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spk12: Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics second quarter 2022 financial results conference call and webcast. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. Should anyone require assistance during the conference, please press star then zero on your touchtone telephone. As a reminder, this call is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Fonning. Executive Director of Investor Relations. Please go ahead.
spk01: Thank you, Cole. Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics' second quarter 2022 financial results and corporate highlights. Leading today's call, we have Bradley Campbell, President and Chief Executive Officer, Daphne Queamy, Chief Financial Officer, Sebastian Martel, Chief Business Officer, and Dr. Jeff Costelli, Chief Development Officer. Joining for Q&A is Dr. Mitchell Goldman. 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 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. 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 and on our quarterly report Form 10-Q for the quarter-ended June 30, 2022, to be filed later today with the Securities and Exchange Commission. At this time, it is my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer.
spk10: Brad? Great. Thank you, Andrew, and welcome, everyone, to our second quarter 2022 results conference call. Before we dive into the results of the quarter, I'd just like to start with a deep thank you to John Crowley. As planned after 17 great years leading Amicus as our founding CEO, John has officially assumed the role of executive chairman of Amicus for a two-year term, after which he is expected to continue as the non-executive chairman of the board. It has been an honor working alongside him for 16 of those years, and it's been through his leadership and unwavering commitment to all of those living with rare diseases that Amicus is in such a great position today. I'm honored now to assume the role of president and CEO and very excited about the opportunities that lie ahead. Amicus has strong business fundamentals and a positive momentum to build on. We are poised now for the next chapter of our growth as we seek to get our second medicine approved and launched around the world. I firmly believe that we have the right people and the right assets to deliver on our mission to continue to bring great medicines to people living with rare diseases and create great value for our shareholders. Building on our commitment to patients, leadership of rare diseases, and global operating platform, I am confident that we can achieve those two objectives. With that, let me get started on today's update. I'm pleased to highlight the successful first half of the year across our business. And as we did in this morning's press release, let me highlight several key accomplishments. First, Gallifold continues its strong performance and remains the cornerstone of our success. We continue to be very pleased with the uptake of Gallifold globally, despite the significant foreign currency headwinds that spaced our industry this year. The first half of the year represented 11% reported revenue growth or 18% in an operational revenue growth basis. In the second quarter, operationally, our growth and key performance indicators are meeting or exceeding our objectives in all key geographies, and we are reiterating our guidance at constant exchange rates. Sebastian Martel, our Chief Business Officer, will provide further detail later in the call. We are also excited to announce that the Gallifold Intellectual Property Estate continues to grow this quarter. This year alone, we have strengthened our IP estate through the issuance of 17 new patents. There are now 44 Orange Book-listed issued patents related to Gallifold in the United States, 28 of which provide protection to 2038 and beyond, and importantly include three newly issued composition of matter patents, bringing the total now to four. We see this patent portfolio, along with our orphan drug exclusivities, providing broad and long-term intellectual property rights well into the late 2030s for this novel precision medicine. And importantly, we believe we are well positioned to address any potential generic challenges to our patents. Looking ahead, we expect continued growth for Gallifold this year, and with this strengthened IT protection, continue to believe it has a long runway well into the next decade. Second, we continue to make progress on our global regulatory filings for APGAA, our novel next-generation therapy for Pompe disease. The US and EU regulatory reviews are progressing very well, and we're very pleased with the level of engagement from both regulatory agencies. Clearly, all eyes are on the FDA inspection at the Wuxi Biologics Facility for APB200, the biologic component of APGAA. We remain in active dialogue with the agency on how best to support an inspection, and we, along with our colleagues at Wuxi, are fully ready to welcome FDA inspectors to the Wuxi facility in China. However, as of today, they have not yet conducted their inspection, If the FDA inspection does not take place in the appropriate time, it goes without saying that it could impact the timing of approval. That being said, the good news is we are in late-stage label discussions and are highly confident in ATGA's potential approval in the United States. And at this time, we continue to expect that the two components of ATGA will be approved together by the October 29th action date. Importantly, in Europe, we're now actively engaged with the EMA on the marketing authorization applications for ATGA We continue to expect a positive CHMP opinion later this year and commercial launch at early 2023. And as a reminder, the EMA has indicated it does not require an inspection of the WUSHI manufacturing site as a condition of their approval. I'm also extremely pleased today with the level of interest we are seeing in our expanded access programs globally. Today, we announced the first reimbursed access to ATGA has been granted in France under their Compassionate Access Program, which was formerly known as the Nonative ATU Program. Additional access programs are in place in the United States, United Kingdom, Germany, and Japan, with a growing number of patients participating in each. Across all of our ongoing clinical studies and access programs, there are now more than 175 patients on ATGA today, which we believe represents 5% or more of the total treated Pompe patients around the world. Our global launch plans continue to move ahead, including pre-launch activities, targeted investments, and additional personnel to support the launch significant investments in the launch and inventory preparations. We are now closer to having another potential treatment option for patients living with Pompe disease, both in the United States and Europe, with further regulatory applications planned in the months ahead. And third, importantly, Anikis has maintained a strong financial position and remains committed to achieving profitability in 2023, as we continue to execute on the global expansion of Galfold and prepare for the global launch of ATGA. we are rapidly approaching two pivotal inflection points for amicus. First, the global launch of a second rare disease medicine with ATGAA, and second, achieving profitability. These are rare feats that we believe will enable amicus to truly enter the upper echelon of rare disease-focused biotechnology companies. I'll emphasize that we are sharply focused on three key objectives, continuing to advance GalaFold to as many patients in as many geographies as possible, securing approvals for and launching APGA globally, and ensuring the financial strength of Amicus. On slide five, we see we're well on our way now towards achieving our key strategic priorities for this year, including continuing to drive Gallifold to more people living with Fabray with amenable variants in existing and in new markets. We look to achieve double-digit global product revenue growth at 15 to 20% with revenue of $350 million to $365 million in constant exchange rates. This reflects the strong momentum and demand behind this precision medicine globally. We remain steadfast in our commitment to advancing APGA regulatory filings and initiating the anticipated launch of APGA in the United States. Leveraging our seasoned global commercial team and experience across all areas needed for an effective drug launch, we are fully prepared and anticipate a very successful launch for APGA. We are strategically advancing our best in class next generation genetic medicines and capabilities. And again, we will continue to maintain a strong financial position as we carefully manage our expenses and investments going forward. With that overview, let me now hand the call over to Sebastian Martel, our Chief Business Officer, who can further highlight the Gallifold performance. Sebastian?
spk08: Thank you, Bradley, and good morning to everyone on the call. I'll start by providing you with more details on our Gallifold performance for the quarter. On slide seven, as you can see, for the second quarter of 2022, Total product revenue reached $80.7 million, driven by strong patient accruals, partly offset by foreign currency impacts, as well as the timing of orders in certain ex-US markets. The geographic breakdown of our revenue during the quarter consisted of $53 million, or 66% of revenue generated outside of the US, and the remaining $28 million, or 34%, coming from within the US. This is roughly in line with a 70-30 split that we expect as we continue to grow both parts of the business. Turning to slide eight, our results in the first half of the year highlight the strengths of our global commercial efforts. The business continues to be incredibly resilient with patients added in all major markets and an operational growth rate of 17.8% over the first half of 2021 at constant exchange rates. The negative impact from foreign currencies was 6.9% in the first half of the year. And as a result, Ganaful reported revenue growth was 10.9% in the first half of 2022. Just to add a bit of color on our geographical performance, in the first half of the year, our sales in the US grew 16.1% at CR, while our ex-US sales grew 18.5% at CR. So Ganaful continues to be the fastest growing product for Fabry disease globally. and has been the greatest contributor to global fabric market growth over the last 12 months. I'm pleased to report that our monthly net patient trends continue to show positive signals. So for example, the three-month trend is higher than the six-month, which is itself higher than the 12-month. In the US in June, we also delivered the highest number of net new patients and PRS since April of 2021. And if you look at the growth in net patients on GalaFold on a global basis, which is perhaps the truest measure of our underlying business performance, we see greater than 19% growth in patients on GalaFold at the end of Q2 this year versus the same period last year. So all indications of the continued demand for GalaFold. We ended the second quarter with a little under half of the global market share for treated amenable patients. And while the global mix remains about 55% switch and 45% naive, In many, many geographies, we're starting to see stronger uptake in naive populations. So while we're achieving high market shares in countries where we've been approved the longest, there's still plenty of opportunity to continue to switch patients over to GalaFold and to continue to grow the market as we penetrate into the diagnosed untreated segment and the newly diagnosed segment. All of that is underpinned by impressive compliance and variance rates that continue to exceed 90%, reiterating our belief that those patients who go on GalaFold generally stay on Gallifold. We did experience some impact due to the timing of orders in the second quarter, and we expect this nonlinear quarterly growth to continue. This order pattern led to a handful of orders being recognized in the beginning of the third quarter. Importantly, the value of Gallifold continues to be recognized by payers, as we have a very strong track record of successfully negotiating and renegotiating reimbursement outside of the U.S. Our relentless focus remains on ensuring access to GalaFold for anyone committed. Next, on slide nine, what we've seen so far this year is that GalaFold uptake continues to track very well, and we're seeing growth across all our major markets, as well as most of our smaller markets. We're on track to achieve full-year revenue guidance of 15% to 20% growth at constant exchange rate, and our first half growth of 17.8%. at CR is right in the middle of that range. So altogether, we view this as a great first half of the year. Moving to slide 10, we know that Galliford has the potential to surpass $500 million in annual revenue over the next few years through three key growth drivers. First, continuing to penetrate into existing markets. Second, expanding into new geographies. And third, broadening the labels. I'm pleased to share that we're making continued progress on expanding into new markets. And just to name a few examples, we expect marketing authorization in Turkey this year. We have five in the second quarter in Hong Kong. And in Chile, we're in pricing and reimbursement discussions. In the longer term, we continue to see significant growth in the overall fabric market globally. This will be driven by diagnosing patients through a variety of measures, including high-risk screening, newborn screening, and other diagnostics initiatives which we continue to support and invest in as well. And finally, we have often exclusivity in the U.S. and Europe, in addition to our now 44 arranged book-listed patents that gives us IP coverage into the late 2030s, 28 of which provide protection through 2038. And that includes three new composition of matter patents. So this gives us opportunity to provide access to GALAFO globally for a long time to come. On slide 11, let's shift gears and I'll provide you here with an update on our launch preparations for ATGA as we're poised for another successful product launch. So unlike when we launched GalaFold and at the time we were hiring and building the commercial infrastructure from scratch, we now have a presence in over 40 countries around the world, including all the major markets. That team will be largely the same that will launch ATGA, with only a handful of UFTs needed, for example, cake managers, PELs. We have experience across all areas that are needed for a successful drug launch, from regulatory to commercial, supply chain, experience with payers, reimbursement and access, and in addition, and maybe most importantly, the key relationships with physicians. We're confident in our world-class commercial organization. We will leverage their experience and relationships and deliver ATGA to people living with Pompe disease around the world. From the team, the medical education, the published phase three data in the highly regarded Lancet Neurology Journal, our experience with reimbursement and access around the world, and again, all the strategic planning that we're doing together with our partners at WUSHI Biologics, we believe we're in a very strong position for a second successful launch of Amicus. With that, let me now hand the call over to Dr. Jeff Cassidy, our Chief Development Officer to highlight our ATGA program pipeline update.
spk15: Yes? Thank you, Sebastian, and good morning, everyone. Moving on to slide 13, we'll start with our ATGA program. We recognize that Pompe disease poses a range of health challenges for people affected by the disease, and having therapeutic options is crucial. Pompe is a severe and fatal neuromuscular disease and one of the most prevalent lysosomal disorders. We've now seen multiple publications in natural history studies that highlight the initial benefit of treatment, often being followed by continued long-term decline on key measures of disease for many individuals. Slide 14 presents a summary of the primary and key secondary endpoints from our phase three study. As a reminder, prepared randomized study addressing and assessing the efficacy and safety of ATGA in adult treatment naive and ERT-experienced participants with late-onset Pompe disease, or LOPD, against the approved therapy, Alglucosidase-alpha. Propel is the only controlled clinical trial to date that included this ERT-experienced patient set, which represents one of the greatest groups of patients with unmet needs. Endpoints across motor function, muscle strength, pulmonary function, patient-reported outcomes, and key biomarkers, including the two most recognized endpoints in Pompe, six-minute walk distance and forced vital capacity, shown here on the slide, favored ATGAA over aglucosidase alpha in the overall population. We believe this consistency of effect across the key disease manifestations illustrates the potential impact of ATGAA for patients living with Pompe. Additionally, in the ERT experience population, where 95 participants were on the standard of care for more than seven and a half years on average, which is generally associated with the decline phase of disease for most patients. We actually saw an increase in six-minute walk distance and stabilization in FDC, which both achieved nominal statistical superiority versus the current treatment and showed a clinically meaningful outcome never before seen in this population. Moving on to slide 15, Adding to the overall body of data behind ATGA, at the 2022 MDA Clinical and Scientific Conference earlier this year, the ANICUS team presented positive long-term data from the Phase 1-2 study of ATGA. As seen here on the slide, these latest data continue to represent very meaningful and durable improvements in functional outcomes, as well as persistent reductions in key biomarkers of muscle damage and disease substrate out to three years. These results have been shared with the regulatory authorities in the US and EU as part of their ongoing reviews. Comparing these results with what is known about the natural history of both untreated and ERT-experienced Pompe patients, these durable results give great hope that ATGA indeed has the potential to become the new global standard of care for people living with Pompe disease. On slide 16, we've highlighted key updates on the ATGA program. First, on the regulatory progress, last year the U.S. FDA accepted for review the BLA for Ciproglucosidase Alpha and the NDA for Miglisat, the two components of ATGA. In May, the agency extended the PDUFA action dates to August 29th for the NDA and October 29th of 2022 for the BLA. As Bradley mentioned, we expect these filings will be approved together by the October 29th action date. dependent, again, on the ability for FDA to conduct an inspection at the WUSHI manufacturing facility. We've also shared that the MEA has been submitted to the European Medicines Agency and is under review. The CHMP opinion is expected later this year. Of note, the EMA has indicated in writing that based on the extensive and prior manufacturing inspections of the WUSHI facility, an inspection is not required for ATGA approval in Europe. Third, we now have multiple expanded access programs in place, including in the U.S., U.K., Germany, France, Japan, and others. This includes the EAMS framework that we announced in which ATJ was granted a positive scientific opinion through the Early Access to Medicine Scheme by the U.K.' 's NHRA. This positive opinion recognizes the high unmet medical needs faced by the Pompeii community and permits eligible adults living with LOPD who have received Aglaucosidase Alpha for at least two years to switch to ATGA, granting access prior to marketing authorization in the UK. As Bradley mentioned, we're seeing significant enthusiasm for ATGA under the EAMS mechanism, with multiple physicians now having requested access across all the leading pump-based centers in the UK, and dozens of patients now receiving this novel two-component treatment. Since the positive scientific opinion, interest, and momentum for ATGA has grown, and we are pleased to be able to provide access to those who are eligible in the UK. In France, as Brad also noted, the National Agency for the Medicines and Health Products Safety granted the first reimbursed access to ATGA under their Compassionate Access Program, formerly known as a nominative ATU program. With this growth in our access programs, we're pleased to report that now more than 175 patients worldwide are being treated with ATGA across our clinical extension studies and our expanded access programs. And we expect that to continue to grow. For the younger Pompe community, we continue to enroll the ongoing open label study in children up to 18 years of age living with LOPD and expect to expand into patients with infantile onset Pompe disease or IOPD later this year. Importantly, in response to the many requests for treatment that we continue to receive for children living with both LOPD and IOPD, our expanded access programs continue to increase. On slide 17, we just announced today an early stage program to explore next generation pharmacological chaperones for Fabry disease through an academic research collaboration agreement with the University of Seville. This new collaboration will search for innovative small molecules with optimal activity and pharmacokinetic properties. Driven by both the science and the needs of people living with Fabry, we will be reviewing Fabry compounds based on several attributes, including potency, number of addressable amenable mutations, and dosing. Of note, the agreement costs at this point are very modest, and we do not expect our fiscal year operating and will not impact our fiscal year operating expense guidance. With that, I would like to now turn the call over to Daphne Kleeme, our Chief Financial Officer, to review our financial results, guidance, and outlook. Daphne?
spk05: Thank you, Jeff, and good morning, everyone. Our financial overview begins on slide 19 with an overview of our second quarter revenue performance and impacts of foreign currency exchange rates. For the second quarter, we achieved Gallifold revenue of $80.7 million, which is a 4.3% increase over the same period in 2021. This includes operational revenue growth of 12.9% offset by a negative currency impact of 8.6%. Given a majority of Gallifold revenue is generated outside of the U.S., we see significant FX exposure to our reported revenue numbers. The Euro, the British Pound, and the Japanese Yen are the currencies our ex-U.S. sales are most exposed to, and on a year-to-date basis, these FX rates have declined by 8%, 10%, and 15% respectively. Applying average July 2022 foreign currency exchange rates, the impact on 2022 full-year Gallifold reported sales would be a negative impact of approximately 9% or $26 million. Slide 20 outlines our income statement for the second quarter ending June 30, 2022. Cost of goods sold as a percentage of net sales was 10.2% in the year as compared to 10.8% for the prior year period. Total gap operating expenses were $133.1 million in the second quarter as compared to $107.9 million in the second quarter of 2021. The increase included non-recurring expenses related to the reprioritization of the gene therapy portfolio. On a non-GAAP basis, total operating expenses were $119.2 million in the second quarter as compared to $93.5 million in the second quarter of 2021. We define non-GAAP operating expense as research and development and SG&A expenses, excluding share-based compensation expense, loss on impairment of assets, changes in fair value of consideration, and depreciation. Net loss for the second quarter of 2022 was 62.2 million, or 21 cents per share, as compared to a net loss of 51.2 million, or 19 cents per share, for the prior year period. At June 30, 2022, we had approximately 280 million shares outstanding. This year, we expect total non-GAAP operating expenses to be at the lower end of our guidance range of $470 million to $485 million, driven by continued investment in the global GALIFO launch and ATGAA clinical studies and prelaunch activities. As we highlighted previously, this guidance also includes an approximate $70 million related to certain non-recurring costs for the manufacture of ATGAA to support the global launch, as well as commitments for the gene therapy portfolio. Importantly, in 2023 and beyond, we would expect non-GAAP operating expense levels to decline below levels we saw in 2021. Turning now to slide 21, we continue to operate from a position of financial strength and remain on track to achieve non-GAAP profitability in 2023, as defined in our press release. We will focus the majority of our investments on our core value-driving franchises in Fabry disease and Pompe disease by continuing to deliver on the global growth of Gallifold, securing approvals and launching ATGAA globally, as well as driving efficiencies, cost savings, and careful expense management. A few comments about our cash position and 2022 financial guidance. Cash, cash equivalents, and marketable securities were $386.8 million at June 30, 2022, compared to $482.5 million at December 31, 2021. Our full-year Gallifold revenue guidance is $350 million to $365 million at constant foreign currency exchange rates, in addition to our non-GAAP operating expense guidance of the lower end of $470 million to $485 million. And with that, let me turn the call back over to Bradley for closing remarks.
spk10: Great. Thank you, Daphne, Jeff, Sebastian, Andrew, and thanks to all of our employees around the world who continue to work tirelessly for people living with rare diseases. And with that, operator, we can now turn the call over to you to open up for questions. Thank you.
spk12: Ladies and gentlemen, if you have a question, please press star and then the number one key on your touch-tone phone. At this time, we ask that you only ask one question. If you have additional questions, please enter back into the queue. If your question has been answered or you wish to remove yourself from queue, please press star then two. Once again, that is star then one to ask your question. And our first question today will come from Anupam Rama with JP Morgan. Please go ahead.
spk03: Hey, guys. Thanks so much for taking the question, and Brad, congrats on ascending to the CEO role. We all knew it was coming, but congrats again, man. Thank you. Brad, I've gotten a couple inbounds on your opening comments that perhaps you sounded a little bit more cautious or hedged around the WUSHI manufacturing inspection. So what is your level of confidence here that the inspection is completed in the near term? and we get a timely sort of approval of ATTA. Thanks.
spk10: Yeah, thanks, Anupam, and appreciate the congratulations. So, yeah, look, we just wanted to be very straightforward with where we are with WUSHI. We continue to be extremely prepared and with our partners at WUSHI to welcome the inspectors in. We're working very collaboratively and are in active dialogue with the inspectors. I think we still have plenty of time for an inspection to be conducted. We just wanted to state, you know, what I guess is fairly obvious, that if that doesn't happen ahead of the October PDUFA date, then there is an opportunity then for delay. But right now, as we said on the call, we remain confident that both products would be approved at the same time and confident that we can hit that October 29th PDUFA date.
spk13: Thanks so much for taking our question.
spk12: And our next question will come from Ritu Baral with Cowan. Please go ahead.
spk04: Good morning. Thanks for taking the questions. And congrats, Brad. It's been a long time coming. Glad to see you in the seat. Thank you. I wanted to ask about the labeling discussions with FDA and how to appropriately frame expectations for how what you see as the likely label will help you address the Pompe market as you see it. And if I can also ask the flip side to that for Europe, I think you guys have the day 120 questions at this point. How would you answer that? How EMA or CHMP is going down the path of helping you address the broadest possible market and get the broadest label?
spk10: Yeah, thanks for two. So, yeah, we are really pleased with where we are with both agencies. And, of course, the reviews are separate, although I think the scenarios you could play out are the same with each. We'll start with the FDA. And I think based on where we are, we are highly confident. The most important thing is in approval. And we're highly confident that we will have a label that will allow us to be successful in our commercialization of ATGAA. I think the most important thing that we're focused on that we've continued to reiterate is that we have what we think is a highly differentiated product, in particular based on the very compelling data that Jeff reviewed around showing nominal statistically significant improvements in six-minute walk and the switch population, as well as stabilization of force vital capacity. Those data have never been seen before in a well-controlled study. And we think those are the most important data to have within the label to be successful. As long as we have those data and as long as we're in line with where we are with the discussion today, I think we're very confident that we'll be able to address the commercial need and the commercial market for ATGAA. I think it's important to remember that there's roughly 3,200 patients on ATGAA today. And so that represents the vast majority of the unmet need in in Pompe disease. And so based on where we are, we're very confident we'll have a successful label to support those patients. I think in Europe, again, it's a separate discussion. And I think the same, you know, scenarios could play out there. I think the same emphasis is there in terms of making sure that we have those key data in the label. We're, Confident that the progress there reflects, again, a very successful outcome, and we're eager to conclude that and looking forward to potential approvals at the end of this year and launching early next year.
spk13: Thanks. And our next question will come.
spk10: Go ahead. I was just going to say, let me just clarify. I think I said last time 3,200 patients on ATGA. It's 3,200 patients on standard of care.
spk12: And our next question will come from Joseph Swartz with SBB Lerink. Please go ahead.
spk11: Thanks so much. I was wondering if you can talk a little bit more about the expanded access experience to date for ATGAA, and are there any unifying characteristics or patient segments that are identifiable here in the adoption to date, and do you think that it's likely that any of these patterns might carry over to the marketplace if and hopefully when ATGA is approved.
spk10: Yeah, thanks, Joe. So first of all, you know, really excited to have the first reimbursed access for ATGA through the Compassionate Access Program in France. I think that's just a really important milestone, exciting, and hopefully a bellwether for more to come. And, you know, I would say there are a few broad buckets of those access programs. Of course, part of it is just our ongoing clinical trial patients who are primarily late onset patients who came into our studies in phase two and phase three. The biggest cohort of patients is the EAMS access program in the UK. And we think that's really important because it's a label that reflects the unmet need in Pompe disease. And it provides an opportunity for patients and for physicians to, in I think a completely kind of unaffected way from amicus, it's not a promotional program, allows them to select going on to ATGA. And I think that population who are, as Jeff mentioned, required to be on therapy for two years before being eligible for access to ATGA. I think that represents the vast majority of the market today, and seeing, I think, a strong preference and strong utilization, now more than a dozen patients entering in that program, I think is a great example of what we can see in the future. And then we do, of course, also see a variety of patients who are either infantile onset, who are really looking for some opportunity for better outcomes, as well as pediatric and some later onset patients as well in other markets. I think that just demonstrates, you know, the unmet need that remains out there and the hope that we can provide with APGA, and we're very much looking forward to continuing to be able to serve those markets over time.
spk11: Thank you very much.
spk12: And our next question will come from Ellie Merle with UVA. Please go ahead.
spk00: Hello. Hey, guys. Thanks for taking the question. Just a follow-up on the U.S. manufacturing inspection. I guess, you know, when typically in the review cycle would you expect the inspection to occur by? And I guess how long ahead of the October 29th PDUFA would it need to be scheduled by for you to be confident that it could be completed ahead of the PDUFA? I guess just in terms of like, you know, the scheduling and how long it would take, you know, one schedule, just any color. that you could give on that. And then just a quick one on Gallifold. You mentioned that in June you saw the highest number of new patients in the U.S. on Gallifold. Is this something that you expect just around seasonality or is this sort of a broader trend that you expect to continue?
spk10: Thanks. Thanks, Ellie. I'll let Sebastian take the Gallifold question. and provide additional color there. But starting in the WUSHI inspection, look, I think we've said before, there are a variety of options the FDA can utilize to support an inspection. There could be paper-based, there could be hybrid, there could be direct inspections from folks from the United States, and we're prepared to support any one of those. We actually know just recently that WUSHI supported a virtual inspection, a paper-based inspection from a different regulatory authority We also know they just hosted the U.S. Commerce Department who inspected on that unverified list. So we know inspectors are able to get in and inspectors are able to be conducted. In terms of timing, you know, don't want to get too cute there, but I think we just wanted to be, you know, fully clear that we're prepared to support an inspection. We're confident that we're poised for approval, but just acknowledge that that does need to happen prior to the PDUCA day in order for the approval to go forward at that point. And then, Sebastian, I want to address Eli's question on the U.S. Gallifold dynamics and maybe broadly what we're seeing in Gallifold.
spk08: Absolutely. Thanks, Eli, for the question. I think that, you know, you asked whether there was some degree of seasonality in what we've seen in the U.S. of late, and my answer would be not really. This is more related to the level of activity that we've seen. Clearly, our interaction with HCPs has been picking up significantly. When we compare beginning of this year versus beginning of last year, we've seen in some countries almost a tenfold increase in face-to-face interaction. That's having an impact. Also, a second element that we're seeing in the U.S. is we continue to see an increase in the number of prescribers of GalaFold, so unique prescribers of GalaFold continue to increase, so we have more physicians And, you know, the trend that we've seen over the last few months in the U.S., you know, seems to continue to play here with July. So we're in a good situation in the U.S.A.
spk13: Great. Thanks.
spk12: And our next question will come from with steeple. Please go ahead.
spk02: Great. Good morning. Thanks for taking my questions and congrats on all the progress. A question from me is on the 2023 financial guidance. Maybe for Daphne, can you speak to the sensitivity around your 2023 projections of non-GAAP profitability and how the non-GAAP OPEX is being lower than 21? I just saw the footnote on the press release where it does kind of talk about the variability and predictability. I just wanted to get a little bit color around that sensitivity. Thank you.
spk10: Yeah, Daphne, do you want to address that?
spk05: Sure. Yeah. Thanks for the question, Dagon. So I think that the comment is really coming from the fact that we do have some, especially in the R&D space, we have some expenses that we've experienced over the past few years, specifically related to ATGAA for the manufacturer of the product. Once it is approved, that spending will move over to the balance sheet and flow through the income statement and cost of goods sold. So there's a large piece of that OPEX that will no longer be there. So when we look out into the future, that's the largest piece, I would say, that's driving that commentary. There is also some expenses this year that are non-recurring in nature as related to the reprioritization of the gene therapy portfolio. So those are expenses that we have this year that will not occur in the future. So it's really related to those two items predominantly is where that comment is coming from.
spk02: Okay, great. Thanks so much for the call. Thanks, Dagan.
spk12: And our next question will come from Salveen Richter with Goldman Sachs. Please go ahead.
spk09: Hey, good morning. This is Matt on for Salveen. Could you guys please just give us an update on the Fabry gene therapy program and then also the next generation chaperones you mentioned? Thank you.
spk10: Yeah, Jeff, maybe I'll start and then I'll kick it over to you. As a reminder, we continue to have, we think, very differentiated approaches in both Fabry and Pompe gene therapy, and those are still important programs for us. We continue to move those technologies forward, but I think in a very measured and targeted way, given the reprioritization of our program, with the idea that I think there are some broader gene therapy questions we're still looking to answer before we can put those forward into the clinic. But I will say, you know, as relates to the next generation chaperone. I think that's a reflection of Amicus's commitment to continue to be at the forefront of developing new therapies for anything for Fabry or Pompe. And, you know, while it's early, I think it's an exciting opportunity for us there. But maybe, Jeff, you can give a little bit more color.
spk15: Yeah, thanks, Brad. And nothing really to add on the Fabry gene therapy in addition to what Bradley commented on. And, you know, for that Fabry chaperone discovery process, collaboration you know we're very excited to enter that it's very early stage you know as we have meaningful data we will you know present that at conferences but right now you know it's it's really trying to see if there's a way to expand the number of amenable mutations that we could you know benefit more patients with a small molecule chaperone and then just you know related to that see if we can improve some of what we believe is an already very strong profile for Gallifold but just see if there's additional benefit we can bring to February patients through a chaperone. But we will provide updates as they come.
spk13: Great. Thank you.
spk12: And our next question will come from Kristen Klauska with Kendra Fitzgerald. Go ahead. Go ahead.
spk06: Good morning. This is Rick on for Kristen. Thank you for taking our question. What, if any, effect do you believe the foreign exchange headwinds could have on the 70-30 split that you've talked about in ex-U.S. and U.S. sales as you grow the Gallifold business? And how are you thinking about this effect as you continue to guide toward expanding into new markets? Thank you.
spk10: Yeah, I think as you saw, and I'm getting a little echo on the line, but I think as you saw, there were slightly greater distribution of revenue coming from the U.S. this year versus ex-U.S., so I think it was like 33% versus 67%, which is still near that 70-30, but that just shows, I would say, the slight impact on Europe. I think in general, going forward, we would expect that 70-30 split on average. To your point, as new markets come on, you do see those will typically be outside the United States. But of course, it's all different currencies. So we're not in the business of predicting FX around the world globally. But I think the most important thing is the growth rates between the two remain strong. We continue to expect significant growth in the U.S., significant growth outside the U.S. And roughly over time, that should balance out to about 70%, 30%.
spk13: Thanks.
spk12: And once again, if you would like to ask a question, please press star then 1. Our next question will come from Ziqiang Xu with Barenburg. Please go ahead.
spk14: Hi, good morning. Thanks for taking my questions and congrats on the progress as well. I want to ask about the EOS 516. You talked about ongoing support of studies on LOPD and IOPD. Can you talk about the implications there and how that relates to your label discussion? And secondly, just looking at Gallifold sales in the first half and four-year guidance, considering the negative impacts on foreign exchange, it looks like the second half, they will be pretty flat, considering the foreign exchange. provide a bit of color on that. Thank you.
spk10: Maybe I'll take the end of that question first, and then, Jeff, you can come back to the development strategy and how it will impact the label over time. So as it relates to Gallifold growth, look, you know, we're not in the business of predicting foreign exchange rates, but I think we've just said, as a point in time, what could the impact be on the actual reported revenue? For us, the most important thing is the underlying business remains strong, remains growing and growing robustly. And I think that point that Sebastian made around the 19% growth from this time last year in terms of patients, that's really the business demand, right? So that's really how the business is growing. And it's growing really strongly and growing right in line with what we said it would. As it relates to the second half of the year, usually we see a greater distribution of revenue in the second half of the year versus the first half of the year. And so we are very confident that we will see that. And from an operational basis, we're reiterating our guidance of 350 to 365. Again, exactly how foreign exchange impacts that is difficult to predict. But for now, we've provided that kind of point estimate for what the impact could be from a reported perspective. But again, for us, the importance is that the business is strong and growing and growing in all key markets. And we continue to anticipate that going forward. But Jeff, you want to talk a little bit about the Pompei development strategy in particular, the different populations, late onset and pediatric.
spk15: Yeah, sure. So as a reminder, Propel was included only adult patients. So, you know, the vast majority of the data in our initial submissions will be focused on adult Pompei patients. And that would be our expected initial labeling. We do have an ongoing pediatric LOPD study. And we do have agreement with regulatory agencies to do an extrapolation of efficacy from the adult patients down into those pediatric LOPD patients. And we are imminently getting ready to start adding IOPD patients to that clinical trial as well. We do need to look at some measures of efficacy and safety in that IOPD population. So we expect initial labels focused on adults. but then as we have data sufficient to add in the pediatric patients, we will. And as I noted on the call, we continue to treat multiple pediatric patients, IOPD, LOPD, through expanded access where there's significant need.
spk14: Great, thank you.
spk12: And our next question will come from Ritu Baral with Cowan. Please go ahead.
spk04: Hi, guys. Thanks for taking the follow-up. I just wanted to drill down a little more into the U.S. dynamics and the sort of return to growth or growth reacceleration. I guess I'm surprised that new prescribers are still growing this long into the launch, and also I'm wondering how much mutations play into it. You guys have the number of mutations on the European label in the slides, but how does that compare to the U.S. label, and are those still growing, the number of mutations in the U.S. label? Is that driving the growth? Is there like a cast you're about to hit which triggered the NextGen program?
spk10: Yeah, thanks for two good questions. So as it relates to the growth dynamic in the United States, I think it really has a more to do with what Sebastian described, which is increasing opportunity for physicians and our sales and medical team to be together. While we did a great job of maintaining those virtual interactions, I think kind of nothing beats face to face. And it probably represents also some improved access for patients and physicians and more frequent access for patients and physicians so that physicians can start patients on therapy. whether it's a bit of a new normal or whether it's some adjustment and ability to now handle COVID in a different way. I think that's really what's driving that kind of resurgence in demand. But I can say that even in July, we're continuing to see great numbers, not just the U.S., but around the world. And again, that 90% growth rate in patients coming onto therapy from end of second quarter versus end of second quarter last year, to me, that says the business is growing strong, and we continue to expect that. As it relates to the mutations piece, no, you're right. Remember, the really interesting and exciting part about the European label is that we were able to characterize all of the theoretical mutations that could be amenable to the chaperone and the Europeans accepted that concept of amenability, and we were able to expand the label so that even though not every mutation had an actual patient diagnosed with that mutation, if we find one who does have those mutations, then they can immediately be eligible for therapy. In the United States, it's slightly different. While they fully accept the amenability concept, In order to update the label in the United States, we are obligated to find a patient with that mutation and then we can subsequently update the label. So, it's just a little bit of a slower process, but eventually, presumably, we'd find majority of those medical patients. As it relates to prescribers, I think, honestly, that's just a reflection of the rare disease space where, you know, these patients and physicians are continued. We continue to find new patients. We continue to then have new physicians. And we do continue to see new prescribers come on board, which I think just, again, reflects the continuing growth opportunity for Gallifold. So all great positive signs for the business for years to come.
spk04: And how many mutations are... I guess, left in the U.S., as you see it, to be included in that label.
spk10: Jeff, you want to give the, what's the European label, Jeff, and then what's the U.S.
spk15: label? Yeah, so I think it's, you know, almost 1,400 amenable mutations in the European label, and it's, you know, around 350 in the U.S. So, look, we continue to add mutations. every year as patients and patient families have a novel mutation. So we do expect that that number will keep coming up over time. I don't think it will ever reach the true theoretical rate, but as Brad said, it really doesn't limit access in the US. It just might cause a slight delay as it might be a mutation that's not in the label. We've already tested them, so we don't have to rerun the assay. We just need to go through the paperwork with FDA to add it to the label.
spk04: I see. Thank you.
spk15: Thanks, Richard.
spk12: And ladies and gentlemen, this will conclude our question and answer session, also concluding today's conference call. We'd like to thank you for attending today's presentation. And at this time, you may now disconnect your lines.
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