Good morning, ladies and gentlemen and welcome to the Amicus Therapeutics Second Quarter 2021 Financial Results Conference Call and Webcast. [Operator Instructions] As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Faughnan, 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 Quimi, Chief Financial Officer; and Dr. Jeff Castelli, Chief Development Officer. Joining for Q&A, we will have Dr. Mitchell Goldman, Chief Medical Officer as well.

As referenced on Slide 2, we may make forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business as well as our plans and prospects. Our forward-looking statements should not be regarded as representation by us that any of our plans will be achieved.

Any or all the forward-looking statements made on this call may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. You are cautioned not to place undue reliance on any forward-looking statements which speak only to the date hereof.

All forward-looking statements are qualified in their entirety by this cautionary statement, and we undertake no obligation to revise or update this presentation and conference call to reflect events or circumstances after the date hereof.

For a full discussion of such forward-looking statements and the risks and uncertainties that may impact them, we refer you to the Forward-Looking Statements and Risk Factors section of our annual report on Form 10-K for the year ended December 31, 2020 and the quarterly report on Form 10-Q for the quarter ended June 30, 2021, to be filed later today with the Securities and Exchange Commission.

At this time, it is 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 Orphan Disease Center with Jim Wilson at the University of Pennsylvania, where I had the honor to serve with him and our deepest consultancies 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, Galafold 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 Galafold uptake globally. The number of patients on Galafold at the end of the quarter continues to exceed our external – our internal expectations as we continue to add new patients from both switch and naive populations throughout the quarter.

And exciting news for Galafold, on Monday this week, we announced that the European Commission has approved the expanded EU label for Galafold for the long-term treatment of Fabry disease in adolescents aged 12 and older with an amenable mutation.

This is a transformative moment for the Fabry 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 AT-GAA 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 AT-GAA, our novel next-generation two-component therapy for Pompe disease, have been completed.

We are also pleased to share that following a positive repertoire and co-repertoire meeting, the EU regulators are supportive of Marketing Authorization Application, or MAA, submissions for AT-GAA. We expect to complete these EMA submissions in the second half of this year.

We continue to have great confidence in AT-GAA 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 Fabry 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 4, we are well on track to achieve our five key strategic priorities for 2021. These include Galafold, our precision medicine for Fabry disease. We will continue to drive Galafold’s availability to more people living with Fabry disease with amenable variance 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 AT-GAA 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.

Four, 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 Galafold performance.

Bradley?.

Thanks, John and good morning everyone. As John mentioned, I will now walk you through in more detail our Galafold performance for the quarter. On Slide 6, we give our global snapshot of the Galafold 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 7, 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 3-month average patient starts is greater than the 6-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 in 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 Galafold, and our field team has been able to achieve a substantial majority of their pre-COVID touch points 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 have 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 million to $315 million in global revenue. Now on Slide 8, we have called out several of the drivers and metrics, which laid the foundation for the growth in 2021 and beyond.

As we’ve mentioned, we ended 2020 with 1,400-plus patients on Galafold globally and we are now at about a 49% global market share of treated amenable patients. So while we are 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 Galafold.

We also know that there are significant numbers of diagnosed untreated patients who remain – who have amenable variants. And while the global mix remains about 60% switch and 40% naive patients on Galafold, in many markets, we’re starting to see stronger uptake in naive patients.

As we’ve said previously, over the next few years, we would 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 Galafold.

All of that is underpinned by compliance and adherence rates that continue to exceed 90%, reiterating our belief that those patients who go on Galafold tend to stay on Galafold. The value of Galafold has also been recognized by payers with nearly 100% of insurance reauthorizations granted in 2021 with U.S.

payers and a very strong track record of successfully negotiating and now renegotiating reimbursement outside of the United States. Our relentless focus on ensuring access to Galafold 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 Galafold 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 Galafold, 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 of further 5% to 10% in Europe, and we’ll continue to work very closely with regulatory authorities and other geographies to secure access to Galafold for eligible patients as quickly as possible.

Finally, to reiterate another important driver of growth for Galafold is continued geographic expansion.

In 2021, we expect to secure reimbursement at least 5 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 the Latin America and Asia Pacific and elsewhere.

As a reminder, Galafold 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 Galafold worldwide has never been stronger, with some queues of potential new Galafold patients building in multiple geographies.

We are confident in our guidance of $300 million to $315 million in full year global sales.

As part of that guidance, as a reminder, we project net new patient 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 9, with several years of performance and a track record behind us, we can confidently say we’re on a path in the next approximately 2 years to the important milestone of $500 million in annual global revenue for Galafold.

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 $1 billion in cumulative revenue over the next 3 years, which will continue – 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 $1 billion peak revenue opportunity for Galafold 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 opportunities to continue to provide access to Galafold globally for a long time to come.

So with that, let me now turn the call over to Dr. Jeff Castelli, our Chief Development Officer. Jeff will highlight our AT-GAA 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 AT-GAA, 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 3 PROPEL clinical trial. All other controlled late-onset Pompe 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 AT-GAA 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 AT-GAA or transition to AT-GAA 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 AT-GAA over alglucosidase alfa in both the overall and ERT-experienced populations.

We believe this consistency of effects across the key disease manifestations of Pompe highlights the potential impact of AT-GAA to address unmet needs for patients living with Pompe.

As a reminder, on the primary endpoint of 6-minute walk distance, patients on AT-GAA outperformed those in alglucosidase alfa 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, a percent predicted forced vital capacity, or FVC, in the overall population, AT-GAA showed a nominally statistically significant and clinically meaningful difference for superiority versus alglucosidase alfa with a difference of 3% and a p-value of 0.023.

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 alglucosidase alfa 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 analysis for the primary endpoint of 6-minute walk and the first key secondary endpoint of FVC, these non-inferiority analyses were highly significant.

Moving on now to Slide 13 we have our next steps surrounding the development, regulatory and manufacturing strategy for AT-GAA, first, as John mentioned, the rolling BLA submission for ATB200 and the new drug application for miglustat, the two components that make up AT-GAA, 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 repertoire and co-repertoire meeting, EU regulators are supportive of marketing authorization application submissions of AT-GAA in the second half of this year, and we expect additional global filings to follow.

In June, we announced AT-GAA was granted a positive scientific opinion through the Early Access to Medicines Scheme, or EAMS, by the UK’s MHRA.

This positive opinion recognizes the high unmet medical need faced by the Pompe community and permits eligible adults living with late-onset Pompe disease who’ve received alglucosidase alfa for at least 2 years to switch and have access to AT-GAA 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 are pleased to report that over 150 patients worldwide are now being treated with AT-GAA.

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 4 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.

To head on Slide 16, we continue to make progress across our preclinical gene therapy programs with Penn, particularly regarding our Fabry 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 7 currently in active preclinical programs.

With that, I would like to now turn the call over to Daphne Quimi 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 Galafold 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 cost reflects the timing of investments in our pipeline, specifically the timing of manufacturing batches of AT-GAA 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 $0.19 per share as compared to a net loss of $52.5 million or $0.20 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 Galafold 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 AT-GAA launch and other products in our pipeline, transition costs associated with the development of AT-GAA 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, 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 Galafold 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. And so with that, operator, we are happy to turn the call over to questions..

[Operator Instructions] Your first question comes from the line of Ritu Baral from Cowen..

Good morning guys. So I wanted to ask about how we should think about expectations for the review period once the AT-GAA 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 neoGAA?.

That’s fine, Ritu. Yes. 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 are 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 6-month review timeline. But we don’t know that yet. That’s up to the regulators. So we will see..

Got it. And then on the same application moving to Europe, the competitor has, I believe, sort of repetitioned EMA for novel chemical status for neoGAA. I’m assuming that’s sort of a bid for exclusivity.

Can you remind us who your repertoires are? And how is the sort of chemical novelty sorted out within EMA?.

Yes, it’s – 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, the nature of the source material or the manufacturing process.

So I will ll ust remind everybody with respect to AT-GAA, 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 am 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, Ritu or did we capture it?.

That was the follow-up actually on the....

It was good. Okay. Very good..

Yes..

Yes, yes, so very interesting dynamics at play, for sure..

Your next question comes from the line of Ellie Merle from UBS..

Hi, guys. Thanks for taking the question. Just another one on the regulatory interactions, curious just in the discussions with the EMA and then also the BLA filing, has there – have you seen any differences in terms of how the U.S.

versus EU is sort of viewing the submission? Any differences in terms of how they’re viewing the clinical data or endpoints?.

Yes. 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 the 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 bodes well..

Okay, thanks..

And your question comes from the line of Kristen Kluska from Cantor Fitzgerald..

Hi. Good morning, everyone. Thanks for taking my questions. 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 Galafold, what the overlap is for centers that also treat for Pompe disease.

And then if you were to expand into more territories that AT-GAA is approved, how do you believe this could also benefit the footprint for Galafold? Thank you..

Yes. Thank you, Kris. I will 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 Galafold. We think we can lever that significantly for AT-GAA.

And again, we are already expanding the Galafold footprint to all the geographies that would be necessary and appropriate for AT-GAA, so great synergies there. But Bradley, I’ll let you comment further..

Yes. Thanks, John. And you definitely hit the highlights. So the good news is lots of leverage between the Galafold commercial organization and what will be the AT-GAA commercial organization. And in fact, right now, no intention to add further field support for the launch of AT-GAA, 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 Fabry and Pompe patients, there is some overlap, in particular, in genetics and metabolic specialists, and there are some other specialties that end up treating both patients.

However, there’s a high degree of overlap in terms of the centers that follow these patients.

And so 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 have 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 will need to support the launch of AT-GAA..

And we have your next question coming from the line of Anupam Rama from JPMorgan..

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

Yes. Anupam, thanks for the question. 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 shortly a little bit on the dynamics that we’re seeing that’s driving that?.

Yes. So Anupam, good question. 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 on 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 UK, etcetera. During COVID, there were some small queues here and there, patients that were disrupted in their ability to get into the hospital.

And so I think there is 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..

And we have your next question from Dae Gon Ha from Stifel..

Good morning. Thanks for taking my question.

Just one follow-up to an earlier question and another follow-up for me, regarding the regulatory side on AT-GAA, I’m not too familiar with the Early Access to Medicine Scheme in the UK, but just looking at the language in the press release, I was just wondering if there is so much, I guess, overlap between the EU and the FDA.

Can you maybe speak to how we should think about the exposure to alglucosidase alfa for 2 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, Dae Gon. Thank you. I will just comment that to remind everybody, back in May, we announced that the MHRA had granted early approval to AT-GAA for patients who were treatment-experienced who had been on for more than 2 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 2 or more years.

So we think there’s significant opportunity prior to full and final approval in the United Kingdom to offer AT-GAA, as requested to many, many patients on the current standard of care. We have 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 ERT to the AT-GAA 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 WuXi Biologics, scale 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 phosphorylated.

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 in – to get into multiple muscle cells.

And from what we have seen pre-clinically, certainly, we see that and I think continue 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..

Yes, sure. Dae Gon, as John said, we know that ATB200 has significantly improved phosphorylation and M6P. In fact, the vast majority of all the protein molecules have an M6P on average. There is 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 sort of maxed out..

Alright..

And your next question is from Salveen Richter from Goldman Sachs..

Thanks for taking the question. This is Andrea on for Salveen.

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?.

Yes.

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

Yes. So the last time we provided an update on the 13 kids treated with CLN6 and the 4 treated with CLN3 was at the World Lysosomal Disease Meeting earlier this year. That dataset included 8 of the patients who had reached 2 years of follow-up in CLN6, and it was 1-year data in the first 3 kids treated with CLN3.

That data continued to show disease stabilization on the Hamburg Motor and Language in CLN6 and the UBDRS physical domain for CLN3 compared to what we’ve seen in natural history, which was really encouraging. We will continue and we do continue to follow those kids. We will have additional updates 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 are really excited by what we’ve seen and continue to see in those kids..

Thank you so much..

And we have a question coming from the line of Yun Zhong from BTIG..

Thank you and good morning. Thanks for taking my question. So on AT-GAA, I think you mentioned that some patients, after long-term treatment with Lumizyme, 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 AT-GAA? 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 Lumizyme treatment?.

Yes. 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. And Yun, 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 6-minute walk, have improvements on FVC and other muscle function is really for about the first 2 years. And even that response can be somewhat variable.

But what’s then seen after 2 years is a pretty much continued decline, almost looking, in many cases, like it was pretreatment.

We do believe with AT-GAA 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 1/2 study and now here in PROPEL, where those patients had been on treatment for, on average, over 7 years and well into that stage where they’re nearly all expected to be declining.

And we see that we can stabilize their FVC and actually lead to improvements in 6-minute walk in those patients. So we do think that, that not only bodes 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 naïve patients longer term when they become more akin to a switch patient. We hopefully will see continued sustained benefit in those patients..

Yes. 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 will 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 how they are doing. And again, we will report that data on an ongoing basis..

And next, we have a question from Gil Blum’s line from Needham & Company..

Thank you for taking my question 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 AdCoM in September, which will discuss safety on AAV9 therapeutics? Thank you..

Yes, great. Thank you, Gil. We think that will be an important meeting. I will just remind everybody that for our Batten’s program for CLN6, we’ve dosed now 13 children, all of them more than 2 years post the dosing.

And we have seen no safety events whatsoever with those children of any concern, and then also 4 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 will just remind everybody too that part of the premise for Amicus’ involvement with gene therapy was the notion that with our protein engineering technologies, together with the next-generation technologies and 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 will 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..

Yes. And 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 meeting..

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 Fabry 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 in a much safer dose as well, lower dose, and that’s what we have demonstrated pre-clinically..

We have your next question from Joseph Schwartz from SVB Leerink..

I am Joori dialing in for Joe.

So assuming AT-GAA is approved, how eager are the patients currently on therapy looking for alternative treatments? Who do you believe are the early adopters of AT-GAA? And how abundant are the opportunities for these patients to switch to therapy – switch to – switch therapies now that there could be several treatment options available for these patients? Any color on that would be helpful?.

Sure. I’ll ask Bradley to comment as well from – to kind of a patient demographic and market perspective. But just to remind everybody, people living with Pompe disease, whether they are 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 AT-GAA 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. Yes, John, I think you had – 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 Lumizyme. 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 AT-GAA. And we would expect, as we – 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 will offer is something that John touched earlier.

Unlike when we launched Galafold, which was a very successful launch, but we were building our commercial organization 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 we are 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..

And our last question comes from the line of Ritu Baral from Cowen..

Hi guys. Thanks for taking my follow-up. Just back on CLN about the Batten’s 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 patents that you’re pursuing?.

Yes, 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 Batten’s indication in CLN3. It’s been a series of interactions focused both on CMC.

Again, a lot of our activities for the last 1.5 years really have been focused on manufacturing, including the tech transfer from the university to scale up, and we’ve now completed GMP manufacture with our partners at Brammer-Thermo 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 regulator’s 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 Batten programs, please..

Sure. I’ll start first, Mitch. So 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 1/2 in terms of general size, single-arm study versus natural history, focused on Hamburg Motor and 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 1/2.

For CLN3, of course, our initial Phase 1/2 study was only the 4 patients. That was all the material we had from Nationwide. We would expect a much larger next study 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 CLN3.

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, etcetera.

Mitch, anything else to add from a high level from your perspective?.

No, Jeff. Thanks. I think you covered it well..

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 to 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..