Q3 2022 Amicus Therapeutics Inc Earnings Call

Speaker 1: household in the United States, 30 of which provide protection to 2038 and beyond, and importantly includes five composition of matter patents. We see this patent portfolio, along with our orphan drug exclusivities, providing broad and long-term intellectual property rights well into the late 2030s for this novel precision medicine. As we've discussed throughout the year and as anticipated, we saw three abbreviated New Drug Application, or ANDA filers, and have received their paragraph 4 certifications. Given our strong and innovative intellectual property state, we believe we are well positioned to address any potential generic challenges to our patents. And we announced this morning, later today, we intend to file infringement lawsuits against three ANDA filers who are requesting approval to market a generic version of GALFOLD. We intend to continue to protect and enforce our broad intellectual property rights. And looking ahead, we expect continued growth for GALFOLD this year and remain confident that with our strong IP protection, it has a long runway well into the next decade. Second, we continue to make progress on our global regulatory filings and commercial planning for ATGAA, our novel next-generation therapy for Pompe disease. As we just announced last week, the U.S. Food and Drug Administration recently deferred action on the Biologics Licensing Application, or BLA, for Cipaglucosidase Alpha, the biological component of ATGAA, which we also call ATB200. The agency cited that due to restrictions on travel related to COVID-19, it was unable to conduct the required inspection of the Wuxi Biologics manufacturing site in China during the review cycle and is deferring action on the application until the inspection is complete. That being said, the good news is that per FDA guidance, a deferral in such circumstances can only be given, quote,

Speaker 1: provided that no deficiencies have been identified in the application otherwise satisfies the requirements for approval." So as we've been saying, we believe this is a matter of when, not if, ATGA is approved. Additionally, the company is now actively engaged in the FDA on this step, and at the agency's direction, the company has requested a Type A meeting with the Office of Pharmaceutical Quality to discuss and agree upon plans and logistics for the pre-approval inspection.

Speaker 1: We at Amicus, along with our manufacturing partner, Wuxi Biologics, are ready for the inspection of the manufacturing facility in China. And as soon as we have more clarity, we will provide an update on when we might expect an approval in the United States.

Speaker 1: As a reminder, we continue to expect the two components of APGEA will be approved together.

Speaker 1: Importantly, in Europe , we are very far along now in the review by the EMA on the marketing authorization application for APGAA. To provide a little more color there, we are announcing today that we are included now in the agenda for an oral explanation in November . And thus, the CHMP opinion is expected at the December meeting, setting us up for a commercial launch in 2023.

Speaker 1: As a reminder, the EMA has indicated that it does not require an inspection of the Wuxi manufacturing site as a condition of their approval.

Speaker 1: We're also extremely pleased with the level of interest and participation we're seeing in our expanded access programs globally. We now have programs in place in the United States, United Kingdom, France, Germany, and Japan with a growing number of patients participating in each. In fact, across all of our ongoing clinical studies and access programs, there are now nearly 190 patients on ATGA today, which we believe represents more than 5% of the total treated Pompeii patients around the world.

Speaker 1: We expect this number to continue to grow as we approach approvals in the United States and Europe .

Speaker 1: In the anticipation of these approvals in the near term, our global launch plans continue to move ahead, including our prelaunch activities, targeted investments, and a handful of additional personnel to support the launch and ongoing investments in building launch inventory.

Speaker 1: We are close now to reaching this much anticipated milestone of ATGA getting across the regulatory finish line and providing another treatment option for people living with Pompe disease both in the United States and in Europe and with further regulatory applications planned in the months ahead.

Speaker 1: And third, Amicus has maintained a strong financial position as we continue to execute on the global expansion of Gallifold and prepare for the global launch of APJ. Despite all the headwinds with FX and the delays with APJ approval in the United States, we will continue on our path to profitability.

Speaker 1: Our goal is to achieve non-GAAP profitability in the second half of 2023.

Speaker 1: This is dependent on a number of factors, including the timing of approvals and the launch of ATJ, but based on the current operating plans and projections, we believe this will happen in the second half next year.

Speaker 1: Additionally, today we entered into an at the market or ATM equity offering of up to 250 million dollars.

Speaker 1: We see this as good financial housekeeping measure and we have no present intention to use the APM this year.

Speaker 1: In 2023 and beyond, we will be judicious about any use of the ATM, and any proceeds will go towards ensuring the continued commercial expansion of Gallifold and maximizing anticipated launches at APGA.

Speaker 1: I'll emphasize that we're sharply focused on our three primary objectives.

Speaker 1: Number one, continuing to advance Gallifold to as many patients in as many geographies as possible. Number two, securing approvals for and launch of ATGA globally. And number three, ensuring the financial strength at Amicus.

Speaker 1: On slide five.

Speaker 1: We see that we're well on our way towards achieving our key strategic priorities for this year, including number one, continuing to drive Gallifold to more people living with Fabry disease with amenable variants and existing in new markets.

Speaker 1: As I mentioned, we're on track to achieve our guidance of double-digit global product revenue growth of 15 to 20 percent at constant exchange rates.

Speaker 1: This reflects the strong momentum and demand behind this precision medicine globally.

Speaker 1: We remain steadfast in our commitment to advancing ATGA regulatory approvals and the anticipated launch of ATGA. Leveraging our seasoned global commercial, medical, and market access teams and our experience across all areas needed for a successful and effective drug launch, we are fully prepared for and anticipate a successful launch at ATGA.

Speaker 1: We continue to judiciously invest in the advancement of our best in class next generation genetic medicines and capabilities, as well as our next generation chaperone for Fabry disease. And again, we'll continue to maintain a strong financial position as we carefully manage our expenses and our investments in the business.

Speaker 1: With that, let me now hand the call over to Sebastian Martel, our Chief Business Officer, who will give further highlights on the Gallup Hold performance for the quarter. Sebastian?

Speaker 2: Thank you, Bradley. So good morning to everyone on the call. I will start by providing you with more details on our Gallopool performance for the quarter.

Speaker 2: On slide 7 for the third quarter of 2022, Gala4 reported revenue reached $81.6 million, driven by strong new patient accruals, partly offset by significant foreign currency headwinds.

Speaker 2: The geographic breakdown of revenue during the quarter consisted of $51 million.

Speaker 2: or 63% of revenue generated outside of the US and the remaining $30 million of 37% coming from within the US.

Speaker 2: When ignoring FX impact, this is in line with a two-thirds to one-third split that we expect as we continue to grow both parts of the business.

Speaker 2: We are pleased to see continued strong patient growth in countries like the USA, Japan, Canada, Spain, Portugal and Poland just to name a few.

Speaker 2: Turning to slide 8, our results in the first nine months of the year highlight the strengths of our global commercial records.

Speaker 2: The business continues to be incredibly resilient, with patients added in all major markets, and an operational growth rate of 16.2% over the same period in 2021 at constant exchange rates.

Speaker 2: The negative impact from foreign currency was 8.3% in the period.

Speaker 2: As a result, GAAS will report its revenue growth of 7.9% in the first three quarters of the year.

Speaker 2: To add a bit of color on our geographical performance, in the first nine months of the year, our sales in the US grew 16.8% while our ex-US sales grew 16% at constant exchange rates.

Speaker 2: On a year-to-year basis, Gannafold continues to be the fastest growing product in 2022 of Fabry disease globally and the greatest contributor to the global Fabry market growth.

Speaker 2: I'm pleased to report that our monthly net patient trends continue to show positive signals.

Speaker 2: Indeed, the 3-month trend is the highest in the last two years.

Speaker 2: And if you look at the growth in end patients on Gala-Co globally, which is perhaps the twelfth measure over the underlying business.

Speaker 2: We see greater than 19% growth in patients on the data fold, and we have two or three this year, versus the same period last year.

Speaker 2: All indications of the continued and growing demand for galapodes.

Speaker 2: We ended the third quarter with over half of the global market share of treated amenable patients.

Speaker 2: And while the global mix remains about 55% switch and 45% naive in many geographies, we're seeing a stronger uptake in naive populations.

Speaker 2: So while we are achieving high market shares in countries where we've been approved the longest, there's plenty of opportunity still to continue to switch patients over to Gallopold and continue to grow the market as we penetrate into the dynos untreated as well as the newly diagnosed segments.

Speaker 2: All of that is underpinned by the impressive compliance and adherence rate that we continue to see exceeding 90%.

Speaker 2: We're curating our belief that those patients who go on gaffold generally stay on gaffold.

Speaker 2: We continue to expect non-linear quarterly growth due to uneven ordering patterns and Netflix fluctuations.

Speaker 2: Importantly, the value of GAAPO continues to be recognized by payers as we have a very strong track record of successfully negotiating and renegotiating reimbursement outside of the US.

Speaker 2: Our relentless commitment remains on entering assets to get a hold for anyone who needs it.

Speaker 2: On slide 9, what we've seen so far this year that Gallifield will take continues to track very well and we're seeing growth across all our major markets as well as most of our smaller markets.

Speaker 2: We are trying to achieve a full year revenue guidance of 15-20% goals at constant exchange rates.

Speaker 2: Altogether, we view this as a great place to be three quarters of the way through the year.

Speaker 2: Moving to slide 10.

Speaker 2: We know that GALA fold has the potential to surpass $500 million in nano revenue over the next few years.

Speaker 2: through three key growth drivers. First, continuing to penetrate into existing markets, second, expanding into new geographies, and third, broadening the label.

Speaker 2: I'm pleased to share that we're making continued progress on expanding in 3D markets.

Speaker 2: Just to name a few examples, we recently received marketing authorization in Turkey.

Speaker 2: We submitted the marketing authorization application in Hong Kong earlier this year, and we're about to submit in New Zealand.

Speaker 2: We've also successfully renegotiated pricing and reimbursement agreements recently for gals in Poland and Spain.

Speaker 2: In the longer term, we continue to see significant growth in the fabric market globally, driven by diagnosis of patients.

Speaker 2: to a variety of measures including high-risk screenings, newborn screening, and all the diagnostic initiatives.

Speaker 2: which we continue to support and invest in as well.

Speaker 2: And finally, we have orphan exclusivity in the US and Europe , in addition to our now 46 orange-booklisted patents that gave us IP coverage into the late 2013s.

Speaker 2: 30 of which provide protections to 2038 and beyond, including side composition of matter patterns

Speaker 2: All of which gives us the opportunity to provide access to GALA4 globally for a long time to come.

Speaker 2: Moving on to ATGA on slide 11, we outline launch preparations as we are poised for another successful product launch.

Speaker 2: Unlike when we launched Gatafold where we were hiring and building the commercial infrastructure from scratch, we now have a presence in over 40 countries around the world, including all the major markets.

Speaker 2: That team, that same team will be largely the one involved in launching ATGDA, with only a handful of new FTs needed. We have experience across all the regions that are needed for a successful drug launch.

Speaker 2: in regulatory, commercial, supply chain, experience with payers, reimbursement and access, and in addition, and perhaps most importantly, we have key relationships with physicians.

Speaker 2: We're very confident in our world-class organization, and we can leverage their experience and relationships to deliver ATGA to people living with Pompe disease around the world.

Speaker 2: From the team, the medical education, the published phase 3 data, and the highly regarded Lancet Neurology Journal, our experience with reimbursement and access around the world, and again, all the strategic planning that we're doing together with building inventory with our partners, Approaching Biologics.

Speaker 2: We believe we are in a very strong position for a second successful launch for Amicus.

Speaker 2: With that, let me now hand the call over to Dr. Jessica Silli, our Chief Development Officer, to highlight our ATGA program and pipeline updates.

Speaker 1: Thank you, Sebastian, and good morning, everyone.

Speaker 1: On slide 13, we'll start with our ATGA program.

Speaker 1: Pompe is a severe and fatal neuromuscular disease and one of the most prevalent lysosomal disorders and we recognize that Pompe poses a range of health challenges for people affected by the disease and having therapeutic choices is crucial.

Speaker 1: Multiple publications and natural history studies highlight the initial benefits of treatment, generally being followed by continued long-term decline for many individuals.

Speaker 1: On slide 14, we present a summary of the primary and key secondary endpoints from our phase 3 study. As a reminder, PROPEL was a double-blind, randomized study assessing the efficacy and safety of ATGA in adult treatment-naive and ERT-experienced participants.

Speaker 1: with late onset Pompe disease or LOPD against the approved therapy of Glucosidase-alpha.

Speaker 1: PROPEL is the only controlled clinical trial to date that included both the ERT experienced patients and ERT-naive with the experienced patients representing one of the sets of patients with the greatest clinical unmet needs.

Speaker 1: Endpoints across motor function, muscle strength, pulmonary function, patient reported outcomes and biomarkers, including the two most recognized endpoints in Pompeii, six-minute walk distance and SEC, shown here in the slide, favored ATGA over out leukocytase alpha in the overall population.

Speaker 1: We believe this consistency of effect across the key disease manifestations of Pompeii illustrates the potential impact of ATGA for patients.

Speaker 1: Additionally, in the ERT experience population, where 95 participants were on the standard of care for more than seven and a half years on average.

Speaker 1: generally associated with continued progression for most patients at this point in treatment. We actually saw an increase in six-minute walk distance and stabilization in that PC after switching to ATGA, which achieved nominal statistical superiority on both endpoints versus a current treatment and showed a clinically meaningful outcome never before seen in this population.

Speaker 1: Moving to slide 15, as part of the growing body of evidence supporting ATGA, the AMICUS team presented additional positive long-term data from the phase 1-2 study of ATGA at the 2022 World Muscle Society Conference.

Speaker 1: As seen here on the slide, these latest data continue to represent very meaningful and durable improvements.

Speaker 1: and functional outcomes, as well as persistent reductions in key biomarkers of muscle damage and diseased substrate.

Speaker 1: Compared with what is known about the natural history of both untreated and ERT-experienced Pompeii patients, the observed durable improvements give great hope that ATGA has potential to become the new global standard of care for people living with LOPD.

Speaker 1: On slide 16, we show key results from an indirect treatment comparison of Pompe ERTs that was also recently presented at the World Muscle Society conference.

Speaker 1: This analysis used published data from the Phase I-II and Phase III studies for the three ERTs currently available or under regulatory review for late onset Pompeii.

Speaker 1: A multi-level network meta-regression accounting for effects of study level covariates was performed using individual patient level data from the PROPEL study and available aggregate data from the other studies.

Speaker 1: The forest plots shown here on the slide represent the estimated relative effects.

Speaker 1: and 95% credible intervals of each treatment comparison in the base case analysis in which all covariates were set to the target population of the PROPEL trial.

Speaker 1: These results suggest cyclic acidase plus Miglostat may potentially have a differentiated clinical profile versus the other ERTs, particularly for individuals with some level of previous ERT treatment.

Speaker 1: On slide 17, we have highlighted key updates on the ATGA program.

Speaker 1: First, on the regulatory progress, as shared previously, last year the USFDA accepted for review the BLA for Cyplicococidase-alpha and the NDA for Migliscat, the two components of ATGA. The yesterday period of petition during committee meetings withisherucks and then came up with a 1978 federal scope measure, and it received a

Speaker 1: And as Bradley summarized earlier, following the recent FDA-deferred action, which was due solely to COVID-related inspection delays, the company is now actively engaged with the FDA and at the agency's direction has requested a Type A meeting with the Office of Pharmaceutical Quality to develop plans and logistics for the pre-approval inspection.

Speaker 1: We continue to expect that the two components of APJ will be approved together, and once we have more clarity, we'll be able to get more color on estimated approval timing.

Speaker 1: We have also shared previously that the MAA has been submitted to the European Medicines Agency and is now in the later stages of review. Following an upcoming oral explanation in November , the CHMP opinion is expected at the December meeting. For more information, visit www.chmp.org

Speaker 1: Of note, the EMA has indicated in writing that based on the extensive and prior manufacturing inspections of the WUSHI facility that an inspection is not required prior to ATGA.

Speaker 1: approval. We now have multiple Expanded Access programs in place including in the US, UK, Germany, France, Japan, and other countries.

Speaker 1: This includes the EAMS framework, of which we have previously announced that ATJ was granted a positive scientific opinion through the Early Access to Medicine Scheme by the UK's NHRA.

Speaker 1: We are seeing 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 ATGA through this program.

Speaker 1: With this growth in our access programs, as Bradley noted, we are pleased to report that approximately 190 patients worldwide are now being treated with ATGA across our clinical extension studies and expanded access programs.

Speaker 1: And for the younger Pompeii community, we continue to enroll the ongoing open-label study in children up to 18 years of age living with LOPD and expect to expand into patients with infantile onset Pompeii disease later this year.

Speaker 1: Importantly, in response to the many requests for treatment that we continue to receive for children living with LOPD and IOPD, our expanded access programs continue to increase.

Speaker 1: With that, I would like now to turn the call over to Daphne Queenie, our Chief Financial Officer, to review our financial results, guidance, and outlook. Daphne? In conclusion may I interrupt these breaks?

Speaker 3: Thank you, Jeff, and good morning, everyone. Our financial overview begins on slide 20 with an overview of our third quarter revenue performance and FX impacts.

Speaker 3: For the third quarter, we achieved total revenue of $81.7 million, which is a 3% increase over the same period in 2021. This includes operational revenue growth of 14%, offset by a negative currency impact of 11%. The rest of the identified

Speaker 3: Given a majority of Gallifold revenue is generated outside the U.S., we see significant FX exposure to our reported revenue numbers.

Speaker 3: The Euro, British Pound, and Japanese Yen are the currencies we are most exposed to, and on a year-to-date basis, these have declined 14%, 18%, and 20% respectively.

Speaker 3: Applying average October 2022 exchange rates, the FX impact on 2022 full year Gallifold reported sales would be a negative impact of approximately 9% or $28.5 million.

Speaker 3: Slide 21 outlines our income statement for the third quarter ending September 30, 2022.

Speaker 3: Cost of goods sold is a percentage of net sales with 16% in the quarter as compared to 15% for the prior year period.

Speaker 3: Total GAAP operating expenses were $102.1 million in the third quarter as compared to $110.2 million in the third quarter of 2021.

Speaker 3: The decrease reflects the reprioritization of the gene therapy portfolio.

Speaker 3: On a non-GAAP basis, total operating expenses were $85.5 million in the third quarter as compared to $93.6 million in the third quarter of 2021.

Speaker 3: We define non-GAAP operating expense as research and development, SG&A expenses, excluding share-based compensation expense, loss on impairment of assets, changes in fair value, of contingent consideration and depreciation.

Speaker 3: Net loss for the third quarter of 2022 was $33.3 million, or $0.12 per share, as compared to a net loss of $50.3 million, or $0.19 per share, for the prior year period.

Speaker 3: Driven by the revenue growth of Gallifold and expense management, we continue to make progress towards our path to profitability in the second half of next year.

Speaker 3: At September 30, 2022, we had approximately 281 million shares outstanding.

Speaker 3: We are updating our full year 2022 non-GAAP operating expense guidance from $470 million to $485 million to $430 million to $440 million, driven by prudent expense management while maintaining ATGAA manufacturing and prelaunch activities.

Speaker 3: Importantly, in 2023 and beyond, we continue to expect non-GAAP operating expense levels to decline the low levels we saw in 2021.

Speaker 3: Turning now to slide 22, we continue to operate from a position of financial strength and our goal remains to achieve non-GAAP profitability in the second half of 2023, as defined in our press release.

Speaker 3: Profitability is dependent on a number of factors, including the timing of approvals and launch of ATGAA.

Speaker 3: We will focus the majority of our investments on our core value driving franchises in Fabry disease and Pompe disease by continuing to deliver on the global growth of Gallifold, securing approval and launching APGAA globally, as well as driving efficiencies, cost savings and careful expense management.

Speaker 3: As a good financial housekeeping measure, today we entered into an at-the-market, or MEC, equity program of up to $250 million.

Speaker 3: We have no current intention to use the ATM this year.

Speaker 3: In 2023 and beyond, we will be strategic and judicious about any use of the ATM.

Speaker 3: A few comments about our cash position and 2022 financial guidance.

Speaker 3: Cash, cash equivalents, and marketable securities were $354.7 million at September 30, 2022, compared to $482.5 million at December 31, 2021.

Speaker 3: Our full year revenue, Gallifold revenue guidance is $350 million to $365 million at constant foreign currency exchange rates, in addition to our non-GAAP operating expense guidance of $430 million to $440 million.

Speaker 3: And with that, let me turn the call back to Bradley for closing remarks.

Speaker 1: Great. Thanks, Daphne, Jeff, Sebastian, for highlighting all the great progress of the quarter. Thanks to everybody at Amicus and all of our employees around the world who work so tirelessly for people living with rare diseases. With that operator, we can now open the call to questions.

Speaker 4: Ladies and gentlemen, if you have a question, please press star and then 11 on your touchtone telephone.

Speaker 4: At this time, we ask that you only ask one question. If you have any additional questions, please enter back into the queue.

Speaker 4: Your first question comes from the line of Ritu Baral with Cowen. You'll want to show up and...

Speaker 3: Good morning, guys. Thanks for taking the question. It's on basically – Good morning, Rachel. Good morning. It's basically on the timeline of ATGAA approval. I guess you outlined today that you're going to request a Type A meeting. Can you – Correct. Can you tell us when you plan on requesting the Type A meeting? Do you need to put a briefing book like usual together in advance, or can this be done more ad hoc and what those timelines might be? And then I have a quick follow-up. Hello?

Speaker 1: Sure, great question. So the request actually has already gone in, so that's already been submitted and that was at the direction of the agency. I think that's important. This is really the appropriate vehicle for us to have formal conversations and we were careful to highlight it with the Office of Pharmaceutical Quality. So you know, we had talked when we put the press release out last week about why we felt confident this was really an active step to get to a solution around conducting the inspection.

Speaker 1: I think having this formal vehicle really helps put a fine point on that. In terms of when we might have an update, and then I'll come to your next question, in terms of when we might have an update, we still hope to have an update in the coming weeks. And as I mentioned last week, as soon as we have more clarity, we can provide some expectations on when we might see an approval. But again, we think this is a very important step that we're having this discussion, and the request indeed already went into the agency.

Speaker 3: Got it. And my quick follow-up is on Europe . Have you responded to the 180-day questions, and were there any surprises or differential content from U.S. review issues for the EMA review? Thanks. …

Speaker 1: Thanks, Ritu. Jeff, do you just want to talk to the progress we're making in Europe and where we are with the oral explanation and the expectation for December ?

Speaker 1: Thanks, Brian . Thanks for the two. We are in very late stage review with CHMP. There have been no, I would say, surprises in terms of the remaining topics being discussed. There was an explanation coming up here shortly and then we still have a lot of confidence that we have an approvable filing and we expect that opinion at the December meeting.

Speaker 1: but very consistent so far with a lot of the U.S. review and questions.

Speaker 1: so far with a lot of the US review and questions. Great. Thanks.

Speaker 4: Thank you.

Speaker 4: Our next question comes from the line of Anupam Rama with JP Morgan. The line is now open.

Speaker 2: Hey guys, thanks so much for taking the question. If I remember correctly, you guys do provide sort of forward year guidance at an investor conference in January with the...

Speaker 1: DHMP decision on the horizon, would you be in a place to give some guidance and metrics around ATGAA, or should we just be thinking it will be focused on Gallup-Bold and expenses? Thanks so much.

Speaker 1: Thanks, Anathom. It's a great question. I think we will be, as you said, be able to give some color on Gallifold and expenses. Let us get a little bit more certainty around the timing of the approvals, which, as you said, we should have more clarity here relatively soon, especially in Europe and hopefully in the U.S. as well. We'll certainly give some metrics to follow in terms of the launch and the launch progress, but stay tuned on exactly what those look like. But we'll do our best to provide the street with some sense for how to make Skilled.

Speaker 5: the FDA has not been receptive to a hybrid inspection to this point? Is an in-person inspection the only path forward? And what plans and logistics will you propose to the FDA in order to get Wuxi, the process they're inspected? Do you have any reason to believe that they'll be receptive to any particular solution?

Speaker 1: Yeah, thanks, Joe. So a couple things. So first of all, I can't speak on behalf of the agency, but we have said all along that despite what we believe are multiple types of inspection the agency could use to satisfy this this pli for APGA, they have always signaled to us that they would like to inspect in person now whether that's in person from Maryland or in person from, you know, a hybrid team.

Speaker 1: I don't know, but they have always said that they'd like to inspect in person. Specifically, what we're working on now is exactly that, which is coming up with logistics and a plan to enable the agency to inspect the Wuxi facility in China in person. And I think the biggest difference here versus some of the commentary we've given over the course of the summer as we approached this latest PDUFA date is that now we have active dialogue and now formal dialogue through this type A.

Speaker 1: meeting request. And again, that was at the agency's direction. And so I think what's changed here is number one, we are

Speaker 1: actively discussing the logistics in particular how to navigate the COVID situation on the ground in China and that it was at the agency's request that we have this formal meeting and they are now actively engaged in that dialogue. So we feel you know a high degree of confidence that we now have an engaged discussion, that we have specifics of a plan and logistics that are being discussed and our hope here again is that in the coming weeks we can finalize that and then we can provide more clarity externally.

Speaker 5: on timing for when an approval might happen. Okay, thanks. And then what are you able to do during this time when you're waiting for FDA approval to get in front of Pompeii physicians and patients in a compliant manner in order to ensure that you can really hit the ground running and not lose too much ground to competition once you're approved in the U.S.?

Speaker 1: Yeah, I think what Jeff highlighted on the call is really the...

Speaker 1: The most important way to do that is really through medical education at ongoing medical conferences. So we had a great presence at the World Muscle Society, presented a host of data there. I don't know, Jeff, do you want to remind us just the high level of the Pompeii data in particular that was presented there, and then kind of a general medical education publication, posters, abstracts, et cetera?

Speaker 1: Thanks, Brian and I, Joe. As I summarized briefly in the call, we've had a very active presence at WorldMuscle. We presented the four-year long-term data from the Phase 1-2 trial. We presented some new indirect treatment comparisons from available data across different ERT.

Speaker 1: products. And we continue to keep planning upcoming conferences, WorldLDN and then other meetings early next year to continue to have lots of new evidence presented and data presented on ATGA. And of course, we're having appropriate disease education and our teams, both the sales team and medical team are all ready to go with materials and messages. So we can do everything that you typically would do prior to.

Speaker 1: approval, and we're going to continue to get ready for the launch. We are ready in many ways, but we'll be even more ready with extra time.

Speaker 1: The only other thing I would add there, Joe, is I think this is a highly anticipated development program and regulatory process. And so the good news here is I think the community, physicians, patients, et cetera, are well aware that ATGA is going through this process. And so I think there's a lot of anticipation as well in addition to the medical education activities that Jeff highlights.

Speaker 5: Thanks for taking my questions.

Speaker 5: Any questions?

Speaker 6: Thank you.

Speaker 4: Our next question comes from the line of Tazeena Maad with Bank of America. You want us to open.

Speaker 7: Hi, good morning. Thanks so much for taking my question.

Speaker 7: Just want to get your thoughts. I know you're not talking about the specifics of what a label language could look like, but in the event that you do get the specification about the switch data patients

Speaker 7: How do you think that would impact your ability to gain traction against your key competitor who's been marketing really without that language? And longer term, how should we think about the split between US and ex-US sales forcontradictions?

Speaker 8: Thank you.

Speaker 1: Sure, maybe I'll turn to Sebastian in a moment on the split between the two, between the geographies in terms of the sales. But in terms of the first question around the ability for us to be successful with ATGA and what some of the label scenarios might suggest, you know, I think the most important thing is the differentiated data set that Jeff highlighted on the call.

Speaker 1: We are the only manufacturer to have studied in an active control setting that switch population. And as we've said before, that makes up probably 90 percent of the opportunity over the next few years. And so I think that differentiated data set and hopefully over time, the long term data that we saw from the phase one to study as we build that body of evidence. I think that gives us a really differentiated.

Speaker 1: product, especially in that switch population for us to build on. The other thing I would remind people is that while I know we've spent a lot of time around what could be scenarios in the United States, obviously we have multiple jurisdictions that we're seeking approval in. And just because one jurisdiction has one label doesn't mean all jurisdictions will have that label. So I think it'll be really important to see how that evolves over the – as we see some of these anticipated.

Speaker 1: approvals in the coming months. So I think people should watch out for that as well. And then the last thing I'll add and then turn it over to Sebastian. Again, we do intend to continue to build the body of evidence in many Pompeii populations. And so there may be an opportunity down the road, of course, if for some reason you have one specific population in your label to add to that over time and potentially expand those labels. So with that, maybe Sebastian just talk a little bit about the distribution of.

Speaker 1: the opportunity between the US and some of the other major markets around the world.

Speaker 1: between the US and some of the other major markets around the world? Yeah, thank you, Brage.

Speaker 2: There are a couple of ways to look at that. You can either look at it from a patient standpoint or look at it from a sales standpoint. So I start with the breakdown of sales across the main geographies. The US represent about 40% of sales. Europe , about 35% of sales. And rest of the world, roughly 25%.

Speaker 2: Now the picture is slightly different when you look at actual patients, mostly because of differences in pricing across the anti-inflammatory portion. So Europe accounts for more than 40% of patients currently treated with co-competed ease, while the US represents around 25% of patients only. So Europe represents a very large opportunity from a patient percentage standpoint.

Speaker 9: Great. Thanks, Sebastian.

Speaker 6: Thank you.

Speaker 4: Our next question comes from the line of Ellie Murrow with UBS. Your line is now open.

Speaker 10: Hi this is Sarah on for Ellie thanks for taking our question. I think two quick ones from us in terms of the type A meeting with the FDA I guess anything we know historically about you know now that the request is submitted sort of how long it may take to start conversations and the duration maybe of that process and then looking at XUS growth in Gallifold.

Speaker 10: What are the key regions that you see driving growth in 23 and sort of maybe cadence of expanding geographically over 2023 as well? Thanks.

Speaker 1: Sure, thanks, Sarah. So on your first question as relates to the Type A meeting, as I mentioned, the request has already gone in. So that process has already started. Our hope is that technically there's a formal clock that we can meet with them as soon as possible. And again, as soon as we have more color there, we'll provide that update. And in terms of sort of how long the process will take, again, our hope is that it can be fairly expedient.

Speaker 1: let us get through those discussions and as soon as we can we'll provide more color. And then on the ex-US growth opportunities for Gallifold, one thing I'll just say at a high level and maybe Sebastian you can provide some specific color. Sebastian talked on the call how Gallifold is actually the largest contributor to that brand revenue growth around the world, which I think is pretty incredible given the fact that we're restricted to the amenable population. The other thing I'll say is that as we look at the numbers and as you look at the metrics we've given.

Speaker 1: What we're seeing is really a continued building of momentum coming out of what was probably the depths of the COVID impact. And so as Sebastian highlighted on the call, seeing the three-month net new patient numbers being the largest they've been for the last two years, I think that gives us great confidence that we are seeing kind of resumed growth and momentum, which is so important for that key franchise. But Sebastian maybe talk a little bit about what are the geographic growth drivers for next year for Galvald.

Speaker 2: As I highlighted earlier, what we've seen this year is actually pretty much the same kind of growth rate in the US and ex-US. So we were at 16.8% in the US and 16% ex-US.

Speaker 2: when you start looking at specific countries, we continue to see a double-g growth rate in countries where we've even been launched for the longest. And that's explained in those markets, where we've been the longest on the market. That's explained by the growing participation we have to put naive patients on treatments.

Speaker 2: There's also countries where we've launched more recently and there you see a much larger proportion of switches initially. But overall we continue to see double growth rates in most markets where we currently launched.

Speaker 2: we're seeing very strong growth in some rest of world markets. So if I take some La Tan market for example, Colombia, Brazil.

Speaker 2: In Eastern Europe , the Polish market has also seen great expansion for Gallifolds. And as I highlighted, we continue to launch in, or to register at least, in markets where Gallifolds has not been launched yet. So I mentioned specifically Turkey. Turkey is quite a sizable market from a total number of patients. The actual number of treated patients in Turkey is close to any of the countries in the world.

Speaker 2: each of the European top five markets. There are still a small number of markets where we've got approval and are working through the pricing and reimbursement process. So these will be new launches in 2023. But again, the core markets and I would say the top 10 markets continue to show where things can go.

Speaker 9: Great. Thanks, Sebastian.

Speaker 9: Great. Thanks, Sebastian.

Speaker 6: Thank you.

Speaker 4: Our next question comes from the line of Dagon Ha with Steve-O. You'll want to open.

Speaker 11: Hey, good morning guys. Thanks for taking the question. I'll stick with one. Just going back to ATGAA, there have been some rumblings on unverified reports of China maybe reopening given the impact of the tech sector and that economy. I guess if you can speak to two different scenarios, one is what sort of your guess is to the timeline towards them reopening and two, in a bear case where they don't, what's the real hypothetical here given that the US Chamber of Commerce was still able to... Okay.

not require any change to the official COVID policy. So we're working on plans with the agency that would allow them to conduct the inspection in the current environment. And so, you know, maybe that is the bare case, but I think we're being conservative there. And again, the intent is that this is something that can happen within a finite amount of time. I know that the key question is exactly what that amount of time looks like. And I wish we had more color there, but we are actively working on it. And again, we feel like in the coming weeks.

from the line of Salveen Richter.

with Goldman Sachs, you'll want it to open.

Good morning. Thanks for taking my question. I know with regard to the launcher and Pompeii, there was a question about cadence, but could you speak to how you think the launch will play out in terms of the competitive dynamics with Sanofi and how you think patients will be triaged between the drugs?

Yeah, so, you know, first and foremost, I think.

from a European perspective as Sanofi went through the

review process and the appeal process around the new act and substance. I think that significantly shortened the time between their launch and ours. So I think that that gives us a good confidence that effectively will be launching roughly contemporaneously based on the timelines that we're on. And so that that I think is a very different, excuse me, different scenario.

As relates to the U.S., as we've mentioned, I think what's important about APGAA is we have a very differentiated data set. And if you look at a number of the market research polls and a number of the cell side research that's been published out there, I think you do see an alignment around the indicated – or, sorry, the populations that were studied. And so –

some alignment around ATGA in the switch population and the other products in the naive population. So I think that data set that Jeff highlighted on the call today is really the key for us that we can show an improvement in patients who switch from enzyme replacement therapy on both six minute walk and four-spinal capacity. And we think those are the data that are really gonna be compelling for physicians.

and look forward to having the opportunity to get out there and promote the product on the other side of an approval.

Thank you. Our next question comes from the line of Yun Zhong with BTIG. Your line is now open.

Your line is open. Please check your mute button.

Hi, thank you. Sorry, I didn't hear my name. Yeah, good morning. Thank you very much for taking the question. So my question is on ATGAA. Can you remind us if the launch in Europe is going to be supported by the island site solely or is that going to be supported by Wuxi side as well? And also, what was your plan in terms of how you were going to coordinate between the two sites and given that you had this issue on inspection, have that changed your plan?

in terms of how you're going to coordinate between the two sides going forward? Yeah, great question. So just as a reminder, as you suggested, we do have the current manufacturing facility in Wuxi City in China and that's where we've been manufacturing.

APP 200, which is the biologic throughout the course of the development, that will support the initial launch in both the United States and Europe . However... That's it.

Wuxi has also now completed the build out and we're now actually in engineering runs for manufacturing of ATB200 at a site in Dundalk, Ireland. That site has actually more capacity than the site in China. And so our anticipation is that material from that site will enter into the commercial supply chain sometime in the 24 timeframe. And that was always the intention. But once that site comes on board, it's likely that it will supply the majority of products.

for both Europe and US and rest of world for that matter with likely a minority of product coming out of China. So we are not too far away here from having dual site manufacturing, which is critically important, but also increasing the capacity. And the intention was for that capacity to come online into the commercial supply chain when you're starting to really get into the meat of the global launch expansion, which would again be in kind of that 24 timeline. So hopefully that gives some clarity in terms of the plans there. And it hasn't really changed.

could potentially convert to commercial product once it's approved. Thank you.

Yes, it's a great question. And the answer very much is yes. As soon as we get regulatory approvals, then we look to convert our clinical trial or expanded access patients as quickly as possible. What we've given is just kind of rough numbers in terms of the breakout of those patients. So probably about half of the 190 are in Europe , with a big portion of those coming from the UK, Germany, and the EU5. The UK with the EAMS program is now the largest number of patients.

on ATGA today. And then likewise in the United States, we've said that 20 or so patients in the US are in our clinical trials and other ongoing access programs. And so again, there too that would be a population we would look to switch very quickly. With Gallifold, the goal was to be able to switch patients from either development drug or expanded access drug within 90 days. And we would have a similar goal here. Thank you.

And then likewise in the United States, we've said that 20 or so patients in the US are in our clinical trials and other ongoing access programs. And so again, there are two that would be a population we would look to switch very quickly with Gallifold. The goal was to be able to switch patients from either development drug or expanded access drug within 90 days. And we would have a similar goal here. Thank you.

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

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