Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics First Quarter 2024 Financial Results Conference Call and Webcast. [Operator Instructions] As a reminder, conference is being recorded..

I would now like to turn the conference over to your host, Mr. Andrew Faughnan, Vice President of Investor Relations. You may begin. .

Thank you, [ Hill ]. Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics' First Quarter 2024 Financial Results and Corporate Highlights. Leading today's call, we have Bradley Campbell, President and Chief Executive Officer; Sebastien Martel, Chief Business Officer; Dr.

Jeff Castelli, Chief Development Officer; and Simon Harford, Chief Financial Officer. Joining for Q&A is Dr. Mitchell Goldman, Chief Medical Officer; and Ellen Rosenberg, Chief Legal Officer. .

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

Any or all the forward-looking statements made on this call may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties and. 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, 2023, and the quarterly report on Form 10-Q for the quarter ended March 31, 2024, to be filed with the Securities and Exchange Commission today..

At this time, it is my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer.

Bradley?.

Great. Thank you, Andrew, and welcome, everyone, to our first quarter 2024 conference call. I'm pleased to report a strong start to the year across our global business.

We continue to build on the momentum of significant top line revenue growth on our way to our first full year of non-GAAP profitability while advancing our mission of bringing hope to patients and families affected by rare diseases.

As we did in this morning's press release, let me just highlight several key points before I turn it over to the team to go to more detail..

First, we continued our excellent commercial execution and delivered strong total revenue of $110 million, representing 28% growth year-over-year. Galafold continues its strong performance, and we remain very pleased with the continued commercial uptake globally.

For the first quarter, Galafold revenue was $99 million globally, representing 16% growth year-over-year on a constant currency basis coming in at the high end of our initial guidance for the year..

For Galafold, we continue to observe strong trends across our key performance indicators in all key geographies in the first quarter, including continued demand through new patient starts from both the switch and naive populations in all of our leading markets and sustained patient compliance and adherence rates of over 90%.

All of this is across the backdrop of the significant growth in the diagnosed and treated patients that we've highlighted previously. .

We see Galafold serving as the foundation of our business for the next decade and more. Based on Galafold's strong performance in the first year, we are pleased to be raising our full year 2024 revenue growth guidance from 11% to 16% to now 13% to 17%..

Second, let me highlight the strong global commercial launch of Pombiliti and Opfolda, our novel two-component therapy for late onset Pompe disease. Now launched in Germany, Austria, the U.K., the U.S.

and also now in Spain, [indiscernible], as we like to call it, is a huge driver of growth for us this year and our progress against our key performance indicators that we've shared previously continues to demonstrate the strength of this launch..

Our #1 focus for this year is to maximize the number of patients on therapy by year-end. And in light of that, it's great to report that the rate of new commercial patients coming on to [indiscernible] in 2024 is double that of last year.

In fact, for the month of April, we saw the largest number of new commercial patients start on Pombiliti and Opfolda since our launch. And as of the end of last month, we had 155 patients on treatment or scheduled for treatment. .

We're incredibly pleased with the patient and physician demand for this new therapy globally and continue to hear inspiring anecdotes from treaters around the world on how their patients are responding to Pombiliti and Opfolda, which will help continue to build the momentum throughout the year and beyond..

Sebastien will provide more details in a moment, but the switch dynamics in the U.S., Europe and U.K. also continue to look strong and we're seeing great progress on the reimbursement front globally, including moving patients more quickly through the insurance process in the U.S. as we anticipated we would.

We've also just launched in Spain and are off to a great start there. And throughout the remainder of 2024, we'll focus on increasing patient access as we gain reimbursement and then launch in additional countries throughout Europe..

Before I turn it over to the team, let me also comment on the new guidance we're providing. As we set upon approval and coming into this year, we needed about 6 to 12 months of trends before we had enough information to provide revenue guidance.

Now with more than 6 months since launch in the 3 largest Pompe markets and the great trends we're seeing, we feel we now have enough information to accurately forecast our performance for the year. .

You'll see in the press release and in the slides, for the first time, we've announced that we expect to deliver $62 million to $67 million in global sales, which will again be a significant contributor to our growth and set us on a great course to achieve our ambition for Pombiliti and Opfolda become the new standard of care in treating this devastating disease.

We are incredibly pleased to be providing a real choice for patients and physicians and challenging therapeutic expectations for people living with Pompe disease. .

Finally, as we continue our excellent commercial execution across both therapies and prudently manage our resources, we are confident we are well on track to achieve full year non-GAAP profitability in 2024..

Ahead on Slide 4, as we laid out at the beginning of the year, we continue to focus on delivering against our 4 key strategic priorities, including sustaining double-digit Galafold revenue growth. On the back of strong sales, again, we've raised our expected annual growth rate of Galafold to 13% to 17% at constant exchange rates.

Successfully executing on multiple commercial launches of Pombiliti and Opfolda, advancing our ongoing studies to support our medical and scientific leadership in Fabry and Pompe disease, and maintaining our strong financial position as we carefully manage our expenses and investments to achieve non-GAAP profitability for the full year..

With that overview, let me now hand the call over to Sebastien to further highlight our commercial performance.

Sebastien?.

Thank you, Bradley, and good morning to everyone on the call. I'll start by providing you with more details on our Galafold performance so far this year. As you can see on Slide 6, for the first quarter 2024, Galafold reported revenue reached $99.4 million, primarily driven by strong patient demand, particularly from our leading markets. ..

We ended the first quarter with more than 60% of the global market share of treated amenable patients, but we know there's still many more potential patients for our therapy.

As Bradley highlighted, given Galafold's strong performance in the first quarter, we're increasing our full year 2024 revenue growth guidance from 11% to 16% to now 13% to 17% growth..

Turning on to Slide 7. Our results in the first quarter highlight the strength of our global commercial efforts. The demand for Galafold globally continues to be strong with patients added in all major markets, delivering operational growth of 16% over the same period in 2023.

We're very pleased to see that Galafold grew at the high end of our initial guidance range in Q1 2024. And Galafold continues to be the fastest-growing treatment for Fabry disease globally..

Our leading markets such as the U.S., the U.K., top EU countries and Japan remain the biggest drivers of patient demand and gives great confidence in the growth this product has over the long term. With the global mix, which is about 42% switch and 58% naive now, we're seeing stronger uptake in naive population.

So we continue to achieve high market shares in countries where we've been approved the longest. .

There's still plenty of opportunity to continue to treat patients over to Galafold and to keep growing the market as we penetrate the diagnosed untreated and newly diagnosed segments.

All of this is underpinned by sustained compliance and adherence rates that continue to exceed 90% and reiterating our belief that those who go on Galafold predominantly stay on Galafold..

As mentioned on past calls, due to a variety of factors, including uneven ordering patterns and FX fluctuations, the rate of growth within the year is typically nonlinear. We expect that to continue in 2024.

So within the table on the right-hand side of the slide, we've provided a 5-year historical snapshot of the percentage of Galafold sales that occur each quarter during a given year. .

The average of quarterly sales distribution over the last 5 years corresponds precisely to what we achieved for the full year 2023. We would expect a similar trend to occur this year. And so as an example, we expect Q2 sales in the current year to be around 24% of full year sales..

On Slide 8, we know that there is significant patient demand for Galafold and that the segments of the global Fabry market made of patients with amenable mutations has the potential to reach up to $1 billion in annual revenue by the end of the decade. We anticipate sustained growth in 2024 and beyond to be driven by several key codrivers..

First, the Fabry market is growing robustly and with a significant portion of growth coming from finding new patients and reaching the diagnosed and treated population.

As we've mentioned previously, there were more than 2,500 individuals on Galafold at the end and of 2023 and about 1,400 of those individuals were naive to any treatment before Galafold..

Second, we've seen many new patients gone through treatment through newborn and family screening and we continue to increase patient identification capabilities through ongoing medical education and support of noble screening initiatives, including the use of artificial intelligence through our partnership with OM1.

Fabry is one of the most underdiagnosed rare diseases, so the more patients that can be identified, the more patients can be eligible for Galafold. We're also seeing many diagnosed untreated patients transition to treatment as the need for earlier treatments, especially in female becomes better appreciated..

The other piece is continuing to drive Galafold's market share of treated amenable patients through continued commercial execution. As noted, Galafold currently has more than 60% of the global amenable market, but we're seeing in our most mature markets that we can reach up to about 85%, 90% of market share.

So we know that there's the potential to reach those levels in the global market share as well. And again, all of these efforts are supported by solid compliance and endurance rates through physician and patient education and support programs..

Additionally, we'll continue to make progress on expanding Galafold into new markets and extending the labels. There's still some markets in LatAm, the Middle East, Asia Pacific region where Galafold is either newly reimbursed or we expect reimbursement. Also important to note here, we have often exclusivity in the U.S.

and Europe, in addition to our now 58 Orange Book-listed patents, 42 of which provide protection into 2038 and beyond, including 12 Composition of Matter patents. .

This provides us the opportunity to provide access to Galafold globally for a long time to come. We intend to continue to protect and enforce our broad intellectual property rights.

And looking ahead, we expect steady double-digit growth for Galafold throughout 2024, and we remain confident that with our strong IP protection, Galafold is a long runway well into the next decade..

Turning now to Pompe disease on Slide 10. We outlined our global launch progress with Pombiliti and Opfolda. For the first quarter 2024, Pombiliti and Opfolda reported revenue reached $11 million. This represents an increase of 30% compared to the fourth quarter of 2023 and provides a strong foundation for 2024.

In the first quarter, we actually achieved the same level of sales as we did in the last 6 months of 2023..

In the U.S., we continue to see a majority of patients switching from Nexviazyme about 73% and the remaining 27% from Lumizyme. This means we're switching patients proportionately from both products. We're also seeing a broadening and deepening of prescriptions with more sites coming online and multiple new prescriptions..

Outside of the U.S., we're seeing patients from all 3 segments, some switching from Myozyme and from Nexviazyme at a proportional rate to the respective market shares and some from the naive population. That's exactly what we want to see at this stage..

A few updates on the launch in Europe. We're happy to announce that Pombiliti and Opfolda is now reimbursed and launched in Spain occurring ahead of our internal expectations. We're very pleased with the fast reimbursement process here and increased access to this therapy throughout the European Union. .

In Germany, we're delighted with ongoing success in one of our largest European markets. Recently, the Federal Joint Committee, the G-BA, designated Pombiliti and Opfolda with minor additional benefits versus alglucosidase alfa or Myozyme based on an extremely stringent review of the data in the PROPEL trial.

This is a great achievement as Pombiliti and Opfolda is the only Pompe treatment to receive this designation and reflects the value [ HTAs ] are seeing in this therapy. This also reinforces our belief that this therapy has the potential to reset treatment expectations and that the improvement is possible..

And finally, we remain very pleased with uptake take of Pombiliti and Opfolda in the U.K., where we are heading towards capturing the majority of market share. Currently, we're close to passing 1/3 of market share within the U.K. with the benefit of [indiscernible], Pombiliti and Opfolda has actually been available for now 2 years in the U.K.

And we believe that the current market share is indicative of how this product can perform over a 3-year period and is a great example of Pombiliti and Opfolda's potential demand and uptake..

Given increased visibility on patient trends and pricing and reimbursement, we're now able to provide full year revenue guidance for Pombiliti and Opfolda. For the year 2024, we anticipate revenue of $62 million to $67 million for Pombiliti and Opfolda.

To put this in perspective, this is roughly 75% more sales than the first full year of sales from Galafold, which was a great launch by all accounts..

Moving on to Slide 11. As Bradley mentioned earlier, there are about 155 patients on treatment or scheduled for treatment as of late April. That's about 130 currently on therapy and about 20 who are scheduled.

We continue to be very pleased with ongoing demand for this therapy as the rate of new commercial patients coming on to Pombiliti and Opfolda continues to increase across all 3 markets..

Of note Q1 was the best quarter yet for new commercial patient starts, doubling the rate of new patient starts from 2023. In particular, April was the strongest month to date for new patient starts and new commercial patients.

This is important as it further supports our thesis that launch momentum will continue to build throughout the year as we move more quickly through the prescription to treatment process in the U.S. and as we launch in new countries in Europe. .

Our launch has leveraged our highly experienced cross-functional team, and we've had great outreach with key opinion leaders. We're seeing an increase in the depth and breadth of prescribers across all 3 markets and in particular, a growing number of prescribers who are not part of our clinical studies or expanded access programs.

All core treating centers have been engaged, and we've had very positive feedback from HCPs and other stakeholders as to our business approach, our support and patient focus..

Finally, we find an important metric to track is our progress with access and reimbursement. We have a highly experienced team who are engaging in positive conversations with payers to demonstrate the value of Pombiliti and Opfolda. In the U.S.

and with the start of the new year, many large payers have already put Pombiliti and Opfolda to their respective formularies. And we've also seen strong acceptance by Medicare medicaid. .

The overall time core from prescription to infusion is now down to around 70 days. The last few commercial patients have actually come in even quicker. We believe that this will continue to improve. Today, we launched in Germany, in Austria, in the U.K., the U.S. and now Spain.

But we remain in active pricing and reimbursement discussions with additional major markets as we focus on securing broad patient access throughout the European Union. .

More than 10 reimbursement dossiers have been submitted. Overall, we're starting off the year strong, and we're very pleased with the building momentum on patient demand. Throughout 2024, our focus will be on maximizing the number of patients on therapy by year-end..

So in summary, we're very pleased with the launches of Pombiliti and Opfolda across the first wave of countries. The strength of our clinical data and the depth of experience and talent we have at Amicus gives us great confidence in our ability to make a real difference for people living with Pompe disease.

We believe Amicus is in a great position with our second successful launch..

And with that, I will hand the call over to Jeff Castelli, our Chief Development Officer, to discuss the ongoing clinical studies and regulatory updates.

Jeff?.

Thank you, Sebastien and good morning, everyone. Moving on to Slide 12. We remind everyone that we continue to build the body of evidence for Pombiliti and Opfolda through our ongoing clinical studies and our registry as we also continue to execute on expanding commercial access through regulatory submissions.

As we enter the second phase of launch, in addition to the 10 different reimbursement dossiers that we're in the process of submitting or have submitted that Sebastien mentioned, we also have multiple ongoing or planned regulatory submissions for marketing approval in new geographies and throughout this year. .

As we speak, our regulatory dossiers are being reviewed in Switzerland, Australia and Canada, and we're working towards a submission in Japan in the second half of this year.

Importantly, for the younger Pompe community, we continue to enroll the ongoing open-label ZIP study for children living with late onset Pompe disease and the open-label [indiscernible] study for children living with infantile-onset Pompe disease.

We see this as an important opportunity to support label expansions into these patient segments in the years ahead and to address the significant unmet needs in these patients..

Through our ongoing studies in the Amicus Pompe registry, we continue to generate evidence on the differentiated mechanism of action and the long-term impact of Pombiliti and Opfolda across endpoints and different patient populations.

As a reminder, in February, we once again had a significant presence and very successful set of interactions at the 20th Annual World Symposium. We had 11 posters and an oral presentation highlighting our continued work across Fabry and Pompe disease. Our medical conference presence is an important part of our education efforts..

Finally, as highlighted in the pipeline side in the appendix for our earlier stage pipeline, we continue to focus on novel approaches for Fabry and Pompe, including delivery of our engineered GLA and GAA transgenes as well as the next-generation Fabry Chaperone..

With that, I would like to turn the call over to Simon Harford, our Chief Financial Officer, to review our financial results, guidance and outlook.

Simon?.

Thank you, Jeff. Our financial overview begins on Slide 14 with our income statement for the first quarter ending March 31, 2024. For Q1, we achieved total revenue of $110 million which is a 28% increase over the same period in 2023. At constant exchange rates, revenue also grew 28%.

The global geographic breakdown of total revenue during the quarter consisted of $73 million or 66% of revenue generated outside the United States, and the remaining $37 million or 34% coming from within the U.S..

Cost of goods sold as a percentage of net sales was 12% in Q1 due to validation costs in the quarter as compared to 8% for the prior year period.

Total GAAP operating expenses increased to $125 million for the first quarter of 2024 as compared to $117 million in the first quarter of 2023, an increase of 6% due primarily to a facilities lease restructuring charge. .

On a non-GAAP basis, total operating expenses increased to $86 million for the first quarter of 2024 as compared to $81 million in the first quarter of last year.

We define non-GAAP operating expenses, research and development and SG&A expenses excluding stock-based compensation, loss on impairment of assets, changes in fair value of contingent consideration, restructuring charges and depreciation..

On a GAAP basis, net loss for the first quarter of 2024 reduced to $48 million or $0.16 per share compared to a net loss of $53 million or $0.18 per share for the first quarter of last year. In Q1 2024, there was a non-GAAP net loss of $4.6 million driven by the negative impact of foreign exchange.

This was in line with our expectations of a small loss in Q1 as absolute dollar revenue is traditionally lower in the first quarter. Cash, cash equivalents and marketable securities were $240 million as of March 31, 2024, compared to $286 million as of the end of December 23..

Turning now to Slide 15. We are guiding to full year 2024 total revenue growth of 25% to 30%. This is driven by the increase of our full year 2024 Galafold revenue growth guidance from 11% to 16% previously to 13% to 17% currently at constant exchange rates.

It is also driven by guidance of $62 million to $67 million for Pombiliti and Opfolda sales for the full year..

On full year 2024 non-GAAP operating expense guidance remains at $345 million to $365 million. With our commitment to full year non-GAAP profitability during the first full year of launch of Pombiliti and Opfolda, we are keeping operating expense growth in low single digits year-over-year at the midpoint of guidance.

As a reminder, we continue to have R&D commitments, including registry studies in both Fabry and Pompe, the ongoing Pompe Phase III study in countries not yet reimbursed as well as next-generation manufacturing for Pombiliti. .

With our total revenue guidance of 25% to 30%, we remain comfortably on track to achieve our first full year of non-GAAP profitability in 2024 as profitability grows quarter-by-quarter for the remainder of the year..

And with that, let me turn the call back over to Bradley for our closing remarks.

Bradley?.

Thank you, Simon, Jeff, Sebastien for the color. So as you can see, we have been highly focused on execution this year across the business, and we've made a strong foundation for what will be another important year of commercial execution.

We're confident in our leadership position in Fabry and Pompe disease and that Amicus can continue to drive sustainable long-term value and deliver life-changing therapies to people in need..

With that, operator, we can now turn the call over to questions. .

[Operator Instructions] The first question comes from Anupam Rama with JPMorgan. .

As you guys were constructing sort of the guidance for Pombiliti and Opfolda and you started looking at Street models, where did you see the biggest disconnect between your guidance and Street models, given that almost $30 million divergence there?.

Yes. Thanks, Anupam. Appreciate the question. I think the most important thing is that when we came into the launch and then into this year as well, we were pretty clear that we needed 6 to 12 months of trends to be able to provide accurate guidance.

I think you've seen historically, once we provide guidance, we do a great job of executing against that as we saw again here at Galafold..

The biggest drivers of what we really needed to understand coming into the year was timing to get new patients through the insurance process in the U.S. And I think we have a clear view of that now.

I think that's probably the biggest disconnect from where just the rate of revenue coming into the year versus what perhaps the Street was initially modeling. .

Of course, we wanted to see the rate of new commercial starts, which as we've seen now, is building momentum, which we expected to see. And then it's also timing of launches in Europe. And as we go through the reimbursement process and as Sebastien highlighted on the call, we're starting to see some real wins there.

We needed to kind of understand that cadence and outcome as well..

I think maybe the last piece is, again, factoring in that time from prescription to infusion, you also get a higher distribution of revenue coming from the European patients, which of course, is a lower price. So I think that probably -- those 2 things that have multiplying capacity. But now, look, we have the information we need.

I think the big picture here is that this is shaping up to be a very successful launch. As Sebastien said, it's almost double the first year that we did for the first full year of Galafold. .

And I think the big picture for us is that this will be a huge driver of growth this year, and it really sets us up for our ambition to become the standard of care in Pompe, which, of course, is that sort of $1 billion product opportunity that we're aiming for.

And I think now we can do what we do best, which is execute against our guidance and drive growth in both of these products and then deliver on our financial performance as well with that non-GAAP profitability. .

The next question comes from Joseph Schwartz with Leerink. .

This is Will, on for Joe. One for us just on kind of manufacturing. We've seen the BIOSECURE headline.

So could you just remind us of how you feel about your ability to navigate the situation? Has the new manufacturing facility come online in Ireland yet? And can you just remind us of where you are in that process and your ability to kind of keep supplying and stockpiling throughout the year?.

Yes. Great question. Thanks, Will. And I'm glad you raised those headlines. They sort of came in right when we were doing the call here. But for those of you who haven't seen it, I think Endpoints reported what we had anticipated coming out, which is the new markup from the Senate of the BIOSECURE bill proposes a 2032 sort of grandfathering phase. .

So effectively, contracts that are existing from what we understand and from what the article reported, contracts that are existing would actually be grandfathered in out to 2032. So that would give us plenty of time to find a second source of manufacturing if that bill ever comes to pass..

And so I know that, that's been a big focus for investors and analysts. It's been a big focus for us as well. But behind the scenes, we have grown increasingly confident that now Congress understands the importance of that transition period. And I think that 8-year proposition would be plenty of time for us to find a second source. .

In the meantime, I think we've made great progress against any kind of supply challenges. So as a reminder, our target is 18 to 24 months of supply throughout the supply chain. And right now, we're trending at about 24 months or the high end of that range..

We also had begun moving products out of China into a central depot in Europe. And now we've started moving that products further into the market, so sitting in the U.S., U.K. and in Europe. More than 65% today of our global supply fits either in Europe or in the U.K. or the U.S.

So I think we've done a great job in continuing to mitigate away from sitting in China..

And then to your last point, yes, making great progress in Ireland. PPQ batches are well underway. We continue to think that, that product will come into the supply chain at the back half of next year or early 2026. So I think we've done a great job in all 3 of those areas.

And we have high confidence that anything that comes out of the BIOSECURE Act, we have plenty of time to be able to react against that. .

Our next question comes from Eliana Merle with UBS. .

In terms of your guidance, can you help us understand the assumptions that go into it for [indiscernible], specifically the mix between U.S. and ex U.S. revenues as patients start. What markets ex U.S.

does this include sales force? And I guess just can you remind us what proportion of the EAP and clinical trial patients are now reimbursed versus the proportion of that are not yet reimbursed?.

Yes. So 2 camps there. First is what goes into the rate of new patient capture. I would say, continuing to build momentum in the current launch countries. So U.K., U.S., Germany, now Spain, Austria as well.

We do expect a number of European countries to come on board throughout the back half of the year, a number of the EU5 or EU4, I guess, remaining countries as well as some of the smaller Northern European countries.

I think all of those will contribute to the patient capture rate and that's why we've talked about, I think, maximizing the number of patients. The more patients we get on to the end of the year, of course, the better the run rate going into next year. So that's a big piece of it..

In terms of distribution of revenue between the U.S. and Europe, remember we had more patients on clinical trial in EAP drug coming out of Germany and the U.K. than we did in the U.S.

So I would say for the majority of this year, it's going to be still weighted more heavily towards Europe and especially as we have more launch countries in the back half of the year. Over time, though, we would expect the revenue, the proportion of revenue to be something like 40-ish percent coming out of the U.S.

and the balance coming out of ex U.S. So you'll see that move towards that 40% over time..

And then, Jeff, do you just want to talk about the remainder of the clinical trial EAP patients in Europe and what we have left to convert there?.

Yes. Thanks, Brad. So in terms of remaining patients and trials expanded access, there's about 65 or 70 of them that are adult, about 40 of those are in Europe. The rest or sort of rest of world being Japan, Australia, Canada, et cetera.

And then of those 40 in Europe, about 20 are in those sort of 10 countries that we are expecting reimbursement this year. But again, that will be staggered towards second half of the year..

We also have a number of pediatric patients. Those actually continue to increase as we continue to enroll Brazil [indiscernible]. But I think from a commercial perspective, thinking about the 65 to 70 adults, 40 in Europe, 20 in countries that would come on later this year. .

The next question comes from Ritu Baral with TD Towen. .

This is Athena, on for Ritu. Another question on BIOSECURE.

If the Ireland plant changes hands, what percentage of the raw material going to Ireland or from China stores? And what percentage are sole-sourced China supply?.

Yes. It's a fair question. We are -- as you might imagine, we are also looking at ways to find material from outside of China as well. And again, I think that 8-year extension period would give us plenty of time to be able to do that. Many of the raw material has actually come from European-based companies already. .

And I think that Congress has clearly now understood that yes, this initiative might be important. But given the number of patients, the millions of patients who take a medicine, not just Pompe, but across many other diseases, take a medicine that has some component part manufactured elsewhere that they need to have that transition period.

So that 8-year period would be plenty of time to do that. .

The next question is from Jeffrey Hung with Morgan Stanley. .

This is Catherine on for Jeff. We just had one on the Amicus Pompe registry.

Can you talk more to what your goals are here? And any expectations that you have on how many patients you might be able to enroll on an annual basis? Especially when it comes to your goal of maximizing Pombiliti and Opfolda patients on treatment by year-end? Any color here would be appreciated. .

Sure. Thanks for the question. And I'll just hit one overview statement, and then I'll let Jeff talk a little bit more to the details. So the registry, I would say, serves 2 really important purposes. The first is, as is almost the case in rare diseases, it is a commitment -- post-marketing commitments. So we do have an obligation to do it.

But I think the real value that comes out of the registry is all the real-world evidence that you start to generate that you could then use to further provide proof to physicians and patients on how they're responding to the [indiscernible] treatment. .

And one unique opportunity we have, and then I'll let Jeff provide more details in terms of the numbers that you were asking for. One unique opportunity we have is we do have a registry coming out of the U.K. EAMS program. Remember those patients have been on drug for 1 year to 2 years.

And so that has sort of a real-world near-term opportunity to provide data out to the prescribers and to the patients out there.

But Jeff, maybe talk a little bit more about the numbers in both the EAMS and then the broad registry?.

Yes. Thanks, Brad, and thanks, Catherine, for the question. So in terms of the Pompe registry, I mean the real vision, as Brad said, it's to cover the reg requirement for safety, but then also similar to Galafold just to continue to collect real-world data in all these patients.

So our plan is to have that registry available in most of the countries that we go commercial in to have hundreds of patients. I can't recall the exact high-level number on the upside that it has, but it's hundreds of patients. ..

Importantly, it's really for commercial patients. So we continue to have patients in access and trials and they remain in those programs, and we continue to collect data in those programs. Generally then when they become commercial patients, the way for us to continue to follow those patients would be through a registry.

So right now, we have the registry targeted in the U.S., U.K. Germany, Spain, where we are going commercial. .

So that's the way to think about it. It doesn't really impact commercial uptake or anything. It's more of a way to capture data in those commercial patients long term, both safety but then importantly, kind of long-term real-world data on quality of life, durability, et cetera. .

The next question comes from Kristen Kluska with Cantor Fitzgerald. .

For Galafold, we haven't really seen much of a slowdown in terms of the ability to continue finding naive patients.

So can you comment on your expectations for the cadence of this moving forward? Or do you see any early signals of this slowing down?.

Thanks, Kristen. Yes, I think that's a really important point. And we highlighted previously in our presentation, just the remarkable growth in this market. Just as a quick reminder, when we launched 7 or 8 years ago, we estimated about 10,000 diagnosed patients, about half of them were treated.

Now we're treating 11,000 patients globally between Galafold and the other therapies, but there are further 6,000 diagnosed untreated patients. .

We actually think that this is going to continue to grow the diagnosis rate. It's a combination of low-cost readily available genetic testing, also much more intelligent screening and then, of course, the work that we're doing, which others are doing as well, looking at artificial intelligence.

So we think that, number one, you're going to continue to treat those diagnosed untreated patients as they move through their disease course. And of course, we've seen that already with Galafold. And then we think you're going to just keep finding more and more patients..

If you look at the statistics, this is the most under-diagnosed genetic disease, and there could be double or triple the number of patients living with Fabry who are not diagnosed today. So that's a really important part of the story of Galafold.

And if you think about what we offer with Galafold, which is an oral medication which has shown to be clearly impacting so many patients around the world. We think that would be a great option for patients that are newly diagnosed with the disease. .

The next question comes from Tazeen Ahmad with BofA Securities. .

Brad, I just wanted to ask you about Pompe.

When you came up with your guidance for the year, what proportion of that guidance is an assumption that you're making? About how long patients are staying on the [indiscernible] products before switching? We have had conversations between us and you as well as the physicians that indicated that, that could conceivably start to switch patients as early as 2 years from the previous drug.

But how is that working out in the real-world setting so far? And what part of your guidance, is that contributing to?.

Yes. Thanks, Tazeen, and looking forward to seeing you at the conference next week. So yes, it's a great question. What we had heard coming into the launch was that physicians were thinking they needed kind of at least a year of treatment before they would think about switching of patients.

And then patients said, look, if I'm not doing well, I'd be willing to switch within 6 months. ..

And I think if you look at the switch dynamics that we highlighted for the United States, we're seeing 75% roughly of our switch patients are coming from Nexviazyme and 25% are coming from Lumizyme. I think that's a pretty fair reflection because Nexviazyme launched a little over 2 years ago.

So you're starting to see a bolus of patients go through that kind of 1-plus year period. .

I do think that there are some physicians sure who will be thinking more about that 2-year period.

And my view and our expectation is better we demonstrate outcomes in those patients who do switch, the more likely that physicians are going to start to think that, "Hey, I should be thinking about doing this sooner, and even I should be proactive." And I think that's what we've talked about is kind of the real battle here is for that "stable middle" and that -- when we win that, the hearts and minds of those patients and physicians, I think that's where that momentum continues to build.

So we're seeing great trends right now. I think what we are seeing is what we expected to see in that kind of 1- to 2-year switch period..

And then outside the U.S., remember where Nexviazyme hasn't been in the market for nearly as long and in many cases, we're launching kind of head-to-head, we're seeing switches from majority Lumizyme because that's the majority of the population, but we're also seeing Nexviazyme switches and we're seeing strong uptake in naive patients.

So I think as long as those trends continue, and we think they'll actually accelerate, that will clearly support our guidance and then much more room to grow from there. .

The next question comes from Dae Gon Ha with Stifel. .

This is Benazir, on for Dae Gon.

Can you speak to your appetite on business development opportunities to kind of bolster the pipeline? And kind of wondering if the volatile markets and depressed valuations are drawing your attention and if so, what therapeutic areas would you be considering?.

Thank you for the question. Yes.

Sebastien do you want to just give an overview of what we've talked about previously in terms of how we're thinking about business development opportunities?.

So as you know, we've got plenty of growth still generated from Galafold as we just discussed, and we're in the midst of the launch rollout of [indiscernible]. Hence, the very strong growth rate that we've provided today in terms of overall sales growth for Amicus as a whole.

Yet, we've been doing our homework from a BD and M&A side of things, have been developing a framework on addressing what potential disease areas or even specific indications might be of interest. .

I think we, over time, have developed a very solid infrastructure from a commercial and medical standpoint as well as from a development and regulatory standpoint and we could clearly be able to leverage that.

We've been looking at what we call adjacencies when it comes to indications, so thinking of Fabry as a rare renal or rare cardiac disease, thinking of Pompe as a rare neuromuscular or more broadly speaking rare neuro. So these are some of the therapy areas that are of interest to us..

When it comes to stage of development, we are more focused and more interested to look at later stage opportunities.

And by that, I actually even include potentially marketed assets, recently approved drugs or products that are still in the launch phase or product programs that are currently undergoing Phase III trials so that we would be initially more focused on assets that could provide a fair amount of accretion fairly quickly as opposed to investing in early-stage tech platform type of opportunities.

.

The final question comes from Salveen Richter with Goldman Sachs. .

This is [indiscernible] on for Salveen.

Can you comment on what you're hearing from physicians in the EU with regard to real-world experience with [indiscernible] and Nexviazyme? And are there any details emerging as the real world accrues? And in the U.S., can you discuss the efforts to decrease the time line from 70 days from prescription to infusion?.

Yes. Thank you for the 2 questions. I would say, for sure, we continue to hear incredibly positive anecdotes coming from physicians and patients in the United States, in particular around their experiences on Pombiliti and Opfolda, I won't speak to the other products.

But I think that will be a huge driver of word of mouth and confidence in this product. We're just seeing things that I think are really inspiring and will inspire others as well..

One place to look for some of that is Dr. Mark Roberts did have a presentation at the World Congress this year, where he presented on some case studies coming out of the EAMS program. He was one of the EAMS physicians in the U.K. So that's a good place to look.

There was also another EAMS site that published a poster, I believe, last year, that also looked at a number of patients and how they were responding to the therapy. .

So I think there is -- and that's something that we will continue to focus on as well as kind of building that body of evidence, both through the registry, as Jeff highlighted, but then also through physicians who are having those experiences. I think that will be a significant driver of momentum going forward..

The second question in terms of the insurance process. So really, there's two key components. The first component, and this is really the long tent in the pole, is when you first launch, you don't -- you're not in any of the formularies.

And so you typically go through what's called a letter of authorization process that takes time and it's a process that we know well from Galafold, but you just have to work through that system. That's probably the longest part. .

And then when you come in at the beginning of the year, you start to come on to formularies, both for hospitals and major insurers and we're doing that. We're also seeing patients go through Medicare and Medicaid very successfully. So all those things are happening kind of when we thought they would..

The second piece of the puzzle is then just purchasing the drug and getting the drug and then scheduling the infusion. And so that takes a little bit of time as well. Our goal is that steady state, this can get down to kind of 30 to 45 days, which is what we see with Galafold. And just as an aside, the 2 most recent commercial patients in the U.S.

were in that time frame. So that's a place that we know we can get to, and we're glad to see the progress so far this year. .

That was your last question. This concludes today's conference call. Have a great day..