Good morning, ladies and gentlemen and welcome to the Amicus Therapeutics Second Quarter 2023 Financial Results Conference Call and webcast. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Mr. Andrew Faughnan, Vice President of Investor Relations. You may begin..

Thank you, Tana. Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics' second quarter 2023 financial results and corporate highlights. Leading today's call we have Bradley Campbell, President and Chief Executive Officer; Daphne Quimi, Chief Financial Officer; Sebastien Martel, Chief Business Officer and Dr.

Jeff Castelli, Chief Development Officer. Joining for Q&A is Dr. Mitchell Goldman, Chief Medical Officer and Ellen Rosenberg, Chief Legal Officer. As referenced on Slide 2, we may make forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, as well as our plans and prospects.

Our forward-looking statements should not be regarded as representation by us that any of our plans will be achieved, any or all the forward-looking statements made on this call may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties.

You are cautioned not to place undue reliance on any forward-looking statements, which speak only to the date hereof.

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

For a full discussion of such forward-looking statements and the risks and uncertainties that may impact them, we refer you to the forward-looking statements and risk factors section of our Annual Report on Form 10-K for the year ended December 31st, 2022 and the quarterly report on Form 10-Q for the quarter ended June 30, 2023 to be filed later today with the Securities and Exchange Commission.

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

Bradley?.

Great thank you, Andrew and welcome everybody to our second quarter 2023 conference call. I'm very pleased to highlight what has been an incredibly successful first half of the year across our global business. As we did in this morning's press release, let me highlight several key points.

First Galafold continues its strong performance and remains the cornerstone of our success. We remain very pleased with the commercial uptake of Galafold globally with $180 million in revenue for the first half of 2023. This represents 16% growth from last year on a constant currency basis.

In the second quarter, operational growth was 17% year-over-year at constant exchange rates. We continue to observe strong trends across our key performance indicators in all key geographies in the second quarter.

This includes increasing demand through new patient starts from both the switch and naive populations, steady growth of in-person visits between our field team and Fabry treaters around the world and sustained patient compliance and adherence rates of over 90% Growth in the second quarter was driven primarily by patient demand and as Sebastien will highlight in a moment, we saw new patients starting on Galafold globally throughout the second quarter at rates we haven't seen since the first few years of launch.

Based on Galafold strong first half performance, we're pleased to be raising our full-year 2023 revenue growth guidance range to 14% to 18% at constant exchange rates.

Second, we continue to make great progress on our global regulatory filings and have now commenced the commercial launch for Pombiliti and Opfolda, our novel 2-component therapy for Pompe disease. Following the EC approval of Opfolda in June, the commercial launch is well underway in Germany.

Our team is in the process of switching over individuals from clinical studies and expanded access programs to commercial supply and we're pleased to share that the first patients have now been dosed with commercial products with multiple additional patients having been scheduled to start their infusion in the coming days and weeks.

Importantly, we're well on track to transition the 20 clinical trials and expanded access to patients within our 90-day target. Outside of Germany, we're focused on broader patient access across Europe, as we navigate the country-by-country pricing and reimbursement process.

In the U.S., we've been pleased to see an increased level of engagement from the agency in recent weeks and are confident now we are on track for FDA approval in Q3. And finally, the U.K. regulatory process for AT-GAA was initiated in December of last year and we've just received word this morning that the MHRA has approved Opfolda.

As a reminder MHRA previously approved Pombiliti and both have received orphan designation. We now expect the nice final assessment document to come in the next few days at which point it will take about 30-days for the NHS to provide funding to local centers to begin commercial infusions.

With our international launch commenced and poised for regulatory approval in the US and additional key markets on horizon, we look forward to providing a real choice and challenging therapeutic expectations for both physicians and the people living with Pompe disease around the world.

Finally, Amicus has maintained a strong financial position as we continue to execute on the global expansion of Galafold and begin the global launch of Pombiliti in October.

Importantly, based on the latest assumptions on approvals and launch of Pombiliti and Opfolda, combined with the strong growth we've seen in Galafold in the first half of the year, we are on track to achieve our target of non-GAAP profitability in the second half this year.

Ahead on Slide 4, we're making great progress of cost -- our key strategic priorities for 2023 including sustaining double digit Galafold growth now at anticipated growth rate of 14% to 18% at constant exchange rates, securing regulatory approvals of AT-GAA by the FDA, EMA and MHRA and executing successful launches in those key markets, continuing to judiciously invest in the advancement of our best-in-class next generation Fabry and Pompe genetic medicines and capabilities, as well as our Next-Generation Chaperone for Fabry disease and as always maintaining a strong financial position as we carefully manage our expenses and investments on our path to non-GAAP profitability.

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

Sebastien?.

Thank you, Bradley and good morning to everyone on the call. I'd start by providing you with more detail on our Galafold performance for the quarter. On Slide 6, for the second quarter 2023, Galafold reported revenue reached $94.3 million, driven by strong patient accruals, particularly in the US, but also in key European markets and Japan.

The geographic breakdown of revenue during the quarter consisted of $57 million or 61% of revenue generated outside of the U.S. and the remaining $37 million or 39% coming from within the U.S. We're very pleased to see continued patient growth in countries across our leading markets.

Turning on to Slide 7, our results in the first half of the year highlighted the strength of our global commercial efforts. The demand for Galafold globally continues to be strong with patients added in all major markets, delivering operational growth rate of 16% over the same period in 2022 at constant exchange rates.

From a year-over-year perspective, the negative impact from foreign currencies was 3% in the period and as a result Galafold reported revenue growth was 13%.

Galafold continues to be the fastest growing treatment for Fabry disease globally and I'm pleased to report that our monthly net new patient trends continue to increase in Q2 and if you look at the growth in net patients on Galafold globally, we've seen significant net patient gains on Galafold at the end of the second quarter.

Throughout the first half of 2023, the number of patients coming on to Galafold has actually exceeded internal expectations and we are therefore raising our full year 2023 revenue growth guidance to 14% to 18% growth at constant exchange rates.

We ended the second quarter with about 60% of the global market share of treated amenable patients and within the global mix we're seeing stronger uptake in naive populations.

And while we're achieving high market shares in countries where we've been approved the longest, there's also plenty of opportunity to continue to switch patients over to Galafold and continue to grow the market as we penetrate into the diagnosed and treated and newly diagnosed segments.

All of that is underpinned by impressive compliance and adherence rates, have continued to exceed 90%, reiterating our belief that those patients who go on Galafold permanently stay on Galafold.

As mentioned on past calls, due to a variety of factors including uneven ordering patterns and FX fluctuations, the rate of growth within the year is typically non-linear.

We expect that to continue throughout 2023 and to support quarterly forecasting, we provide a table showing distribution of GAAP or revenue by quarter in the past 5 years in the appendix section of our IR presentation.

On Slide 8, we know that there is significant patient demand for Galafold and at the segments on the global [indiscernible] bucket made of those amenable mutations has the potential to surpass a $1 billion in annual revenue in around 5 years. We anticipate sustained growth throughout 2023 to be driven by several key growth drivers.

First, continuing to penetrate into the existing markets, further uptake into the diagnosed untreated population and expanding into new geographies and label extensions. All of these efforts are supported by positive reimbursement and access mechanisms around the world.

I'm pleased to share that we continue to make progress on expanding Galafold into new markets and extending the labels, just to name a few examples. We recently received reimbursement in Taiwan for individuals over the age of 16 year old. The Fabry market within Taiwan is quite sizable with over 350 individuals diagnosed with Fabry disease.

Of note, Galafold was designated the first-in-line therapy for all amenable patients living with Fabry disease in Taiwan. Additionally, we submitted a marketing authorization application in New Zealand and we've entered into pricing and reimbursement negotiations for Galafold in Turkey.

In the longer-term, we continue to see significant growth in the Fabry market globally, driven by diagnosing patients through a variety of measures including high risk screening, newborn screening and other diagnostic initiatives, which we'll continue to support and invest in as well. With that, let me now hand the call over to Dr.

Jeff Castelli, our Chief Development Officer to highlight the regulatory updates on our AT-GAA program.

Jeff?.

Thank you, Sebastian and good morning, everyone. Starting on Slide 10, we remind everyone that late Onset Pompe is a severe and fatal neuromuscular disease and one of the most prevalent lysosomal disorders.

Within LOPD individuals may experience impaired motor function and respiratory difficulties as the disease progresses, but these potentially debilitating symptoms tending to become more serious and problematic over time and orphan respiratory failure being a major cause of mortality in LOPD.

Multiple publications and natural history studies continue to show that the initial benefits of treatment are often followed by continued long-term decline for many individuals. We recognize that Pompe disease continues to pose a range of health challenges for people affected by the disease and having therapeutic options is crucial.

Moving on to Slide 11, we briefly outline the current regulatory status of AT-GAA by key markets. First, as noted in June, Pombiliti and Opfolda both were approved in EU and the commercial launch is underway, as Sebastien will detail in more in the next section. And in the U.S.

as Bradley noted, we're pleased to see the increased level of engagement from the agency in recent weeks and remain confident we are on track for approval in the third quarter for both components of AT-GAA.

And finally just this morning, we were very excited to receive the final full approval and orphan designations for both Pombiliti and Opfolda by MHRA and now the team can begin launching this important new therapy for people living in the U.K. with Pompe disease leveraging that positive reimbursement appraisal from NICE.

Moving on to Slide 12, we remind everyone of our ongoing clinical studies and multiple mechanisms of expanded access that support much of the early demand for AT-GAA.

For the younger Pompe community, we continue to enroll the ongoing open label ZIP study in children up to 18 years of age living with LOPD and have begun enrolling the open label Rosella study for children living with infantile onset Pompe disease.

We have multiple expanded access programs in place in countries where we are not yet approved and interest and momentum for AT-GAA continues to grow and we're pleased to be able to provide access to those who are eligible through those programs.

As a reminder, at the time of our first approvals, which was first in the EU during that last week of June, there were approximately 200 patients worldwide being treated with AT-GAA across the clinical extension studies and expanded access programs.

And importantly experience with AT-GAA is quite broad with approximately 75 centers, participating in trials and various access programs around the world.

Finally, as highlighted in the Pipeline Slide in the appendix for our earlier stage pipeline, we continue to focus on novel approaches for Fabry and Pompe including gene therapies to deliver our engineered GLA and GAA transgenes and next generation Fabry chaperone program.

With that, I will turn the call back over to Sebastien to discuss the early commercial launch progress of Pombiliti and Opfolda.

Sebastien?.

Thank you, Jeff. On Slide 13, we outline the initial launch progress and market opportunity for Pombiliti, Opfolda in EU. Pombiliti+Opfolda is approved as the first and only two competent therapy available in the EU for the treatment of adults living with late onset Pompe disease.

We're very pleased with the strong indication for Pombiliti+Opfolda, which addresses all adults living with LOPD. The EU market represents a sizable opportunity of $450 million plus and is a key market to support these early stages of global launch.

Within Europe, there are currently around 1300 patients, estimated to be on treatment and of that 1300, currently 60 patients are being treated with Pombiliti+Opfolda and around 20 of those in Germany and Austria. As of today, we are launched in Germany with progress being made on all fronts and we're seeing the start of a very strong uptake.

Importantly, in Germany, the Federal Joint Committee or GBA has classified Pombiliti as a new active substance. As a result, Pombiliti will undergo the benefit assessment under the AMNOG process with the free pricing period after which there'll be negotiations and the final reimbursed price.

Based on feedback from key treaters through our clinical development, access and medical affairs, we're very pleased with the progress made towards transitioning patients over to commercial supply. We've been successful in engaging with the top prescribers in Germany within the first 30 days.

We've also been very pleased with the positive feedback from the expanded access program [CPAP] from both the physician and patient perspective.

As Bradley mentioned, the first patients have been recently moved to commercial supply and more are scheduled in the coming weeks, so we're well underway to achieving our goal of converting all of the 20 or so expanded access patients and clinical trial extension patients within the first 90-days of launch.

On Slide 14, as you know, we've been preparing for the commercial launch of Pombiliti+Opfolda and I'm both excited and confident that through our world-class commercial and medical organizations, we're in a very strong position for a second successful launch at Amicus.

In these early days, we're leveraging this experienced team to transition the first group of clinical trial and expanded access program patients in the EU on to commercial supply.

Given the significant overlap of treatment centers, hospitals and physicians between Fabry and Pompe disease, we have the existing relationships with KOL and the commercial infrastructure necessary to support a seamless transition.

As of today, we've had the first patients infused and multiple additional patients are scheduled to start their infusions. Within these early days, we find an important metric to track is our progress with access and reimbursement.

We have a highly experienced team who are engaging in positive interactions with payers to demonstrate the value of Pombiliti+Opfolda. Today, we launched in Germany both -- we're also in active pricing and reimbursement discussions with additional European countries, as we focus on securing broad patient access through the EU.

We're working in partnership with physicians to ensure they have all the information they need on Pombiliti+Opfolda for their patients and believe this two competent therapy is poised to have a significant commercial opportunity in the EU and additional markets as they come online.

As Jeff indicated from the late-breaking news, we're thrilled with today's approval of MHRA approval for Opfolda. We also were granted orphan designation for Opfolda like we did with Pombiliti in the UK. Market opportunity within the UK includes more than 200 people with Pompe disease, estimated to be on treatment.

45 of these 200 individuals are already in Pombiliti+Opfolda and that's a remarkable number, either through a clinical trial or through the early access to Medicine Scheme. As we've mentioned previously, all leading centers across the U.K. have requested access to Pombiliti+Opfolda through IMS.

Now that approval has been granted, our team anticipates a transition of all patients in the U.K. on to commercial product within 90-days. And importantly, that transition will be supported by the very positive NICE recommendation for reimbursement of Pombiliti+Opfolda within the NHS, which is an achievement we are incredibly proud of.

As stated in the guidance, NICE concluded that the cost-effectiveness estimates for Pombiliti+Opfolda showed a positive net health benefit and therefore has recommended Pombiliti+Opfolda for adults with LOPD as first line and later lines of therapy.

With that, I'd like to now turn the call over to Daphne Quimi, our Chief Financial Officer, to review our financial results, guidance and outlook.

Daphne?.

Thank you, Sebastian and good morning or afternoon, everyone. Our financial overview begins on Slide 16 with our income statement for the second quarter ending June 30, 2023. For the second quarter, we achieved total revenue of $94.5 million, which is a 17% increase over the same prior year period in 2022.

This includes year-over-year operational revenue growth measured at constant currency exchange rate of 17% and a negligible currency impact at 0%. Cost of goods sold as a percentage of net sales was 9.6% as compared to 10.2% for the prior year period.

Total GAAP operating expenses decreased to $104.2 million for the second quarter of 2023, as compared to $133.1 million in the second quarter of 2022.

On a non-GAAP basis, total operating expenses decreased to $84 million for the second quarter of 2023 as compared to $119.2 million in the second quarter of 2022, primarily reflecting decreased program spend.

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

Within other expenses in the income statement in the second quarter, we recorded approximately $11 million in unrealized foreign exchange losses. This compares to a $7 million gain in the second quarter of 2022. We are currently taking steps to mitigate our future exposure.

Net loss for the second quarter of 2023 was $43.2 million or $0.15 per share as compared to a net loss of $62.2 million or $0.21 per share for the prior year period, driven by the revenue growth in Galafold and careful expense management, we continue to make progress towards our path to non-GAAP profitability in the second half of this year.

As of June 30, 2023, we had approximately 287 million shares outstanding. Turning now to Slide 17. With a focus on achieving non-GAAP profitability, I'm pleased to share that we have revised both our revenue and operating expense guidance for the year.

We are raising full year Galafold revenue growth guidance to 14% to 18% at constant exchange rates, driven by patient demand. We are also reducing our full-year 2023 non-GAAP operating expense guidance to $330 million to $350 million.

The 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 Galafold, AT-GAA clinical studies, nonrecurring costs for manufacturing, as well as global launch activities.

We anticipate operating expenses to be nonlinear this year due to the pre launch and launch expenses. We also expect to see a larger portion of our operating expenses allocated to G&A this year, as we align our resources to support the launch of AT-GAA and the continued growth of Galafold.

Cash, cash equivalents and marketable securities were $265.6 million as of June 30, 2023, compared to $293.6 million as of December 31, 2022. And with that, let me turn the call back over to Bradley for our closing remarks..

Great. Thanks, Daphne, Jeff, Sebastian. As you can see, we've been relentlessly focused on execution across our global business and we look forward to embarking on this next phase of Amicus as a company with 2 commercial therapies.

Thank you to all of our employees who've enabled us to achieve these recent corporate milestones and we're always committed to our patient-focused mission of delivering life-changing therapies to people in need.

Before I hand the call over to Q&A, as you may have also seen in this morning's filing after 15 incredible years at Amicus, Daphne, our long-time Chief Financial Officer, leader and friend has decided to retire.

She'll remain in her current role as CFO until we appoint her successor at which point she'll remain on with Amicus through the end of the year in order to support a smooth transition. A search is underway and we've already identified a number of highly qualified candidates.

I also just want to add that I'm personally grateful to you, Daphne, for your years of exemplary service here at Amicus and in particular for helping lead us on our course to achieve non-GAAP profitability later this year.

On behalf of the Amicus Board of Directors and the entire executive team, I'd like to take this opportunity to formally thank you. You've been a significant part of the growth at Amicus and instrumental in guiding us to the sound financial position we're in today. With that, operator, we can now open up the call to questions..

Certainly. [Operator Instructions] And our first question comes from Tazeen Ahmad of Bank of America..

Brad, just wanted to clarify on the time line that you've stated forward for GAA is still expecting approval in 3Q.

Do you get a sense that the responses that you gave FDA post the WuXi inspection facility have been sufficient for the agency, if not, what do you think are the remaining gating factors regarding questions around the facility in order to get approval?.

Just as a reminder, we were very pleased with the outcome of the pre approval inspection at WuXi.

We do feel like our responses were all adequate and the color we provided in the call here today, I think is important, which is in the last few weeks, we’ve seen an increased level of engagement from the agency and so that gives us great confidence, we’re on track for Q3 approval..

And our next question will come from Anupam Rama of JPM..

And Daphne I'll miss you at the conference this coming year.

On the Galafold guidance increase, maybe from a regional perspective, where is that coming from? Is it coming from deeper penetration in core countries or progress in some of the new emerging countries?.

Yes, I'm happy to have Sebastian add a little bit of color, but honestly, [indiscernible] is coming from all of those things. So most importantly, what we're seeing is across all of our key geographies, as we mentioned on the call, rates of net new patient starts at levels that we haven't seen since the first couple of years of launch.

And so clearly, demand for this product is growing. But Sebastian, maybe touch on a few of the different growth drivers that Anupam highlighted us, give a little bit more color there..

Yes, I'd just add, for example, in the U.S. alone, remember, we launched in 2018. The current rate of net new patients that we've seen in the second quarter is as strong as what we saw in 2019. So we're really in a post-COVID world as we speak and we're seeing strong patient accruals.

This is also the case in Europe and remember, in Europe, we were launched a couple of years earlier. So our penetration rate within the amenable population is slightly greater and yet we're seeing very strong demand. A lot of naive patients actually go on Galafold when they're diagnosed.

So we've essentially established Galafold as the new first in line treatment for Fabry patients with amenable mutations in those markets..

Yes, maybe on the other things I’d highlight, sorry, I didn’t mean to cut you off, I was just going to say the other thing I’d highlight is and Sebastian mentioned it on the call, not only are we seeing great penetration rates, we’re opening up new geographies. So we have some important countries coming on board this year.

It’s also in the backdrop of a very healthy and growing fabric market. So diagnosis continues to be strong and as we find those patients, as a reminder, typically, you find one undiagnosed Fabry patient, newly diagnosed Fabry patient because it’s an X-linked disease that typically leads to 4 to 5 additional family members who are diagnosed.

So in addition to, I think, executing incredibly well, which we’ve continued to do, we’re also seeing just a healthy growth of market and as Sebastian highlighted, we’re actually the fastest growing of the Fabry treatments for patients with mutations..

Our next question will come from Ritu Baral of TD Cowen..

I want to go back to the WuXi inspection and follow-up on Tazeen's question.

Brad, can you give any additional detail on the points of the increased level of engagement that the agency has had just wrapping all of this up? Do you think that there's any possibility of requiring the re-inspection? Or do you feel that the outstanding items are addressable over written or verbal interactions.

Any additional detail would be helpful?.

No, we do not believe that there'll be any additional inspections needed at WuXi, we are very confident and we're very pleased with the outcome of the inspection.

And again, just based on the kind of level of reengagement we've seen, the increased level of engagement we've seen in the last couple of weeks, it feels to us as you said, that they're wrapping things up and we feel like we're getting close to an approval here as we suggested on track for Q3. So we're really excited. The team is ready.

We're really pleased to see the U.K. news this morning, so I think the momentum is building and really eager to see the remaining months of the year play out..

If I can squeeze one more in about how much supply do you -- thanks -- how much supply from the open label are German and U.K.

patients sort of sitting with before they start on the path to commercial conversion?.

Yes, we have -- our target is about 2 years of go-forward supply. Remember, we've made quite a bit....

I'm sorry, I meant like how much supply clinic -- how much drug supply do they have sitting from the open label....

That they’re working through, right, right. Got it. Sorry. Thanks for the clarity. Yes, the good news is, unlike Galafold, where you would typically – because it was a long shelf life, et cetera, you could then be sitting on kind of 3 months of supply of Galafold as we were winding down the clinical studies and transitioning over to commercial.

In this case, it’s a much tighter supply situation and the clinical operations team at Amicus, who, of course, has already done this once before with Galafold works very closely with the medical affairs team, with the sites themselves.

And so it’s a really fine and precise level of supply and that’s what allows us to very carefully manage and have that goal of 90-day transition. And in Germany, so far, as I’ve said, even in the first kind of 30-days of launch now, we are making those transitions and we’re confident we’ll be able to execute that within the first 90-days.

And I think likewise in the U.K. and then the U.S. when we see the approval..

And our next question will be coming from Eliana Merle of UBS..

Just if you could provide us a little bit more color on how you're thinking about new patient starts in Germany and the U.K. beyond the patients that are on expanded access. So maybe just of the 200, I think you said Pompe patients total in the U.K. and I think you said 45 were already on AT-GAA.

How should we think about the other 150 patients? And maybe what proportion might be on Nexviazyme already and just the time lines for when you expect the NICE reimbursement to kick in from a revenue perspective? And then in Germany, I know you mentioned you have 20 patients already on AT-GAA, but just if you could give us a sense of maybe how many Pompe patients there are in Germany? And how you think about the landscape there relative to Nexviazyme?.

I'll take some of those and then I'll ask Sebastian to add some color as well, that was a cleverly worded one question, multi-question props, but happy to address all those.

So first of all, yes, the first priority as we've said in each of those markets, because we have such a large bolus of patients is to convert the expanded access in clinical trial patients. But of course, in parallel, we're also working to start to begin bringing on new patients as well.

We should be able to provide more color on that in the November call. But again, first priority low-hanging fruit patients on AT-GAA already and then in parallel start to bring on new patient starts as well.

And then maybe Sebastian just give the color that we know based on publicly available information, what progress has been with Nexviazyme in those 2 markets and a sense for how large the German market is outside the 20 patients already on AT-GAA?.

So the -- I can share with you the breakdown between Nexviazyme and Myozyme across Europe is virtually 80/20 or 77%, 23%, to be precise. So the vast majority of patients are still on Myozyme, again, 77% across Europe and 23% for Nexviazyme. If you look at the U.K. numbers, you have them, you just quoted them, Eli.

So 200 patients total 45, which is probably the largest number of patients we have in a country on clinical trial plus early access. And so as Brad mentioned, we think that given the fact that the 6 key centers have all had experience with Pombiliti and Opfolda, they both have patients transition from either clinical study or IMS.

They have experienced, they've used the product before. They have, obviously, the feedback also from patients who have been on it. So we think that the uptake and our ability to convert commercial patients from Myozyme or Nexviazyme is high in this market. In Germany, the market is a lot more fragmented than in the U.K.

The number of patients is also higher, somewhere between 300 and 350 total patients. We did mention here that we've got around 20 in Germany and Austria. So those will be the first patients onto commercial product.

But as I mentioned, our team has been visiting top prescribers in Germany for a number of weeks now and have established those contracts and will be working with those physicians to convert and switch patients from their existing treatment onto Pombiliti+Opfolda over the next weeks and months..

And I think you had maybe one more question, Eli, on the reimbursement process in the U.K. So as I mentioned in the call, once you have MHRA approval, what's remarkable here is we've already had the initial recommendation for reimbursement by NICE, which we think is one of the fastest ever to get to that answer prior to MHRA approval.

The process from here should take a few days to a week to get to the final appraisal document by NICE, the draft is already posted, so that should come here relatively shortly.

And then it takes around 30 days for NHS to provide funding to the local centers and that's when we'll start actually converting those expanded access in clinical trial patients. But in the meantime, with the approval, our sales team can go out into the field, visit the physicians.

And again, along with medical affairs and clinical operations team can begin scheduling those infusions ahead of time. So effectively, launch is underway and we're waiting about 30-days for that reimbursement process to kick in at the local centers..

And our next question will be coming from Joseph Schwartz of Leerink Partners..

I was wondering beyond the EAP conversion of those patients to commercial status, how should we be thinking about the cadence of uptake for AT-GAA? And what metrics will you be providing us in order to gauge your progress with that? And are there any analogues that you can think of that might be helpful for us when envisioning the launch curve? And then can you remind us of your most recent thoughts around pricing and how this relates to the current price of Sanofi's products?.

All good questions. So as it relates – I’ll start with the last one first, as a reminder, our pricing philosophy is parity or modest discount to standard of care. And we have shown with Galafold that, that is an incredibly successful strategy. We went through the pricing and reimbursement process with Galafold much faster than industry average.

And I think it’s because the healthcare systems are recognizing that we’re bringing significant value, but we’re pricing at roughly parity, which takes the pricing decision off the table and focuses on the value of the product and we saw is that way you ca’ maximize access to therapy and maximize the number of patients on therapy as quickly as possible versus taking time to negotiate for some extra dollars on the price.

And I think the nice appraisal that we saw here, which again I think is one of the fastest ever in our industry is a great reflection of that value that the payers are seeing. So we’re confident that strategy will be very successful here and we’ll roll that out as we go through the process in Europe, in the U.S. and in other markets.

On the first one in terms of key performance indicators that we share, I think what you’ve heard on the call today is some of the qualitative things we’ll talk about in terms of getting out to see the key centers in terms of having patient started infusions and convert from clinical trials to commercial product.

We haven’t given any forward-looking guidance for this year just because it’s such a stub year, but I think you’ll hear on the November call that we’ll provide an update on the number of commercial patients on drug, so that will be a nice milestone to wait for.

In terms of kind of analog, it’s so unusual to have a second-generation product launched into the rare disease space. I don’t know if there are great analogs. The one thing I would point to though is kind of a thought experiment, perhaps is remember, we were – we qualified for that IMS program in the U.K. about a year ago.

And within a first year, remember that you can’t promote on that product, it’s simply offering it and it’s purely demand-driven. And we were able to get to a 15% to 20% market share through that program alone, again, with no promotion. So for me, that gives you a great perspective on imagine what we can do once we’re out there promoting the product.

So we’ll do our best to give good color on how the launch is going and hopefully that gives you a flavor of how we can talk to that over the coming days and weeks. And again, November, I think, will be a really important update there..

And our next question will be coming from Dae Gon Ha of Stifel..

One clarification, the slides as first patients as [en plural] has been infused with LP, I guess, AT-GAA product.

Just wanted to clarify that it was more than one and then my actual question was the physician feedback and engagement, what are you guys hearing in terms of the line-up that physicians will take once next year, I guess, AT-GAA becomes available as a third line, I mean does it get kind of placed at a third line? Or do you see it being used sort of in the -- in between Myozyme, Nexviazyme or Nexviazyme on to AT-GAA? Any color on that would be helpful..

So first and foremost, the feedback we've received has been incredibly positive from physicians and we're hearing through them that the experience from patients has also been very positive, so we feel like everything is going really well.

Yes, to clarify your first question, it is multiple patients have been converted, which is great and multiple patients have been scheduled for their infusions and we're working to schedule the remaining conversions within that 90-day target. So really, really good progress as we've gotten started here.

And then -- sorry, remind me the second part of your question, oh, in terms of positioning, yes. So, reminder in Europe, the indication statement is for all patients late onset Pompe disease patients. And so we'll position this and we think this will be a great treatment option for all of those patients.

Remember, though, that the vast, vast majority of the market opportunity here is patients currently on Myozyme.

And so you should see -- just like we saw with Galafold, you should see the vast majority of growth in all of our markets coming from patients who we switch from Myozyme or Nexviazyme frankly to AT-GAA and I think that's an important point, right, which is the indication is for all patients with LOPD in Europe who are on label and that means that we can target any patient on therapy or frankly any new patient that's diagnosed or has already been diagnosed..

And just to add to what you were saying, Brad, I think to give a little bit of color on the global opportunity from a patient standpoint, there are 3,500 to 4,000 patients being treated worldwide for Pompe disease today. We estimate that depending on the year, you've got somewhere between 100 to 200 naive patients put on treatment every year.

So the commercial opportunity as of this point is really looking to switch patients whether they are on Myozyme or whether they're on Nexviazyme -- this is the main patient group that we're going to go after..

And the last thing I'll say there is, remember, the real promise of this medicine is that we're the only product in a well-controlled clinical study that shows that patients who are on an existing ERT can switch to AT-GAA and see improvement in 6-minute walk and forced vital capacity.

So we think that's a truly differentiated component of this therapy and we're just so pleased and eager to get this out to as many patients as possible as quickly as possible..

And Daphne, thanks so much for your service..

And our next question will be coming from Jeff Hung of Morgan Stanley..

Congratulations on the MHRA approval of Opfolda and congrats to Daphne on her upcoming retirement. You've reduced expenses to support your path to non-GAAP profitability.

Can you just talk about the importance of that relative to further bolstering your pipeline and advancing your next-gen pipeline programs?.

Yes, so the vast majority of our expenses go towards both the ongoing clinical studies to support post-marketing commitments and remaining clinical study extensions in Pompe disease, also manufacturing until recently when now we have commercial product, so that ends up showing up in cost of goods, but that's the vast majority.

And then of course, the G&A that goes along with that. We do have some modest spend towards the pipeline and we are making, I think, good progress there.

I think you should expect to hear us talk more about the pipeline as we come into next year, but you should know that this laser focus on non-GAAP profitability does include a modest amount of investment in the pipeline, that's an important part of the future of Amicus and again we'll talk more about that probably coming into next year..

And our next question will be coming from Salveen Richter of Goldman Sachs..

This is [Sinatra] on for Salveen. First, on Galafold, in your view, how much of the growth that you need to get to your prior guidance of $1 billion peak sales for Galafold will be driven by new patient diagnostics like genetic screening, et cetera, versus the naive patients who are already diagnosed and switched patients.

And on AT-GAA, if you could provide some more color on the reimbursement process in Germany?.

Yes, so a couple of points there. So if you think about just the market today for Fabry, the global market, you've got a little over $2 billion in global sales and here we are sitting at with guidance of kind of $375 million to $388 million.

If you assume a 1/3 to half of the patients on drug today have amenable mutation, then you've got another maybe doubling of the current revenue base just by existing diagnosed and treated patients today, so lots of opportunities continue in switch patients, which is great.

Some of that comes through market expansion and some of that comes through execution in our existing markets. We also know if you look kind of globally, the global -- that sort of over $2 billion in global sales represents about 11,000 treated patients and we believe there's roughly another 5,000 or 6,000 diagnosed untreated patients.

And so again, if you take that kind of 1/3 to a half number, that's an additional, call it, 3,000 or so diagnosed untreated patients who have a amenable mutation, so another significant chunk of existing patients today. I think that gets you sort of well towards that peak market opportunity that we've talked about.

But then as Sebastian and Jeff have highlighted in previous calls, we're seeing significant growth in the underlying diagnosis, maybe 10% or so a year. And so you put all those together, I think it's easy to see a way towards $1 billion product opportunity here.

And then you had asked a little bit about Germany, maybe Sebastian, do you want to talk to the dynamics in Germany again?.

So as I mentioned, in Germany, the GBA has classified Pombiliti as a new active substance, we’re very pleased with that. And as a result of that designation, Pombiliti will undergo benefit assessment on the AMNOG process. We have a 6-month free pricing period and after that there will be negotiations on a final reimbursed price.

So you should expect to see agreed upon published price sometimes around Q3 of 2024. We think we’ve set a competitive price for the combination of Pombiliti+Opfolda versus other Pompe therapies available in the German market. And the price is, again, very much in line with the pricing policy that Bradley mentioned early on..

And our next question will be coming from Kristen Kluska of Cantor Fitzgerald..

And congrats on the additional approval this morning and also sending my best to Daphne. I know it's early days in Europe, but can you talk about what have been the biggest selling points in terms of generating interest over other therapies now that you have an approval in place beyond the prep work.

So for example, is the mechanism, the full data set across the different patient populations, open label, a certain endpoint that they're focusing on? Or is it really just a combination of this?.

I'll hit the top -- start with that, I'll hit the top line and then maybe Jeff talk about the broader data that we've showed in previous calls. So from a label perspective, clearly, the most important two data points are the 6-minute walk test and the forced vital capacity, which as I mentioned before, we've shown significant differentiation.

We're the only therapy that's shown improvement in those measures in patients who switch from existing ERT to AT-GAA and so I think that's a really powerful story and one that physicians will clearly focus on. But I do think another important part of this is the really broad data set that we've published now in various places.

It won't necessarily show up in the label, but as we continue our medical education strategy, we'll be able to share those.

So maybe Jeff, talk about what we've already published across those other endpoints and any other color you might want to provide?.

As Brad noted, the key there is showing the improvement on 6-minute walk in [FDC] and the switch patients in a controlled trial. But it’s really that consistency across endpoints. We’ve shown some of that previously at a high level.

We’re going to continue to really focus on that here in upcoming conferences just to show the range of improvements that we’re seeing across endpoints for these patients. And I’d say the other thing is the emerging durability data as well.

We’ve now shown out to 4 years from our Phase ½ that the initial improvements observed across I patients, switch patients in those trials have been maintained long-term. So we think that, that’s going to be a continued focus of physicians and a strength so far of what we’ve seen with AT-GAA.

But what’s really strong core of data, I think the MoA is also something that gives people a reason to believe in some of those clinical observations that there is a very differentiated MoA and that’s also something that I think we’re going to continue to provide publications and more information there as we continue to learn about the MoA..

And our next question will be coming from Ethan Markowski of Needham & Company..

Just a quick one on the current SG&A spend. So -- you're currently relying somewhat on the existing sales force for Galafold, but we've definitely seen an uptick in SG&A. Just to give us an idea now that you're rolling out Pombiliti and looking at a U.S.

launch, how much more of the SG&A spend increase should we expect in the near-term?.

Daphne, I'll let you talk to the accounting treatment that I think is describing a lot of that change.

From an infrastructure perspective, what we've said before is, we literally have hired less than a dozen employees globally to support the launch of AT-GAA that includes some Amicus Assist, which is our take management hub in the United States, so patient education liaisons, some direct marketing and medical affairs people, but hugely leverageable, existing commercial infrastructure.

But maybe Daphne talk to the trends that the question was speaking to..

Yes, sure. So I would remind everyone, in prior years, we had a portion of the support for both Galafold and now AT-GAA in the research and development line. But now as we are aligning resources to support two commercial products, some of that spend is now shifting from the R&D line to the SG&A line.

So it is a bit of a re -- it's a classification issue when you look at current year versus prior year..

Yes, so it's not actually....

...part of the true increase [indiscernible]..

Exactly, yes. Thanks, Daphne. So you should not expect to see significant additional increases in G&A, it was really more of a change in the classification for some of those employees who support the global business..

And our next question will be coming from Tazeen Ahmad of Bank of America..

Brad, just to maybe put people minds at ease.

In terms of the -- going back to the GAA question about your time line for 3Q, just because PDUFA has officially passed, how are you getting your confidence that they will -- the FDA will provide an answer this quarter? And also as we head into the later part of August, I think the assumption is that the folks at FDA kind of shut down for holiday and so if it's slipped into September, is there anything to read into that?.

Thanks, Tazeen, we’ll provide as much color as we can here. So the confidence really comes from 2 places.

The first is, if you remember back when we announced the inspection, we estimated that if you look on average, even though we don’t have a specific PDUFA date on average, it takes about 30-days from the inspection to finish the inspection report and then it’s about 50 to 90 days for the agency to complete their review and so we’re kind of right in that zone.

So we feel very comfortable that it’s kind of in the time line that we’ve seen when you look on average.

And then the other piece that gives us good confidence to your point about whether the FDA is round or not as we have seen in the last couple of weeks, an increase in the engagement by the review division and that gives us good comfort ’hat they're wrapping up their work. And again, we expect the decision here in Q3 and we’re very confident in that..

And that was our last question. I'd like to turn the call back to Bradley Campbell for closing remarks..

Great. Thank you, everybody for tuning in today and hope everybody has a great day. Take care..

Ladies and gentlemen, this concludes today's conference. Thank you and have a great day..