Good morning, everyone, and welcome to the Amicus Therapeutics Second Quarter 2023 Financial Results Conference Call and webcast. This conference is being recorded. I will now hand it over to your host, Mr. Andrew Faughnan, Vice President of Investor Relations. Please proceed.

Thank you, Tana. 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 Quimi, Chief Financial Officer; Sebastien Martel, Chief Business Officer and Dr. Jeff Castelli, Chief Development Officer. Joining for Q&A is Dr. Mitchell Goldman, Chief Medical Officer and Ellen Rosenberg, Chief Legal Officer. As referenced on Slide 2, we 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 will be achieved, any or all the forward-looking statements made on this call may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. You are cautioned not to place undue reliance on any forward-looking statements, which speak only to the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and we undertake no obligation to revise or update this presentation and conference call to reflect events or circumstances after the date hereof. For a full discussion of such forward-looking statements and the risks and uncertainties that may impact them, we refer you to the forward-looking statements and risk factors section of our Annual Report on Form 10-K for the year ended December 31st, 2022 and the quarterly report on Form 10-Q for the quarter ended June 30, 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, Galafold continues its strong performance and remains the cornerstone of our success. We remain very pleased with the commercial uptake of Galafold globally with $180 million in revenue for the first half of 2023. This represents 16% growth from last year on a constant currency basis. In 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 naïve populations, steady growth of in-person visits between our field team and Fabry 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 Sebastien will highlight in a moment, we saw new patients starting on Galafold globally throughout the second quarter at rates we haven't seen since the first few years of launch. Based on Galafold'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 exchange rates. Second, we continue to make great progress on our global regulatory filings and have now commenced the commercial launch for Pombiliti 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 the 20 clinical trials 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 reimbursement 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 are on track for FDA approval in Q3. And finally, the U.K. regulatory process for AT-GAA was initiated in December of last year and we've just received word this morning that the MHRA has approved Opfolda. As a reminder, MHRA previously approved Pombiliti 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, Amicus has maintained a strong financial position as we continue to execute on the global expansion of Galafold and begin the global launch of Pombiliti in October. Importantly, based on the latest assumptions on approvals and launch of Pombiliti and Opfolda, combined with the strong growth we've seen in Galafold 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 4, we're making great progress on our key strategic priorities for 2023 including sustaining double-digit Galafold growth now at an anticipated growth rate of 14% to 18% at constant exchange rates, securing regulatory approvals of AT-GAA 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 Fabry and Pompe genetic medicines and capabilities, as well as our Next-Generation Chaperone for Fabry 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 Sebastien Martel, our Chief Business Officer to further highlight our commercial performance. Sebastien?

Thank you, Bradley and good morning to everyone on the call. I'd start by providing you with more detail on our Galafold performance for the quarter. On Slide 6, for the second quarter 2023, Galafold reported revenue reached $94.3 million, driven by strong patient accruals, particularly in the US, but also in key European markets and Japan. The 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 U.S. We're very pleased to see continued patient growth in countries across our leading markets. Turning on to Slide 7, 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 an 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 continue to increase in Q2. 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 on to Galafold has actually exceeded internal expectations and we are therefore raising our full-year 2023 revenue growth guidance to 14% to 18% growth at constant exchange rates. 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 naïve 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 have continued to exceed 90%, reiterating our belief that those patients who go on Galafold permanently stay on Galafold. As mentioned on past calls, due to a variety of factors including uneven ordering patterns and FX fluctuations, the rate of growth within the year is typically non-linear. We expect that to continue throughout 2023 and to support quarterly forecasting, we provide a table showing distribution of GAAP revenue by quarter in the past 5 years in the appendix section of our IR presentation. On Slide 8, we know that there is significant patient demand for Galafold and at the segments on the global patient bucket made of those amenable mutations has the potential to surpass $1 billion in annual revenue in around 5 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 untreated 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. The Fabry market within Taiwan is quite sizable with over 350 individuals diagnosed with Fabry disease. Of note, Galafold was designated the first-in-line therapy for all amenable patients living with Fabry disease in Taiwan. Additionally, we submitted a 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'll 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 AT-GAA program. Jeff?

Thank you, Sebastien, 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, but these potentially debilitating symptoms tend to become more serious and problematic over time, with orphan respiratory failure being a 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 AT-GAA by key markets. First, as noted in June, Pombiliti and Opfolda both were approved in the EU, and the commercial launch is underway, as Sebastien 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 Q3 for both components of AT-GAA. Finally, just this morning, we were very excited to receive the final full approval and orphan designations for both Pombiliti and Opfolda by MHRA and now the team can begin launching this important new therapy for people living in the U.K. 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 AT-GAA. 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 AT-GAA 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 AT-GAA across the clinical extension studies and expanded access programs. Importantly, experience with AT-GAA is quite broad, with approximately 75 centers participating in trials and 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 Pompe including gene therapies to deliver our engineered GLA and GAA transgenes and next generation Fabry chaperone program. With that, I will turn the call back over to Sebastien to discuss the early commercial launch progress of Pombiliti and Opfolda. Sebastien?

Thank you, Jeff. On Slide 13, we outline the initial launch progress and market opportunity for Pombiliti, Opfolda in the EU. Pombiliti+Opfolda are approved as the first and only two-component therapy available in the EU for the treatment of adults living with late-onset Pompe disease. We're very pleased with the strong indication for Pombiliti+Opfolda, which addresses all adults living with LOPD. The EU market represents a sizable opportunity of over $450 million and is a key market to support these early stages of global launch. Within Europe, there are currently around 1300 patients estimated to be on treatment and of that 1300, currently, 60 patients are being treated with Pombiliti+Opfolda and around 20 of those in Germany and Austria. As of today, we have 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 Pombiliti as a new active substance. As a result, Pombiliti will undergo the benefit assessment under the AMNOG process with a free pricing period after which there'll be negotiations and 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 from both the 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 Pombiliti+Opfolda and I'm 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 supply. 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 Pombiliti+Opfolda. Today, we launched in Germany, and we're also in active pricing and reimbursement discussions with additional European countries, as we focus on securing broad patient access through the EU. We're working in partnership with physicians to ensure they have all the information they need on Pombiliti+Opfolda 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 MHRA for Opfolda. We also were granted orphan designation for Opfolda, like we did with Pombiliti in the U.K. The 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 in Pombiliti+Opfolda, and that's a remarkable number, either through a clinical trial or through the early access to Medicine Scheme. As we've mentioned previously, all leading centers across the U.K. have requested access to Pombiliti+Opfolda through IMS. Now that approval has been granted, our team anticipates a transition of all patients in the U.K. onto commercial product within 90 days. Importantly, that transition will be supported by the very positive NICE recommendation for reimbursement of Pombiliti+Opfolda 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 Pombiliti+Opfolda showed a positive net health benefit and therefore has recommended Pombiliti+Opfolda 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 Quimi, our Chief Financial Officer, to review our financial results, guidance, and outlook. Daphne?

Thank you, Sebastien 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 a constant currency exchange rate of 17% and a negligible currency impact at 0%. Cost of goods sold as a percentage of net sales was 9.6% compared to 10.2% for the prior year period. Total GAAP operating expenses decreased to $104.2 million for the second quarter of 2023, 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 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 the 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 $0.15 per share, compared to a net loss of $62.2 million or $0.21 per share for the prior year period, driven by the revenue growth in Galafold 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'm pleased to share that we have revised both our revenue and operating expense guidance for the year. We are raising full-year Galafold 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 Galafold, AT-GAA clinical studies, nonrecurring costs for manufacturing, as well as global launch activities. We anticipate operating expenses to be non-linear this year due to the 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 AT-GAA and the continued growth of Galafold. 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've enabled us to achieve these recent corporate milestones and we're 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 long-time 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 you, 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. And our first question comes from Tazeen Ahmad of Bank of America.

Brad, 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 WuXi 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?

Just as a reminder, we were very pleased with the outcome of the pre-approval inspection at WuXi. 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 we’re on track for Q3 approval.

And our next question will come from Anupam Rama of JPM.

And Daphne I'll miss you at the conference this coming year. On the Galafold 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?

Yes, I'm happy to have Sebastian add a little bit of color, but honestly, the growth is coming from all of those things. Most importantly, what we're seeing is across all of our key geographies, as we mentioned on the call, rates of net new patient 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.

Yes, I'd just add, for example, in the U.S. 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 slightly greater, and yet we're seeing very strong demand. A lot of naïve patients actually go on Galafold when they're diagnosed. So we've essentially established Galafold as the new first-line treatment for Fabry patients with amenable mutations in those markets.

Yes, maybe on the 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 it 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 Fabry market. So diagnosis continues to be strong, and as we find those patients, as a reminder, typically, you find one undiagnosed Fabry patient, a newly diagnosed Fabry patient, because it’s an X-linked disease, that typically leads to 4 to 5 additional family members who are diagnosed. So in addition to executing incredibly well, which we’ve continued to do, we’re also seeing just a healthy market growth and, as Sebastian highlighted, we’re actually the fastest-growing of the Fabry treatments for patients with mutations.

Our next question will come from Ritu Baral of TD Cowen.

I want to go back to the WuXi inspection and follow-up on Tazeen'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 the re-inspection? Or do you feel that the outstanding items are addressable over written or verbal interactions? Any additional detail would be helpful?

No, we do not believe that there'll be any additional inspections needed at WuXi. 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 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 U.K. news this morning, so I think the momentum is building and really eager to see the remaining months of the year play out.

If I can ask one more question about how much supply the German and U.K. patients currently have from the open label before they begin the process of commercial conversion?

Yes, our target is about two years of supply moving forward. We've produced quite a bit to support this goal. Unlike Galafold, which had a longer shelf life and allowed for a three-month supply during the clinical study winding down, this situation requires tighter supply management. The clinical operations team at Amicus, who previously managed Galafold, collaborates closely with the medical affairs team and the sites. We are maintaining a precise level of supply, which helps us carefully manage the goal of a 90-day transition. In Germany, even within the first 30 days of launch, we are making those transitions, and we are confident in our ability to execute this within the first 90 days. I expect the same in the U.K. and the U.S. once we receive approval.

And our next question will be coming from Eliana Merle of UBS.

Just if you could provide us a little bit more color on how you're thinking about new patient starts in Germany and the U.K. beyond the patients that are on expanded access. So maybe just of the 200, I think you said Pompe patients total in the U.K. and I think you said 45 were already on AT-GAA. How should we think about the other 150 patients? And maybe what proportion might be on Nexviazyme 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 AT-GAA, 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 Nexviazyme?

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 props, but happy to address all those. So first of all, yes, 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 in 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, first priority low-hanging fruit patients on AT-GAA 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 publicly available information regarding the progress with Nexviazyme in those 2 markets and a sense of how large the German market is outside the 20 patients already on AT-GAA?

I can share that the breakdown between Nexviazyme and Myozyme across Europe is around 80/20, or more specifically, 77% for Myozyme and 23% for Nexviazyme. Most patients, 77% across Europe, are still using Myozyme. In the U.K., there are a total of 200 patients, with 45 likely being the largest group in a single country involved in clinical trials and early access. These patients will be the first to transition to commercial products. As Brad mentioned, the six key centers have experience with Pombiliti and Opfolda, having transitioned patients from clinical studies or IMS, which gives us confidence in the market's potential for switching commercial patients from Myozyme or Nexviazyme. In Germany, the market is more fragmented, with a higher total of around 300 to 350 patients. We've identified approximately 20 patients in Germany and Austria who will be among the first to receive the commercial product. Our team has been engaging with top prescribers in Germany for several weeks, establishing contracts and planning to switch patients from their current treatments to Pombiliti and Opfolda in the coming weeks and months.

And I think you had maybe one more question, Eli, on the reimbursement process in the U.K. 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 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 in 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, we 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.

And our next question will be coming from Joseph Schwartz of Leerink Partners.

I was wondering beyond the EAP conversion of those patients to commercial status, how should we be thinking about the cadence of uptake for AT-GAA? 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?

All good questions. So as it relates – I’ll start with the last one first, as a reminder, our pricing philosophy is parity or modest discount to standard of care. And we have shown with Galafold that, that is an incredibly successful strategy. We went through the pricing and reimbursement process with Galafold much faster than the 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. 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 some extra dollars on the price. 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, in the U.S. and in other markets. On the first one in terms of key performance indicators that we share, I think what you’ve heard on the call today are some of the qualitative things we’ll talk about in terms of getting out to see the key centers in terms of having patients started infusions and converting from clinical trials to commercial product. 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 the drug, so that will be a nice milestone to wait for. In terms of kind of analog, 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 were – we qualified for that IMS program in the U.K. 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. We were able to get to a 15% to 20% market share through that program alone, again, with no promotion. So for me, that gives you a great perspective on imagine what we can do once we’re out there promoting the product. 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 days and weeks. And again, November, I think, will be a really important update there.

And our next question will be coming from Dae Gon Ha of Stifel.

One clarification, the slides mentioned that the first patients have been infused with the AT-GAA product. I wanted to confirm that it was more than one patient. My actual question pertains to the feedback and engagement from physicians. What are you hearing regarding the position physicians will take once AT-GAA becomes available as a third-line option next year? Will it be placed as a third line, or do you anticipate it being used in between Myozyme and Nexviazyme, or from Nexviazyme to AT-GAA? Any insights on this would be appreciated.

The feedback we have received has been very positive from physicians, and they are reporting that patients are also having a positive experience. Everything is progressing well. To clarify your first question, we have successfully converted multiple patients, and many more have been scheduled for their infusions. We are working to schedule the remaining conversions within the 90-day target, so we are making good progress. Regarding your second question about positioning, in Europe, the indication statement covers all patients with late-onset Pompe disease. We believe this will be an excellent treatment option for these patients. However, it's important to note that the majority of the market opportunity lies with patients currently receiving Myozyme. Thus, similar to what we experienced with Galafold, significant growth in all our markets is expected to come from transitioning patients from Myozyme or Nexviazyme to AT-GAA. This is crucial because the indication allows us to target any patient on therapy as well as any newly diagnosed patient.

To expand on what you were saying, Brad, I want to provide some insight into the global opportunity from a patient perspective. Currently, there are between 3,500 and 4,000 patients being treated for Pompe disease worldwide. We estimate that each year, there are around 100 to 200 new patients starting treatment. Therefore, the primary commercial opportunity lies in switching patients who are currently on Myozyme or Nexviazyme, as this will be our key target demographic.

And the last thing I'll say there is, remember, 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 AT-GAA and see improvement in the 6-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.

And our next question will be coming from Jeff Hung of Morgan Stanley.

Congratulations on the MHRA approval of Opfolda 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?

Yes, so the vast majority of our expenses go towards both the ongoing clinical studies to support post-marketing commitments and remaining clinical study extensions in Pompe disease, also manufacturing until recently when now we have commercial product, 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, and that's an important part of the future of Amicus, and again we'll talk more about that probably coming into next year.

And our next question will be coming from Salveen Richter of Goldman Sachs.

This is Sinatra on for Salveen. First, regarding Galafold, how much of the growth needed to reach your previous guidance of $1 billion in peak sales for Galafold will come from new patient diagnostics like genetic screening, versus patients who are already diagnosed and switched patients? And for AT-GAA, could you provide more details on the reimbursement process in Germany?

Yes, there are a few points to consider. Currently, the global market for Fabry stands at just over $2 billion in sales, while our guidance is between $375 million and $388 million. If we estimate that one-third to half of the patients currently on treatment have amenable mutations, we could potentially double our current revenue based just on the patients who have already been diagnosed and treated. There are still significant opportunities for switching patients, which is positive. This growth can be attributed both to market expansion and effective execution in our existing markets. Looking at the data globally, the over $2 billion in sales corresponds to around 11,000 treated patients, and we estimate there are approximately 5,000 to 6,000 diagnosed but untreated patients. Assuming that one-third to half of these also have an amenable mutation, this gives us an additional roughly 3,000 diagnosed untreated patients to consider. This represents a substantial group that already exists within our market. When you combine all these factors, it becomes clear that we have a pathway towards a $1 billion product opportunity. Additionally, as previously mentioned by Sebastian and Jeff in earlier calls, we are noticing significant growth in the underlying diagnoses, around 10% annually. With all these elements taken into account, I believe we can reach our projected peak market opportunity. Now, regarding Germany, Sebastian, would you like to elaborate on the dynamics there?

So as I mentioned, in Germany, the GBA has classified Pombiliti as a new active substance, we’re very pleased with that. As a result of that designation, Pombiliti will undergo benefit assessment on the AMNOG process. We have a 6-month free pricing period and after that, there will 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 a competitive price for the combination of Pombiliti+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 early on.

And our next question will be coming from Kristen Kluska of Cantor Fitzgerald.

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 the mechanism, the full data set across the different patient populations, open label, a certain endpoint that they're focusing on? Or is it really just a combination of this?

I'll begin by discussing the top-line results, and then Jeff will address the broader data we've shared in previous calls. From a labeling standpoint, the most crucial data points are the 6-minute walk test and the forced vital capacity, where we've demonstrated significant differentiation. We are the only therapy that has shown improvement in these measures for patients transitioning from existing enzyme replacement therapy to AT-GAA. I believe this is a compelling story that will capture physicians' attention. Additionally, it's important to highlight the extensive data set we've published in various forums. While it may not be reflected in the label, we will be able to share this information as we advance our medical education strategy. So, Jeff, could you discuss what we've published on those other endpoints and any additional insights you might want to add?

As Brad noted, the key there is showing the improvement on the 6-minute walk in forced vital capacity in the switch patients in a controlled trial. But it’s really that consistency across endpoints. 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 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. We’ve now shown out to 4 years from our Phase ½ that the initial improvements observed across patients, switch 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 AT-GAA. But what’s really strong core of data, I think the MoA is also something that 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 provide publications and more information there as we continue to learn about the MoA.

And our next question will be coming from Ethan Markowski of Needham & Company.

Just a quick question about the current SG&A spending. You're currently depending somewhat on the existing sales team for Galafold, but we've certainly observed an increase in SG&A. Now that you're launching Pombiliti and preparing for a U.S. introduction, how much more of an increase in SG&A spending should we anticipate in the near term?

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 AT-GAA, that includes some Amicus Assist, which is our take management hub in the United States, so 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.

Yes, sure. I would like to remind everyone that in previous years, we allocated part of the support for both Galafold and now AT-GAA to the research and development line. However, as we are directing resources to support two commercial products, some of that spending is now being moved from the R&D line to the SG&A line. Thus, it's more of a classification issue when comparing the current year to the previous year.

Yes, so it's not actually...

...part of the true increase.

Exactly, yes. 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.

And our next question will be coming from Tazeen Ahmad of Bank of America.

Brad, to reassure everyone regarding your timeline for the third quarter in relation to the GAA question, could you share how your confidence in receiving a response from the FDA this quarter has developed since the PDUFA date has passed? Also, considering that we are approaching late August, there's a general understanding that FDA personnel might take a break for the holiday. If things push into September, should we interpret that in any particular way?

Thanks, Tazeen, we’ll provide as much color as we can here. So the confidence really comes from 2 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 50 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 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 wrapping up their work. And again, we expect the decision here in Q3, and we’re very confident in that.

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.