Q4 2022 Amicus Therapeutics Inc Earnings Call

Speaker 1: You.

Speaker 2: The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 1-1.

Speaker 3: The reason.

Speaker 4: Good morning, ladies and gentlemen, and welcome to the Amicus Therapeutics full year 2022 Financial Results Conference call-in 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 is being recorded.

Speaker 5: full year 2022 financial results and corporate highlights. Leading today's call, we have Bradley Campbell, President and Chief Executive Officer, Daphne Quimby, Chief Financial Officer, Sebastian 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 two, we may make forward-looking statements within the meaning of the private security litigation reform act of 1990.

Speaker 5: 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 thereof. 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.

Speaker 6: 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, Gallifield continues its strong performance and remains the cornerstone of our success.

Speaker 6: We continue to be very pleased with the strong demand for and growth of Gallifold globally, with now over 2,000 people living with Fabry disease taking Gallifold 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 Gallifold 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.

Speaker 6: new patents over the last year. There are now a total of 46 Orange Book listed.

Speaker 6: issued patents related to Gallifold 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.

Speaker 6: the regulatory approval and launch of ATGAA in the United States will be during the third quarter of 2023. Additionally, in Europe , we're on track with the regulatory reviews by both EMA and MHRA on the marketing authorization applications for ATGAA. As a reminder, in December , the CHMP adopted a positive opinion of Cipa glucosidase alpha producer, but waits to see when forecasts look to the UNC for option 2.

Speaker 6: to be marketed as POMBILITY with the European Commission of Proof-O-Expected Discoordor. We anticipate a CHMP opinion from MIGWISTAT, the end-zone stabilizer component of ATGA in the second quarter of this year. And as a reminder, the EMA has indicated that it does not require an inspection of the WUSHI manufacturing site as a condition of their approval. In the UK, the regulatory submission process for ATGA was initiated in December and is on track for an expected approval in the third quarter of this year.

Speaker 6: As we've observed throughout 2022, we continue to see significant interest in participation in our expanded access mechanisms for ATGA globally. Programs are now in place in the US, United Kingdom, France, Germany, and Japan, with a growing number of patients participating in each. Across all of our ongoing clinical studies and expanded access programs, we're now over 195 patients on ATGA today, which we believe represents more than 5% of the total treated Pompeii patients around the world. We expect this number to continue to grow as we approach approvals in the United States and Europe and beyond. In anticipation of these approvals in the near term, our global launch plans...

Speaker 6: Importantly, based on the projected strong growth of GALFOLD, our latest assumptions that approvals and launch for ATGA, our current operating plan and continued careful management of expenses, we remain on track to achieve non-GAB profitability, which we continue to expect in the second half of 2023.

Speaker 6: And finally, just to round out the key highlights and progress we've made across our Fabry and Pompe disease programs, I do want to mention that we once again had significant presence at the 19th Annual World Symposium held this February in Orlando, Florida. Anikas had two oral presentations and 11 posters highlighting data from our development programs in Fabry and Pompe disease.

Speaker 6: Most notably, as Jeff will go into more detail later in the call, we represented for the first time encouraging long-term efficacy and safety data from the Phase III Open Label Extension study of ATGA in laid-outs at Pompade disease.

Speaker 6: demonstrating consistency and durability of effect in patients now out to two years. Also noteworthy we provided the first results from our own Follow Me Fabaret Pathfinder's registry showing stability and EGFR out to three years in that population. And this will be a key part of our efforts to continue to build the body of evidence supporting GALFOL. Finally in slide four, as we laid out last month, we are focused on achieving our key strategic priorities for 2023. Include.

Speaker 6: perspective and participated launches.

Speaker 6: Given our experience and success with Gallifold and our seasoned global commercial medical and market access teams, we are fully prepared for and anticipate a successful launch of ATGA.

Speaker 6: Number three, we will continue to judiciously invest in the advancement of our best-in-class next-generation Fabry and Pompeii genetic medicines and capabilities, as well as our next-generation chaperone for Fabry disease. And number four, as always, we will maintain a strong financial position as we carefully manage our expenses and investments on our path to non-GAAP profitability. With that, let me now hand the call over to Sebastian Martel, our chief business officer here.

Speaker 7: to further highlight the Gallifold performance. Thank you, Bradley, and good morning to everyone on the call. I'll start by walking you through in more detail our Gallifold performance for the year. On slide six, as you can see for the full year 2022, Gallifold reported revenue reached $329 million, driven by strong new patient accruals, offset by significant foreign currency headwinds. The geographic breakdown of revenue during the full year consisted of $213 million, or 65% of revenue.

Speaker 7: generated outside of the US and the remaining $116 million, or 35%, coming from within the US. This is in line with the two-thirds, one-third split that we expect as we continue to grow both parts of the business. We're pleased to see continued patient growth in countries like the US, Japan, Germany, Italy, and the UK, just to name a few of our key markets. Turning to slide 7, our results for the full year highlight the strengths of our global commercial efforts. The demand for Gallifault globally continues to be incredibly strong, with patients added in all major markets, delivering operational growth rate of 16% over the same period in 2021 at constant exchange rates.

Speaker 7: The negative impact from foreign currencies was 8% in 2022. As a result, Galaphol reported revenue growth was 8% for the full year. In 2022, Galaphol continued to be the fastest growing treatment for Fabry disease globally and the greatest contributor to the global Fabry market growth. That's remarkable. I'm pleased to report that our monthly net new patient trends continues to increase and the three month trend was the highest in the last two years.

Speaker 7: And if you look at the growth net patients on GalaFold globally, which is perhaps the truest measure of the underlying business, we saw greater than 19% growth in patients on GalaFold at the end of 2022 versus the same period in 2021. Old indications of the continued and growing demand for GalaFold. As Brad mentioned earlier, we ended the year with more than 2,000 patients on GalaFold, which is over half of the global market share of treated, amenable patients.

Speaker 7: And while the global mix remained about 55% switch and 45% naive, in many geographies, we're seeing stronger uptake naive populations. So while we're achieving high market shares in countries where we've been approved the longest, the still plenty of opportunity to continue to switch patients over to California to continue to grow the market as we penetrate into these dynos and treated and newly dynos segments.

Speaker 7: All of that is underpinned by impressive compliance and adherence rates that continue to exceed 90%. This is really reiterating our belief that those patients who go on Gallifold stay on Gallifold.

Speaker 7: The value of GALAFOL continues to be recognized by payers, and we have continued on our strong track record of successfully negotiating and renegotiating reimbursements outside of the U.S. Our relentless commitment remains on ensuring access to GALAFOL for anyone who needs it. What we've seen in the full year 2022 is that GALAFOL have taken continues to track very well. And for the first two months of 2023, we're seeing those trends continue with growth across all our market markets.

Speaker 7: The value of GALA fold continues to be recognized by payers, and we have continued on our strong track record of successfully negotiating and renegotiating reimbursements outside of the US. Our relentless commitment remains on ensuring access to GALA fold for anyone who needs it. What we've seen in the full year 2022 is that GALA fold update continues to track very well. And through the first two months of 2023, we're seeing those trends continue with growth across all our key markets. Turning on to slide eight.

Speaker 7: Gallifault growth remains strong with $88 million in the fourth quarter. 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 non-linear. We expect that to continue through 2023.

Speaker 7: In the table on the right-hand side of the slide, we've provided you with a five-year historical snapshot of the percent of manifold sales that occupy each quafter during a given year. We would expect a similar trend to occupy this year. And so while we don't provide quarterly guidance, the historical breakdown is a very good benchmark for revenue distribution by quafter. As an example, we've also observed in the last two years that Q1 sales in the current year tends to be generally aligned with Q3 sales in the prior year. Moving on to slide 9, we know that there's a significant patient demand for Gallifold.

Speaker 7: and that it has potential to surpass $500 million nano revenue over the next few years. We anticipate sustained growth through 2023 to be driven by several key goal drivers. First, continuing to penetrate into existing market.

Speaker 7: Second, further uptake into the DINOS and treated population, and third, expanding into new geographies and label extension. As we just mentioned, all of these efforts are supported by solid compliance and adherence rates and policy reimbursement and access mechanism throughout the world. Thank you.

Speaker 7: I'm pleased to share that we're making continued progress on expanding into new markets, to name a few examples. We received last year market authorization in Turkey and are in the pricing and reimbursement process as we speak. We have submitted the marketing authorization applications in Hong Kong and New Zealand and hope to see those countries as new countries for Gallup polls in the near future. We have successfully renegotiated pricing and reimbursement agreements for Gallup polls in countries like Italy, Spain, Poland, Switzerland and Iceland.

Speaker 7: In the longer term, we continue to see significant growth in the fabric market globally, driven by diagnosing patients through a variety of measures, including high-risk screening, newborn screening, and other diagnostics initiatives, which we continue to support and invest in as well. Also important to note, we have often exclusivity in the US and in Europe , in addition to our now 46 orange booklisted patents that gives us IP coverage into the late 2030s.

Speaker 7: which provides us the opportunity to give access to the local global to patients who need it for a long time to come. On flight 10, we outlined launch preparations for a TJA as we are posed for another successful product launch. Amicus today has a presence in over 40 countries around the world, including all the major Fabri and Pompeii markets. That team will be largely the same that launch HGAA, but only a handful of new FTEs needed. We have experienced across all areas that are needed for successful draw launch, regulatory, commercial supply chain, experience with payers, reimbursement and access, and in addition, and perhaps most importantly, key relationships with physicians. We're very confident in our world-class organization.

Speaker 7: that we can leverage their experience and relationships and deliver HEDGA to people living with pump disease around the world. From the team, the medical education, the published phase three data, our experience with reimbursement and access around the world, and again, all the strategic planning we've been doing together with building inventory without partners at WUSHI bioblogics, we believe we are in a very strong position for a second successful launch for Amicus. With that, let me now hand the call over to Dr. Jeff Cafting on Chief Development Officer. Jeff. Thank you Sebastian and good morning everyone. On slide 12, we'll start with our NKGA program. We recognize that pump A disease continues to pose a range of health challenges for people affected by the disease and having therapeutic choices is crucial. Pump A is a severe and fatal neuromuscular disease and one of the most prevalent life-as-home disorders.

Speaker 6: 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 on to slide 13, as Bradley mentioned, we are very excited to now be anticipating potential regulatory approvals and launches into three of the largest Pompeii markets in the third quarter of this year. Here on the slide we've highly bestatest for our anticipated regulatory milestones this year by market.

Speaker 7: First, in the EU, the European Commission approval of Pumbility is expected in this first quarter later this month. And for Miglostat, we're making great progress on the confirmatory testing and are on track to submit those validated final data TMA for an expected CHMP opinion in the second quarter, which would then be followed by EC approval in the third quarter. And in the US, the required pre-approval inspection of the WuXi Biologics manufacturing site in China, where Cipa Glucosidase Alpha is manufactured, has been scheduled with the FDA for the second quarter and we anticipate approval of both components of ATGA in the third quarter pending a successful inspection. Finally, the regulatory submission process for ATGA in the UK.

Speaker 6: requests for treatment that we continue to receive for children living with both LOPD and IOPD, our expanded access programs continue to increase. We now have multiple expanded access programs in place in a number of countries around the world including the U.S., UK, Germany, France, Japan, and others.

Speaker 6: This includes the EAMS framework of which we previously announced that ATJ was granted a positive scientific opinion through the early access to medicine scheme by the UK's MEETER AING

Speaker 6: And we continue to see significant enthusiasm for ATGA under the EAMS mechanism, with multiple physicians having requested access across the leading Pompeii centers in the UK, and dozens of patients now receiving this novel two-component treatment. Since the positive scientific opinion in December , interest and momentum for ATGA has grown, and we are pleased to be able to provide access to those who are eligible. With this growth in our access program, as Bradley noted, we are going to continue to see significant enthusiasm for ATGA under the EAMS mechanism. And we are pleased to be able to provide access to those who are eligible for ATGA under the EAMS mechanism. And we are pleased to be able to provide access to those who are eligible for ATGA under the EAMS mechanism.

Speaker 6: We are pleased to report that approximately 195 patients worldwide are now being treated with ATJ across our clinical extension studies and these expanded access programs. And worldwide experience with ATJ is growing with approximately 75 centers now currently participating in trials and access programs. We've gone to slide 15 as Bradley mentioned as part of the growing body of evidence supporting ATJ. We just presented at the world meeting last week positive long term efficacy and safety data from a global phase three open label extension of the propel study of ATJ and Leon set pump A disease.

Speaker 6: As seen here on the slide, these latest data demonstrate a consistency and durability of effect in patients after two years on the key clinical endpoints, so six-minute walk distance and FDC. Importantly, these results are consistent with the even longer term four-year data we've seen presented from our phase one, two studies. Together, these really support the long-term benefit of treatment for people living with LOPD. On the slide here, we're showing the results for the large subset of ERT-experienced patients. We observed similar results for the ERT United patients group as well. We were also very pleased by the continued reduction in the key biomarkers of glycogen storage and muscle damage.

Speaker 7: suggesting a positive effect on muscle tissue, particularly in participants who switched from Algocosities alpha to ATGA in the open label extension. This growing body of evidence from all of our long-term clinical studies gives us further confidence that ATGA has the potential to become the new global standard of care for people living with Pompe disease. With that, I would like to now turn the call over to Daphne Queeney, our Chief Financial Officer, to review our financial results, guidance, and outlook. Thank you, Daphne.

Speaker 4: Thank you, Jeff, and good morning, everyone. Our financial overview begins on slide 17 with our income statement 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 a negative currency of 8%. Cost of goods sold is a percentage of net sales with 11.7% in-year as compared to 11.3% in the prior year periods.

Speaker 4: Total GAP operating expenses increased to 502.8 million for the full year 2022 as compared to 477.5 million in 2021. On a non-GAP 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 the gene therapy portfolio offset by decreased program spend. We define non-GAP operating expense as research and development and S-GNA expenses.

Speaker 4: 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 with 236.6 million or 82 cents per share as compared to a net loss of 250.5 million or 92 cents per share for the prior year period. Driven by the revenue growth of Gallifold and careful expense management, we continue to make progress towards our path to profitability in the second half of this year.

Speaker 4: 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-gap profitability in the second half of 2023 as defined in our press release.

Speaker 4: Proctability is dependent on a number of factors, including, of course, the timing of approvals and the launch of ATGA. Our full year 2023 non-GAP operating expense guidance is $340 million to $360 million. The expected decrease in operating expense for 2023 as compared to 2022 will be achieved by continuing to drive efficiencies and prudent expense management, offset by continued investment in the global growth of GALAFOLD.

Speaker 4: and pre-launch and launch activities for ATGA. We will also incur certain non-recurring costs for manufacturing to support the global launch of ATGA. We expect to see a larger portion of our operating expense be allocated to GNA this year as we reallocate our resources to support launch of ATGA and the continued growth of Gallifold. In 2023, we may look to execute sales under our previously announced at the market or ATM equity program in a strategic and judicious fashion as we look to maintain a strong cash balance to appropriately fund our operations. A few comments about our cash position in 2023 financial guidance. Cash equivalents and marketable securities were 293.

Speaker 6: 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.

Speaker 4: Certainly. Ladies and gentlemen, if you have a question, please press star 11 on your touchtone telephone. At this time, we ask that you ask one question. If you have any additional questions, please enter back into the queue. Thank you. One moment. And our first question comes from Anupam Rama of JP Morgan. Your line is open. Hey, guys. Thanks so much for taking the questions.

So, with the regulatory decisions coming here in 3Q, as you look at the next year's design and the Sanofi launch here, what are some key learning similarities, differences that you would highlight as we think about the ATGAA launch curve? Thanks so much. Yeah, 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 ongoing 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 ATGAA. 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 UK.

We think that patients and physicians are just really excited to have a new treatment option. 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 our question. One moment for our next question. And our next question comes from Ritu Bural of Cohen. Your line is open. Good morning, guys. Thanks for taking the question. The question itself is, you know, how fast should we start booking revenues after we know of the inspection? I guess, you know, of course, my question has three parts. One, how fast should we be taking the inspection? How fast should we be thinking about approval after the inspection? You know, is it a week kind of thing? How do we model changeover to commercial?

from the 1095 patients that are in your extended access programs across the world. And you expect all of them to fall under the approved label finalist. Thanks. Yeah, thanks for two. I'll try to hit all three of those. So the first one is related to timing from inspection to

approval in the U.S. What our team's estimated that takes about two months to go through that process. And so that's why we've said the inspection is in Q2 and we expect approvals in Q3. In terms of converting patients from clinical trial or expanded access 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 Gallifold 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 in the trial on set patients, but that would be.

a very small portion, I think the vast majority between the phase one, two studies, the phase three study and then expanded access programs are gonna be late onset patients who fall within the anticipated labels. So I think the majority of those patients would be eligible. And of course, not all of them are in the first three launch countries, US, UK and Germany, but certainly the majority have been. Just to give you a flavor of the distribution between regions, about 60 of those patients are in Europe , about 50 in the United States, about 40 in the United Kingdom and the balance 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 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 ATGA, of course with the expanded access and ongoing 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.

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 ATGA, of course with the expanded access and ongoing 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 looking at the question. Thanks for too.

One moment for our next question. And our next question comes from Tazine 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 inspection has been scheduled, does that mean that SEA kind of just decides who they want to send over and that team just goes? Or does there have to be some process that includes, for example, you know, the State Department needing to pre-clear it? Just wondering what the technicalities are on that. Thanks. Yeah, thanks to Zine for the question. At this point, it, you know, what we understand from the FDA is kind of business as usual is related to the inspection. So of course, they'll need, you know, visas 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, you know, be very confident in those dates. Of course, you know, copy out it 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 the inspection. Okay. Thank you. Thanks to Zine. 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. Just in some of maybe your pre-commercial work, how should we think about the uptake in switches from Lumazime or Myazime relative to, say, switches from Nexviazime, I guess, in the U.S.? And then, I guess, just what's the feedback from physicians on how often they see their Pompeii patients and whether patients might, say, be called in, whether it has been to get Nexviazime or whether it would be to get ATGAA given the potential approval? Thanks. Sure. Thanks, Ellie, for the question. I'll take a stab at the first one 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 launch in the United States, where I think we anticipate a label for experienced patients, we would 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 lumenzyme patients as well as the neck-to-eye-zyme patients. And again, I would just, you know, the thing that we are most focused on is the unique data that we have from the only study that's studied in the controlled portion.

patients who are on end-to-end replacement therapies, 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? Yeah, thanks, Fred. Thanks, Ellie. So physicians typically, you know, will at least see their patients every six months or pretty comprehensive assessment. Obviously, it depends if they're getting infusions at the clinic, or they may or may not see them more regularly.

of the patients from the next design studies or that have switched to have 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 Sebastian, maybe just give us a color for some of the distribution of reported sales.

on a global basis. Outside of the US, this is actually a lot higher than that, 93% of sales were coming from myozyme, rest of world was 85%, and in the US, still 60% also still 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 both well for the switch strategy we've spent. Thanks, Sebastian. Thank you, Ellie. Anything else? Thanks, Beth. Perfect. One moment for our next question. And our next question comes from Joseph Schwartz of SBB Securities. Your line is open. Hi. Thanks for the update.

I was wondering if you could comment on your Pumbility 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 could not be used? And what's your strategy for continuing to build supply? Yeah, thanks for the question. So, we have, I think, prudently continued to manufacture ATGA and I think we noted last year in our financials that Daphne highlighted.

in the United States, we've actually begun to move product 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, you know, 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 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 manufacture 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.

be really when you're starting to see the meat of the balance of Europe coming on board and starting to see some rest world countries as well. So that will become, I think, the primary source of capacity for the long-term manufacturer of the product. 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, Fred. And could you comment also?

So, open-level extensions, studies, it's been a walk, data as percent predicted, six minute walk, rather than change from baseline. As it was done previously, how does that change the interpretation of the novel? And what feedback did you hear in general from physicians who saw all the data that you reported in the world? Yeah, Joe, you've dated a little bit. I think the question, the first part of the question was, in the way we displayed the data, when we presented as percent predicted value, excuse me, versus change from baseline. And then the second question was, what was the response from the audience in the world? I'll take the second one first and then Alice Jeff to comment on the first one. So, so I think overall it was great to be in person at world, as you can imagine.

you know, tons of activities with patients, with physicians, excuse me, both in Pompeii and Fabray. I think the overall receptivity was fantastic. And you know, to continue seeing 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, do you want to talk specifically about Joe's question around the change from baseline versus present predicted and why that makes sense? Yes, sorry, and thanks to over the question. So, you know, you percent predicted six-minute walk is, you know, takes an account, things like patients high, but importantly age.

And as you go on longer durations of follow-up, it's pretty standard to use percent predicted six-minute lock to kind of account for the fact that, you know, over two years, over four years, patients are certainly aging and that should be accounted for in the calculation of how far they should lock in six minutes. So you know, over a one-year study like Propel, you know, 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 lock. But we did report in the supplement world the meters data and it looks very comfortable 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, you know, positive reception to that data. We also had our four-year data represented, which was very consistent showing kind of that durability of effect in the phase one, two out to four years and here in Propel over the two years. Thank you. In one moment for our next question,

And our next question comes from DeGonha of Diffle. Your lines open. Great. Good morning, guys. Taking my questions and congrats on the progress. Two-part question on the ATGA, 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 pre-next-seasim take was based on your data that's been generated in propels, well, it's for these one two and post-next-seas I just wanted to see if they have a differing view there or what the evolution on that process is. Second part is now that you have the OLE data presented at world, maybe digging a little deeper on Joe's question. What's been for the physician feedback on the naive segment? What's been sort of the research?

happening around how ATGA revenue impacts our goals for non-gap profitability for second after year. So as relates to the first one, honestly, I said another call and I'll highlight it again here. I think the most differentiating data we have is in those switch patients. And-

And I think that will continue to be a hallmark and a highlight of the labels that we have that we anticipate as well as the information we're presenting to physicians. And frankly, that's kind of regardless of what happens on the next slide. Again, we're the only company to have sponsored in the control arm of our pivotal study experienced patients switching from enzyme one end of replacement therapy to ATGA. 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 the long two year data from from propel. And then as Jeff highlighted the reprise of the four year data from the phase one to 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 naive patient segments from the long term extension and then death?

You know, on 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 observations. But, you know, it's certainly routine really robust improvement in six minute walk and stability in FEC in those 98 patients.

From our phase one to, you know, out the four years, we saw improvements in both six-minute lock and FEC and those night patients that were maintained for the four years. So net net, you know, I think it's physicians look at the data. Certainly the bulk of our data is in the ear to experience the Brad said, the more difficult to treat patients. And I think they assume that the benefits observed there would carry over to the night and then our night data is also supportive. So you know, I think we offer a good value proposition for night. We've done a lot of positive feedback from physicians obviously. We'll see where the labels are and different geography is and that could play part in terms of, you know, describing for nights, but we believe we have a great, you know, value proposition for both experience and nights.

I do want to remind everyone of that. ATGA revenues will have a modest impact, so it will definitely help profitability, but also just a reminder that once approved, the production costs will move from the P&L, so from OPEX, and move onto the balance sheet. So I think it's like combination of all of that. So, yes, the approval is key, but it's...

It will impact the P&O in a couple of different ways, not just from the reference side. Great. Thanks for taking our questions. One moment for our next question. Our next question. Excuse me. We'll come from Kristen Kluska of Cancer Fistural. Your line is open. Good morning, everyone. This is Rick on for Kristen. Thanks for taking our question. We've just got one for you this morning. You previously mentioned mock inspection at the WUSHI facility in the lead up to scheduled inspections. Have you been doing or planning any mock inspections at a 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. Yeah, great questions. So we were able to conduct a very successful mock inspection. And 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 WUSHI, the manufacturing.

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 a line of sight to what we hope will be the eventual approval. Thank you.

One moment for our next question. And our next question comes from Jeff Hong of Morgan Stanley , your lines open. Hi, good morning. This is Katherine 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 by the Victoria Dories for make loose that?

And just as a quick follow up, what kind of risk, if any, is there that you could take longer for a CHMP opinion? Thank you. Yeah, Jeff, do you want to just give a little bit more color there what we've spoken to before? Yeah, thanks, Catherine. You know, we haven't disclosed exactly what the requested testing was, but we have said as it was something that is during the submission we had provided in silico data, all sorts of sort of modeling to show that. There was, you know, we addressed all the requirements, per regulations. What we got to be at feedback was, but we needed to have the test actually measure.

for this confirmatory testing of these molecules. So we, as we said during the call, initially we are well-entracked. We don't believe they're currently as any risk to that timeline. We ask for the four month clock delay. We're on track to provide that validated data with the validated assay and to be on track for that CHNP opinion here in the second quarter. One moment for our next question. And our next question will come from a salveen Richter of Goldman Sachs. Your line is open.

We've told quick ones, will you be updating the street post-wed inspection of the WUSH side Can you provide any color on the pricing of ADGA, now that we have, we do for date timeline? Yeah, thanks for the questions. So, it's related to the update for the 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 and do course. As 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 a parody or modest discount standard of care. Our focus is to maximize access to therapy. And we've found with Gellifold, that that's the best way to execute 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 Jan Zhang of BTIG. Your line is open. Hi. Good morning. Thanks very much for taking the question. So on GALAFUL, the 65 versus 35 XUS versus US sales, is that mainly depending on or driven by the number of patients? Given that it's been a few years after the US approval. And I was wondering what could be the implication for ATGA? Do you think there could be any big differences in terms of a disease prevalence depending on geographic regions? Can that can potentially impact your launch strategy for ATGA? versus what you did for ATGAFUL?

Hi, you and thanks for the question. Sebastian, maybe talk a little bit about the distribution of revenue in February and what we might expect based on current distribution of sales and patients for pump agencies. 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 our market share within the amenable population. 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 the UK or France. All France for example.

As we look at the split of revenues on a global basis, if you consider Pompeii, there's a bit of a difference from a pricing standpoint between pricing the US and price in Europe . So overall, the US market is the largest market. We see the Pompeii market being made of about 40% of sales coming from the US, 36, 37% coming from Europe , and 23% coming from rest of the world. From a patient number standpoint, the actual number of patients treated, we estimate in Europe is greater than the US. We estimate north of 1,300 patients treated for Pompeii.

within continental Europe , you know, the 200th from the UK. And in the US, that compares with around slightly north of 800 patients. So I think that gives you, you know, the overall geographical split. But that highlights that, you know, the European approval, then the UK approval, are also some very significant opportunities for us. Thanks, Lashen. Our next question will come from Gil Blum of Needham Capital. Needham Company, your line's open. Hey, good morning, and thank you for squeezing me in a bit of a follow up on earlier question about.

I'm a Zion and Nexazine Dynamics. Do you guys have any detail on how many of those new Nexazine patients are naive versus switch if at all? Thank you. A little hard to tease that out, and I don't want to speak on behalf of Stanford, obviously, but we know that they're, I'm sure, in the United States putting on naive patients as well as switch patients based on their public commentary. And you look, we believe 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 now we're just eager to provide a third treatment option for patients. So, you know, a little tough to tell exactly what the distribution is, but I'm sure there's some component of that going on.

And, J.L. something we've seen very much in the Fabrii market 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 disease are unfortunately significantly underdinos and under-treated. So as you see Amicus come into the public market, you will see more efforts to raise disease awareness, to support dyno-stics initiatives, and hopefully get, you know, more. Overall, more patients having choices of therapies. Thank you. One moment for our next question. And our next question comes from Ziqui-Anxue of Berenberg. Your line is open. Again, our next question comes from Ziqui-Anxue of Berenberg. Your line is open. Again, our next question comes from Ziqui-Anxue of Berenberg. Your line is open. Thank you, M.I. Sorry, I was on mute. Thanks for taking a question. Congrats on the progress. I was wondering if you can comment on the significance of achieving...

profitability in the second half and the odd confidence maintaining that status going forward. And maybe related to that, wondering your thoughts on continued investment in the early stage of discovery programs? Thanks very much. Yeah, thank you for the questions. Look, I think from a profitability perspective, I think that's a really important milestone milestone for any company who started as a pre-clinical research based company and now made it to launching our second product. So I think for Amicus, for our employees, for our investors, I think that's just a really important milestone. We haven't given guidance yet on what that means in the long term, but we certainly see ourselves continuing 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 the 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 I'm really excited for at the second half of this year. And then, yeah, sorry, I was just asking my colleagues on the second question around investment in early stage programs. Yeah, 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 so the next year, we begin to give better line of sight in terms of what our vision is for those programs. We still very much believe we have differentiated transgenes in Pompeii and Fabray. And I'm very excited about the opportunity to deliver those effectively in those therapies. And again, we also see the next generation shaperone as a really important part of our commitment to continuing to develop medicines for Fabray disease. So more to come there, but right now again, it's a very judicious, but I think appropriate.

portion of our investment. Thanks 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 with today. You have a great day. Thank you. Thank you. Thank you. Thank you.

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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 is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Falen and 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 Queemey, Chief Financial Officer, Sebastian 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 two, we may make forward-looking statements within the meaning of the Private Security 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...

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, Gallifold continues its strong performance and remains the cornerstone of our success. We continue to be very pleased with the strong demand for and growth of Gallifold globally, with now over 2,000 people living with Fabry disease taking Gallifold as their only treatment for Fabry.

What an amazing milestone for this precision medicine. And despite the significant foreign currency headwind experience throughout last year, in 2022, we reported Gallifold revenue growth of 8%, or 16%, than 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 patient starts from both the switch and naive populations, continued growth in in-person visits between our field teams and Fabrate treaters throughout the world, and sustained patient compliance and adherence rates of over 90%. In 2023, we expect to see continued double-digit Gallifold growth fueled by significant demand from patients and physicians. We're also pleased by the growing Gallifold 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 Gallifold 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 continue to make progress on our global regulatory filings and commercial launch planning for ATGA, our novel two component therapy for pump A disease. We are thrilled today to announce the U.S. FDA has scheduled the required pre-approval inspection of the WUSHI Biologics Manufacturing Site in China during the second quarter of this year.

will be during the third quarter of 2023. Additionally, in Europe , we're on track with a regulatory review by both EMA and MHRA on the marketing authorization applications for ATGA. As a reminder in December , the CHMP adopted a positive opinion of SIPHICU COXIDACE-ALFA to be marketed as PUMBILITY with the European Commission of Proof-Oxpected Discoordor. We anticipate a CHMP opinion from MIGWESTAT, the enzyme stabilizer component of ATGA in the second quarter of this year, and as a reminder, the EMA has indicated that it does not require an inspection of the WUSHI manufacturing site as a condition of their approval. In the UK, the regulatory submission process for ATGA was initiated in December and is on track for an expected approval in the third quarter of this year.

continue to move ahead, including our pre-launch activities, target investments, and additional personnel and capabilities to support the launch and ongoing investments in building a launch inventory. We're closer to reaching this much anticipated milestone of getting ATGA across the regulatory finish line and providing another treatment option for people living with Pompey disease in the United States, Europe , and the United Kingdom.

with further regulatory applications planned in the month ahead. And third, anarchists have maintained a strong financial position as we continue to execute in the global expansion of Gallifold and prepare for the global launch of ATGA. Importantly, based on the projected strong growth of Gallifold, our latest assumptions that approvals and launch for ATGA, our current operating plan and continued careful management of expenses, we remain on track to achieve non-GAB profitability, which we continue to expect in the second half of 2020. And finally, just around the key highlights and progress we've made across our fabric and pump a to these programs, I do want to mention that we once again have significant presence at the 19th annual World Symposium held this February in Orlando, Florida.

Anacas had two oral presentations and 11 posters highlighting data from our development programs in Faberay and Pompey disease. Most notably, as Jeff will go into more detail later in the call, we represented for the first time encouraging long-term efficacy and safety data from the Phase III Open Label Extension study of ATGA in late-opted Pompey disease.

demonstrating consistency and durability of effect in patients now out to two years. Also noteworthy, we provided the first results from our own Follow Me Fabaret Pathfinder registry showing stability and EGFR out to three years in that population. This will be a key part of our efforts to continue to build the body of evidence supporting GALFOL. Finally in slide four, as we laid out last month, we are focused on achieving our key strategic priorities for 2023, including number one, sustaining double-digit GALFOL revenue growth of 12 to 17% at constant exchange rates, while delivering GALFOL to more people living with Fabaret disease with a minimal variance in existing and in new markets. Number two, we remain laser focused on securing ATGA regulatory

With that, let me now hand the call over to Sebastian Martell, our Chief Business Officer, to further highlight the Gellhold Performance.

Thank you, Bradley, and good morning to everyone on the call. I'll start by working you through in more details our Galaful Performance for the year. On slide six, as you can see for the full year 2022, Galaful reported revenue reached $329 million, driven by strong new patient accruals, upset by significant foreign currency headwinds.

The geographic breakdown of revenue during the full year consists of $213 million or 65% of revenue generated outside of the US and the remaining $116 million or 35% coming from within the US. This is in line with the two thirds, one third split that we expect as we continue to grow both parts of the business. We're pleased to see continued patient growth in countries like the US, Japan, Germany, Italy and the UK just to name a few of our key markets. Turning to slide seven, our results for the full year highlight the strengths of our global commercial efforts. The demand for Gallafol globally continues to be incredibly strong with patients added in all major markets delivering operational growth rate of 16% over the same period in 2021 at constant exchange rate.

The negative impact from foreign currencies was 8% in 2022. As a result, GALAFO reported revenue growth with 8% for the previous year. In 2022, GALAFO continued to be the fastest growing treatment for FABDG globally and the greatest contributor to the global FABDG growth. That's remarkable. And please to report that our monthly next-new patient trends continues to increase and the three-month trend was the highest in the last two years. And if you look at the growth net patients on GALAFO globally, which is perhaps the truest measure of the underlying business, we saw greater than 19% growth in patients on GALAFO that the end of 2022 versus the same period in 2021. Both indications of the continued and growing demand for GALAFO. As Brad mentioned earlier, we ended the year with more than 2,000 patients on GALAFO.

which is over half of the global market share of treated amenable patients. And while the global mix remains about 55% switch and 45% naive, in many geographies, we're seeing stronger uptake naive populations. So while we're achieving high market shares in countries where we've been approved the longest, there's still plenty of opportunity to continue to switch patients over to Gallup Island to continue to grow the market as we penetrate into these dinos and treated and newly dino segments. All of that is underpinned by impressive compliance and adherence rates that continue to exceed 90%.

This is really reiterating our belief that those patients who go on Garafold stay on Garafold. Importantly, the value of Garafold continues to be recognized by payers, and we have continued on our strong track record as successfully negotiating and renegotiating reimbursement outside of the U.S. Our relentless commitment remains on ensuring access to Garafold for anyone who needs it. What we've seen in the full year 2022 is that Garafold have taken continues to track very well. And for the first two months of 2023, we're seeing those trends continue with growth across all our key markets. Turning on to slide 8, Garafold growth remains strong with 88 million dollars in the fourth quarter.

As mentioned on past calls, due to a variety of factors, including uneven ordering patterns and effects with certain sessions, the rate of growth within the year is typically nonlinear. We expect that to continue through 2023. In the table on the right hand side of the slide, we've provided you with a five-year historical snapshots of the percent of gunnaful sales that alter each quattro during a given year.

We would expect a similar trend to observe this here. And so while we don't provide quarterly guidance, the historical breakdown is a very good benchmark for revenue distribution by Quarters. As an example, we've also observed in the last two years that Q1 sales in the current year tends to be generally aligned with Q3 sales in the prior year. Moving on to site 9, we know that there's a significant patient demand for GalaFold and that it has potential to surpass $500 million in annual revenue over the next few years.

We anticipate sustained growth through 2023 to be driven by several key goal drivers. First, continuing to penetrate into existing market. Second, further uptake into the dyno and treated population. And third, expanding into new geographies and label extension. As we just mentioned, all of these efforts are supported by solid compliance and adherence rates and policy reimbursement and access mechanism throughout the world.

I'm pleased to share that we're making continued progress on expanding into new markets. To name a few examples. We received last year market authorization in Turkey and are in the pricing and reimbursement processes we speak. We have submitted the marketing authorization applications in Hong Kong and New Zealand and hope to see those countries, as new countries, for Gallup holds in the near future. We have successfully renegotiated pricing and reimbursement agreements for Gallup hold in countries like Italy, Spain, Poland, Switzerland and Iceland.

In the longer term, we continue to see significant growth in the Farbeam market globally driven by diagnosing patients through a variety of measures including high risk screening, newborn screening and other diagnostics initiatives which will continue to support and invest in as well. Also important to note, we have often exclusivity in the US and in Europe in addition to our now 46-orange booklisted patents that gives us IP coverage into the late 2030s which provides us the opportunity to give access to get out for globally to patients who need it for a long time to come. On slide 10, we outline launch preparations for 18JA as we are posed for another successful product launch. I'm curious today as a presence in over 40 countries around the world including all the major Fabri and Pompeii markets.

That team will be launched at the same that launch HGGA, but only a handful of new FTEs needed. We have experience across all areas that are needed for successful draw launch, regulatory, commercial, supply chain, experience with payers, reimbursement and access, and in addition, and perhaps most importantly, key relationships with physicians. We're very confident in our world class organization that we can leverage their experience and relationships and deliver HGGA to people living with pump disease around the world. From the team, the medical education, the published phase three data, our experience with reimbursement and access around the world, and again, all the strategic planning we've been doing together with building inventory without partners at Wushy Bioburgics. We believe we are in a very strong position for second successful launch for Amicus. With that, let me now hand the call over to Dr. Jeff Caffledin, and I'm Chief of Law and Officer. Jeff.

Thank you, Sebastian, and good morning, everyone. On slide 12, we'll start with our NKGA program. We recognize that Pompeii Disease continues to pose a range of health challenges for people affected by the disease and having therapeutic choices is crucial. Pompeii is a severe and fatal neuromuscular disease and one of the most prevalent Lyceusomo 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 on to slide 13, as Bradley mentioned, we are very excited to now be anticipating potential regulatory approvals and launches into three.

of the largest Pompeii markets in the third quarter of this year. Here on the slide we've highly bestatest for our anticipated regulatory milestones this year by market. First in the EU, the European Commission approval of Pompility is expected in this first quarter later this month, and for MIGLISTAT we're making great progress on the confirmatory testing and our on-track to Smith's so invalidated final data TMA for an expected CHMP opinion in the second quarter, which would then be followed by EC approval in the third quarter. And in the US, the required pre-approval inspection of the WUSI Biologics Manufacturing Site in China, where CIPAA Glucosidase Alpha is manufactured, has been scheduled with the FDA for the second quarter, and the anticipated approval of both components of ATGA in the third quarter pending a successful inspection. Finally, the regulatory submission process for ATGA in the UK was initiated in December via the recognition procedure based on the CHMP opinion, and we're on track for an expected MIGLISTAT approval also in the third quarter. Moving on to slide 14 to highlight our ongoing clinical studies and providing expanded access to multiple mechanisms that support the demand of ATGA. First of the younger POMBATES, we've got a lot of data on the data. In the community, we continue to enroll the ongoing open-label study in children up to 18 years of age, living with LOPD, and our expanding into patients with infantile onset POMPE disease ongoing throughout this year. Importantly, in response to the many requests for treatment, that we continue to receive for children living with both LOPD and IOPD, our expanded access programs continue to increase.

We now have multiple expanded access programs in place in a number of countries are on the world, including the US, UK, Germany, France, Japan, and others. This includes the EAMS framework of which we previously announced that ATJ was granted a positive scientific opinion through the early access to medicine scheme by the UK's MHRA. Can we continue to see significant enthusiasm for ATGA under the EAMS mechanism with multiple positions having requested access across the leading pom-based energy in the UK and dozens of patients now receiving this novel to component treatment since the positive scientific opinion in December interest and momentum for HG is grown and we are pleased to be able to provide access to those who are eligible. With this growth and our access programs is probably noted, we are pleased to report that approximately 195 patients worldwide are now being treated with ATGA across our clinical extension studies and these expanded access programs. And worldwide experience with ATGA is growing with approximately 75 centers now currently participating in trials and access programs. We've gone to slide 15 as Bradley mentioned as part of the growing body of evidence supporting ATGA. We just presented at the world meeting last week positive long-term efficacy and safety days from the global phase three open label extension of the propel study of ATGA and Lainon-Sit Pump A disease. As seen here on the slide, these latest data demonstrate a consistency and durability of the fact in patients after two years on the key clinical endpoints of six-minute lock distance and FEC. And importantly, these results are consistent with the even longer term for your data we've seen presented from our phase one two studies. And together, these really support the long-term benefit of treatment for people living with LOPD. On the slide here, we're showing the results for the large subset.

of ERT experience patients, and we observe similar results for the ERT-Ni-patient group as well. We were also very pleased by the continued reduction in the key biomarkers of glycogen storage and muscle damage, suggesting a positive effect on muscle tissue, particularly in participants who switched from aglicocides alpha to ATGA in the open label extension. This growing body of evidence from all of our long-term clinical studies gives us further confidence that ATGA has potential to become the new global standard of care for people living with pump-aid disease. With that, I would like to now turn the call over to Daphne Queenie, our chief financial officer, to review our financial results, guidance, and outlook. Daphne? Thank you, Jeff, and good morning, everyone. Our financial overview begins on slide 17 with our income statement 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 a negative currency of 8%. Cost of good salt is a percentage of net sales with 11.7% in the year as compared to 11.3% in the prior year periods.

Total GAP operating expenses increased to 502.8 million for the full year 2022 as compared to 477.5 million in 2021. On a non-GAP 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 the gene therapy portfolio offset by decreased program spend. We define non-GAP operating expense as research and development and S-GNA expenses, excluding share-based compensation expense, loss and impairment of assets, changes in fair value, contingent consideration and depreciation. Net loss for the full year 2022 was 236.6 million or 82 cents per share as compared to a net loss of 250.5 million or 92 cents 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 281.5 million per year. We continue to operate from a position of financial strength and our goal remains to achieve non-GAP profitability in the second half of 2023 as defined in our press release.

Our full year 2023 non-GAP operating expense guidance is $340 million to $360 million. The expected decrease in operating expense for 2023 as compared to 2022 will be achieved by continuing to drive efficiencies and prudent expense management, offset by continued investment in the global growth of Gallifold and pre-launch and launch activities for ATGA. We will also incur certain non-recurring costs for manufacturing to support the global launch of ATGA. We expect to see a larger portion of our operating expense be allocated to GNA this year as we reallocate our resources to support launch of ATGA and the continued growth of Gallifold. In 2023, we may look to execute sales under our previously announced at the market or ATM equity program in the strategic and judicious fashion as we look to maintain a strong cash balance to appropriately fund our operations. A few comments about our cash position in 2023 financial guidance.

Cash equivalents and marketable securities were 293.6 million at December 31, 2022 compared to 482.5 million at December 31, 2021. Our full year Gala fold revenue guidance is revenue growth of 12% to 17% at constant exchange rates. In addition to our non-gap operating expense guidance of 340 million to 360 million. With that, let me turn the call back over to Bradley for our closing remarks.

Great, thanks, Daphne, Jeff, Sebastian. 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 this year. And we continue to advance the growth of our two franchises in Fabriid disease and Ponte disease, which we believe can enable us to create sustainable long-term value and deliver life-changing therapies to people in need. Operated with that, we can now open the call to questions. Certainly, ladies and gentlemen, if you have a question, please press star 11 on your touchtone telephone. At this time, we ask that you ask one question. If you have any additional questions, please enter back into the queue. Thank you.

One moment. And our first question comes from a new Pam Rama of JP Morgan. Your line is open. Hey guys, thanks so much for taking the questions. With the regulatory decisions coming here in 32, as you look at the next years, I'm in the Santa Fe launch here, where are some key learning similarities, differences that you highlight as we think about the ATGA launch for thanks so much. Yeah, thanks, Anna Palm, to 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 1, 2 study, as well as from our Phase 3 propel study and the ongoing extension there. We continue to believe that showing that impact in patients switching from end-to-end replacement therapy is going to be the key differentiator for ATGA. And as we look at all of the demand for expanded access and those mechanisms that we see.

to commercial from the 1095 patients that are in your extended access programs across the world. And you expect all of them to fall under the approved label finally. Thanks.

Yeah, thanks for two. I'll try to hit all three of those. So the first one is relates to timing from inspection to approval in the US. What our case estimate is that takes about two months to go through that process. And so that's why we've said the inspection is in Q2 and we expect approvals in Q3. In terms of converting patients from clinical trial or expanded access.

to commercial product. Our goal has been to do that within 90 days. We were able to execute on those timelines with GALFOLD and we have the same goals here. In terms of numbers of patients within that 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 that that's the majority between the phase one, two studies.

The Faith 3 study and then expanded access programs are going to be laid on to patients who fall within the anticipated labels. So I think the majority of those patients would be eligible. And of course, not all of them are in the first three launch countries, US, UK and Germany, but certainly the majority have. And just to give you a flavor of the distribution between regions, about 60 of those patients are in Europe , about 50 in the United States, about 40 in the United Kingdom, and the balance is rest of the 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 caution people is that it 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 ATGA, of course, with the expanded access and ongoing 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. Thanks for looking at the question. Thanks for too. One moment for our next question. Thank you.

And our next question comes from Tazin Ahmed of Bank of America. Your line is open. Hi guys, good morning and thank you for taking my question. Brad, just a simple one for me. So when you say that the inspection has been scheduled, does that mean that SEA kind of just decides who they want to send over and that team just goes? Or does there have to be some process that includes, for example, you know, the State Department needing to pre-clear it? Just wondering what the technicalities are on that. Thanks. Yeah, thanks Tazin for the question. At this point, you know, what we understand from the FDA is it kind of business as usual is related to the inspection. So of course, they'll need, you know, visas 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 executing on, 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, you know, all the reasons we've discussed for, for a number of years now. So our understanding is that its business is usual and we should, you know,

be very confident in those dates. Of course, you know, caveated 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 the inspection. Okay, thank you. Thanks, Susanne. One moment for our next question. And our next question will come from Ellie Merle of EBS. Your line is open. Hey guys, thanks so much for taking the question. Just in some of maybe your pre-commercial work. How should we think about the uptake in switches from Lumavine or Mayavine relative to say switches from next VSI, I guess in the US. And then I guess just what's the feedback from positions on how often they see their pump patients and like what their patients might say, V.

called in whether it has been to get next the asylum or whether it would be to get ATGA given the potential approval. Sure. Thanks, Ellie, for the question. Maybe I'll take a stab at the first one 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 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 loom? patients as well as the next eye's eye patients. And again, I would just, you know, the thing that we are most focused on is the unique data that we have from the only study that's studied in the controlled portion patients who are on end-to-end 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? Yeah, thanks, Fred. Thanks, Ellie. So physicians typically, you know, will at least see their patients every six months or pretty comprehensive assessment. Obviously, it depends if they're getting infusions that the clinic, though they may or may not see them more regularly if they're the ones doing the infusions. But, you know, that larger work of 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 patients, their 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 a final kind of call or first call on whether they're doing well enough.

percent for the fourth quarter on a global basis. Outside of the US this is actually a lot higher than that. 93% of sales were coming from myozine. Rest of the world was 85%. And in the US still 60% and also still coming from myozine.

But the majority of patients by the time we launch will likely still be on biosign. I think the switch data that we have both well for the switch strategy we expect. Thanks, Lesha. Thank you, Ellie. Anything else? Perfect. Great thing, guys. Perfect. One moment for our next question. And our next question comes from Joseph Schwartz of SBB Securities. Your line is open. Hi, thanks for the update. I was wondering if you could comment on your Pumbility 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 could not be used? And what's your strategy for continuing to build supply?

Yeah, thanks for the question. So we have, I think, prudently continued to manufacture ATGA, and I think we noted last year in our financials, we definitely 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, you know, country at advanced, 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

and then likewise in the 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, with our partners in Rushi, 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 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 world countries as well. And so that will become, I think, the primaries.

And what feedback did you hear in general from physicians who saw all the data that you reported at world?

Yeah, Joe, you stated a little bit, I think the question, the first part of the question was in the way we displayed the data, we presented as present, predict, percent, predict, 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 Alice, Jeff, to comment on the first one. So I think overall, it was great to be in person at World, as you can imagine, you know, tons of activities with patients, with physicians, excuse me, both in Pompeii and Fabre.

I think the overall receptivity was fantastic, you know, 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 exciting and energizing, and I think it really teases up well for the continued prelaunch activities headed into the third quarter. Jeff, do you want to talk specifically about Joe's question around the change from baseline versus present predicted and why that makes sense? Yes, sorry, Brad, and thanks, Joe, for the question. So you know, you – percent predicted six-minute walk is – you know, it 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, you know, over a one-year study like Propel, you know, using meters makes sense, but as we go longer, from follow-up, I think you'll see across programs, people usually use percent-predicted six-minute walk. But we did report in the supplement at world the meters data and it looks very comfortable 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, you know, positive reception to that data. We also had our four-year data represented, which was very consistent showing kind of that durability of effect in the phase one, two out to four years and here in Propel over the two years.

Thank you. In one moment for our next question. And our next question comes from Dave Gahnha of Diffle. Your line's open. Great. Good morning, guys. Thanks for taking my questions and congrats on the progress. Two part question on the ATGA 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 pre-next fiasime take was based on your data that's been generated in propels. Well, it's phase one two and post next fiasime. Just wanted to see if they have a differing view there or what the evolution on that process is. Second part is now that you have the oily data presented at world. Maybe digging a little deeper on Joe's question. What's things for the physician feedback? What's been sort of the reset?

our goals for non-gap profitability for the second half of the year. So as relates to the first one, honestly, I said it on the call and I'll highlight it again here. I think the most differentiating data we have is in those switch patients. And I think that will continue to be a hallmark and a highlight of...

of the labels that we have that we anticipate, as well as the information we're presenting to physicians. And frankly, that's kind of regardless of what happens on the next slide, as I'm side, again, we're the only company to have sponsored in the control arm of our pivotal study, experienced patients switching from ends at one end of replacement therapy to ATGA. 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 the long two-year data from from the PEL. And then as Jeff highlighted the reprise of the four-year data from the Phase 1-2 study. So I think that consistency and durability is also really important. Jeff, you want to talk quickly about the impact we also saw in the naive patient segments from the long-term extension, and then definitely can get to the financial question. Yep, thanks, Brad. And thanks, Dave, on to the question.

As we think about the naive patients, as a reminder, and propellant was 80% of the year, the experienced patients and only 20% were naive. And in the naive group, we saw both the Umazim arm and the HG arm perform better than any other arms we've seen in naive patients and other studies. They were very similar kind of in the quite significant benefit we saw. What we weren't heard by in the additional year of follow-up is we saw patients continue to show least ability even increases on needs, you know, from that large increase they had. So the two year results and those naive patients combining sort of the Umazim and ATTA together, or two years of ATTA, are really quite remarkable in terms of the increases.

You know, an 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 observations. But, you know, it's certainly routine really robust improvements in six-minute lock and stability in FEC in those nine patients. And from our phase one to, you know, out the four years, we saw improvements in both six-minute lock at FEC in those nine patients that were maintained over the four years. So net net, you know, I think it's physicians look at the data. Certainly the bulk of our data is in the ERT experience, as Brad said, the more difficult to treat patients. And I think they assume that the benefits observed there would carry over to the naive. And then our naive data is also supportive. So, you know, I think we offer a good value proposition for naive. We've generally heard positive feedback from physicians. Obviously, we'll see where the labels are and different geography is, and that could play part in terms of

you know, prescribing for knives, but we believe we have a great, you know, value proposition for both experience and knives. Yeah, thanks, Chef. Of course, I would remind folks that, you know, how this product is positionable, of course, is done on, you know, which region and what the final labels look like, but I think all of Jeff's points are very important. Daphne, do you want to speak quickly to the contribution of revenue from HGAA to the profitability goal? Sure. So just to remind everyone that the profitability metrics, the biggest contributor to that will actually be galical revenues. I do want to remind everyone of that. ATGA revenues will have a modest impact, so it will definitely help profitability, but also just a reminder that once approved.

The 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 is key, but it will impact the P&L in a couple of different ways, not just from the reference. Great. Thanks for taking our question. One moment for our next question. Our next question. Excuse me. We'll come from Kristen Kluska of Cancer Fistural. Your line is open. Good morning, everyone. This is Rick on for Kristen. Thanks for taking our question. We've got one for you this morning. You previously mentioned mock inspections at the WUSHI facility in the lead up to scheduled inspections. Have you been doing or planning any mock inspections at a part of the preparation? And is there any clarity based on what you heard? From the agency.

we are sending our team over in the coming weeks who will continue to help prepare and make sure everything is 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 itself.

We've done dozens of successful manufacturing runs at commercial scale under the quality key process parameters, critical quality attributes that are part of the overall quality control of the product. For all those reasons, we feel really excited and prepared for the inspection. 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 Heng of Morgan Stanley , your lines open.

Hi, good morning. This is Catherine 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 regulatory authorities for me glue that. And just as a quick follow up what kind of risk, if any, is there that it could take longer for a CH MP opinion. Thank you. Yeah, Jeff, do you want to just give a little bit more color there what we've spoken to before.

Yeah, thanks, Catherine. You know, we haven't disclosed exactly what the requested testing was, but we have said as it was something that during the submission we had provided in silico data, all sorts of sort of modeling to show that, you know, there was, you know, we had addressed all the requirements for regulations. Well, we got the feedback was, but we needed to have the 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 they're currently as any risk to that timeline.

We asked for the four-month clock delay. We're on track to provide that validated data with the validated assay and to be on track for that CHNB opinion here in the second quarter. One moment for our next question. And our next question will come from a salveen Richter of Goldman Sachs. Your line is open.

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. Okay. 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 Shraddha on for Salveen. Thank you for taking our question. We'll do a quick one.

Will you be updating the street post-phys section of the WUSH site by the FDA? Yeah, thanks for the questions. So it's related to the update for the 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. But of course, if there's a material change or impact, then we would provide that in due course. As 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 a parody or modest discount standard of care. Our focus is to maximize access to therapy. And we found with Gellifold that that's the best way to execute against that strategy and to maximize the number of patients who are eligible to receive therapy. One moment, part next question.

And our next question will come from Yun Zhang of BTIG. Your line is open. Hi. Good morning. Thanks very much for taking the question. So, on Gallifold, the 65 versus 35X US versus US sales, is that mainly, depending on or driven by the number of patients, given that it's been a few years after US approval? And I was wondering what could be the implication for ATGA? Do you think there could be any big differences in terms of disease prevalence, depending on geographic regions, that can potentially impact your launch?

strategy for ATG versus what you did for Calphal? Hi, Ian, thanks for the question. Yeah, Sebastien, maybe talk a little bit about the distribution of revenue in Faberay and what we might expect based on current distribution of sales in patients for Pompe disease. Yeah, so the performance in the US 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 our market share within the amenable population.

You know, 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 the UK or France, for example. And as we look at, you know, the split of revenues on a global basis, if you consider Pompeii, you know, there's a bit of a difference from a pricing standpoint between pricing the US and price in Europe . So overall, the US market is the largest market. We see the Pompeii market being made of about 40% of sales coming from the US. 36, 37% coming from Europe and 23% coming from rest of the world. From a patient to a patient's number standpoint.

The actual number of patients treated, we estimate in Europe is greater than the US. We estimate north of 1300 patients treated for Pompeii within continental Europe , you know, the 200 from the UK. And in the US, that compares with around slightly north of 800 patients. So I think that gives you, you know, the overall geographical split. So that highlights that, you know, the European approval, then the UK approval are also some very significant opportunities for us.

Thanks, Lesha. One moment for our next question. Our next question will come from Gil Blum of Needham Capital. Needham Company. Hey, good morning, and thank you for squeezing me in. A bit of a follow-up on earlier question about Luma's eye and neck's design dynamics. Thank you.

Do you guys have any detail on how many of those new nexusign patients are naive versus switch if at all? Thank you Little hard to tease that out and I don't want to speak on behalf of Sanity obviously But we know that they're I'm sure in the United States putting on naive 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 now we're just eager to provide a third treatment option for patients so You know a little tough to tell exactly what the distribution is but I'm sure there's some components

One moment for our next question. And our next question comes from Ziqui Ng Xiu of Berenberg. Your line is open. Again, our next question comes from Ziqui Ng Xiu of Berenberg. Your line is open. Again.

Sorry, I was on mute. Thanks for taking a question, congrats on the progress. I was wondering if you can comment on the significance of achieving a profitability in the second half and your confidence maintaining that status going forward. And maybe it related to that. Wondering your thoughts on you continued investment in the early stage of discovery programs? Thanks very much. Yeah, 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 pre-clinical research based company has now made it to launching our second product. So I think for Amicus, for employees, for investors, I think that's just a really important milestone. We haven't given guidance yet on what that means in the long term, but we certainly see ourselves continuing 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 I'm really excited for at the second half of this year. And then, yeah, sorry, I was just asking my colleagues on the second question around investment in early stage programs. Yeah, 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 start of next year. We begin 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 Pompeii and Fabray. And I'm very excited about the opportunity to deliver those effectively in those therapies. And again, we also see the next generation shaperone as a really important part of our commitment to continuing to develop medicines for Fabray 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. 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 with you, Dad. Thank you.