year versus prior year. Yeah, so it's not actually – Versus a true increase. Let's put it that way. Exactly.

Yeah, thanks, Daphne. So you should not expect to see significant additional increases in G&A. It was really more of a change in the classification for some of those employees who support the global business.

Thanks. That was very helpful.

Thank you. One moment for our next question. And our next question will be coming from Tazeen Ahmad of Bank of America. Your line is open.

Hi, guys. Thanks for taking my follow-up. Brad, just to maybe put people's minds at ease, in terms of going back to the GAA question about your timeline for 3Q, just because the PDUZA has officially passed, how are you getting your confidence that the FDA will provide an answer this quarter? And also, as we head into the later part of August, I think the assumption is that the folks at FDA kind of shut down for holiday. And so if it's listed into September, is there anything to read into that? Thanks.

Yeah, good questions. Thanks, Nazeen. We'll provide as much color as we can here. So the confidence really comes from two places. The first is, if you remember back when we announced the inspection, we estimated that if you look on average, even though we don't have a specific PDUFA date, on average, it takes about 30 days from the inspection to finish the inspection report, and then it's about 60 to 90 days for the agency to complete their review. And so we're kind of right in that zone. So we feel very comfortable that it's kind of in the timeline that we've seen when you look on average. And then the other piece that gives us good confidence to your point about, you know, about whether the FDA is around or not, is we have seen in the last couple of weeks an increase in the engagement by the review division, and that gives us good comfort that they're, you know, wrapping up their work, and again, we expect a decision here in Q3, and we're very confident in that.

Okay. Thanks, Brett.

Thanks, Christine.

And that was our last question. I'd like to turn the call back to Bradley Campbell for closing remarks.

Great. Thank you, everybody, for tuning in today, and hope everybody has a great day. Take care.

Ladies and gentlemen, this concludes today's conference. Thank you and have a great day.