Amicus Therapeutics, Inc.

Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics Second Quarter 2021 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. If anyone should require assistance during the conference, please press star and then zero on your touchtone telephone. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Fongan, Head of Investor Relations. You may begin.

Thank you, Operator. Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics second quarter 2021 financial results and corporate highlights. Speaking on today's call, we have John Crowley, Chairman and Chief Executive Officer, Bradley Campbell, President and Chief Operating Officer, Daphne Queeney, Chief Financial Officer, and Dr. Jeff Costelli, Chief Development Officer. Joining for Q&A will have Dr. Mitchell Goldman, Chief Medical Officer as well. 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 of 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, 2020, and the quarterly report on Form 10Q for the quarter ended June 30th, 2021, to be filed later today with the Securities and Exchange Commission. At this time, it's my pleasure to turn the call over to John Crowley, Chairman and Chief Executive Officer. John?

Great. Thank you, Andrew, and welcome everyone to our second quarter 2021 results conference call. Before we begin, I just want to note yesterday the sudden death of Dr. Tachi Yamada. Tachi, as many of you know, is a giant in our industry, and among his many contributions, he was a passionate advocate for research for people living with rare diseases, and I came to know Tachi well as he chaired the Orkin Disease Center with Jim Wilson at the University of Pennsylvania, where I had the honor to serve with him, and our deepest consolances to his family. I am pleased to report for Amicus that the second quarter of 2021 reflects execution across our strategic priorities that we outlined at the beginning of the year. As we did in this morning's press release, I'd like to highlight several key accomplishments. First, Gallifold continues its strong performance and remains the cornerstone of our success. With $77 million in second quarter revenue, we are very pleased with the continued momentum of the Gallifold uptake globally. The number of patients on Gallifold at the end of the quarter continues to exceed our internal expectations as we continue to add new patients from both switch and naive populations throughout the quarter. And exciting news for Gallifold. On Monday this week, we announced that the European Commission has approved the expanded EU label for Gallifold for the long-term treatment of February disease in adolescents aged 12 and older with an amenable mutation. This is a transformative moment for the February community in the European Union, where pediatric patients now aged 12 and above have a new treatment option for the first time in over 15 years. Second, our key regulatory initiatives for ATGAA remain on track, and our R&D pipeline of gene therapies continues to advance. I am pleased to share today that the rolling BLA and the NDA submissions for ATGAA, our novel next-generation two-component therapy for Pompe disease, have been completed. We are also pleased to share that following a positive rapporteur and co-rapporteur meeting, the EU regulators are supportive of marketing authorization application, or MAA, submissions for ATGAA. We expect to complete these EMA submissions in the second half of this year. We continue to have great confidence in ATGAA to benefit people living with Pompe disease, and we intend to move it rapidly through these regulatory submissions towards approval. Within our gene therapy pipeline, we continue to further lead batten programs for CLN3 and CLN6, as well as our most advanced preclinical gene therapy programs. And through our broad research collaboration with Dr. Jim Wilson and the University of Pennsylvania, we are highly encouraged by the continued preclinical data and the progress we have seen thus far from our Febre and Pompe disease gene therapy clinical candidates. And third, the amicus cash position is sufficient to achieve self-sustainability under the current plan without the need for any future dilutive financings. Our continued revenue growth prudent expense management, and growth potential has allowed us to reach this important milestone as we continue to realize our vision of delivering groundbreaking and potentially curative new medicines for people living with rare diseases around the world. Turning to slide four, we are well on track to achieve our five key strategic priorities for 2021. These include Gallifold, our precision medicine for February disease, We will continue to drive Gallifold's availability to more people living with Febre disease with amenable variants in existing and in new markets. We look to achieve global product revenue of $300 million to $315 million this year, which reflects strong momentum and demand behind this precision medicine globally. Second, we remain steadfast and passionate in our commitment to advancing ATGAA through global regulatory submissions for the benefit of as many people living with Pompe disease and as quickly as possible. Third, we are advancing our industry-leading rare disease gene therapy portfolio. Stemming from our global research and gene therapy center of excellence in Philadelphia, we will be advancing the clinical development, manufacturing, and regulatory discussions across multiple programs in our gene therapy pipeline. In addition, we are progressing our manufacturing capabilities and capacity to build world-class technical operations to support all amicus gene therapy programs. And finally, again, we continue to maintain a strong financial position as we carefully manage our expenses and investments. Again, we remain fully funded through all major milestones. So with that introduction, let me go ahead now and hand the call over to Bradley Campbell, our President and Chief Operating Officer to further highlight the Gallifold performance. Bradley.

Thanks, John, and good morning, everyone. As John mentioned, I'll now walk you through in more detail our Gallifold performance for the quarter. On slide six, we give our global snapshot of the Gallifold commercial progress. For the quarter, total product revenue was $77.4 million, driven by strong patient demand, new patient starts, and business continuity. Global compliance and adherence rates continue to exceed 90%. The geographic breakdown of revenue during the quarter was 53.7 million, or 69% of revenue generated outside the United States, with the remaining 23.7 million, or 31%, coming from within the United States. As we've mentioned before, this is in line with the roughly 70-30 split that we expect to see as we continue to grow both parts of the global business. Now turning to slide seven, Q2 was another great quarter for our global commercial efforts. The business continues to be incredibly resilient with patients added in all of our major markets. In fact, the month of June was the second best month in net new patient starts in our international market since launch. And globally, the rolling three-month average patient starts is greater than the six-month and 12-month average respectively, which should include building momentum going into the second half of the year. Second quarter revenue reflected increased patient demand and also benefited slightly from the timing of orders in ex-U.S. geographies and a continuing FX tailwind. As we highlighted in our Q1 call, we continue to see some sporadic COVID-related slowdowns and new patient starts due to delays at the point of care between patient identification and initiation of treatment. Importantly, though, our supply chain remains fully intact. Our customers have confidence they can access Gallifold, and our field team has been able to achieve a substantial majority of their pre-COVID touchpoints through a combination of in-person, digital, telephonic, and other means of interacting with physicians. We continue to monitor the pandemic's impact, but the good news is we observed improvements in the second quarter so that many of our field personnel saw an increased ability to interact with physicians in person. The first two quarters of 2021 have been in line with our expectations. And as we've mentioned on previous calls, while we continue to see and expect growth versus the same quarter last year, due to a variety of factors, the rate of growth from quarter to quarter within the year is typically nonlinear. So usually in a given year, 2Q and 4Q are stronger quarters than first quarter and third quarter. And that pattern has continued so far this year with a great performance now here in the second quarter. Based on this momentum and continuing to anticipate a second half recovery from COVID, we're confident in meeting our full year 2021 guidance of $300 to $315 million in global revenue. Now on slide eight, we've called out several of the drivers and metrics which lay the foundation for the growth in 2021 and beyond. As we've mentioned, we ended 2020 with 1,400 plus patients on Gallifolds globally, and we're now at about a 49% global market share of treated amenable patients, So while we're achieving higher market shares in countries where we've been approved the longest, there's still plenty of opportunity to continue to switch patients over to Gallifold. We also know that there are significant numbers of diagnosed untreated patients who have amenable variants. And while the global mix remains about 60% switch and 40% naive patients on Gallifold, in many markets we're starting to see stronger uptake in naive patients. As we've said previously, over the next few years, we'd expect to see that rate of switch in naive patients to be about 50-50. And in the long term, we expect to see that percentage reverse in favor of naive patients, reflecting further market growth for Gallifold. All of that is underpinned by compliance and adherence rates that continue to exceed 90%, reiterating our belief that those patients who go on Gallifold tend to stay on Gallifold. The value of Gallifold has also been recognized by payers with nearly 100% of insurance reauthorizations granted in 2021 with US payers and a very strong track record of successfully negotiating and now renegotiating reimbursement outside of the United States. A relentless focus on ensuring access to Gallifold continues to be a strength. And as John just briefly touched upon, I'm thrilled to announce that the European Commission approved the expanded European label of Gallifold in the adolescent population. So now for the first time in over 15 years, individuals aged 12 to 16 years old with an amenable mutation have a new treatment option with Gallifold, which is of course the only oral therapy approved for the long-term treatment of Fabry disease. This approval will allow us to expand the eligible treatment population a further five to 10% in Europe, and we'll continue to work very closely with regulatory authorities and other geographies to secure access to Gallifold for eligible patients as quickly as possible. Finally, to reiterate, another important driver of growth for Gallifold is continued geographic expansion. In 2021, we expect to secure reimbursement in at least five new countries as we look to expand access to Fabry patients with amenable variants around the globe. And we expect to see continued traction in our newer markets in Latin America and Asia Pacific and elsewhere. As a reminder, Gallifold has received regulatory approval in now over 40 countries, and we have commercial sales in over 30 of those today. So despite the recent COVID related headwinds in certain geographies, demand for Gallifold worldwide has never been stronger with some cues of potential new Gallifold patients building in multiple geographies. We are confident in our guidance of 300 to 315 million in full year global sales. As part of that guidance, as a reminder, we project net new patients starts this year will be even greater than in 2020. And we do expect growth in the number of patients and corresponding revenue to be weighted to the second half of the year as the COVID impact continues to ease. On slide nine, with several years of performance and a track record behind us, we can confidently say we're on a path in the next approximately two years to the important milestone of $500 million in annual global revenue for Gallifold. The exact timing of this milestone will be dependent on how quickly things return to normal post-COVID, but we continue to expect to generate billion in cumulative revenue over the next three years, which will contribute a significant amount towards funding our R&D and OpEx over that period. We also have even further confidence in the over billion-dollar peak revenue opportunity for Gallifold as we continue to see significant growth in the Fabry market globally, driven by continued diagnosis from high-risk screening, newborn screening, and other diagnostic initiatives, which we continue to support and invest in as well. And finally, as a reminder, we have orphan exclusivity in the U.S. and Europe, in addition to our 26 Orange Book-listed patents that give us IP coverage into the late 2030s, 13 of which provide protection through 2038. So a lot of opportunity to continue to provide access to Gallifold globally for a long time to come. So with that, let me now turn the call over to Dr. Jeff Costelli, our Chief Development Officer. Jeff will highlight our ATGAA program and our gene therapy pipeline. Jeff? Thanks, Brad, and good morning, everyone. Moving on to our R&D updates, on slide 11, we wanted to start with ATGAA, our novel next-generation therapy for Pompe disease. First, we believe it's always important to recognize the significant unmet need that remains for people living with Pompe, despite having one approved therapy on the market. Pompe disease is a severe and fatal neuromuscular disease and one of the most prevalent lysosomal disorders. In addition to the numerous individual human tragedies, we've seen multiple publications in natural history studies of Pompe patients that highlight the initial benefit of treatment being followed by continued long-term decline on key measures of disease for many patients. As a reminder, the sustaining high unmet need for ERT-experienced patients has only ever been studied in a controlled setting in our Phase III PROPEL clinical trial. All other controlled late-onset pump A disease studies have been in participants naive to treatment. Moving now to slide 12, we present a summary of the primary, key secondary, and biomarker endpoints recently presented at the International Congress on Neuromuscular Diseases in May. As a reminder, PROPEL was a double-blind randomized study assessing the efficacy and safety of ATGAA in adult treatment naive and ERT-experienced participants against the currently approved therapy. We enrolled 123 study volunteers at 62 sites in 24 countries. 117 of these patients completed the study, and all 117 voluntarily enrolled in the extension study to continue on ATGA or transition to ATGA as their only disease-modifying treatment for Pompe. Here on the slide, grouping these endpoints into domains of motor function, muscle strength, pulmonary function, patient-reported outcomes, and biomarkers, you can see that the vast majority of endpoints across all of these domains favor ATGA over aglucosidase alpha in both the overall and ERT experience populations. We believe this consistency of effect across the key disease manifestations of Pompe highlights the potential impact of ATGA to address unmet needs for patients living with Pompe. As a reminder, on the primary endpoint of six-minute walk distance, patients on ATGA outperformed those on agglucosidase alpha in the overall population with a difference between groups of 14 meters, which did not reach statistical significance for superiority. However, on the first key secondary endpoint of percent predicted force vital capacity, or SVC, In the overall population, ATGA showed a nominally statistically significant and clinically meaningful difference for superiority versus agglucosidase alpha with a difference of 3% and a p-value of .023. This is an impressive finding as progressive loss of pulmonary function is a leading cause of mortality in Pompe. And this was the main endpoint upon which agglucosidase alpha was initially approved. We remind everyone that the PROPEL study tested for superiority versus approved therapy, not placebo, and that the bar for approval of a second-generation product generally requires demonstration only of non-inferiority versus approved therapy. As shown on prior calls, in post hoc non-inferiority analyses for the primary endpoint of 6-minute walk and the first key secondary endpoint of FEC, these non-inferiority analyses were highly significant. Moving on now to slide 13, we have our next steps surrounding development, regulatory, and manufacturing strategy for ATGAA. First, as John mentioned, the rolling DLA submission for ATB200 and the new drug application for Miglistat, the two components that make up ATGAA have both been submitted to FDA. The clinical modules were completed and submitted to FDA in the second quarter. The CMC module was completed and submitted in July. which completed the last parts of the rolling BLA into FDA. We are pleased to also share that following a positive EMA rapporteur and co-rapporteur meeting, EU regulators are supportive of marketing authorization application submissions of ATGA in the second half of this year, and we expect additional global filings to follow. In June, we announced ATGA was granted a positive scientific opinion through the Early Access to Medicine Scheme, or EAMS, by the UK's MHRA. This positive opinion recognizes the high unmet medical needs faced by the Pompe community and permits eligible adults living with late onset Pompe disease who have received aglucosidase alpha for at least two years to switch and have access to ATGA prior to marketing authorization in the UK. For the younger Pompe community, we will look to expand our ongoing open label adolescent study in 12 to 18 year olds, and our clinical study for Pompe patients with infantile onset disease is expected to begin this year. At this point, we're pleased to report that over 150 patients worldwide are now being treated with ATGA. And to put this figure into perspective, this is close to 5% of people with Pompe disease today currently on treatment. And finally, in response to the many requests for expanded access that we've received for children living with infantile onset Pompe, our expanded access programs for both those with infantile onset and adult onset, we continue to expand for multiple individuals. Moving on now to slide 15, to briefly highlight our industry-leading portfolio of gene therapies for rare diseases. We continue to follow the first 13 participants and the four participants in our CLN6 and CLN3 Phase 1-2 studies, where data from both studies continue to show the potential to stabilize disease progression in these children when compared to natural history. We're really excited about this result, as these are devastating neurodegenerative diseases with early mortality. We remain focused on the manufacturing activities and regulatory discussions for both programs, to enable dosing additional patients with GMP clinical-grade material in future registration-directed studies. Ahead on slide 16, we continue to make progress across our preclinical gene therapy programs with Penn, particularly regarding our FABRE and POMPE gene therapy programs. Data from these programs further validate our innovative approach to gene therapy by combining amicus' protein engineering expertise with Penn's gene transfer technologies. We continue to build out manufacturing capabilities for both programs ahead of the expected IND-enabling studies. We believe this is just the beginning. As part of this collaboration, AMICUS has rights to over 50 diseases, including seven currently in active preclinical programs. With that, I would like to now turn the call over to Daphne Queney to review our financial results, guidance, and outlook. Daphne?

Thank you, Jeff, and good morning, everyone. Our financial overview begins on slide 18 with our income statement for the second quarter ending June 30, 2021. For the quarter, we achieved Gallifold revenue of $77.4 million, which is a 24% increase over the second quarter of 2020. This includes year-over-year operational growth of 17.2%, measured at constant currency exchange rates. Total operating expenses of $107.9 million in the second quarter of 2021 were relatively flat as compared to $107 million in the second quarter of 2020. On a non-GAAP basis, total operating expenses were $93.5 million in the second quarter of 2021 as compared to $95.9 million in the second quarter of 2020. The decrease in research and development costs reflects the timing of investments in our pipeline. specifically the timing of manufacturing batches of ATGAA and other research costs, which we expect to incur in subsequent quarters. We define non-GAAP operating expense as research and development and SG&A expenses, excluding share-based compensation expense, changes in fair value of contingent consideration, and depreciation. Net loss for the second quarter of 2021 was 51.2 million, or 19 cents per share, as compared to a net loss of 52.5 million, or 20 cents per share for the prior year period. As of June 30, 2021, we had approximately 266 million shares outstanding. Turning now to slide 19, with our current cash position, we are on a path to self-sustainability without the need for any future dilutive financing. We have achieved this milestone through our revenue growth with Gallifold, as well as driving efficiencies, cost savings, and continued expense management. For the third year, straight year, we expect total non-GAAP operating expenses in 2021 to remain relatively flat as we leverage the global commercial infrastructure that is already in place for the ATGAA launch and other products in our pipeline. transition costs associated with the development of ATGAA to multiple gene therapy programs in our pipeline, and maintain financial discipline while meeting our objectives. To reiterate, all high-priority research programs in gene therapy are moving ahead, and we continue to support the work with the Wilson Lab at Penn. A few comments about our cash position and 2021 financial guidance. Cash equivalents and marketable securities were $383.1 million on June 30, 2021, as compared to $483.3 million at December 31, 2020. We are reiterating our full-year Gallifold revenue guidance of $300 million to $315 million, and our non-GAAP operating expense guidance of $410 million to $420 million. And with that, I will turn the call back over to John for closing comments.

Great. Thank you, Daphne, and also Jeff and Bradley. As you can see, we have been relentlessly focused on execution and performance across the business, driven by a global team of passionate entrepreneurs at Amicus who have led and will continue to lead us on our patient-focused mission. I am confident that as the world emerges from this COVID pandemic, Amicus will emerge even stronger. So with that, Operator, we're happy to turn the call over to questions.

Thank you. Ladies and gentlemen, if you have questions, please press star and then the number one key on your touchstone telephone. At this time, we ask that you only ask one question. If you have any additional questions, please enter back into the queue. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. Thank you. Your first question comes from the line of Vitu Beral from Cowan. Your line is open.

Good morning, guys. Thanks for taking the question. So I wanted to ask about how we should think about expectations for the review period once the ATGAA, BLA and NDA are accepted. I guess priority review is an option, but is there anything that either necessitates priority review or would trigger priority review or standard review, and then I have a very quick follow-up on the program.

That's fine, Ritu. Good morning. Yeah, so now with the BLA and NDA submissions complete and into FDA, we'll expect to hear back hopefully this quarter. We would expect to hear back from the FDA on their acceptance of that. As part of the submission, as you know, we did request a priority review. Reminder to everybody, we do have breakthrough therapy designation for this product. That also in part recognizes the significant unmet need in the community as well as the uniqueness of the data here. So we're hopeful that the FDA will look favorably upon that, but we'll find out once they hopefully accept the filing of the submission. With the priority review, of course, that would trigger a six-month review timeline. But we don't know that yet. That's up to the regulators, so we'll see.

Got it. And then on the same application, moving to Europe, The competitor has, I believe, sort of re-petitioned EMA for novel chemical status for Neo-GAA. I'm assuming that's sort of a bid for exclusivity. Can you remind us who your rapporteurs are and how is this sort of chemical novelty sorted out within EMA?

Yeah, it is. First of all, I don't want to speculate on discussions for a competitor, but I'll just remind everybody, per the EMA's definition, in order for a product to qualify as a new active substance, it has to either be a biological substance not previously authorized or a biological substance previously authorized but differing significantly in safety and or efficacy due to the differences in one or a combination of its molecular structure or the nature of the source material, or the manufacturing process. So I'll just remind everybody, with respect to ATGAA, we know it's differentiated. We believe it's differentiated on key structural differences. It's differentiated on its dual component therapy. And it has a differentiated clinical efficacy. So again, I'm not going to comment on the denial of that for the Neo product. but we're very confident of the uniqueness of our product and certainly in the data that we have.

Got it. Thanks.

Did you have a quick follow-up or two, or did we capture it?

Oh, that was the follow-up, actually.

It was good. Okay, very good. Yeah, yeah. So very interesting dynamics at play, for sure.

Your next question comes from the line of Rumi Maru, from you, Ed. UBS, your line is open. Hey, guys.

Thanks for taking the question. Just another one on the regulatory interactions. I'm curious, you know, in the discussions with the EMA and then also, you know, the BLA filing, have you seen any differences in terms of, you know, how the U.S. versus EU is sort of viewing the submission? Any differences in terms of, you know, how they're viewing the clinical data or endpoints? Thanks.

Yeah, it's actually been remarkably similar, Ellie. And again, I'll remind everybody, this Pompe program, the amicus Pompe program, we were the first company to utilize the joint scientific advice. So that began in the fall of 2018 as we were proposing to propel study. So we had received prior to study start harmonized feedback from both EMA and FDA together on the trial design and the statistical analysis plan. And we've also seen very, very similar feedback now from EMA and FDA on the regulatory path forward. So we think, we hope that that bodes well.

Great, thanks. And your next question comes from the line at .

Hi, good morning, everyone. Thanks for taking my question. So as there are multiple specialists often involved for the treatment of both Pompe and Fabry diseases, I wanted to ask, of your existing commercial team for Gallifold, what the overlap is for centers that also treat for Pompe disease? And then if you were to expand into more territories if ATGAA is approved, how do you believe this could also benefit the footprint for Gallifold? Thank you.

Yeah, thank you, Chris, and I'll have Bradley answer this. I'll just highlight that we think there is great leverage from the global commercial infrastructure that we've built for Gallifold. We think we can lever that significantly for ATGAA, and again, we're already expanding the Gallifold footprint to all the geographies that would be necessary and appropriate for ATGAA, so great synergies there, but Bradley, I'll let you comment further.

Yeah, thanks, John. And you definitely hit the highlights. So the good news is lots of leverage between the Gallifold Commercial Organization and what will be the ATGA Commercial Organization. In fact, right now, no intention to add further field support for the launch of ATGA, which is great. Just a few more details to help explain that. So in terms of the sort of the specialties that typically treat these these Fabry and Pompe patients, there is some overlap in particular in genetics and metabolic specialists. And there are some other some other specialties that end up treating both patients. However, there's high degree of overlap in terms of the centers that that follow these patients. And so, you know, Typically, an academic center or LSD treating center will be following multiple patients with different lysosomal storage disorders, including Fabry and Pompe. And that's really what gives you the leverage to be able to use one commercial organization to support both programs. And we've also taken the approach of really hiring more key account managers, so somebody who's used to supporting an entire academic center, not just one specific physician, in terms of how they help support the understanding and utilization of these products. So we feel really good about that leverage and, again, see very little increase in the commercial infrastructure that we'll need to support the launch of ATGA.

Thank you. And we have your next question coming from the line of Anupam Rama from J.P. Morgan. Please go ahead.

Hi, guys. Thanks so much for taking the question. Quick one on Gallifold on the new patient international ads in June being the second best since launch. Is this really being driven by deeper penetration into the region or maybe new country ads that you saw in the first half of 2021. Thanks so much.

Yeah, Anupam, thanks for the question. Good to hear your voice. I'll turn it to Bradley. Just to highlight, you had mentioned June. It was actually through this. It was in the second quarter that we had seen the most significant number of new patient starts, second most significant since product launch. But, Bradley, do you want to comment further, drill down a little bit on the dynamics that we're seeing that's driving that?

Yeah, so Anupam, good question. Again, good to hear from you. So I think it's a few things. First of all, it is some new countries. Central and Eastern Europe, for example, have been later in the reimbursement cycle, and we're starting to see those countries come on. I think we talked about Poland as an example, which is a great new opportunity for patients there. But it's also seeing patients come on in our existing larger markets, Germany, the U.K., etc., During COVID, there were some small cues here and there of patients that were disrupted in their ability to get into the hospital, and so I think there's some of that going on. But it's also increasing penetration into naive patients, so it's reflective of market growth. So we think those are all great signs of the underlying business, and it's a combination of a number of factors that, again, we think should continue as we go into the back half of this year, but beyond as well.

Thank you. And we have your next question from Dave Gunha from CFO. Your line is open.

Good morning. Thanks for taking my questions. Just one follow-up to an earlier question and another follow-up from me. Regarding the regulatory side on ATGAA, I'm not too familiar with the early access to medicine scheme in the UK. Just looking at the language and the press release, I was just wondering if there is so much, I guess, overlap between the EU and FDA. Can you maybe speak to how we should think about the exposure to glucosidase alpha for two years or more? And then secondly, I guess going back to the biology of ATB200, the M6P modification, maybe a question for Jeff. Can you speak to the degree of M6P modification on this biologic and whether you think having a better modification profile will produce an even better clinical outcome. Thank you.

Sure, Dagon. Thank you. I'll just comment that to remind everybody, back in May we announced that the MHRA had granted early approval to ATGAA for patients who were treatment experienced who had been on for more than two years. That was the initial indication, and again, through the process, we would expect that to be for all switch patients. as well as for naive patients as well. The reality is the vast majority of patients in the United Kingdom on the current approved ERT have been on for two or more years. So we think there's significant opportunity prior to full and final approval in the United Kingdom to offer ATGAA as requested to many, many patients on the current standard of care. We've seen great momentum and enthusiasm since that announcement just a couple of months ago. there really continues to be a significant unmet need for that particular Pompe population. That is now working its way through the local health authorities, and based on feedback and proactive requests from physicians, we would expect in the months ahead to see significant numbers of requests for patients to be switched from current DRT to the ATGAA product. With respect to M6P modification, I'll ask Jeff to comment as well, but again, what we've developed at Amicus is a novel biologic known as ATB200. It is a naturally occurring cell line that we have selected, cultivated, and now with our partners at WUSHI Biologics, scaled to commercial scale, maintaining the proper glycosylation, we think optimal glycosylation, and very high levels of naturally occurring mannose 6-phosphate, including the carbohydrate structure that is bisphosphorylated. And in all of our in vitro studies, preclinical studies, and now consistent with the clinical data, we've seen significantly higher uptake of the protein. And again, a protein with that naturally occurring carbohydrate structure that is highly phosphorylated that has the ability to not only get into multiple muscle cells, and from what we've seen preclinically, certainly we see that and I think continued now with the clinical data, into cardiac tissue. We see it into skeletal muscle, smooth muscle, diaphragm. And with that, we think it's a very differentiated product, again, with the enzyme stabilizer, the chaperone product. So together, we think that's a very novel product for people living with Pompe and we think it has an optimal level of M6P, again, not post-translationally modified, but with the cell line that we've selected and cultivated. Jeff, if I missed anything, please feel free to add.

Yeah, sure. Hi, Dagon. You know, as John said, we know that ATB200 has significantly improved phosphorylation in M6P. In fact, the vast majority of all the protein molecules have an M6P on average. there's at least one bis M6P for every single ATB200 molecule. So we think that we've really managed to create something that is pretty optimally targeted. We don't think that having additional M6P would notably or meaningfully change our uptake. We've sort of maxed out.

Oh, sorry.

Great. Thank you, Dagan. Yeah.

Thank you. And your next question is from Salvin Richter from Goldman Sachs. Your line is open.

Thanks for taking the question. This is Andrea on for Salvin. Maybe one on your Batten disease program. Just wondering when we can expect the next data and what would you look to understand from that data release?

Yeah, Jeff, do you want to comment on the Batten program?

Yeah, so the last time we provided an update on the 13 kids treated with CLN6 and the four treated with CLN3 was at the World Lysosomal Disease Meeting earlier this year. That data set included eight of the patients who had reached two years of follow-up in CLN6 and it was one year data and the first three kids treated with CLN3. That data continued to show disease stabilization on the Hamburg Motor Language in CLM6 and the UBDRS physical domain for CLM3 compared to what we've seen in natural history, which is really encouraging. We will continue and we do continue to follow those kids. We will have additional updates, you know, as we have significant amount of new data. That could happen. We haven't specifically said when, but typically key venues where we do provide updates are either at the Child Neurology Society meeting in the fall or at the World meeting early in the year. So those are two places where you can expect potential updates as we have more data to share. But we're really excited by what we've seen and continue to see in those kids.

Great. Thanks so much.

Thank you. And we have a question coming from the line of Yun Song from DTIG. Your line is open.

Great. Thank you. And good morning. Thanks for taking the question. So, excuse me. On ATGAA, I think you mentioned that some patients, after long-term treatment with lumizine, they start to decline, losing response, and I believe the reason is still not very well understood, so I wonder, I know it's too early to tell, but is there any evidence to suggest that this observation might not happen to ATGAA? And in your clinical study, in the Pompe study, did you by any chance enroll any patients who might have entered that declining phase from receiving imzumabine treatment?

Yeah, thank you, Yun. Maybe Jeff, if you want to field that, and Mitch after Jeff, if you have any color to add, please. Sure. Thanks, John.

What we've seen here now in multiple studies is that there's initial benefit on treatment with the current standard of care. We see patients improve on six-minute walk, have improvements on FEC and other muscle function. It's really for about the first two years, and even that response can be somewhat variable, but What's then seen after two years is a pretty much continued decline, almost looking in many cases like it was pre-treatment. We do believe with ATGA and addressing the improved M6P binding and uptake and also the stability in the blood with the stabilizer, that that will hopefully help to better penetrate deeper into tissues and clear glycogen that might not have been cleared. and that could be the cause of that continued progression. We are really encouraged by the results we've seen in our ERT-experienced patients, both in our Phase I-II study and now here in Propel, where those patients had been on treatment for, on average, over seven years and well into that stage where they're nearly all expected to be declining. And we see that we can stabilize their FEC and actually lead to improvements in six-minute walk in those patients So we do think that that not only goes really well for those ERT-experienced patients to offer them something that could change the trajectory of their disease, but hopefully that reads through to naive patients longer term when they become more akin to a switch patient. We hopefully will see continued sustained benefit in those patients.

Yeah, this is Mitch. I'll just add that I think what Jeff said during the call was important. To reiterate, the majority, 117 patients, went on to the extension study. We'll continue to follow them, look at regular data cuts, and release those at appropriate venues. And to your point about individual heterogeneity, we also think that's important. And, again, we look at every patient that's ongoing in that trial and look to find out how they're doing. And, again, we'll report that data on an ongoing basis.

Thank you. And next we have a question from Gil Bloom's line from Needham Company. Your line is open.

Thank you for taking my questions, and congratulations on the execution. Maybe a bit of a question on the Batten Disease Program. Do you guys have any thoughts about this upcoming ad comm in September, which will discuss safety in AAV9 therapeutics?

Thank you. Yeah, great, thank you, Gil. We think that'll be an important meeting. I'll just remind everybody that for our BATNS program for CLN6, we've dosed now 13 children, all of them more than two years post the dosing, and we have seen no safety events whatsoever with those children of any concern, and then also four children with CLN3, and again, one of them even at a higher dose. So with the intrathecal delivery, of the low dose of AAV9 that we're using there. We've not seen any safety considerations. I'll just remind everybody, too, that part of the premise for Amicus's involvement with gene therapy was the notion that with our protein engineering technologies, together with the next generation technologies in gene therapy coming from Jim Wilson's lab, that our collaboration looks to address exactly the problem of safety, particularly with these AAV capsids. So we think actually we'll be very favorably positioned. We continue to have concerns in the field broadly around high-dose systemic AAV. We think that does present complications and dangers for patients, so we think it's terrific that the FDA is taking this on to review, and we would expect to be actively engaged in those discussions. But I think, again, very differentiated from the amicus approach here. Jeff or Mitch, feel free to comment as well. John, you covered it pretty well.

I don't have anything specific to add.

This is Jeff. I'll just say that we welcome the FDA Advisory Committee to look into these things to provide color to the field as it evolves and gives us output that we can incorporate into our clinical thinking and the safety of patients is paramount. So we really look forward to the output of the meetings.

Great. And again, Gil, I'll just direct you to some of the work that we've published and discussed now publicly with respect to our Febre and Pompe gene therapy programs utilizing AAV technologies and systemic delivery. We think, again, with our unique ability to engineer the transgenes, that we not only may have potentially better efficacy and much better ability to manufacture those gene therapies, we actually hope that we can deliver them at a much safer dose as well, lower dose. And that's what we've demonstrated preclinically.

Okay, thank you. We have your next question from Joseph Schwartz from SBB Learing. Your line is open.

Hi, I'm Jerry Dalyan for Joe. Thank you for taking our question. So assuming ATGAA is approved, How eager are the patients currently on therapy looking for alternative treatment? Who do you believe could be early adopters of ATGAA, and how abundant are the opportunities for these patients to switch therapies now that there could be several treatment options available for these patients? Any color on that would be helpful. Thank you.

Sure, Andrea. I'll ask Bradley to comment as well from kind of a patient demographic and market perspective. But just to remind everybody, people living with Pompe disease, whether they're infants all the way through late adulthood, for 15 years have had the option of only one approved enzyme replacement therapy. So we think it's terrific that they'll have the potential ahead very shortly to have potentially multiple options for new next generation therapies. Again, we think ATGAA has demonstrated overwhelmingly clinically meaningful and significant benefits for these patients. So you'll see a hunger and a great need in the patient community and with the physicians as well for new, novel, next-generation therapies. So, Bradley, if you want to talk about how we see the patient population demographics, speak to the early adopters. That would be very helpful.

Sure. Yeah, John, I think you hit it. Sorry about that. Switching over so we can avoid the echo there. John, I think you hit the important highlights from a need for alternative treatments for the patient population. A couple of other important points to make. One thing, of course, is that the market today is about 3,000 or so patients treated today, we estimate, and that's the $1.1 billion revenue globally for Lumazine. So that's a huge population of potential switch patients. It is growing at high single-digit rates, the market, so it's continuing to bring on some naive patients as well. Importantly, too, we have today over 150 patients on ATGAA, and we would expect, depending on the utilization through various expanded access and further clinical development programs, that number could even grow. And so when we launch this product or we anticipate launching this product, you'll have a significant base of clinical trial patients to convert over. And we think that gives you a lot of momentum coming into the launch. And the last thing I'll offer is something that John touched earlier. You know, unlike when we launched Gallifold, which was a very successful launch, but we were building our commercial organization, you know, from scratch at that time. Here we have a well-experienced global commercial team. already, as I mentioned before, covering many of the same centers and many of the same physicians who are treating Pompe disease and were present in the major markets around the world. And so we have a great experienced team of commercial and medical passionate entrepreneurs focused on getting our products out to patients. So we think we've got a great base to start from and should have great momentum going into the launch.

Thank you. And our last question comes from the line of Lee Tuberdahl from Cowan. Your line is open.

Hi, guys. Thanks for taking the follow-up. Just back on CLN, well, the BATNS program in general, I wanted to round back on FDA interactions. I believe you were going to have a meeting recently or soon, and can you just address the current thinking on the strategy for proposed pivotal trials around CLN6, CLN3, and the other BATNs that you're pursuing?

Yeah, of course, Ritu. Again, we continue to put great effort into the lead programs that we expect to enter pivotal studies for both CLN6 and, of course, the very large BATNs indication of CLN3. It's been a series of interactions. focused both on CMC. Again, a lot of our activities for the last year and a half really have been focused on manufacturing, including the tech transfer from the university, the scale-up, and we've now completed GMP manufacture with our partners at Brammer Thermal Fisher. A lot of work on the assays, including the potency assays to make sure that we have all the analytical tools. We saw the field trending toward that and the regulators in particular leading people in that direction. as early as the fall of 2019, so I think we were ahead of the curve there. With that, we've also had interactions on our clinical data and on our thinking and the regulators' feedback on future studies. Those continue to be ongoing, but maybe Jeff and Mitch, if you want to give some idea broadly how we're thinking about those pivotal studies for the lead BATN programs, please.

Sure. I'll start first, Mitch, and then Hira, too. As John mentioned, we continue to be focused on all the enabling CMC work and our regulatory interactions across different topics. As for the current thinking on the next clinical studies, first they would be done with the thermo GMP commercial process material. For CLN6, we believe it would be a study similar to what we did in Phase I-II in terms of general size, single arm study versus natural history focused on Hamburg motor language. So we feel really confident about our ability to succeed on that study in terms of design power based on what we've seen already in our phase one, two. For CLN3, of course, our initial phase one, two study was only the four patients. That was all the material we had from nationwide. We would expect a much larger next study you know, in the several dozens of patients. Again, we believe it should be a single arm study compared to the very robust natural history data that exists in CLM3. We believe the UBDRS physical domain is the likely primary endpoint. We think there's a lot of data with that endpoint available. But again, of course, discussions with agencies about all those key components, control arm, endpoints, size of study, et cetera. Mitch, anything else to add from a high level from your perspective?

No, Jeff, thanks. I think you covered it well. Great. Thank you, Ritu. Yeah, of course.

So, operator, I think that's all the questions we show in the queue, correct?

Yes, that is all the questions. I would now like to turn the conference back to Mr. John Crowley, Chairman and CEO, for closing remarks.

Great. Thanks again, Operator. Thank you all for listening and for the great questions. It was an incredibly strong second quarter for Amicus, and you can see across the execution of all of our programs, and we look forward to a very full and exciting second half of the year. Thank you, everybody. Have a good day.

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