PTC Therapeutics - Earnings Call - Q1 2025

Executive Summary

• Q1 2025 reported total revenues of $1.176B driven by the $986.2M Novartis PTC518 collaboration; net product and royalty revenue was $189.9M. Diluted EPS was $10.04, and cash reached $2.03B as of March 31, 2025.
• Management narrowed 2025 total revenue guidance to $650–$800M (from $600–$800M in February), citing strong execution and pending regulatory clarity (Sephience, vatiquinone, Translarna).
• Positive CHMP opinion for Sephience with a broad label and launch sequencing for Europe (Germany first) and U.S. underway; management expects European revenue contribution in 2025 via early access and named patient programs.
• Q1 call emphasized defense of the DMD franchise (Translarna shipments via EU Article 117 pathways; Emflaza holding despite generics), and positive PIVOT-HD signals supporting potential accelerated approval path with Novartis partnership.

What Went Well and What Went Wrong

What Went Well

• Sephience CHMP positive opinion with a broad label across ages and severities; EU launch preparation prioritized for Germany and early access pathways. “We look forward to initiating the European launch immediately following the adoption of this positive opinion”.
• Strong cash position enabling launches and BD without raising capital. “We closed Q1 with over $2 billion on our balance sheet… reach cash flow breakeven without the need to access additional capital”.
• DMD franchise resilience: Q1 DMD revenue $134M (Translarna $86M; Emflaza $48M). “Quarterly net revenue [Emflaza] remained strong… impact was not significant on Q1 revenues”.

What Went Wrong

• Net product revenue declined vs prior year due to Translarna pressure and Emflaza genericization (Q1 2025 net product revenue $153.4M vs $177.6M in Q1 2024).
• EU regulatory overhang for Translarna with EC withdrawal decision; mitigation requires country-by-country mechanisms and Article 117, creating revenue lumpiness and uncertainty.
• SG&A increased y/y (GAAP $81.0M vs $73.3M; non-GAAP $71.6M vs $63.9M), reflecting launch readiness and portfolio expansion costs.

Transcript

Operator (participant)

Ladies and gentlemen, thank you for standing by. Welcome to PTC Therapeutics' First Quarter 2025 earnings conference call. All participants are in the listen-only mode. After the presentation, there will be a question-and-answer session. Today's conference is being recorded. I would now like to turn the conference over to Ellen Cavaleri, Head of Investor Relations. Please go ahead.

Ellen Cavaleri (Head of Investor Relations)

Good afternoon, and thank you for joining us to discuss PTC Therapeutics' first quarter 2025 corporate update and financial results. I'm joined today by our Chief Executive Officer, Dr. Matthew Klein, our Chief Business Officer, Eric Pauwels, and our Chief Financial Officer, Pierre Gravier. Today's call will include forward-looking statements based on our current expectations. These statements are subject to certain risks and uncertainties, and actual results may differ materially. Please review the slide posted on our Investor Relations website in conjunction with the call, which contains information about our forward-looking statements and our most recent quarterly report on Form 10-Q and annual report on Form 10-K filed with the SEC, as well as our other SEC filings, for a detailed description of applicable risks and uncertainties that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements.

Additionally, we will disclose certain non-GAAP information during this call. Information regarding our use of GAAP to non-GAAP financial measures and a reconciliation of GAAP to non-GAAP are available in today's earnings release. I will now pass the call over to our CEO, Dr. Matthew Klein.

Matthew Klein (CEO)

Thank you all for joining today. Following a year of outstanding execution across every part of the company, we're off to a great start in 2025. We achieved $190 million of revenue in the first quarter, made great progress on our preparations for the anticipated global launch of Sephience, and continued to work with regulatory authorities on our several pending approval applications. In addition, we closed the quarter with over $2 billion in cash, providing us the necessary resources to support all key commercial and R&D efforts as we continued to move towards becoming cash flow break-even. Let me begin with our revenue performance. We closed the quarter with $190 million in total product and royalty revenue, with continued strong contributions from the DMD franchise. With this revenue performance, we are narrowing our 2025 full-year revenue guidance to $650 million-$800 million.

We expect a further narrow guidance pending regulatory actions and additional clarity on influenza performance for the remainder of 2025. We recently announced the positive CHMP opinion on the marketing authorization of Sephience, with an expected broad label including the full spectrum of PKU patients of all ages. As we await European Commission adoption of the opinion, which is expected in June, we are preparing for our European launch. In terms of launch sequence, we are prioritizing Germany and other countries where we can achieve early access through named patient programs. Eric will provide more details on the Sephience launch plan in Europe as well as in the U.S. ahead of the anticipated FDA decision.

In the first quarter, we shared updated data from the ongoing Sephience long-term studies that continue to support the ability of Sephience to address all key patient market segments and provide patients the ability to liberalize their diet. The most recent analysis of Affinity long-term extension data demonstrates that 97% of participants in the feed tolerance study were able to increase their dietary phe intake, with two-thirds of patients reaching or exceeding the recommended daily allowance of protein intake for an individual without PKU. Notably, these effects were also observed in classical PKU patients. We also shared results of the genetic variant analysis of the phase III Affinity trial, which demonstrated meaningful treatment effect in classical PKU subjects with non-BH4 responsive genotypes, providing further evidence that Sephience can provide benefit to all disease subtypes. Discussions with the FDA on the Sephience NDA are progressing well.

We are far along in labeling discussions, and I want to emphasize that we have seen no impact of recent FDA changes on the Sephience NDA review. As we have discussed, we believe we can achieve over $1 billion in revenue from Sephience, a significant revenue opportunity that will provide the foundation for PTC's future growth. Similar to the Sephience NDA review, we have not seen any impact of recent FDA changes on our other approval applications. FDA review of the Vatiquinone NDA for the treatment of children and adults with Friedreich's ataxia is progressing at the typical cadence for an application under priority review. The FDA is in the process of conducting inspections, and we have been told that FDA does not plan to hold an AdCom meeting. For the Translarna NDA, we have been receiving information requests, and clinical site inspections have already been conducted.

Turning to the PTC 518 Huntington's disease program, yesterday we announced positive top-line results for the PIVIT-HT phase II study. The study met its primary endpoints of blood HTT lowering and safety, and the results on the full study population are consistent with the previously reported evidence of dose-dependent HTT lowering, favorable safety profile, and early signals of dose-dependent clinical effect at 12 months in stage II patients. In addition, after 24 months of treatment, there were continued trends of dose-dependent favorable clinical effect relative to a propensity-matched natural history cohort, as well as dose-dependent NFL lowering, supporting that over a longer treatment period, we are seeing effects of HTT lowering on multiple aspects of disease. We plan to complete additional analyses and look forward to discussing next development and regulatory steps, including the potential for accelerated approval. Finally, I want to highlight our strong cash position.

We closed Q1 with over $2 billion on our balance sheet. As we have discussed, this cash position enables us to support all planned commercial and R&D activities, participate in strategic business development activities, and reach cash flow break-even without the need to access additional capital. The timing of cash flow break-even will be determined by the ramp of PKU commercial sales, as well as the outcome of FDA approval applications for vatiquinone and Translarna. In addition, this cash position provides us with insulation from global macro uncertainties. In summary, PTC is off to a strong start in 2025. I look forward to our team's continued execution as we build PTC for successful 2025 and beyond. I will now turn the call over to Eric to discuss our commercial performance. Eric?

Eric Pauwels (Chief Business Officer)

Thanks, Matt. Our global customer-facing teams have kicked off the first quarter of 2025 on a strong footing, delivering $153 million in revenue for our five marketed products. Our team is focused on the continued defense of our DMD franchise and diversification within our current commercial portfolio and executing on new product launch preparations globally this year. We delivered strong first-quarter revenue of $134 million for our global DMD franchise, which resulted from our defense strategies to maximize Translarna revenue in Europe and to successfully protect the influenza business in the U.S. While we remain disappointed with the European Commission decision to withdraw Translarna's marketing authorization in Europe, we have planned for this scenario for many months by working at a country level in Europe to identify pathways to continue to commercialize Translarna.

In fact, we already have confirmation from many countries in the EU seeking continued access to Translarna via local reimbursement mechanisms and have already shipped product to multiple countries the first few weeks following the EC decision at the end of March, leveraging Article 117 of the EU Directive. In markets outside of Europe, we continue to receive orders in Latin America, Commonwealth of Independent States, and the Middle East and North Africa regions, and we expect to see continued access to Translarna therapy moving forward for both new and existing nonsense mutation DMD patients. As Matt mentioned, the Translarna NDA is currently under review by the FDA, and if approved, our experienced U.S. team is prepared for a rapid and effective launch. As for Emflaza, quarterly net revenue remains strong, demonstrating ongoing brand loyalty from healthcare providers and patients despite generic entries.

While we have seen new additional generic approvals, the impact was not significant on Q1 revenues. Moving to Translarna and Waylivra, we continue to grow these franchises in Latin America through patient identification efforts as well as geographic expansion in the region. For Upstaza, we continue to focus our commercial efforts in countries where patients are identified, including those countries with AADC deficiency founder effects. Now, turning to Sephience, we continue to accelerate our global launch plans. We are pleased with the recent CHMP positive opinion and are prepared to launch in key European markets as soon as European Commission ratification occurs. We implemented an early access program in Germany that will enable us to convert patients rapidly to commercial product, and we are exploring other early access mechanisms in parallel with health technology assessments in Europe.

Worldwide, there are approximately 58,000 addressable patients with PKU in markets where Sephience could be reimbursed. We expect to roll out the global launches in 25 markets over the next 12 months, prioritizing the launches in Germany, the U.S., and Japan. Sephience is a highly differentiated therapy that we believe will deliver transformative outcomes for patients living with PKU. Our data have consistently demonstrated the significant and meaningful efficacy of Sephience in both classical and non-classical PKU patients, underscoring its broad commercial potential across the full spectrum of patients. Our research and in-person meetings with key healthcare providers indicate their understanding of the potential of Sephience to help more patients reach their dietary goals. Diet liberalization is a critical factor for PKU patients, physicians, and payers, and is expected to drive early adoption of Sephience.

Patients with PKU are often connected through social media, where we see posts suggesting they are well-informed about the benefits of Sephience. We have heard from many key opinion leaders that patients have been reaching out to their treatment centers in advance of our anticipated launch and enrolling in our disease awareness programs. Now, moving to vatiquinone for Friedreich's ataxia, there remains a significant unmet need for children as well as adults with FA. Vatiquinone's differentiated mechanism of action and strong safety record and evidence of clinical benefit in both children and adult patients support a broad potential commercial opportunity for those under 16 for whom there is no approved therapy, as well as for FA patients of all age groups. In preparation for a potential launch, our team has worked to understand the different dynamics of the pediatric and adult patient markets.

In the U.S., the estimated prevalence is approximately 6,000 patients with FA, about one-third of whom are children typically treated in small numbers of children's hospitals, with whom PTC has established long-term relationships. Many other centers of excellence in the U.S. also treat adult FA patients, and our customer-facing teams are actively profiling these neurology centers to identify unmet needs and prepare for a successful launch following the potential FDA approval this summer. With that, I will now turn the call over to Pierre for a financial update. Pierre?

Pierre Gravier (CFO)

Thank you, Eric. I'll now share the financial highlights of our first quarter of 2025. Beginning with top-line results, total products and royalty revenue for the first quarter was $190 million, including DMD franchise revenue of $134 million. Starting with the DMD franchise, Translarna net product revenue in the quarter was $86 million, and Emflaza net product revenue was $48 million. For SMA, Roche achieved first quarter global revenue of approximately $470 million U.S. dollars, resulting in royalty revenue of $36 million for PTC. For the first quarter of 2025, non-GAAP R&D expense was $100 million, excluding $9 million in non-cash stock-based compensation expense, compared to $107 million for the first quarter of 2024, excluding $9 million in non-cash stock-based compensation expense.

Non-GAAP SG&A expense was $72 million for the first quarter of 2025, excluding $9 million in non-cash stock-based compensation expense, compared to $64 million for the first quarter of 2024, excluding $9 million in non-cash stock-based compensation expense. Cash, cash equivalents, and marketable securities total $2,027 million as of March 31, 2025, compared to $1,140 million as of December 31, 2024. This strong financial position provides us with the resources to execute on our strategy and to achieve all our anticipated milestones, as well as advance and expand our R&D efforts and explore business development opportunities to augment our commercial portfolio and pipeline. I will now turn the call over to the operator for Q&A. Operator?

Operator (participant)

Thank you. At this time, we will conduct a question-and-answer session. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from Kristen Kluska at Cantor Fitzgerald. Your line is open.

Kristen Kluska (Equity Research Analyst)

Hi, everyone. Thanks for taking the questions and congrats on a great quarter. On Sephience, you noted that you're far along in discussions with the FDA. I don't know what you're able to discuss there, but a bit of a positive surprise given we're still a couple of months away from the PDUFA. You also noted that you're hearing that patients are reaching out to doctors requesting information ahead of a potential launch. Are you able to comment on what the dynamic is? Are these mostly patient-naive patients? Are these patients that have tried other therapies and either failed or couldn't tolerate? Is there a particular reason that's driving all of the inbound traffic to the doctors? Thank you.

Matthew Klein (CEO)

Thank you for the questions, Kristen. I'll take the first one, and I'll pass it over to Eric to handle the second question. We are through several rounds of label negotiations. We believe we're near the end. We've gone through package insert discussions, carton and crate, patient information labeling. As you pointed out, things are pretty far along in the review process. That gives us a great deal of confidence that, one, the review is on track. I know there's been a lot of concerns with changes in FDA that there could be an impact to upcoming decisions. We've seen none of that impact. If anything, as you alluded to, we feel like things may be a little bit ahead of schedule. We still have a late cycle meeting to go.

That's scheduled for this month, as would typically be done based on the PDUFA date. We remain confident that, one, of the approval and, two, of there not being any delays or any impact from any of the changes at FDA. I'll point out, given the recent news of an hour ago, that all of our applications are in CDER, and the teams that we've been working with for all of our NDAs have appeared to be intact. The contact people are saying the teams will be the same. Overall, no impact on the Sephience NDA nor any of our other applications, nor do we anticipate any.

In terms of the second question, before I turn it over to Eric, I'll just say this has just been what we've seen, and I think you alluded to this in the note that you had put out a few months back, right? Social media, patients communicating from all different types. Those who are on therapies, those who are therapy naive, sharing their experiences, and a lot of social media activity that I think is driving a lot of the interest. I will let Eric give a little bit more detail.

Eric Pauwels (Chief Business Officer)

Yeah, thanks, Kristen, for the question. I mean, our activities are really a lot engaged with a number of the key centers as well as healthcare providers, but a lot of patient activity. We have a disease awareness website, PTC Reimagines PKU. It's basically a disease website where a lot of the patients, healthcare providers, families are engaging. They'll enroll in the program, and we see a very steady cadence of every week, every month, that number increasing. As Matt said, there's really been no specific patient type. It has been all patients. There have been younger patients. There's been healthcare providers with a bolus of patients that are ready to go. Some of them are just really interested not only in sharing the information, but getting updates about the status of Sephience ultimately when it will be approved.

I mean, we're very pleased right now that a lot of the activity is going through social media and then channeling that to our disease awareness site. We anticipate that that will continue. Of course, publications, scientific information, and all of that is shared widely as well.

Kristen Kluska (Equity Research Analyst)

Thank you.

Operator (participant)

Our next question comes from Eric Joseph at JPMorgan.

Eric Joseph (Executive Director of Biotech Equity Research)

Hi. Good afternoon. Thanks for taking the questions. Just on Sephience in Europe, wondering whether it's reasonable to expect any contribution to top line, any sales performance in 2025, and that you might actually see some pull-through through named patient access programs beginning in Germany. Secondly, I know that you obviously have lots going on with multiple new product launches and a focus on cash flow breakeven. That said, just given the balance sheet, I'm wondering whether you can talk a little bit about sort of your appetite from a business development perspective, areas that you might be focused in, and whether sort of the broader pressure that we're seeing on valuations might kind of spur that activity or that interest a little bit further. Thank you.

Matthew Klein (CEO)

Thank you for the questions, Eric. On the first one, yes, we absolutely expect revenue in 2025 from Europe. As Eric alluded to, we'll be ready to launch in Germany once we have the adoption of the opinion, and then we'll also be leveraging other early access programs to garner revenue in 2025 and as soon as possible. I think this is a, for us, we have a well-established global commercial infrastructure, including in Europe. Our teams are very well versed in launching products, launching rare disease products, and also understanding the country-by-country nuances and the country-by-country programs that enable us to accelerate revenue opportunities in cases where we can ahead of formal pricing and reimbursement discussions.

In terms of business development, let me turn it over to Pierre to talk a little bit about how we're thinking about potential opportunities as we turn some cards over the rest of the year.

Pierre Gravier (CFO)

Yeah, first of all, we're very happy with our strong financial position of our $2 billion in this environment. Obviously, it gives us a lot of flexibility to continue all our activities and not worry about cash anytime soon. Furthermore, in terms of PD, we're absolutely looking at business development opportunities, both commercial and pipeline assets, as PTC has done historically. Obviously, we'll hone in one way or the other as we get further clarity on our portfolio.

Eric Joseph (Executive Director of Biotech Equity Research)

Great. Thanks for taking the questions.

Operator (participant)

Our next question comes from Judah Fromer at Morgan Stanley.

Judah Frommer (Senior Equity Research Analyst)

Hi. Thanks for taking the questions, guys. Maybe just following up on Sephience, is there any indication you can give us of, I guess, relatively recent interest from the nutritionist community? Are you able to delineate between commercialization efforts and ramp in Europe versus in the U.S.? What is being done differently in each? Thank you.

Matthew Klein (CEO)

Yeah. Thank you for the questions, Judah. Let me just start by saying that our entire launch plan has had nutritionists and dietitians intimately involved. We appreciate that patient centers of excellence have physicians who play a clearly important role for patient management, but so do nurse practitioners, nurses, and dietitians. They're often the front line of contact with patients who aren't on the therapy as diet management is such a key part of the PKU patient daily life. We have done a lot of work to make sure that we understand the needs of the nutritionists, hear from them, and we've bolstered our own medical team with nutritionists and dietitians so we can provide appropriate peer-to-peer support.

Let me turn it over to Eric to give a little bit more detail on that, as well as talk about how we're thinking about relative ramps in the commercialization of Sephience.

Eric Pauwels (Chief Business Officer)

Yeah. Interestingly enough, we will be launching both in Germany and the U.S. in a very similar timeframe. The ramps are going to be very interesting in the context that we've been doing a lot of work in the pre-marketing area. As I mentioned earlier, in the U.S., we've had a number of patients that have come up to centers, have opted in to our disease website. These would be the very first ones that are being targeted, clinical trial patients as well. In Germany, we implemented a compassionate use program. That program actually had more than half of the sites in Germany that treat patients that are enrolling patients now before. These patients will be available at commercial launch immediately once we end up launching and pricing the product in Germany. We believe that the U.S.

Germany will be very significant contributors to revenue in the second half of 2025.

Judah Frommer (Senior Equity Research Analyst)

Thanks.

Operator (participant)

Our next question comes from Brian Abrahams at RBC.

Hi. This is John for Brian. Thanks for taking our question. I just wanted to ask on Huntington's. So you've had a little more time to look at the data. Do you have any updated thoughts on how to best balance accelerating potential approval timeline and maximizing the chance of demonstrating drug benefits more clearly? Any thoughts on how you could potentially shorten the approval timeline, like interim read at a certain percentage of patients would be very helpful? Thank you.

Matthew Klein (CEO)

Yeah. Thanks. Thanks, John, for the questions. We haven't been that much time. We've been a little busy. I will say that our impressions of the data from yesterday remain very similar. We were very pleased with the results. When you look at this in terms of the phase two trial in a neurodegenerative disease, to be able to demonstrate that the drug does what it's supposed to do in terms of target engagement and the dose-dependent Huntington lowering we observed, it goes where it's supposed to go, getting not only adequate CNS exposure, but we have higher exposure in the CSF than free drug exposure in the CSF than the plasma. The drug is demonstrating itself to be safe and well tolerated.

We're seeing signals both of important clinical and biomarker effect at 12 months and at 24 months that confirm that things are moving in the exact direction they need to. Finally, I'll add, I know we got a lot of questions about the stage three patients and what does that do to our thoughts about the program. That was an incredibly important learning to make. One of the important hypotheses of the PIVIT-HD trial was that stage two patients may be the optimal clinical trial population. Now, let me just make clear, clinical trial population is different than a patient population in whom the drug may ultimately have benefit. It's a population in whom, over the typical length of a clinical trial, you're well positioned to show that you're modifying disease progression in a strong enough way that you can meet an efficacy endpoint.

We have talked a lot about being concerned that the stage two patients may be so advanced that it is going to be very difficult to capture modification in that population. That was our hypothesis going into PIVIT-HD, and that was proven out. That is a very important learning as we think about the next stage in development to know that the stage two population is likely the optimal one in whom we can establish efficacy. In terms of accelerating the path, we continue to believe that we have demonstrated that we are lowering HTT levels. Our discussions with the agency indicated that they are aligned scientifically that HTT lowering is likely to predict clinical benefit. We believe that we have additional evidence that Huntington lowering is associated with favorable things.

At 12 months, we see dose-dependent lowering on the disease rating scale driven by the things in stage two that they should be driven by, TMS and SDMT. As we moved up to 24 months, we're now able to show additional associations with significant effect relative to natural history on the disease rating scale and the dose-dependent lowering of NFL, which now provides biological evidence of potential neuroprotection, which really, again, supplements this concept that HTT lowering is associated with favorable things that in the long term can result in efficacy and efficacious therapy for all Huntington's disease patients. Again, we're very much where we were yesterday in our view of the data and look forward to the discussions with Novartis as we chart additional steps in terms of regulatory discussions and further development plans.

I'd say the only thing that's come between yesterday and today is a lot of outreach from patients and KOLs hearing their enthusiasm for the data, including experts like Dr. Ed Wiles, who's probably one of the main experts in biomarkers of HD disease, who was incredibly enthusiastic about the NFL data and HTT lowering and the safety and tolerability. If anything, what we've heard from outside has increased our belief of the strength of this dataset for this disease.

Operator (participant)

Our next question comes from Kelly Sheehy at Jefferies.

Hi, Dr. Joseph or Kelly. I have a question about PKU, specifically on diet liberalization for Sephience. I wonder if you could please remind us how you can leverage your findings for pay and reimbursement purposes, especially for patients who respond to generic standard of care. In other words, what's the clinical utility in your view of even higher diet liberalization that could support reimbursement in this segment with minimal payer pushback? Thanks.

Matthew Klein (CEO)

Thank you very much for the question, Jose. Let me just give a quick overview, and then I'll let Eric go into detail a bit about the payer dynamics and the importance of the tolerance data. I think the tolerance is something that's very important to patients, incredibly important for patient uptake, physician uptake, and as you pointed out, has a role in payers. I think one of the things to point out is that our data have shown in the clinical studies, and it's also based on mechanism, that patients who may be enjoying benefits of sapropterin and BH4 therapy, branded or generic, have shown to have a greater amount of lowering with sepiapterin. That's something we saw in our clinical trial with the 27 subjects who came into the trial on sapropterin.

Again, it makes sense mechanistically when you consider that we're able to get much greater intracellular concentrations of BH4 through sepiapterin administration and sapropterin administration. Of course, for those who are not considered to be BH4 responsive or have mutations that are considered to be not BH4 responsive, we've been able to show that we've been able to have a significant effect not only in terms of phenylalanine lowering, but also in terms of the ability to allow patients to have diet liberalization. That includes the more severe classical PKU patients and a lot of the patients who are in that therapy naive bucket. Eric, do you want to talk a little bit about how we're thinking about the PTOLERANCE data in terms of the payer discussions and dossiers?

Eric Pauwels (Chief Business Officer)

Yeah. Thanks for the question. In fact, we actually have presented—we have the AMCP dossier, but we have presented all the data live. We have also tested market research with a number of key U.S. payers, both commercial and government. The first thing they do see is an incredibly differentiated profile. To Matt's point, they see fee reductions that are substantially better and different than anything that we currently have in terms of standards of care. Their reaction to the number of patients reaching goals is impressive. In addition to that, the diet liberalization is one of the things that really triggers their appetite, if you will, to say that the product is highly differentiated and superior to Kuvan as it stands. When we have actually pressed and looked at the various things in terms of potential steps or prior authorizations, we believe there will be prior authorizations to the label.

Only naive patients might be going through steps because the vast majority of patients—90% of the patients in the U.S.—are not on any kind of current medical treatment, which means more than half or more have actually tried and failed. We will be able to avoid many of those because the prior authorizations will allow for clinical information on the patient. If we have to go through step edits, they are very short. So far, the payer dynamics have been very favorable, and we will continue to test that as we engage and become closer to the launch.

Very helpful. Thank you.

Operator (participant)

Our next question comes from Eliana Merle at UBS.

Hi, this is Jasmine. I'm for Ellie. Thanks so much for taking our question and congratulations on the progress. We just have one on Emflaza. What have you been seeing in terms of volumes and gross nets and generic approvals, and what do you expect to see here going forward this year? Can you talk about some of your strategies to defend the brand against generic erosion? Thank you.

Matthew Klein (CEO)

Thanks for the question. Thanks for the question, Jasmine. Let me turn it over to Eric. Obviously, we're very proud of the continued Emflaza performance through the first quarter and really a testament to terrific efforts by our teams. Eric?

Eric Pauwels (Chief Business Officer)

Yeah. The teams have continued to, if you will, garner brand loyalty from the Duchenne community. I mean, I think the secret sauce is we've been with them for the last eight years, and we've been providing them exceptional services. Our teams have actually focused on dispenses written and copay assistance, but also have strong relationships with each one of these Duchenne patients. Now, while we have seen some generics come in, the pricing happens to be very similar. Your question around gross to net, we haven't seen that much change at all with our gross to net because it's unclear for us whether the generics are rebating at a higher rate. Now, we do expect some erosion. We'll continue to expect erosion as more generic entrants come in.

One thing we've been able to do is every single month in the quarter, we've been able to add new patients, and we've been able to maintain a number of the existing patients with minimal disruption. I think all in all, I have to say that our U.S. team is really dedicated in terms of managing and giving that sort of white-glove service to every single Duchenne patient. That's been the secret sauce.

Great. Thank you.

Operator (participant)

Our next question comes from Geoff Meacham at Citigroup.

Geoff Meacham (Managing Director)

Great. Thanks. Yeah. Just had another one on diet liberalization and PKU. I guess more of a commercial one, though. The question is, how rapidly do you think real-world use could reflect this? I wasn't sure what success looks like in the U.S. And then are there differences when you think commercially between the European and Japanese market just on this topic? Thank you.

Matthew Klein (CEO)

Thanks very much for the question. I mean, when you think about it, I guess by commercial, you mean in sort of real life when the drug is out there and being taken by people. I think one very good indicator we have of that is what feedback we've gotten and things we see on social media, which is patients being incredibly enthusiastic about the ability to liberalize their diet, whether it's a small amount of liberalization or complete liberalization away from the diet. This has not only benefits to them in terms of daily life, but also can have other important benefits, especially to kids in school in terms of socialization and peer interaction. I think this plays out very well.

It's not something that is actively monitored in the commercial setting, but it is something that we know that is going to be important for patients to try. This is part of the reason for the earlier question. We've been working so closely with the dietitians and nutritional therapists to help manage things appropriately so patients can liberalize their diet in a very thoughtful, rational way so they're set up for success and can gradually do so. Those that can get to full liberalization will be able to get there. Those that can get some liberalization can do that and help understand if it's a kid that they can have their lunch at school now and sit with the other kids and have a typical lunch and maybe have less protein in other meals. All of that are things that will play out in the commercial setting.

It's why we've staffed our medical team and are working so closely with the nutritionists and the expert centers. Eric, I don't know if you had any additional comment on differences in Japan or Europe.

Eric Pauwels (Chief Business Officer)

No, we haven't actually seen any differences. In fact, I think diet liberalization has been well embraced by our healthcare providers. Obviously, Europe and Japan, there's patient information that is out there on PKU, but the physicians really drive a lot of that education. They're incredibly impressed with diet liberalization. The dietitians have embraced it as one of the reasons to really revolutionize or really transform the way patients not only socialize, live, but importantly, they have to change their diet for greater increases in protein intake. It has been a really important catalyst, not just at the patient level, but at the physician level. It's a piece of data that really is impressive.

Operator (participant)

Our next question comes from Tazeen Ahmad at Bank of America.

Tazeen Ahmad (Managing Director of Equity Research)

Good afternoon, guys. Thanks for taking my question. For me, I just wanted to ask another question on Friedreich's. Can you just clarify for us what doctor feedback is on the undermet need? If you are able to get approved in this indication, what would prevent, let's say, every patient from being put on it? Secondly, on your comments about FDA coming back and saying that you should not expect to have an AdCom, is that based on discussions you've had specifically with the agency and the agency feels that the data itself is clear enough, or is there a different reason why at this time they're not planning on holding an AdCom? Thanks.

Matthew Klein (CEO)

Tazeen, thank you very much for the questions. Let me start with the second one. The communication about not having an AdCom was something that was raised by the agency at our mid-cycle meeting that was held last month. They said at this point in the review, they do not see a need and do not expect to hold an AdCom meeting. They did not give any further detail on that. As we said all along, we believe the agency understands the disease, understands the endpoints both from their experience with this Glyceris review as well as the number of other phage protective therapies and developments. I think they are very involved in conversations. In our discussions regarding the Tikvenol package, it has become very clear that they understand the MPHARS endpoint. They understand the dynamics involved with upright stability.

They understand the long-term registry that was an important part of our confirmatory evidence. We were not surprised by the decision to not hold the AdCom. In terms of accessing populations, I think, look, there's nothing available for patients under the age of 16, and that's certainly a population where we've been able to show benefit as well as safety in the trials. We have safety data with vatiquinone going down to children less than one year of age, and we have experience in adult populations as well. I believe that we have the opportunity to be a therapy not only for children who don't have alternatives now, but also to be an additional potential safe and well-tolerated and effective therapy for adults.

Eric, I don't know if you wanted to provide any more color on the work that your team has been doing in terms of understanding the.

Eric Pauwels (Chief Business Officer)

Yeah. Thanks for the question, Tazeen. I mean, our teams have been very active. We've been in pediatric neurology now for over eight years. We understand and know the dynamics in these children's hospitals where the vast majority of patients are either diagnosed or treated. The feedback is obviously a very high unmet need. The burden of illness, the disability, the comorbidities in children is very, very high. There's no approved therapy. When physicians, particularly the pediatric neurologists, see the profile, they're very convinced, and we believe there'll be a rapid uptake. In addition, a lot of them are treating adults. As Matt said, we believe that this is going to be a broad use, especially for patients who are naive and not have been on OMAP therapy or those who are poorly controlled or dropped out. The opportunity is very large.

The first thing that our healthcare providers see is the efficacy, an efficacy that is at least as good or currently with the current treatment available. The safety profile is a big winner here because it is very safe, and there is very limited or no monitoring involved, particularly for children. They all recognize that there is a very differentiated mechanism of action, something that is unique and different. They see that value. What we are doing is obviously working in those centers that we have a ton of experience in over the last eight years or so to put out disease awareness and ensure that we can focus on a lot of the unmet needs and prepare the market for the launch of Sephience.

Operator (participant)

Our next question comes from Gina Wang at Barclays.

Hang Hu (AVP of Biotech Equity Research)

Hi, this is Hang Hu for Gina Wang. Thanks for taking our question. We have a question for Translarna. We know that you have agreements with ex-EU countries based on the EU approvals. In light of the EC withdrawal decision in EU, could you share with us the status and expectation in ex-EU countries and how sustainable the revenue would be?

Matthew Klein (CEO)

Han, thank you very much for the question. As Eric pointed out, we're even in the EU through the European Commission's directive of the ability to use Articles 117 and Article 5 for individual countries in Europe to continue to make commercial product available. We are still able to generate revenue within Europe. I just want to emphasize that, as Eric said in his presentation. Eric, do you want to talk about what we're seeing outside Europe, which has been virtually no impact?

Eric Pauwels (Chief Business Officer)

Yeah. There's been actually no disruption, especially in Latin America. We've already negotiated a contract with Brazil. We've begun shipping product in Brazil. These are group purchase orders that we'll be shipping in the natural cadence over the course of the year in other smaller Latin American markets as well. We see that the U.K. license is still in place, and we can continue to work through that. We've had orders in the Middle East and North Africa. Very little disruption outside of Europe. As Matt said, we are working country by country to find the right mechanisms for reimbursed Translarna within Europe.

Hang Hu (AVP of Biotech Equity Research)

Yeah. Thanks for that. Really helpful. The last one, we also want to go back to Huntington's disease data you reported yesterday. In 24-month data, you compared the results with natural history controls. We noticed that you used two different references. In the functional outcome, you compared your data with Enroll-HD disease registry. For NFL, Neurofilament Light, you compared the data with a Lancet publication. Could you share with us what's the rationale when selecting the natural history controls and why do you use different reference datasets?

Matthew Klein (CEO)

Yeah. Hang, let me clarify that. The only comparative analysis performed that we reported yesterday was a comparison of the treated patients for 24 months on functional measures with a large Enroll registry, which has over 20,000 entrants, and allowed us to get a robust propensity-matched comparator population so that we could really understand the benefit we were observing with PTC 518 treatment on those different scales. We did not perform a comparative analysis of the NFL data. What we did show was that we have the dose-dependent lowering of NFL and made reference to the most recent natural history publication from Park and the group in London showing that in stage two patients, there tends to be an increase in NFL of about 12.5% per year. There are registries that have NFL data such as TRACK-HD and others, and we'll go ahead and look at that.

We wanted to just communicate the concept, which has been consistently shown in every study, that over the course of time, NFL increases in HD patients. We wanted to give a reference to the magnitude that's most recently reported for the stage-specific patients. The only direct match comparison was done for the functional outcomes that generated the comparative values and the P-values showing the evidence of significant effect relative to that matched natural history on the CUHDRS, the TFC, as well as the SDMT scales.

Hang Hu (AVP of Biotech Equity Research)

That's really helpful. Thanks so much.

Operator (participant)

Our next question comes from Peyton Bohnsack at TD Cowen.

Peyton Bohnsack (VP of Biotechnology Equity Research)

Hi, guys. Good afternoon. Thanks for taking our questions. I guess kind of in a more broad sense, can you talk about any impacts some of the global macro factors we've been seeing over the past couple of weeks would influence your financial guidance? Maybe such things as tariffs or the manufacturing executive order yesterday or most favored nations. How that would impact your decision to conduct business development moving forward. Thank you.

Matthew Klein (CEO)

Thanks for the questions, Peyton. Look, none of us have a crystal ball to predict exactly what's going to happen in terms of tariffs, what's going to happen in terms of most favorite nation. The discussions so far have been around maybe Medicaid. There's a bill that Hawley and others are putting through. We don't have a crystal ball, but let's just start with the tariffs. We expect to have minimal impact on our business for a number of reasons, particularly for our U.S. products. The IP is domiciled in the U.S., so there's no transfer pricing as the product remains U.S.-owned throughout. Any potential tariff would be on cost of goods and would be quite minimal impact to our business. Similarly, on most favorite nation, as Eric alluded to, we're very thoughtful about establishing our pricing corridor.

That's something we do independent of an MFN situation to ensure that we're getting the maximum value for our products. I think we'd be very well positioned. In terms of other macro things going on, as I mentioned, the recent changes in CBIR, all of our applications are in CDER. All of our pending applications are relying on clinical efficacy from clinical trials, both placebo-controlled as well as, in each case, longer-term studies that confirm the benefit we saw in the placebo-controlled study. I think we're sitting in a position that would not be affected good or bad by any of the changes going on in CBIR. As I mentioned, despite all the changes in FDA, everything remains on schedule for us, and we've observed no impact.

I would say there have been a great deal of macro things, a great deal of anxiety and uncertainties, but we believe we're pretty well insulated from each of them.

Peyton Bohnsack (VP of Biotechnology Equity Research)

Maybe if I could just ask a quick follow-up on that, on the Sephience, has your pricing strategy changed at all due to any of the macro updates, or has everything stayed about the same?

Matthew Klein (CEO)

No. We have no changes in our strategy. Again, our strategy anticipates a lot of these things prior to even the introduction of discussion of legislation or orders or anything like that.

Peyton Bohnsack (VP of Biotechnology Equity Research)

Great. Thank you, guys.

Operator (participant)

Our next question comes from Joel Beatty at Baird.

Hi. This is Chris on for Joel. Thanks for taking our question. Regarding the vatiquinone, just getting maybe a little deeper into the patient breakdown, are you able to provide some general color on the percentage of patients you're anticipating will come from that pediatric 16 and under population versus adults? Thanks.

Matthew Klein (CEO)

Yep. Thanks for the questions, Chris. I think we've talked about that there's about 6,000 patients in the U.S. with phenylketonuria, and we said about a third of them we believe would be in that pediatric bucket.

Operator (participant)

Our next question comes from Joseph Schwartz at Leerink Partners.

Hi, guys. This is Ginny on for Joe. Thank you for taking our question. The majority of your products and candidates are either approved or at the regulatory approval stage of development with the exception of PTC 518. This leaves a bit of a pipeline gap with a little less going on in terms of earlier stage development, at least for what's been publicly disclosed. Is there anything exciting that you're working on internally that you might highlight soon? Additionally, this market environment could be advantageous for companies like you guys who have cash on hand that could be deployed for BD. Are there any opportunities that you're actively pursuing or general areas you might be interested in? Thank you.

Matthew Klein (CEO)

Thanks for the questions, Ginny. The answer to both is yes. We do have pipeline programs that we've been working on. We disclosed some of them at the JPMorgan discussion. We've put a lot of effort just as we've focused a lot of our development and commercial efforts. We've also done a lot of work to focus our earlier programs to ensure that we're leveraging unique scientific platforms, including splicing and our fibromatosis inflammation platform. I think the experience of PTC 518 following on the heels of Evrysdi is really a testament to our unique ability to get small molecule splicing therapies into the clinic, into patients, and moving forward through development and being able to show that we can favorably affect splicing and do so safely.

We have a number of splicing programs that we're working on that are at various stages of preclinical development that we look forward to moving into the clinic very soon, and we'll be detailing them soon. We shared at the JPMorgan conference that we have a program with a DHODH inhibitor that we expect to be phase II ready by the end of the year that we're looking at for a number of different neuroinflammatory indications given the importance of DHODH to immunoinflammatory response. We also shared an NLRP3 inhibitor program that's peripherally based that we're looking at for a number of potential indications where the NLRP3 inflammasome has been intimately linked to disease pathology. More to come on all of that.

In addition, we are looking, as Pierre said, at business development opportunities in the things that we think that can complement our existing R&D portfolio. As you know, business development is sort of a long-term proposition. We have been working on it for a while. We have a number of different potential things that we are looking at that some are earlier stage, some are even commercial stage, some are geographic licenses, all different opportunities that we continue to look at. As we understand better our commercial portfolio later this year, pending the regulatory decisions for Translarna for the Tikvenon in the U.S., that will also help direct where we might move. The key part is we are looking at a number of different opportunities.

As we always have, we'll continue to be very strategic in how we think about utilizing business development to supplement the R&D and/or commercial portfolios.

Thank you.

Operator (participant)

Our last question comes from Paul Choi at GS.

Hi. This is Daniel on for Paul. Thank you for clarifying that you are mainly working with CDER. I still have a question regarding vatiquinone. Could you share any color or feedback from the agency regarding the utilization for natural history for the approval, especially the long-term open-label start part for Move FA? Thank you very much.

Matthew Klein (CEO)

Thanks for the question, Daniel. As we've talked about, the comparison of our long-term data following Move FA with the robust FACOMS, so FACOMS natural history databases, was an important part of our confirmatory evidence. We, in fact, provided a comparison with the Move FA data, long-term data to the FACOMS database where we were able to show 50% slowing in disease progression over three years. We did a similar comparative analysis from the long-term study of a previously conducted placebo-controlled study in adults, both ambulatory and non-ambulatory, where again, we demonstrated a significant multi-point slowing in disease progression, in that case, over 24 months. I would point out that the FACOMS registry is probably one of the most robust rare disease registries.

This has been established by FARA, and they've done an incredible job of ensuring a reliable network of centers that contribute high-quality data to this registry with frequent assessments that allow for a granular comparison with data that we would collect in a clinical study. The FDA, of course, is familiar with the FACOMS registry because that was used as the confirmatory evidence in the Skyclarys authorization back in 2023. It is something they know well, and it is something that I think many have called out, the FACOMS registry as the type of natural history database that can support regulatory decision-making.

We're happy that it's, we're grateful to FARA and the FA community and the patients who have contributed their data to that registry because it really allows us to inform a really important data point, which is the long-term benefit we see with vatiquinone in both children and adults with Friedreich's ataxia.

Very helpful. Thank you.

Operator (participant)

This concludes the question-and-answer session. I would now like to turn it back to Dr. Matthew Klein for closing remarks.

Matthew Klein (CEO)

Thank you all again for joining the call today. We're very excited about our excellent progress we made in the first quarter and look forward to continued successes in 2025 and beyond. Thank you again.

Operator (participant)

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.