Good morning ladies and gentlemen and welcome to the Amicus Therapeutics Full Year 2022 financial results conference call and webcast. At this time, all participants are in a listen-only mode. Later we will conduct a question-and-answer session and instructions will follow at that time. As a reminder, this conference call 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.

Great. Thank you operator. Good morning everyone. Thank you for joining our conference call to discuss Amicus Therapeutics full year 2022 financial results and corporate highlights. Leading today’s call we have Bradley Campbell, President and Chief Executive Officer; Daphne Quimi, Chief Financial Officer; Sébastien Martel, Chief Business Officer; and Dr. Jeff Castelli, Chief Development Officer. Joining for Q&A is Dr. Mitchell Goldman, Chief Medical Officer, and Ellen Rosenberg, Chief Legal Officer. As referenced on Slide 2, we may make forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business as well as our plans and prospects. Our forward-looking statements should not be regarded as representation by us that any of our plans will be achieved. Any or all of the forward-looking statements made on this call may turn out to be wrong and can be affected by inaccurate assumptions we might make, or by known or unknown risks and uncertainties. You are cautioned not to place undue reliance on any forward-looking statements which speak only as of 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 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, 2022 to be filed with the Securities and Exchange Commission today. At this time, it’s my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer. Bradley?

Great. Thanks Andrew and welcome everyone to our full year 2022 results conference call. I’m pleased today to highlight the progress we’ve made across our business throughout 2022 and now into the start of 2023. As we did in this morning’s press release, let me highlight several key points. First, Galafold continues its strong performance and remains a cornerstone of our success. We continue to be very pleased with a strong demand for and growth of Galafold globally, with now over 2000 people living with Fabry disease, taking Galafold as their only treatment for Fabry. What an amazing milestone for this precision medicine. And despite the significant foreign currency headwinds experienced throughout last year, in 2022, we reported Galafold revenue growth of 8% or 16% on an operational or constant currency basis. Throughout last year and into this year, we continue to see strong trends across a number of our key performance indicators, including increasing demand through new patients starts from both the switch and naive populations, continued growth and in person visits between our field teams and Fabry traders throughout the world and sustain patient compliance and adherence rates of over 90%. In 2023, we expect to see continued double digit Galafold growth fueled by significant demand from patients and physicians. We’re also pleased by the growing Galafold Intellectual Property estate through the issuance of 19 new patents over the last year. There are now a total of 46 Orange Book listed issued patents related to Galafold in the United States, 30 of which provide protection to 2038 and beyond. And importantly, this includes five composition of matter patents. We see this patent portfolio, along with our orphan drug exclusivity, providing broad and long-term intellectual property rights well into the late 2030s for this novel, precision medicine. Second, we…

Thank you, Sébastien, and good morning everyone. On Slide 12, we’ll start with our AT-GAA program. We recognize that Pompe disease continues to pose a range of health challenges for people affected by the disease, and having therapeutic choices is crucial. Pompe is a severe and fatal neuromuscular disease and one of the most prevalent lysosomal disorders, and multiple publications and natural history studies continue to highlight the initial benefits of treatment, generally being followed by continued long-term decline on key measures of disease for many individuals. Moving onto Slide 13 as Bradley mentioned, we are very excited to now be anticipating potential regulatory approvals and launches into three of the largest Pompe markets in the third quarter of this year. Here on the slide we’ve highlighted the status or our anticipated regulatory milestones this year by market. First in the EU, the European Commission approval pumpability is expected in this first quarter later this month. And for miglustat we’re making great progress on the confirmatory testing and are on track to snip those validated final data EMA for an expected CHMP opinion in the second quarter which would then be followed by EC approval in the third quarter. And then the U.S. the required pre approval inspection of the WuXi Biologics manufacturing site in China was typically [Indiscernible] manufactured, has been scheduled with the FDA for the second quarter, and we anticipate approval of both components of AT-GAA in the third quarter pending a successful inspection. Finally, the regulatory submission process for AT-GAA in the U.K. was initiated in December. They had a recognition procedure based on the CHMP opinion, and we’re on track for an expected MHRA approval also in the third quarter. Moving on to Slide 14, to highlight our on-going clinical studies, and providing expanded access…

Thank you, Jeff. And good morning, everyone. Our financial overview begins on Slide 17, with our income statements for the full year ending December 31, 2022. For the full year, we achieved total revenue of $329.2 million, which is an 8% increase over 2021. This includes year-over-year operational revenue growth measured at constant currency exchange rates of 16% impacted by negative currency of 8%. Cost of goods sold as a percentage of net sales was 11.7% in the year as compared to 11.3% in the prior year period. Total GAAP operating expenses increased to $502.8 million for the full year 2022 as compared to $477.5 million in 2021. On a non-GAAP basis, total operating expenses were $413.2 million for the full year 2022 as compared to $406.9 million in 2021 reflecting non-recurring expenses related to the reprioritization of Gene therapy portfolio offset by decreased program spent. We define non-GAAP operating expense as research and development and SG&A expenses excluding share based compensation expense, loss on impairment of assets, changes in fair value, contingent consideration and depreciation. Net loss for the full year 2022 was $236.6 million or $0.82 per share, as compared to a net loss of $250.5 million or $0.92 per share for the prior year period. Driven by the revenue growth of Galafold and careful expense management, we continue to make progress towards our path to profitability in the second half of this year. As of December 31, 2022, we had approximately 281 million shares outstanding. Turning now to slide 18, we continue to operate from a position of financial strength, and our goal remains to achieve non-GAAP profitability in the second half of 2023 as defined in our press release. Profitability is dependent on a number of factors, including, of course, the timing of approvals and the…

Great, thanks, Daphne, Jeff, Sébastien. As you can all see, we have been relentlessly focused on execution across the business. We continue to operate from a position of financial strength and remain on the path to profitability in the second half of this year. And we continue to advance the growth of our two franchises in Fabry disease and Pompe Disease, which we believe can enable us to create sustainable long-term value and deliver life changing therapies to people in need. Operator with that, we can now open the call to questions.

[Operator Instructions] And our first question comes from Anupam Rama of JPMorgan. Your line is open.

Hey guys, thanks so much for taking the questions. With the regulatory decisions coming here in 3Q, as you look at the next few years and the Sanofi launch here, what are some key learning similarities differences that you would highlight as we think about the AT-GAA launch firm? Thanks so much.

Yes, thanks, Anupam for the question. Look, for us it really just comes back down to the data and the population we studied. We were really excited to be able to present the long-term data both from the Phase I/II study as well as from our Phase III propel study and the on-going extension there. We continue to believe that showing that impact in patients switching from enzyme replacement therapy is going to be the key differentiator for AT-GAA. And as we look at all of the demand for expanded access, and those mechanisms that we discussed on the call in particular in the U.K., we think that patients and physicians are just really excited to have a new treatment options. And we’re thrilled now to have a clear line of sight to timing and to be able to move forward as quickly as we can to approvals and then to the launch

Thanks so much for taking the question.

One moment for our next question. And our next question comes from Ritu Baral of Cowen. Your line is open.

Good morning, guys. Thanks for taking the question. The question itself is, how fast should we start booking revenues after we know, the inspection? I guess? Of course, my question has three parts one, how fast should we be thinking about approval after the inspection? Is it a week kind of thing? And how will the model changeovers to commercial from these 195 patients that are in your extended access programs across the world, and we expect all of them to fall under the approved label finally? Thanks.

Yes, thanks Ritu, I’ll try to hit all three of those. The first one is relates to timing from inspection to approval in the U.S. What our team’s estimate is that takes about two months to go through that process. And so that’s why we’ve set the inspection is in Q2, and we expect approvals in Q3. In terms of converting patients from clinical trial, or expanded access to, to commercial product, our goal has been to do that within 90 days. And we saw that we were able to execute on those timelines with Galafold. And we have the same goals here. In terms of numbers of patients within that kind of 195, again, that number we think will continue to grow, I would say there is a small portion of them who might be infantile onset patients. But that would be a very small portion, I think the vast majority of between the Phase I/II studies, the Phase III study, and then expanded access programs are going to be late onset patients who fall within the anticipated labels. So I think the majority of those patients would be eligible. And, and of course, not all of them are in the first three large countries, U.S., U.K. and Germany. But certainly the majority happened. Just to give you a flavor of the distribution between regions, about 60 of those patients are in the in Europe, about 50 in the United States, about 40 in the United Kingdom, and the balances is rest of world. So hopefully that gives you kind of a flavor of the numbers of patients. And then in terms of revenue. Look, I think what we’ve cautioned people is that will be a modest contribution to revenue this year. But I think you hit on the really important point, which is our job this year is to put as many patients as possible who are appropriate onto AT-GAA, of course, with the expanded access and on-going extension studies, but then of course, with the new commercial patients as well. So our focus is maximize the number of patients on therapy. And that gives you a really strong run rate going into next year.

Great Thanks for taking the questions.

Thanks Ritu.

One moment for our next question. And our next question comes from Tazeen Ahmad of Bank of America. Your line is open.

Hi, guys. Good morning. And thank you for taking my question. Perhaps just a simple one for me. So when you say that the infection has been scheduled, does that mean that FDA kind of just decides who they want to send over, and that team just goes? Or does there has to be some process that includes for example, the State Department needing to pre clear it, just wondering what the technicalities are on that? Thanks.

Yes, thanks Tazeen for the question. At this point it, what we understand from the FDA, this kind of business, as usual, is relates to the inspection. So of course, they’ll need, pieces and those kinds of things. But that process is underway. From what we understand, we feel very confident that they now have an inspection scheduled and we’ll be able to, to execute upon that inspection. To give you an example, we have our own team members who are now going to China to visit the site who haven’t been able to get there for all the reasons we’ve discussed for a number of years now. So our understanding is that it’s business as usual. And we should be very competent in those days, of course, caveat [Ph] by you never know what’s going to happen. But I think where we are at this point, what we’ve seen, what we’re seeing from our own team, is that it’s business as usual, and there’s no special requirements in order for them to be able to execute inspection.

Okay, thank you.

Thanks Tazeen.

One moment for our next question. And our next question will come from Ellie Merle of UBS. Your line is open.

Hey guys thanks so much for taking the question. Jeff, in some of maybe your pre commercial work, how should we think about the uptake in switches from Lumizyme or Myozyme relative to say switches from [Indiscernible] I guess in the U.S. And then I guess just what’s the feedback from physicians on how often they see their Pompe patients and like whether patients might say be called in whether it has been to get [Indiscernible] or whether it be to get AT-GAA given the potential approval? Thanks.

Sure. Thanks, Ellie for the questions. Maybe I’ll take a stab at the first one. And then and then Jeff can talk to the kind of frequency of interactions with physicians and patients. So in terms of who we would be targeting, for our, our launch in the United States, where I think we anticipate a label for experienced patients. We would I think, target any segment where physicians or patients feel like there’s a need or an opportunity to try new therapy. And so for us, that could mean both the lumizyme patients as well as the Nexviazyme patients. And again, I would just, the thing that we are most focused on is the is the unique data that we have with from the only study that studied in a controlled portion, patients who are on enzyme replacement therapy switching to another therapy during that controlled phase. And we think those data will be highly differentiated and highly compelling for physicians and patients across the population. Jeff, do you want to talk a little bit about the kind of frequency of interactions between physicians and patients?

Yes, thanks, Brad and thanks Ellie. So physicians, typically will atleast see their patients every six months or a pretty comprehensive assessment. Obviously, it depends if they’re getting infusions at the clinic, they may or may not see them more regularly, if they’re the ones doing the infusions. But that larger workout every six months, is really when they get a sense of how the patients are doing from the last kind of comprehensive exam they had. So as Brad mentioned you know, is patient or physicians and patients are thinking about treatment changes, if they’ve started a new treatment, they probably would go about 12 months before they make the final kind of call or first call on whether they’re doing well enough and might consider a new treatment. But, as we’ve seen, at least in the U.S. many of the patients from the next design studies that have switched to been on that treatment now for much over a year. So I think there’s certainly an opportunity we expect from a labeling perspective, from a potential need perspective to have switches from both of the products that are available currently.

And Sébastien, maybe just give us a color for some of the distribution of recorded sales of the product. Sébastien Martel: Yes, Ellie, just add that as we look at to, to the last quarterly sales reported by Sanofi, looking at the speed within miles on the Nexviazyme, the vast majority of sales continue to be on miles on 77% for the fourth quarter on a global basis. Outside of the U.S., this is actually a lot higher than that 93% of sales were coming from myozyme, rest of world was 85%. And in the U.S. to 60% also feel coming from myozyme. So the majority of patients by the time we launch will likely still be on myozyme. I think the switch data that we have bodes well for switch quality weeks.

Thanks, Sébastien. Sébastien Martel: Thank you, Ellie. Anything else?

Perfect. Thanks for that.

One moment for our next question. And our next question comes from Joseph Schwartz of SVB Securities. Your line is open.

Hi, thanks for the update. I was wondering if you could comment on your Pombiliti launch readiness in terms of manufacturing supply? How much are you accruing? And is there any reason that any of the supply you’re building ahead of the launch should not be used? And what’s your strategy for continuing to build supply?

Yes, thanks for the question. So we have I think, prudently continued to manufacture AT-GAA and I think we noted last year in our financials, and Daphne highlighted quite a bit of an investment there. So we’re on track to have significant supply for all of our anticipated launches, we feel really good about that. We typically move products into, country in advance. And so with the positive progress in Europe, I think we’ve talked about now being able to start the process of release testing around Pombiliti, which is the ERT there. And then likewise, in United States, we’ve actually begun to move products here as well. So we feel really good about launch inventory. Our overall supply strategy I think we’ve described before which is we have plenty of capacity and supply coming out of China to support the first, year or two of launch. However, we, with our partners in WuXi have already started the process of standing up the new facility in Ireland. And I think, as we’ve mentioned before, we expect that capacity to come online, in in sort of the 24, 25 timeline. And that would be really when you’re starting to see the meat of the balance of Europe coming on board and starting to see some rest of world countries as well. And so that will become I think, the primary source of capacity for the long-term manufacturer of the product. So really feel really good about where we are today with a clear plan of how to continue to grow and support the globalization of the product launch.

Thanks Brad. And could [Technical Difficulty] it was done previously, how does that change? The interpretation, if at all, and what feedback did you hear in general from physicians who saw all the data that you reported it world?

Yes, Joe, what you stated a little bit, I think the question the first part of the question was, in the way we displayed the data, and we presented it -- as present predict present perfect predicted value, excuse me, versus change from baseline. And then the second question was, what was the response from the audience at world? I’ll take the second one first. And then and then I’ll ask Jeff to comment on the first one. So I think overall, it was great to be in person at world as you can imagine, tons of activities with patients, with physicians, excuse me, both in Pompe and Fabry. I think the overall receptivity was fantastic. And to continue to see new data coming out from our program. And again, just being having a chance to interact in person at the World Conference was really was really exciting and energizing. And I think it really teases up well for the continued pre-launch activities headed into the third quarter. Jeff, you want to talk specifically about Joe’s question around the change from baseline versus present predicted and why that makes sense.

Yes, and thanks Joe for the question. So you percent predicted six minute walk is, takes into account things like patient's height, but importantly, age. And as you go on longer durations of follow up, it’s pretty standard to use percent predicted six minute walk to kind of account for the fact that over two years over four years, patients are certainly aging and that should be accounted for in the calculation of how far they should walk in six minutes. So over a one year study, like propel, using meters makes sense. But as we go longer-term follow up, I think you’ll see across programs, people usually use percent predicted six minute walk. We did report in the supplement world, the meters data, and it looks very comparable to the percent predicted, it’s just that that’s kind of the more standard way for long-term follow up. And as Brad said, I think we had a really positive reception to that data. We also had our four year data represented, which was very consistent showing kind of a durability of effect in the Phase I/II throughout the four years in here and propel over the two years.

Thank you.

And one moment for our next question. And our next question comes from Dae Gon Ha of Stifel. Your line is open.

Good morning, guys. Thanks for taking my questions. And congrats on the progress.Two part question on the HVGA [Ph] if I may. Just thinking about your market research and your physician interactions, kind of curious if you can maybe walk us through what the CRE next fee is -- take was based on your data that’s been generated and PROPEL as well as Phase I/II, and post Nexviazyme just wanting to see if they have a different view there or what the evolution of that process is. Second part is, now that you have the OLV data presented at World, maybe digging a little deeper on Joe’s question, what's been sort of the physician feedback on that naïve segment? What’s been sort of the receptivity or willingness to try AT-GAA for the naïve patients? And then separate question for Daphne, understanding the pushes and pulls of variability throughout this year. But if we think about modest contribution revenue wise from AT-GAA, I guess, how much or should we really be thinking about given that the second half non-GAAP profitability kind of also hinges on that progress? I hope that makes sense

Okay, so thanks for the questions, first of all. So we’ve got sort of impressions of data pre and post, I guess, launch of next Lyzyme. And then Jeff, talking a little bit more about the different segments we showed at, at world, both the switch patients and naïve patients. And then I guess one last question to Daphne around how AT-GAA revenue impacts our goals for non-GAAP profitability for the second half of the year. So, as relates to the first one, honestly, I then I said in the call and I’ll highlight it again here. I think the most differentiating data we have is in is in those switch patients. And, and I think that will continue to be a hallmark and highlight of, of the labels that we have that we anticipate, as well as the information were presenting to physicians. And frankly, that’s, that’s kind of regardless of what happens on the next Lyzyme side. Again, we’re the only company to have sponsored in the control arm of our pivotal study, experience patients switching from that one as a replacement therapy to AT-GAA. And I think that’s just a critical difference. The other thing, of course, we were really pleased to see was the consistency and the durability of those data, as we now see that the long two year data from PROPEL. And then as Jeff highlighted the reprise of the four year data from the Phase I/II study. So I think that consistency and durability is also really important. Jeff, do you want to talk quickly about the impact we also saw in the naïve patient segments from the long-term extension, and then Daphne can get to the financial question.

Yes. Thanks, Brad. And thanks Dae Gon for the question. So as we think about the naïve patients as a reminder, and PROPEL was 80% about your experience patients and only 20% were naïve. And then the naïve where we saw both the Lumizyme arm and ATZ [Ph] arm perform better than any other arms we've seen in naïve basis and other studies, they were very similar kind of in the quite significant benefit we saw. We were encouraged by in the, additional year of follow up is we saw patients continue to show at least stability even increases on gains, from that large increase they had. So the two year results, and those naïve patients, combining sort of Lumizyme and AT-GAA together or two years at AT-GAA are really quite remarkable in terms of the increases. No FEC, because these patients had much higher baselines, we did see sort of both groups had that small decline. It was good to see that that stabilized, whether that was a true decline or not in the original kind of [Indiscernible]. But certainly we’re seeing really robust improvements and six minute walk and stability and FEC and his naïve patients. And for Phase I/II after four years, we saw improvements in both six-minute walk and FEC and citations that were maintained for four years. So net net, I think as physicians looked at the data, certainly the bulk of our data is in the year he experienced, as Brad said, the more difficult to treat patients. And I think they assume that the benefits observed there would carry over to the 90s. And then our naïve data is also supportive. So I think we offer a good value proposition for naïve. We generated positive feedback from physicians, obviously, we’ll see where the labels are in different geographies. And that could play a part in terms of prescribing for naïves, but we believe we have a great value proposition for both experienced and naïve.

Yes, thanks, Jeff. Of course, I would remind folks that how this product is positioned will, of course, depend on which region and what the final labels look like. But I think all just points are very important. Daphne, do want to speak quickly to the contribution of revenue from AT-GAA to the profitability goal.

Sure. So just to just to remind everyone that the profitability metrics, the biggest contributor to that was actually the Galafold revenues. I do want to remind everyone that AT-GAA revenues will have a modest impact, definitely help profitability, but also just a reminder that once approved, the cost, production costs will move from the P&L. So from OpEx and move on to the balance sheet. So I think it’s a combination of all of that. So yes, the approval has p, but it’s, it will impact the P&L in a couple of different ways, not just from…

Great, thanks for taking the question.

One moment for our next question. Our next question excuse me, will come from Kristen Kluska of Cantor Fitzgerald. Your line is open.

Good morning everyone. This is Rick [Ph] on for Kristen. Thanks for taking our question. We’ve got one for you this morning. You previously mentioned mock inspections at the WuXi facility in the lead up to scheduled inspections. Have you been doing or planning any mock inspections that are part of the preparation? And is there any clarity based on what you heard from the agency on what to expect from the real inspection now that it is on the calendar? Thanks.

Yes, great questions. So we were able to conduct a very successful mock inspection. Last year, actually, we had a consultant who was on the ground, who was from China, and then supported by our team here in the United States. So we feel really good about the status of WuXi in manufacturing. And I would just add a few other points that give us confidence in the outcome of that inspection. The first is that, we’ve mentioned this before WuXi, the facility in WuXi, China is a well inspected facility from multiple agencies, both in person and hybrid, for multiple approved products. So they have a very successful, positive history of inspections. Previously, as you mentioned, we’ve done mock inspections and a whole host of pre-approval inspection activities. As I said, on the call, we’re actually sending or actually answer a question from the follow up, we are sending our team over in the coming weeks, and we will continue to help prepare and make sure everything’s buttoned up. We also as a reminder, a big chunk, and we talked about this during the review, a big chunk of the agency’s review was on the manufacturing. So there are a whole host of questions that we’ve already answered satisfactorily for the agency. And then finally, we’ve pointed to the rich manufacturing history with our product self. We’ve done dozens of successful manufacturing runs at that commercial scale, under the quality key process parameters, critical quality of quality attributes that are part of the overall quality control of the product. So for all those reasons, we feel really excited and prepared for the inspection. And we’re thrilled now that we have one scheduled and kind of have line of sight to what we hope will be the eventual approval.

One moment for our next question. And our next question comes from Jeff Hung of Morgan Stanley. Your line is open.

Hi, good morning. This is Catherine [Ph] on for Jeff, thank you for taking our question. We just had one. Can you remind us of what confirmatory analytical testing was requested by the EU regulatory authorities for miglustat? And I just have a quick follow up what kind of risk if any, is there that it could take longer for a CHMP opinion? Thank you.

Yes, Jeff, do you want to just give a little bit more color than what we’ve spoken to before?

Yes, thanks, Catherine. We haven’t disclosed exactly what the requested testing was. What we have said is it was something that during the submission we had provided in silico, data, all sorts of sort of modeling to show that there was – we’d address all the requirements for regulations, what we got CSC doc was, like we needed to have a test to actually measure for this confirmatory testing of these molecules. So we are, as we said, during the call initially, we are well on track, we don’t believe there currently is any risk to that timeline, the app for the four month clock delay, we’re on track to provide that validated data with a validated assay. And to be on track for that CHMP opinion here in the second quarter.

One moment for our next question. And our next question will come from Salveen Richter of Goldman Sachs. Your line is open.

Hi, it’s [Indiscernible] on for Salveen. Thank you for taking our question. Two quick ones. Will you be updating the street post the inspection of the WuXi site by the FDA? And can you provide any color on the pricing of AT-GAA now that we have PDUFA timeline?

Yes, thanks for the questions. So it relates to the updates and manufacturing. As long as there’s no material impact to our anticipated timelines, we won’t provide any updates on the outcome of the manufacturing, inspection of course if there’s a material change or impact, then we would provide that in due course. As it relates to pricing, I think we’ve described previously is that we would continue to follow our pricing and access strategy and promise which is parody or modest discount standard of care. Our focus is to maximize access to therapy. And we've found with Galafold that that’s the best way to execute on against that strategy and to maximize the number of patients who are eligible to receive therapy.

One moment for our next question. And our next question will come from Yun Zhong of BTIG. Your line is open.

Hi, good morning. Thanks very much for taking the question. So on Galafold, the 65 versus 35 ex-U.S. versus U.S. sales, is that mainly, depending on or driven by the number of patients, given that it’s been a few years after U.S. approval? And I was wondering what could be the implication for AT-GAA? Do you think there could be any big differences in terms of both disease prevalence, depending on geographic regions can that can potentially impact your launch strategy for AT-GAA versus what you did for Galafold?

Hi, and thanks for the question. Yes and Brad maybe talk a little bit about the distribution of revenue and Fabry. And, and what we might expect based on current distribution of sales and patients for Pompe Disease.

Yes, so the performance in the U.S. was very strong. Last year, we had a strong growth in the fourth quarter of 21.4%. We talked about, the trends we’ve seen over the last six to eight months in terms of, new patient ads. We’ve also talked about, in general terms about market share within the amenable population. And the U.S. is, one of these markets where we gradually see a greater proportion of naive patients contributing to growth, but there’s still a fair amount of switches probably more than some of the markets where we’ve been the longest like, like the U.K. or France, for example. As we look at the split of revenues on a global basis, if you, if you consider Pompe, there’s a bit of a difference from a pricing standpoint, between price in the U.S. and price in Europe. So overall, the U.S. market is the largest market. We see the Pompe market being made of about 40%, of sales coming from the U.S. 36%, 37%, coming from Europe and 23% coming from rest of world. From a patient number standpoint, the actual number of patients treated we estimate in Europe is greater than the U.S. We estimate north of 1300 patients treated for Pompe within Continental Europe, another 200 from the U.K, and in the U.S., that compares with around slightly north of 800 patients. So I think that gives you the overall geographical split that highlights that, the European approval and the U.K. approvals are also some very significant opportunities for us.

Our moment for our next question. Our next question will come from Gil Blum of Needham Company. Your line is open.

Hey, good morning, and thank you for squeezing me in. A bit of a follow up on earlier question about Lumizyme and Nexviazyme dynamics. You guys have any detail on how many of those new Nexviazyme patients are naïve versus switch if at all? Thank you.

Little hard to tease that out. And I don’t want to speak on behalf of Sanofi obviously. But we know that there I’m sure United States putting on naïve patients as well as switch patients based on their public commentary. And you look we believe that, that it’s great for patients to have choice and for a new therapy to be out there. And so I think it’s fantastic for the community that there are multiple treatment options, and that were just eager to provide a third treatment option for patients. So a little tough to tell exactly what the distribution is, but I’m sure there’s some component of that going on. And Gil something we’ve seen very much in the public market is, as you see more players entering a rare disease space, you also see stronger growth for the overall market. We need to keep in mind that those diseases are unfortunately, significantly under diagnosed and undertreated. So as you see Amicus coming to the Pompe market, you will see more efforts to raise this awareness, to support diagnostics initiatives, and hopefully get overall, more patients having choices of therapies.

Thank you.

One moment for our next question. And our next question comes from Zhiqiang Shu of Berenberg. Your line is open. Again, our next question comes from Zhiqiang Shu of Berenberg. Your line is open.

Sorry, I was on mute. Thanks for taking the question. Congrats on the progress. I was wondering if you can comment on the significance of achieving profitability in the second half and your confidence, maintaining that status going forward? And maybe related to that wondering your thoughts on continued investment in the early stage of discovery programs. Thank you very much.

Yes. Thank you for the questions. Look, I think from a profitability perspective, I think that's a really important milestone for any company, who started as a preclinical research phase company has now made it to launching our second product. So I think for Amicus for our employees, for our investors, I think it’s just a really important milestone. We haven’t given guidance yet. And what that means the long-term, but we certainly see ourselves continuing to, to be prudent in our financial use of resources, but also seeing our top line revenue continue to grow. And hopefully now with the addition of a second product. So we’ll talk more about kind of what that looks like in the future as we get closer to 2024. But the first step is, of course, getting there, which, which we’re really excited for at the second half of this year. And then, yes, sorry, I was just asking my colleagues on the second question around investment in early stage programs. Yes. So there, what we have said is right now, that is an outcome of the difference between the revenues, we bring in the expenses, we have to support those revenues. And then that goal of profitability, so this year, it’s a very judicial amount of investment. However, we are answering key questions, I think across each of those three programs. Our goal would be to continue to make progress there over the course of this year, and I think you’ll hear us towards the end of the year and sort of next year begins to give better line of sight in terms of what our vision is for those programs. We still very much believe we have differentiated trans genes in Pompe and Fabry and are very excited about the opportunity to deliver those effectively in those therapies. And again, we also see the next generation chaperone is a really important part of our commitment to continue to develop medicines for Fabry disease. So more to come there but right now, again, it’s a very judicious but I think appropriate portion of our investment.

Thank you very much.

Thank you. That was your last question. This concludes today’s conference call. Thank you and have a great day.

Thank you, everybody. Appreciate the questions. Good luck. Good day.