Earnings call: Amicus Therapeutics reports solid growth and profitability

Amicus (NASDAQ:FOLD) Therapeutics (NASDAQ: FOLD) has reported a strong performance for the full year of 2023 during its recent earnings call.

The company's flagship product, Galafold, generated $388 million in global revenue, marking an 18% increase from the previous year. Amicus also celebrated its first quarter of non-GAAP profitability in Q4 2023 and anticipates a full year of non-GAAP profitability in 2024.

Total revenue for the company reached $399 million in 2023, a 21% rise from the prior year. With a focus on rare diseases, Amicus is poised for continued growth, driven by new product launches, patient identification efforts, and market expansion.

Key Takeaways

• Galafold's global revenue climbed to $388 million in 2023, an 18% year-over-year growth.
• Amicus Therapeutics launched Pombiliti and Opfolda in Germany, the UK, and the US with favorable patient and physician demand.
• The company achieved non-GAAP profitability of $2.6 million in Q4 2023.
• Cash, cash equivalents, and marketable securities stood at $286 million as of December 31, 2023.
• Full-year Galafold revenue growth guidance for 2023 is between 11% and 16% at constant exchange rates.
• Non-GAAP operating expense guidance for 2023 is projected to be between $345 million and $365 million.
• A large number of patients in the US are switching to Amicus's drugs from Nexviazyme and Lumizyme.
• The use of AI and machine learning in partnership with OM1 aims to identify more patients with Fabry disease.

Company Outlook

• Amicus Therapeutics forecasts double-digit revenue growth for Galafold in 2024.
• The company's strategic priorities for 2024 include the continued success of Galafold, the launch of Pombiliti and Opfolda, and the advancement of medical and scientific studies.
• Intellectual property protection and plans to introduce Galafold into new markets are also on the agenda.

Bearish Highlights

• The company's cash and cash equivalents saw a slight decrease from $294 million at the end of 2022 to $286 million at the end of 2023.

Bullish Highlights

• Amicus Therapeutics achieved its first quarter of non-GAAP profitability in Q4 2023.
• There is increasing patient and physician demand for the newly launched products Pombiliti and Opfolda.
• The company is focused on securing broad patient access and reimbursement globally, with an increasing number of patients being accepted through Medicare and Medicaid.

Misses

• There were no specific misses reported during the earnings call.

Q&A Highlights

• Bradley Campbell, CEO of Amicus Therapeutics, emphasized the importance of patient outcomes over specific medications, which has led to a majority of patients in the US switching from Nexviazyme to their drug.
• The company is maximizing the number of patients on therapy for Pombiliti and Opfolda, with no specific targets provided.
• Amicus Therapeutics plans to test the effectiveness of an AI-driven approach to identify patients with Fabry disease in a large academic center in the US, with results expected by midyear.

Amicus Therapeutics has demonstrated a robust financial and operational performance in 2023, with significant growth in revenue and a strategic focus on profitability and market expansion. The company's commitment to delivering innovative treatments for rare diseases and creating shareholder value remains strong, as evidenced by the successful launch of new products and the anticipation of continued growth in the coming year.

InvestingPro Insights

Amicus Therapeutics has shown a promising trajectory with their financial performance in the last year. Here are some insights based on the latest data from InvestingPro that could provide additional context to the company's financial health and market position:

• The company's Gross Profit Margin for the last twelve months as of Q4 2023 stands at an impressive 90.65%, indicating efficient cost management and a strong competitive edge in its market segment. This aligns with the company's non-GAAP profitability reported in Q4 2023.

• Despite not being profitable over the last twelve months, with a P/E Ratio (Adjusted) of -27.59, Amicus Therapeutics maintains a strong liquidity position. Their liquid assets surpass short-term obligations, which is a positive sign for meeting upcoming financial commitments without the pressure of immediate profitability.

• With a Market Cap of $3.76 billion and a high Price / Book multiple of 23.5, the company is trading at a premium, reflecting investors' confidence in its growth prospects and intellectual property value, especially considering its focus on rare diseases and recent product launches.

For those considering an investment in Amicus Therapeutics, it's worth noting that analysts do not anticipate the company will be profitable this year, and it does not pay a dividend to shareholders. However, the company has achieved a high return over the last decade, which might be compelling for long-term investors.

For a deeper analysis and more InvestingPro Tips, including whether Amicus operates with a moderate level of debt or the implications of their high Price / Book multiple, visit https://www.investing.com/pro/FOLD. There are 5 additional tips available on InvestingPro, and by using the coupon code PRONEWS24, you can get an extra 10% off a yearly or biyearly Pro and Pro+ subscription.

Full transcript - Amicus Therapeutics (FOLD) Q4 2023:

Operator: Good morning ladies and gentlemen and welcome to the Amicus Therapeutics' Full Year 2023 Financial Results Conference Call and Webcast. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host Mr. Andrew Faughnan, Vice President of Investor Relations. You may begin.

Andrew Faughnan: Great. Thank you, Didi. Good morning. Thank you for everyone. Thank you for joining our conference call to discuss Amicus Therapeutics' full year 2023 financial results and corporate highlights. Leading today's call we have Bradley Campbell, President and Chief Executive Officer; Sebastien Martel, Chief Business Officer; Simon Harford, Chief Financial 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 might 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 and 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, 2023 to be filed 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?

Bradley Campbell: Great. Thanks Andrew and welcome everybody to our full year 2023 conference call. This year, our call falls a day before Rare Disease Day, so before I dive into our results, I just wanted to take a minute to acknowledge this important day for the rare disease community. This year's theme is achieving true health equity for the nearly 300 million people around the world living with a rare condition. Since our inception, Amicus has been dedicated to serving the needs of those in the rare disease community in extraordinary ways and we are committed to advocating for patient communities and fighting on behalf of those whose voices have not been heard. Rare Disease Day serves as a global call to action to collectively work towards equity and social opportunity, health care, and perhaps most importantly, access to medicines for people living with rare diseases. So, I just ask that all of you join me in commemorating this important day for the global rare disease community. So, with that, let me to shift into our financial results and outlook and I'm very pleased to highlight what tremendous progress we made across our global business last year and into the start of 2024. As you saw in this morning's press release, I'll highlight several key points before I turn it over to the team to go through more detail. So, first Galafold continues its strong performance and it remains the cornerstone of our success. We are very pleased with the continued uptake of Galafold globally. We now have over 2,400 people living with Fabry disease who take Galafold or were taking Galafold at the end of 2023. For the full year, that translated to Galafold revenue of $388 million globally, representing 18% growth year-over-year, outperforming our expectations and our initial guidance for the year. Throughout 2023, we continue to observe strong trends across our key performance indicators in all of our key geographies including continued demand through new patient starts from both switch and naive populations in all of our leading markets. We saw steady growth of in-person visits between our field team and Fabry treaters and we've continued to see sustained patient compliance and adherence rates of over 90%. Growth in 2023 was driven primarily by patient demand from net new patient starts, continuing to switch patients in our newer launch markets, and continued penetration into the diagnosed and untreated population, which we expect to continue to be a major driver of growth in 2024 and beyond as the Fabry market continues to see improved diagnosis and medical education and finding patients. Just to put that in perspective for a minute. As a reminder, just over eight years ago, we estimated there were 5,000 treated Fabry patients and 5,000 patients who are diagnosed with untreated. Today, there are more than 11,000 treated patients. So, the treated market has more than doubled in that time, while the untreated market has also increased to almost 6,000 patients. These underlying market dynamics will provide the opportunity to grow Galafold for many, many years to come, including in 2024, when we expect another great year with 11% to 16% projected growth at constant exchange rates. Second, the global commercial launch of Pombiliti and Opfolda is underway and is off to a great start in the three largest Pompe markets. Our teams have made significant progress in the initial commercial launch in Germany, the UK and the US, and we remain incredibly pleased with the launch so far. Seven weeks ago at JPMorgan (NYSE:JPM), we shared that 120 patients were on treatment or scheduled for treatment, including 15 new commercial patients. And as we said at the conference, we're not going to give mid-quarter updates, but I can share more color on how incredibly pleased we are with the continued patient and physician demand for this new therapy. The key performance indicators that we talked about last time continue to improve and continue to give us confidence in the strength of this launch. Specifically, the rate of new commercial patients coming on to Pombiliti and Opfolda continues to increase in all three markets, as we progress through the early weeks of the year. We anticipate launches in additional countries will add to that growth through the latter part of the year. And importantly, for our new commercial patients, we continue to see prescriptions proportionally coming from Nexviazyme and Lumizyme, as well as naive patients in ex-US markets. So that means in the US, the majority of new patients are switching off of Nexviazyme and coming on to Pombiliti and Opfolda, whereas in Europe, where Lumizyme has the majority market share, most of our switch patients are coming from that therapy, and we're seeing an increasing number of naive patients as well, so all the patient segments are performing as we would expect. In a moment, Sébastien will provide further color on the ongoing launch of these key performance indicators, but overall, we're very pleased by the launch and the great momentum we're seeing across each of our markets. Throughout 2024, we'll continue to focus on increasing patient access by expanding into additional European countries, as we navigate the country-by-country pricing and reimbursement process and focus on additional regulatory submissions as well. We are incredibly pleased to be providing a real choice for patients and challenging therapeutic options for both physicians and people living with Pompe disease. Third, Amicus has maintained an incredibly strong financial position as we continue to execute on the expansion of Galafold and advance the global launch of Pombiliti and Opfolda. We are pleased to share today that as we promised, we delivered our first quarter of non-GAAP profitability in the fourth quarter of 2023. This is obviously a significant milestone as we now look to deliver our first full year of non-GAAP profitability in 2024, supported for the first time by well over $0.5 billion in combined product sales, as well as prudent expense management to really significant milestones in the evolution of Amicus as a biotechnology company in the rare disease space. Our key strategic priorities for 2024 are laid out in the slide four. As we laid out last month, we are focused on achieving our key strategic priorities for 2024, including: number one, again, sustaining that double-digit Galafold revenue growth of 11% to 16% at constant exchange rates, continuing our successful launch of Pombiliti and Opfolda and executing multiple successful new commercial launches throughout the year, advancing our ongoing studies to support our medical and scientific leadership in Fabry and Pompe disease, and finally, maintaining our strong financial position as we carefully manage our expenses and investments in order to achieve a full year of non-GAAP profitability. With that, let me now hand the call over to Sébastien, who can give further highlights on our commercial performance. Sébastien?

Sebastien Martel: Thank you, Bradley. Good morning or good afternoon to everyone on the call. I'll start by providing you with more details on our Galafold performance for the year. On slide 6, for the full year 2023, Galafold reported revenue reached $387.8 million. Galafold growth in 2023 was primarily driven by strong patient demand, particularly from our leading markets. Turning to slide 7. Our results in the full year highlight the strength of our global commercial efforts. The demand for Galafold globally continues to be strong with patients added in all major markets, delivering operational growth of 18% over the same period in 2022 or 17% at constant exchange rates. We finished the year strongly, with fourth quarter 2023, Galafold reported revenue of $106.6 million, up 21% or 19% at CER. We're pleased to share that 2023 was the strongest year for net new Galafold patients since 2019. Our leading markets such as the UK, the US, EU 5 countries and Japan remain the biggest drivers of patient demand and gives great confidence in the growth this product has over the long run. As Brian mentioned, we ended the year with more than 2,400 patients on Galafold, which is roughly over half of the global market share of treated amenable patients. Galafold that's captured 60% to 65% of the global market share of treated amenable patients. But the good news is there are still many more patients to put on to therapy. Within the global mix, which is about 43% switch and 57% naïve, we're seeing stronger uptake in naive populations. So we continue to achieve high market shares in countries where we've been approved the longest there's still plenty of opportunity to continue to switch patients over to Galafold and keep on growing the market as we penetrate into the diagnosed and treated and newly diagnosed segments. All of that is underpinned by sustained compliance and adherence rates that continue to exceed 90%. Reiterating our belief that those patients who go on Galafold for them to please stay on Galafold. As mentioned on past calls, due to a variety of contributing uneven ordering patterns and FX fluctuations, the rate of growth within the year is typically nonlinear. Additionally, we've historically seen Q1 revenues come in slightly below prior Q4 due to the timing of orders and the reauthorization process in the U.S. and we expect that to continue into 2024. So within the table. On the right hand side of the slide, we've provided a five-year historical snapshot of the percentage of Galafold sales, and after each quarter during a given year. Interestingly, the average of quarterly sales distribution over the last five years corresponds precisely to what we achieved for the full year 2023. We would expect a similar trend to occur this year. So, as an example, we expect Q1 sales of the current year to be around 22% of full year sales for Galafold. On Slide 8, we know that there's a significant patient demand for Galafold and the segment of growth of the global Fabry market made of patients with amenable mutations as the potential to reach up to $1 billion in annual revenue by the end of the decade. We anticipate sustained growth in 2024 and beyond to be driven by several key growth drivers. First, continuing to increase patient identification through ongoing medical education screening and improved diagnosis. As you know probably is one of the most under diagnosed rare disease. So the more patients are identified for more patients can be eligible for Galafold. Second the other piece is continuing to drive Galafold's market share of treated amenable patients through continued commercial execution. As noted, Galafold currently has 60% to 65% of the global amenable market. What we're seeing in our most mature market is that we can reach up to about 85% or 90% of market share. So we know that there's potential to reach two levels in the global market share as well. Importantly, as Bradley highlighted earlier, this is a robustly growing Fabry market with a significant portion of growth coming from finding new patients and penetrating into the nine diagnosed untreated population. Just within the 2,400 patients on Galafold for the end of 2023 about 1,400 of these individuals were naive to any treatments before coming on Galafold. We've been successful in finding new patients through newborn screening and other diagnostic initiatives as well as artificial intelligence through our partnership with [indiscernible]. And again all of these efforts are supported by solid compliance and adherence rates from physicians and patient education and support programs. We'll continue to make progress on expanding Galafold into new markets and extended the labels. There are still some markets in that time some in the Middle East and Asia Pacific regions where Galafold is either newly reimbursed or we expect reimbursement. Also important to note here, we have often exclusivity in the US and Europe in addition to our 57 orange-bophystic patents 41 of which provide protection into 2038 and beyond including 11 composition of matter patents. This provides us with the opportunity to provide access to Galafold globally for a long time to come. We intend to continue to protect and enforce our broad intellectual property rights. Looking ahead we expect steady double-digit growth for Galafold throughout 2024 and we remain confident that our strong IP protection will provide Galafold a long runway well into the next decade. Turning now on to Pompe Disease on Slide 10. we outline our global launch progress with Pombiliti and Opfolda. So full year 2023, Pombiliti and Opfolda reported revenue reached $11.6 million for the full year and $8.5 million for the fourth quarter. At the beginning of the year, 2024, 120 patients were on treatment or scheduled for treatment, of which approximately 105 were from our clinical trial and early access programs, and 15 from competitor ERTs or naive to treatment. We've been pleased with the continued demand for this new therapy. As Brad said, and as anticipated, I would say, the rate of new commercial patients coming onto Pombiliti and Opfolda continues to increase across all three markets. In the US, we continue to see a majority of patients switching from Myozyme, roughly about 75% of the switches we've seen, and the remaining 25% coming from Lumizyme. This means we're switching patients proportionally from both products. Outside of the U.S., we're seeing patients switching from all three segments, from Myozyme, Nexviazyme and naive population, at a proportional rate, exactly what we want to be seeing at this stage. Our launch has leveraged our highly experienced cross-functional teams, and we've had great outreach with KOLs. We're seeing an increase in depth, as well as breadth of prescribers, across all three markets and in particular, see a growing number of prescribers who are not part of our clinical studies or expanded access programs. All core treating centers have been engaged with, and we have had very positive feedback from HCPs and other stakeholders as to our business approach, support and patient focus. Finally, we find an important metric to track is our progress with access and reimbursement. We have a highly experienced team who are engaging in positive conversations with payers to demonstrate the value of Pombiliti and Opfolda. In the US, and with the start of the new year, many of the large payers have already put Pombiliti and Opfolda onto their respective formularies, and we've also seen strong acceptance by Medicare and Medicaid as well. Today, we're launched in Germany, the UK, the US, and Austria. We're also in active pricing and reimbursement discussions with additional major European markets as we focus on securing broad patient access throughout the EU. More than 10 reimbursement dossiers have been submitted. Overall, we're starting off the year strong, and we're very pleased with the building momentum on patient demand. Over the course of 2024, our focus will be on maximizing the number of patients on therapy by year-end. So, in summary, we're very pleased with the launches of Pombiliti and Opfolda across all the first wave of countries, the strengths of our clinical data, the depth of experience and talent we have at Amicus gives us great confidence in our ability to make a real difference to people living with Pompe disease. We believe amicus is in a great position for our second successful launch. And with that, I will hand the call over to Jeff Gatseli, our Chief Development Officer, to discuss the ongoing clinical studies as well as regulatory timelines. Jeff?

Jeff Castelli: Thank you, Sebastian, and good morning, everyone. On Slide 11, we remind everyone that we continue to build the body of evidence for Pombiliti and Opfolda through our ongoing clinical studies as we also continue to execute on expanding commercial access through regulatory submissions. As we enter the second phase of launch, in addition to the various reimbursement dossiers that we have or that we are in the process of submitting, we also have multiple ongoing or planned regulatory submissions for marking and approval in new geographies throughout this year. For the younger Pompe community, we continue to enroll the ongoing open-label ZIP study for children living with late-onset Pompe disease and the open-label RZELA [ph] study for children living with infantile-onset Pompe. We see this as an important opportunity to support label expansions into these patient segments and provide access to these kids much in need in the years ahead. Through ongoing clinical studies and the Amicus Pompe registry, we expect to continue generating evidence on our differentiated mechanism of action and long-term data supporting the impact of Pombiliti and Opfolda across endpoints and patient populations. I am very excited to announce that we have actually now begun enrolling patients into the amicus Pompe registry globally. And here in February, we once again had a very engaging conference and a significant presence at the 20th Annual World Symposium that was held in San Diego. Amicus had 11 posters and an oral presentation highlighting our continued work across Fabry and Pompe disease. Of note Amicus was honored with the WORLDSymposium 2024 New Treatment Award for Pombiliti and Opfolda, which recognizes companies that have made important achievements in advancing treatments for lysosomal diseases and have obtained regulatory approval. It's an honor to achieve an award based on our scientific innovation, but even more importantly the meaningful difference we can make in the lives of so many people living with these rare diseases. 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 day including delivery of our engineered GLA and GAA transgenes and the next-generation Fabry-Chaperone. With that, I would like to now turn the call over to Simon Harford, our Chief Financial Officer to review our financial results, guidance and outlook. Simon?

Simon Harford: Thank you, Jeff. Our financial overview begins on slide 13 with our income statement for the full year ending December 31, 2023. We had a very successful year full year, achieving total revenue of $399 million, which is a 21% increase over the same period in 2022. At constant exchange rates, revenue grew strongly 20%, a global geographic breakdown of total revenue for 2023 consisted of $250 million or 63% of revenue generated outside the United States and the remaining $147 million or 37% coming from within the US. Cost of goods sold as a percentage of net sales was 9.3% for the full year 2023 as compared to 11.7% for the prior year period. Total GAAP operating expenses decreased to $439 million in 2023 as compared to $503 million in 2022, a decrease of 13%. On a non-GAAP basis, total operating expenses decreased to $342 million for 2023 as compared to $413 million in the prior period, a decrease of 17%. We define non-GAAP operating expense as research and development and SG&A expenses excluding stock-based compensation, loss on impairment of assets, changes in fair value of contingent consideration and depreciation. Net loss for the full year 2023 reduced to $152 million or $0.51 per share including a $14 million or $0.05 per share expense related to the extinguishment of prior debt following our Blackstone (NYSE:BX) refinancing that compared to a net loss of $237 million or $0.82 per share for 2022. In the fourth quarter as Bradley mentioned, we achieved our goal of non-GAAP profitability, which was $2.6 million. Cash, cash equivalents and marketable securities were $286 million as of December 31, 2023 and that compared with $294 million at the end of 2022. Turning now to slide 14. I'm pleased to share our full year Galafold revenue growth guidance of 11% to 16% at constant exchange rates. Our full year 2023 non-GAAP operating expense guidance is $345 million to $365 million. We are pleased to share that amidst a launch year, we have kept operating expense growth minimal. As a reminder, we continue to have R&D commitments including registry studies in both Fabry and Pompe, the ongoing Pompeii Phase 3 study in countries not yet reimbursed as well as next generation of manufacturing for Pombiliti. There is very minimal investment in preclinical activities, which we expect to continue in 2024. Following the achievement of non-GAAP profitability in Q4 of 2023, we anticipate to achieve non-GAAP profitability for the full year of 2024 driven by our first year of well-over $0.5 billion in combined revenue, as well as continued prudent expense management. As we think about profitability throughout the year, we anticipate a similar non-GAAP profit in Q1 2024 as we saw in Q4 2023. And non-GAAP profit is expected to build sequentially quarter-over-quarter after that. And with that, let me turn the call back over to Bradley for our closing remarks.

Bradley Campbell: Great. Thanks Simon, Jeff, Sebastian, as well a huge thanks to all of our employees around the world, who I know continue to work tirelessly for people living with rare diseases. Looking 2024, we will continue to drive significant top-line revenue growth supported by sustained double-digit Galafold performance and the successful ongoing global commercial launch upon building up for that, which puts us on track for our first full year of non-GAAP profitability. As I said in my opening comments, Amicus is at a major inflection point. We are strongly positioned to continue to advance our mission of delivering groundbreaking new medicines to thousands of people living with rare diseases around the world and creating value for our shareholders. With that, operator, we can now open up the call to questions.

Operator: Thank you. [Operator instruction] And our first question comes from Anupam Rama of JPMorgan.

Malcolm Kuno: Hi. Thank you for taking the question. This is actually Malcolm Kuno on for Anupam. So, in the US with regard to pump pay, are you seeing switches from patients that are clearly progressing or patients who are stable but just not gaining a benefit from their current treatment?

Bradley Campbell: Yes, great question. I think the answer is a little bit of both. So, you know we know that some patients we've heard, I should say that some patients who were new commercial patients not in clinical studies. I've heard by word of mouth or through relatives, who might be participating in those studies about how well they thought that those patients stayed in the study. And so those patients, I think were eager to start pumping up folder kind of regardless of their own status. And then, I know that others, I'm sure were in a declining phase and therefore wanted to switch with the hopes of seeing different outcomes, which of course, as per the label where we have the drug is indicated for patients who are not improving on current therapies. So, I think we're seeing healthy dynamics from both of those segments.

Malcolm Kuno: Great. Thanks Brad.

Operator: Thank you. One moment for our next question. And our next question comes from Ritu Baral of TD Cowen.

Ritu Baral: Good morning, guys. Thanks for taking the question. To drill down a little further on that Brad and Sebastien, how are you guys seeing clinicians in the field define the decliners and the two symposiums that world, both yours and your competitors, having spent a lot of time on defining decliners, defining stable. What do you see in your conversations during the conference on the tools that clinicians are using to define that in their own head? Have you done any market research on segmentation of the population into sort of that definition of decliner that definition of stable as you see it now?

Bradley Campbell: Sure. Yes. Great question, Ritu. Thanks very much. I'm going to let Jeff talk to the first part of your question, which is sort of what are the tools and end markers that clinicians might use to follow or determine whether a patient is stable or declining. I would remind you though that the indication statement is for patients not improving on therapy, which means that either stable or declining patients are eligible for us from a market research perspective. But the work that we did leading into the launch, suggested that about 50% of patients would historically be defined as stable. Although, I think Jeff will talk us through why in fact they may be suddenly declining as well. About a quarter of patients, are clearly declining and about a quarter of patients are likely in some sort of improvement phase, which is what we would expect based on historical data. But Jeff maybe talk through how physicians the obvious ways that they would look for declining patients and then maybe the not so obvious more subtle but equally important ways that that patients may be declining.

Jeff Castelli: Yes. Thanks, Brad. And thank you for the question Ritu. So first of all, just in terms of the follow up typically the cadence for Pompe patients is about every six months. They come in and visit with their primary treating physician and care team. They do measure the quantitative endpoints you know on motor function respiratory function that are cited in the trials things like six minute walk distance forced vital capacity other measures of motor function respiratory parameters. So what we see is that a lot of what they do is really more qualitative in terms of some of the formal questionnaires, but really just asking the patient how are they doing during activities of daily living. And then of course they also do look at biomarkers depending on the site they may put more or less some importance on the biomarkers. So it's very much a holistic assessment of different parameters. And what we're learning is that actually does differ across sites and across countries. And one of the things that we're looking to do is trying to help in the community of physicians of looked at trying to standardize some of those assessments more moving forward? So in terms of as Brad mentioned you know it's as we look in the US, for example it's about 25%. We would estimate improving 25% clearly worsening. And then that 50% in the middle overseeing as physicians now have more treatment options and are really digging into how patients are doing. I tried to say who is declining, who is stable, who is improving. We're starting to hear that many of those patients that they might have perceived as stable as they do that deeper holistic assessment of they're finding out that while six minute walk or forced vital capacity might be generally stable that patients reporting having a much harder time climbing stairs or going out and doing tours or their fatigue when they're sleeping. So we do think a significant chunk of that 50% sort of stable middle patient segment is actually declining when physicians start to dig in more holistically. So it's definitely an evolving space in terms of how physicians monitor patients especially related to switching there's been a lot of different symposium and meetings on this topic. So it's something that we'll certainly keep an eye on. But as I said it's really this holistic approach. It's not one or two parameters that they used to define sort of status and when patients might switch and how they do after switch?

Bradley Campbell: Thanks Jeff. I would think that's really the exciting opportunity. Ritu is for us to challenge the expectations of therapy. Now that as Jeff said we have more choices for physicians and patients.

Ritu Baral: Great. Thanks.

Operator: Thank you. One moment for our next question. And our next question comes from Dae Gon Ha of Stifel.

Dae Gon Ha: Good morning, guys. Thanks for taking our question on Pompe, if you can just remind us on the 15 that were new and not part of the expanded access or clinical trial. Did you guys ever break them down in terms of geographies? And I guess what I'm thinking about is 2024 how we should think about the cadence of patient onboarding given that you have these multiple launches going on? Thanks so much.

Bradley Campbell: Yes, thanks, Dae Gon. What we had said at the at JPMorgan which will remind you here is those patients came roughly equally from each of the launch countries. Remember, we launched in Germany and the UK first and then the US later in the year. So we thought that was very positive. The other thing we saw which we highlighted in the call here is in each of those markets we're pulling and this trend continues. We're pulling kind of proportionately from of the patients who are treated on the various medications. So in the US is Sebastian highlighted the majority of our patients are coming from next Myozyme that makes sense because the majority of patients in the US are not treated with Nixviazyme. And then in Europe we're pulling from both Lumizyme as well as next Nixviazyme and increasingly in naive patients which is an important segment there as well. And then to your last point I think the color we provided here is that we're seeing the rate of new patient starts increasing at an increasing rate. So the first two months of the year and then a faster net new patient acquisition versus the months over the course of launch last year so all of those things for us point to continued building momentum and gives us great confidence in the launch.

Dae Gon Ha: But any visibility on ex-US versus US kind of the cadence of growth that you anticipate this year?

Bradley Campbell: Yes. I think you'll see just because the US is such a larger market you'll start to see more patients coming on in the United States. I think that's just a volume point. And I think typically what we'll see is that will that will carry us through the various markets. The bigger markets have more patients to bring on and you'll start to see that play out.

Dae Gon Ha: Excellent. Thank you very much.

Operator: Thank you. One moment for our next question. And our next question comes from Joseph Schwartz, Leerink Partners.

Joseph Schwartz: Thanks so much and congrats on the progress. It's interesting that you're getting more switches from Nexviazyme and Lumizyme. So I was wondering, if you could talk about why that might be? Maybe give us some color in terms of the proportion of each of those sub-segments that you think might be deemed to not be improving. And yeah, just give us any color in terms of that dynamic that would be helpful. Thank you.

Bradley Campbell: Yeah. Thanks Joe. I think one of the big questions that everybody had was boy, in the markets where next Nexviazyme has been launched the longest, maybe those patients are going to be too sticky and you'll have a really hard time penetrating into those markets. I think what we've seen you know it's still early days, but what we've seen is no. And in fact, we're -- as we said the majority of the patients in United States and that has continued into this year are coming from next Nexviadyme. So I think what it really is, physicians and patients are focused much more on how they're doing as Jeff described versus what medication they're on. And so if a patient is stable or declining, they may be looking for better outcomes. And with choice you have a chance to challenge those outcomes. So I don't think that it's a question of which drug, am I on? I think it's a question of, how am I doing? And what are my expectations for therapy. And that's where we're really excited to really challenge those expectations. And as Jeff said, drive that question for physicians and patients to think a lot more carefully about how they're performing on their current medication. So that's why I think we've seen so far, in the US again with the majority of patients on Nexviazyme. We're switching the majority of our new patients are switching from next Nexviazyme, although we are getting some Lumizyme patients as well. And then outside the US where it's still a majority Lumizyme market. We're getting a majority of switches from Lumizyme, although we are getting Nexviazyme patients and we're getting naïve patients as well. So we think all of those dynamics are really healthy and will continue.

Joseph Schwartz: Great. Just to, follow-up if I could. Does it indicate or could it indicate at all that patients on that Nexviazyme patients are essentially self selecting to be more severe and there might be more people on Lumizyme in the United States that are satisfied and they might be harder to switch.

Bradley Campbell: I don't think that's necessarily the case. I think it's likely that patients who have just started a medication i.e. Lumizyme or Nexviazyme are going to be at a, how am I doing mode for a period of time. And that's that kind of 25% of the segment that we talked about when we did the market research and I think physicians said about 25% of the patients are in an improving phase. I don't think patients or physicians would necessarily look to switch those patients initially. It's really more of those stable or declining patients where we have a real opportunity. And again, we estimate that's about 75% of market.

Joseph Schwartz: Very helpful. Thank you.

Bradley Campbell: Thanks, Jeff.

Operator: Thank you. One moment for our next question. And our next question comes from Ellie Merle of UBS.

Ellie Merle: Hey guys congrats on the progress. And thanks for taking the question. Just if you could talk a little bit more income pay in terms of the numbers of centers or physicians that you're targeting as the key prescriber base here? And I guess what proportion of these have already written a script for possibility of full data, like you mentioned that you're seeing increasing starts at an increasing rate. Are you seeing something similar in terms of the specific new physicians? Or is it a deepening of prescriptions from those sites that were already prescribing or involved in the clinical trials? Thanks.

Bradley Campbell: Yeah. Great question, Ellie. So as Sebastian mentioned on the call we're seeing both increasing breadth and depth. So it's kind of both of what you asked. So the physicians who have already been writing prescriptions are continuing to write prescriptions. But then we're seeing expanding numbers of centers in particular in the US and Germany that weren't involved in the clinical trials who are now starting to write prescriptions as well, so both of those segments are improving. I would know in the UK all of the centers participated in the AIMS program or the Clinical Trial Program. And so they all have were already writing prescriptions and continued to do so. So I think yes really healthy dynamic so far.

Eliana Merle: And then just of the 120 patients that you mentioned at JPMorgan I guess any color on what proportion of these are already reimburse them?

Bradley Campbell: Yeah, majority of them are already reimbursed. And I would say that as a reminder it takes about 90 days to go from prescription to commercial infusion at this point in time. So that means the people who got their prescriptions in December and January may still be in that process. But of course, as we highlighted in the call, we're continuing to add more patients into the funnel which is great. And the other thing we're seeing is that the newer commercial patients are going through the process more quickly as we continue to see possibility unfold to added to more and more formularies in the United States. And so we could we would continue to expect that number to come down as we progress through the launch. That was the same trend we saw as you might remember with Galafold as well where it sort of started in that 90 day range. And then overtime winnowed down to where we sit today which is around 30 days.

Eliana Merle: Great. Thanks so much.

Operator: Thank you. One moment for our next question. And the next question comes from Jeff Hung of Morgan Stanley (NYSE:MS).

Jeff Hung: Thanks for taking my question. I mean, you talked about the seasonal patterns you've seen in the past with Galafold going from Q4 to Q1. How should we think about the potential seasonal trends for probability and unfold. I know would you expect them to move similarly? Or do you think that maybe it doesn't apply as much this year given that the launch is still fairly early? Thanks.

Bradley Campbell: Yeah, good question. I think probably the answer is too soon to tell. I think in a launch year, you would expect to continue to build momentum throughout the year, which is I think a natural phenomenon as you get more and more physicians and patients with experience as we add countries over the course of the year. And so I guess, the answer is too early to tell, as we are able to provide color there going forward. Of course, we'll share that with you. But I think in general you could just expect momentum to build throughout the year given it's a larger.

Jeff Hung: Thank you.

Operator: Thank you. One moment for our next question. And our next question comes from Kristen Kluska of Cantor Fitzgerald.

Kristen Kluska: Hi, good morning, everybody. The patient diagnosis growth has been really impressive. Fabric growing 70% from 2015 to 2023. So, since part of this growth came from new therapies on the market including your own. Curious how you're thinking about some of the growth we might see in the postpaid market numbers with the recent launches?

Bradley Campbell: Yes. Thanks Kristen. And I think it's a phenomenon you typically see right which is when more companies are involved when more therapeutic options are out there. I think you do tend to see and increased focus in Diagnosis & Treatment. So I wouldn't at all be surprised if that's part of the driver of growth although we would also remark. And maybe Jeff you can share some of the details here, while not quite as under diagnosed as Fabry is believed to be. We -- in the last sort of 10 years have seen significant evidence that in fact Pompe's is significantly more prevalent than what was originally reported in the literature. So maybe just talk a little bit about kind of the data excuse me from newborn screening and from high-risk screening and that would lead us to believe that Pompe should also benefit from increased diagnosis over time. Yes.

Jeff Castelli: Yeah. Thanks, Brad, and thanks for the question Kristen. There's a few dynamics and importantly leading to better diagnosis across rare diseases. One is doing better education of physicians and other importantly is a better diagnostic tools and low cost genetic testing there. Also our newborn screening initiatives in many countries importantly in the US. So I think a lot of that is similar in Fabry and Pompe for Fabry. The extra benefit is the fact it's an X-linked dominant disease and you find one patient and then you can screen the whole family. Pompe is more of a recessive disease. So you need to find each patient independently of themselves or siblings but you know the Pompe similar to Fabry. When you look classically it was thought to be one in 40,000 more than 50,000 screening studies both newborn as well as looking at people just with elevated CK levels, or limb-girdle muscular dystrophy weakness type symptoms. Many of them have Pompe and the Apex actual estimate of Pompe is more like one in 15,000. So two to three times more common than what has been thought. So a lot of patients still left to be diagnosed in Pompe a lot of the same underlying factors that are helping us diagnose more patients. I think Fabry is just sort of a little bit ramped up, because of that X-linked factor, but we do expect significant underlying growth of new patients, coming onto therapy being diagnosed and definitely having multiple companies helping with some of that diagnostic initiatives in education will certainly help drive that as well.

Kristen Kluska: Thank you.

Operator: Thank you. One moment for our next question. And our next question comes from Salveen Richter of Goldman Sachs (NYSE:GS).

Q – Unidentified Analyst: Hi this is for Shrinachal [ph] on for Salveen. Thank you for taking our question. You mentioned in the slides that your focus in 2024 is to maximize the number of patients on therapy for Pombiliti and Opfolda, is there a target number that you have in mind in this aspect and on payer coverage particularly for Medicare and Medicaid? Or when do you expect to see publish Pombiliti and Opfolda there. Thank you.

Bradley Campbell: I'm sorry I just missed it first part of the question. I got the second one, can you repeat that?

Q – Unidentified Analyst: Sure. In the first part I – I asked given that your focus and training force to maximize the number of patients on therapy on Pombiliti and Opfolda. Is there a target number that you have in mind that you want to achieve by the end of 2024?

Bradley Campbell: Great question. As I think we've said before, we can't give guidance at this point just given the fact that it's a launch year but of course, we have our own internal targets. But I think at this point, we're still in the early part of the launch. So it wouldn't be prudent to give guidance yet, as soon as we have more color. And I'm sure going into next year, we'll be able to provide I think more clarity and more guidance on revenue in particular and we will continue from a quarterly basis to report patients on therapy as we have done. And I'll give you a flavor for the -- for the ramp As it relates to your second question. Yes, good news is as Sebastien mentioned in addition to being adding to a number of major payer formularies in that process will continue to increase and over the first few weeks of the year, we have already seen a number of patients accepted through both Medicare and Medicaid. And so both government patients and private insurance patients are being accepted and getting through process.

Q – Unidentified Analyst: Thank you.

Operator: Thank you. One moment for our next question. And our next question comes from Gil Blum Needham.

Q – Unidentified Analyst: Hi. This is Ethan [ph] on for Gil. Thank you for taking our question. Moving to Fabry for a second. How important do you think your partnership with OM1 and the recent advances in AI and machine learning in general are to identifying more patients and further driving market penetration for Galafold? Thank you.

Bradley Campbell: Yes, great question. I'll start but then Jeff can give more color on that that collaboration. I think that machine learning will have a major impact on diagnosing, all different sorts of patients. We're already starting to see some of that. And but I'm really excited to see the outcome of that out of that partnership, and in particular in Fabry. But again, I think that will be an industry-wide and hopefully disease wide phenomenon. But Jeff maybe, give a little bit of color on what we're doing with OM1 the partnership and what the intent is there?

Jeff Castelli: Yes. Thanks for the question. So really the approach with OM1 and other similar AI electronic medical record initiatives is to create sort of a medical record fingerprint of Fabry disease so that you know all of the healthcare records or people that have given consent within a health system can have their medical records and symptoms kind of scan by the AI, and you basically flag a bunch of people that very may well have Fabry disease and don't know it. And then testing could be offered through different programs to those patients on. We're very excited that we published on the development of the outgrowth algorithm and Fabry it looks like it can do a very good job. And we're actually just on the cusp here of testing it in a very large academic center here in the States. And by midyear, we should know how well that did. And we actually could see how many people are opting into potentially getting tested through the health provider. So that in February in particular, we're really excited about this because with being an X-linked disease when you find patients within a certain health care system potentially, with this type of approach, you could then also help that family find people living around the country around that globe or around the globe. You don't have to kind of screen every single health care system. We are going to certainly look to see if, it's successful and valuable to see if that could be used in other systems as well. And this is not only for Fabry, there's actually been similar programs and initiatives done already for other diseases like Pompeii and that has shown a similar approach works there as well.

Q – Unidentified Analyst: Thank you.

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

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