PTC Therapeutics (PTCT) Q1 2025 Earnings Call

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DATE

Tuesday, May 6, 2025 at 4:30 p.m. ET

CALL PARTICIPANTS

Chief Executive Officer — Matthew Klein

Chief Operating Officer — Eric Pauwels

Chief Financial Officer — Pierre Gravier

SUMMARY

PTC Therapeutics, Inc. (NASDAQ:PTCT) reported $190 million in first-quarter revenue, primarily driven by its Duchenne muscular dystrophy (DMD) franchise. The company narrowed its 2025 full-year revenue guidance to a range of $650 million–$800 million, with management signaling further adjustments to guidance pending regulatory outcomes and additional market data for Emflaza. A positive Committee for Medicinal Products for Human Use (CHMP) opinion was received for Cefiance (SUFIANCE) in Europe, covering the full spectrum of PKU patients, with the formal European Commission decision anticipated in June and commercial launch prepared for Germany and select countries via named patient and early access programs. U.S. commercial readiness for SUFIANCE aligns with an upcoming FDA decision, with late-cycle review meetings still pending but described by management as "pretty far along in the review process" and with "no impact" observed from FDA process changes. The Huntington's disease program PTC518 achieved primary endpoints in the phase 2 PIVOT study, showing dose-dependent lowering of blood huntingtin (HTT) and neurofilament light (NFL), as well as early clinical effect signals. For vatiquinone, FDA review for Friedreich's ataxia proceeded at standard priority review pace, and the agency communicated it does "not plan to hold an AdCom meeting." Non-GAAP R&D expense decreased sequentially, while non-GAAP SG&A expense increased. The company's cash, cash equivalents, and marketable securities reached $2.7 billion as of March 31, 2025, positioning PTC to fund commercial expansion, R&D, and business development opportunities without near-term capital needs.

Royalty revenue from Roche for Evrysdi (IVZD) was $36 million based on Roche's approximately $470 million in first-quarter global sales.

Emflaza net product revenue remained stable at $48 million in the quarter despite additional generic approvals, with minimal gross-to-net impact identified.

Translarna net product revenue totaled $86 million, and shipments continued to multiple EU countries under Article 117 following EC withdrawal of authorization, as well as through contracts in Latin America, the Middle East, and North Africa.

Approximately 58,000 addressable PKU patients exist in reimbursable markets targeted for SUFIANCE global launch, with plans to commercialize in 25 markets over twelve months, including Germany, the US, and Japan.

Vatiquinone's addressable patient population in the U.S. is estimated at 6,000, with roughly one-third being children, and the company is targeting both pediatric and adult segments for launch readiness upon anticipated approval.

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TAKEAWAYS

Total Revenue: $190 million for Q1 2025, with a narrowed full-year outlook of $650 million–$800 million.

DMD Franchise Revenue: $134 million for Q1 2025, including Translarna at $86 million and Emflaza at $48 million.

Royalty Revenue: $36 million from Roche's global Evrysdi (IVZD) sales of approximately $470 million.

Non-GAAP R&D Expense: $100 million, excluding $9 million in noncash stock-based compensation, down from $107 million (excluding the same SBC) in the comparable prior period.

Non-GAAP SG&A Expense: $72 million, excluding $9 million in noncash stock-based compensation, up from $64 million (excluding the same SBC) in the first quarter of 2024.

Cash Position: $2.7 billion in cash, cash equivalents, and marketable securities as of Q1 2025—up from $1.4 billion at 12/31/2024.

SUFIANCE European Launch: Commercial launch to begin in Germany and via early access programs, pending June European Commission decision; company expects revenue contributions in 2025.

SUFIANCE U.S. Regulatory Status: NDA review described as "pretty far along," with no observed delays or impact from FDA process changes, and a late-cycle meeting scheduled for the current month.

Cefiance Efficacy Data: AFFINITY long-term extension showed 97% of participants in the feed tolerance study increased dietary protein, based on data shared in the quarter, with two-thirds reaching or exceeding recommended daily allowance; efficacy was also observed in classical PKU and non-VH4 responsive subgroups.

PTC518 (Huntington's): Phase 2 PIVOT study met primary endpoints (blood HTT reduction and safety); 24-month data indicated continued dose-dependent clinical effects and NFL lowering vs. a propensity-matched cohort.

Vatiquinone (Friedreich's Ataxia): FDA review proceeding without AdCom; confirmatory evidence from long-term data compared to FA-COMS natural history registry showing a reported 50% slowing in disease progression over three years.

Translarna Commercial Access: Despite EC withdrawal in Europe, product shipped to multiple countries under Article 117, with existing contracts in Brazil and continued sales in Latin America, MENA, and the CIS regions.

Emflaza Revenue Resilience: Brand loyalty and similar generic pricing led to continued strong revenue and minimal gross-to-net changes, despite increasing generic approvals.

Business Development Plans: Company is actively seeking business development opportunities in both commercial and pipeline assets, supported by its current cash position.

Cash Flow Breakeven: Management reiterated its ability to fund operations and reach cash flow breakeven without external financing, dependent on the ramp of PKU sales and outcomes of regulatory submissions, as stated in the quarter.

INDUSTRY GLOSSARY

CHMP: Committee for Medicinal Products for Human Use—a European Medicines Agency (EMA) committee that reviews drug marketing authorization applications for the EU.

PDUFA: Prescription Drug User Fee Act—a U.S. law giving the FDA a target date for drug approval decisions.

PKU: Phenylketonuria—a rare inherited metabolic disorder targeted by SUFIANCE (Cefiance).

BH4: Tetrahydrobiopterin—a cofactor involved in amino acid metabolism and a therapeutic target in PKU.

NDA: New Drug Application—the regulatory submission to request approval to market a new pharmaceutical in the U.S.

AdCom: Advisory Committee—a panel convened by the FDA to provide guidance on regulatory decisions; not every application requires an AdCom.

NFL: Neurofilament light—a biomarker of neurodegeneration measured in Huntington’s disease studies.

FA-COMS: Friedreich's Ataxia Clinical Outcome Measures Study—a disease-specific natural history registry used to compare long-term clinical trial outcomes.

DMD Franchise: Group of products (Translarna and Emflaza) addressing Duchenne muscular dystrophy marketed by the company.

CIS: Commonwealth of Independent States—a regional intergovernmental organization of former Soviet Republics, referenced as a market for Translarna.

Full Conference Call Transcript

Matthew Klein: Thank you all for joining today. Following the 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 SUFIANCE, 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 continue to move towards becoming cash flow breakeven. 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 to $800 million. We expect to further narrow guidance pending regulatory actions and additional clarity on Emflaza performance for the remainder of 2025. We recently announced the positive CHMP opinion on the marketing authorization of Defiance 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 Cefiance launch plan in Europe as well as in the US ahead of the anticipated FDA decision. In the first quarter, we shared updated data from the ongoing CFIANCE long-term studies that continue to support the ability of SUFIANCE 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 fee 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 three AFFINITY trial, which demonstrated meaningful treatment effect in classical PKU subjects with non-VH4 responsive genotypes, providing further evidence that Cefiance can provide benefit to all disease subtypes. Discussions with the FDA on the Cefiance 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 Suffiance NDA review. As we have discussed, we believe we can achieve over $1 billion in revenue from Cefiance, a significant revenue opportunity that will provide the foundation for PTC's future growth. Similar to the supply and NBA 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 PIVOT phase two 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 twelve months in stage two patients.

In addition, after twenty-four 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 breakeven without the need to access additional capital. The timing of cash flow breakeven will be determined by the ramp of PKU commercial sales as well as the outcome of FDA approval applications for vitiquinone 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 Pauwels: 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 Emflaza business in the US.

While we remain disappointed with the EC 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 decision at the 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 US team is prepared for a rapid and effective launch. As for Emflaza, quarterly net revenue remained strong, demonstrating ongoing brand loyalty from health care providers and patients despite generic entries. While we have seen new additional generic approvals, the impact was not significant on Q1 revenues. Moving to TEGSEDI, WAYLIVRA. We continue to grow these franchises in Latin America, through patient identification efforts as well as geographic expansion in the region.

For Upstate's incapability, we continue to focus our commercial efforts in countries where patients are identified, including those countries with AADC deficiency founder effects. Now turning to Sophiance. 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 EC 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 fifty-eight thousand addressable patients with PKU in markets where Cefiance could be reimbursed.

We expect to roll out the global launches in 25 markets over the next twelve months, prioritizing the launches in Germany, the US, and Japan. Defiance is highly differentiated that we believe will deliver transformative outcomes for patients living with PKU. Our data have consistently demonstrated the significant and meaningful efficacy of Saviance 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 health care providers indicate their understanding of the potential of SUFIANCE to help more patients reach their dietary goal. Diet liberalization is a critical factor for PKU patients, physicians, and payers and is expected to drive early adoption of Sefiance.

Patients with PKU are often connected through social media, where we see posts suggesting they are well informed about the benefits of suffice. 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 program. Now moving to vadiquinone for Frederick's ataxia. There remains a significant unmet need for children as well as adults with FA. Vutiquinone'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 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 US, the estimated prevalence is approximately six thousand patients with Frederick's attack here. 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 US 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 Gravier: 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 IVZD, Roche achieved first-quarter global revenue of approximately $470 million 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 noncash stock-based compensation expense, compared to $107 million for the first quarter of 2024 excluding $9 million in noncash stock-based compensation expense.

Non-GAAP SG&A expense was $72 million for the first quarter of 2025, excluding $9 million in noncash stock-based compensation expense, compared to $64 million for the first quarter of 2024 excluding $9 million in noncash stock-based compensation expense. Cash, cash equivalents, and marketable securities total $2.7 billion as of 03/31/2025 compared to $1.4 billion as of 12/31/2024. 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. And I will now turn the call over to the operator for Q&A.

Operator: Thank you. At this time, we will conduct a question and answer session. And wait for your name to be announced. To withdraw your question, please press 11 again. Our first question comes from Kristen Kluska at Cantor Fitzgerald. Your line is open.

Kristen Kluska: Hi, everyone. Thanks for taking the questions, and congrats on a great quarter. So on SUFIANCE, 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 PDUFA. And then 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?

And then is there a particular reason that's driving all of the inbound traffic to the doctors? Thank you.

Matthew Klein: Thank you for the questions, Kristen. I'll take the first one, then I'll pass it over to Eric to handle the second question. So we are through several rounds of legal negotiations. We believe we're near the end. We've got a few package insert discussions, cart and crate, patient information, etc. So as you pointed out, things are pretty far along in the review process. So 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 at FDA, if there could be an impact to upcoming decisions. We've seen none of that impact.

And 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 we typically got to be done based on the PDUFA date, but 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 CEDAR, and the teams that we've been working with for all of our NDAs have appeared to be intact.

We have the contact people the same, the teams do the same. So overall, no impact on the supply and NDA nor any of other applications nor do we anticipate any. In terms of the second question before I turn 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 are on therapies. Those are the therapy naive, sharing their experiences. And a lot of social media activity that I think is driving a lot of the interest, but I'll let Eric give a little bit more detail.

Eric Pauwels: 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 health care 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, health care 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. There and as Matt said, there's really been no specific patient type. It had been all patients. There have been younger patients. There's been health care providers with a bolus of patients that are ready to go.

And some of them are just really interested not only in sharing the information but getting updates about the status of Sophiance ultimately when it will be approved. So, 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. So we anticipate that will continue. And, of course, public publications, scientific information, and all of that is shared widely as well.

Operator: Thank you. Our next question comes from Eric Joseph at JPMorgan.

Eric Joseph: Hi. Good afternoon. Thanks for taking the questions. Just on Cepheid in Europe, wondering if 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 named patient access programs beginning in Germany. And then secondly, I know that you have obviously, you lots going on with multiple new product launches. And a focus on cash flow breakeven. That said, just given the balance 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 kinda spur that activity that interest a little bit. Further. Thank you.

Matthew Klein: 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 '25 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 to the rest of the year.

Pierre Gravier: Yeah. First of all, we're very happy with a strong financial position over $2 billion in this environment that we see gives us sort 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. And, obviously, we'll hone in one way or the other as we get further clarity on our portfolio.

Eric Joseph: Right. Thanks for taking the questions.

Operator: Our next question comes from Judah Frommer at Morgan Stanley.

Judah Frommer: Hi. Thanks for taking my questions, guys. Just following up on Defiance. Is there any indication you can give us of I guess, relatively recent interest from the nutritionist community? And then, are you able to delineate between commercialization efforts and ramp in Europe versus in the US and what's being done differently in each? Thank you.

Matthew Klein: Thank you for the questions, Judah. Let me just start by saying that our entire launch plan has nutritionists and dietitians intimately involved. We appreciate that patient centers of excellence have physicians who play a clearly important role in 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 and diet management is such a key part of the PKU, patient daily life. So we have done a lot of work to make sure that we understand the needs of the nutritionists, hear from them, and the 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 supply issue.

Eric Pauwels: Yeah. Interestingly enough, we will be launching both in Germany and the US in a very similar time frame. And the ramps are going to be very interesting in the context that we've been doing a lot of work in the premarketing area. As I mentioned earlier in the US, we've had a number of patients that have come up. Two centers have opted in. Our disease website. These would be the very first ones that are being targeted clinical trial patients as well. In Germany, 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 and these patients will be available at commercial launch. Immediately once we end up launching and pricing the product in Germany. So we believe that the US and Germany will be very significant contributors to revenue in the second half of 2025.

Judah Frommer: Thanks.

Operator: Our next question comes from Brian Abrahams at RBC.

Joe: Hi, this is Joe on 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. You have any updated thoughts on how to best balance accelerating approval timeline and maximizing the chance of demonstrating drug benefits more clearly. Any thoughts on how you could potentially shorten approval timeline, like interim read at a certain percentage of patients? Would be very helpful. Thank you.

Matthew Klein: Yeah. Thanks, Joe, for the questions. It hasn't been that much time. We've been a little busy but I will say that our impressions of the data from yesterday remain very similar. You know, we were very pleased with the results. When you look at this in terms of the phase two trial in 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 huntingtin lowering we observe. It goes where it's supposed to go getting not only adequate CNS exposure, but we have higher exposure in the CSF than a free drug exposure in the CSF than the plasma.

The drug is demonstrating itself to be safe, and well tolerated. And we're seeing signals both of important clinical and biomarker effects in both over at twelve months and at twenty-four months that confirm that things are moving in the exact direction they need to. And 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 PIVOT 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 their a patient population 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. And we talked a lot about being concerned that the stage two patients may be so advanced it's going to be very difficult to capture modification in that population. That was our hypothesis going into PIVOT HD, and that was proven out.

So that's a very important learning as we think about the next stage in development to know that stage two population is likely the optimal one in whom we can establish efficacy. In terms of accelerated path, you know, we continue to believe that we've demonstrated that we are lowering HTT levels and our discussions with the agency indicated that they are aligned scientifically that HTT lowering is likely to predict clinical benefit, and we believe that we have additional evidence that Huntington lowering is associated with favorable things. At twelve months, we see dose-dependent lowering on the disease rating scale driven by things in stage two that they should be driven by, TMS and SDMT.

As we moved out to twenty-four months, we're now able to show additional associations with significant effect relative to natural history and 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 an efficacious therapy for all Huntington's disease patients. So again, we're very much where we were yesterday in our view of the data and look forward to 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 Wilde, who's probably one of the main experts in biomarker of FVC disease who is incredibly enthusiastic about the NFL data in safety and tolerability. So if anything, what we've heard from outside has increased our belief in the strength of this dataset for this disease.

Operator: Our next question comes from Kelly Shi at Jefferies.

Jose: Hi. Good afternoon. This is Jose for Kelly. I have a question about PKU, specifically on for suppliants. 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, you know, what's a clinical utility? Your view of even higher diet liberalization that could support reimbursement in this segment with minimal payer pushback. Thanks.

Matthew Klein: 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, as you pointed out, has a role in payers. I think one of the things to point out is that the data our data has shown in the clinical studies, and it's also based on mechanism, that patients who may be enjoying benefits of saproteren BH4 therapy, even branded or generic, have shown to have a greater amount of lowering with sepiaTaren.

That's something we saw in clinical trial with the 27 subjects who came into the trial on saproteren. And, again, it makes sense mechanistically when you consider we're able to get much greater intracellular concentrations of BH4 through sepiaTaren administration and saproteren administration. And then, 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 bile mineralization.

And that includes the more severe classical PKU patients and then 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 feed tolerance data in terms of the discussions and DUSCs?

Eric Pauwels: Yeah. Thanks for the question. In fact, we actually have presented we have the AMC P dossier, but we also have presented all the data live, and we've also tested market research with a number of key US payers, both commercial and government. The first thing they do see is an incredibly differentiated profile. And 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.

And 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've actually pressed and looked at the various things in terms of potential steps or prior authorizations, we believe there'll be prior authorizations to the label. And only naive patients might be going through steps. Because the vast majority of patients and ninety percent of the patients in the US not on any kind of current medical treatment. Which means more than half or more have actually tried and failed.

So we'll be able to avoid many of those because the prior authorizations will allow for clinical information on the patient. And if we have to go through step edits, they're very short. So far, the payers have the dynamics have been very favorable. And we will continue to test that. As we engage and become closer to the launch.

Jose: Very helpful. Thank you.

Operator: Our next question comes from Eliana Merle at UBS.

Jasmine: It's Jasmine on for Ellie. Thanks so much for taking our question and congratulations on the progress. We just have one on Emflaza. So, what have you been seeing in terms of volumes and gross to net since generic approvals, and what do you expect to see here going forward this year? And can you talk about some of your strategies to defend the brand against generic erosion? Thank you.

Matthew Klein: Thanks for the question, Jasmine. Let me just turn it over to Eric. And, obviously, we're very proud of the continued Imflaza performance through the first quarter and really attest to terrific efforts by our teams. Eric?

Eric Pauwels: 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 in with them for the last eight years. And we've been providing them exceptional services. Our teams have actually focused on dispenses written and co-pay 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. So 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. So I think all in all, I have to say that our US team is really dedicated in terms of managing and giving that sort of white glove service to every single Duchenne patient. And that's been the secret sauce.

Jasmine: Great. Thank you.

Operator: Our next question comes from Jeff Hung at Citigroup.

Jeff Hung: 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 US. And then are there differences when you think commercially the European and Japanese market just on this topic? Thank you.

Matthew Klein: 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 we feedback we've gotten and things we see on social media. Which is patients being incredibly enthusiastic about the ability to liberally liberalize their diet, whether it's a small amount of liberalization or complete liberalization away from the diet. And this is not only benefits to them in terms of daily life, but also, have other important benefits especially the kids in school in terms of socialization and peer interaction.

So 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 to patients to try. And this is part of the reason, 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. So, those that can get to full liberalization were able to get there.

Those that can get some liberalization can do that and help understand, you know, if it's a kid that they can have their lunch at school now and stay the other kids and have a typical lunch and maybe, have less protein than other meals. So all of that are things that will play out in the commercial setting and is 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: No. We haven't actually seen any differences. And in fact, I think diet liberalization has been well embraced by our health care 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, and the dietitians have embraced it as one of the reasons to really revolutionize or really transform the way patients not only socialize, live, but, you know, importantly, they have to change their diet for greater increases in protein intake. So 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: Our next question comes from Tazeen Ahmad at Bank of America.

Tazeen Ahmad: Good afternoon, guys. Thanks for taking my question. For me, I just wanted to ask another question on Friedreich. Can you just clarify for us what doctor feedback is on the unmet need? So if you are able to get approved in this indication, 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: 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, don't see a need and don't expect to hold an AdCom meeting. They didn't give any further detail on that. And as we said all the time, we believe the agency understands the disease, understands the endpoints both from their experience with this Glyclaris review as well as the number of other future protective therapies and developments.

I think they're very involved in conversations in and in our discussions regarding the etiquinol package, it's become very clear that they understand the mFARS endpoint. They understand the dynamics involved with upright stability. They understand the long term. That was an important part of that confirmatory evidence. So we were not surprised by the decision to not hold the AdCom. In terms of accessing populations, I think, look. You know, 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 going down to children less than one year of age, and we have experience in adult populations as well. And so 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 a safe 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 what the work that your team's been doing in terms of understanding.

Eric Pauwels: Yeah. Thanks for the question, Tazeen. I mean, our teams have been very You know, 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. You know, the feedback is obviously a great a very high unmet need. The burden of illness, the disability, the comorbidities, in children is very, very high. There's no approved therapy. And when physicians particularly the pediatric neurologists, see the profile, they're very convinced, and we believe there'll be a rapid uptake. But in addition, a lot of them are treating adults.

And 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 therapy or those who are poorly controlled or dropped out. So the opportunity is very large. And the first thing that our health care providers see is the efficacy, an efficacy that is at least as good or currently with the current treatment available. But the safety profile is a big winner here because it's very safe, and there's very limited or no monitoring involved, particularly for children. And they all recognize that there's a very differentiated mechanism of action. Something that's unique and different. So they see that value.

And what we're 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 vutiquinone.

Operator: Our next question comes from Gena Wang at Barclays.

Han Hu: Hi, this is Han Hu for Gena Wang. Thanks for taking our question. I have a question for Translarna. We know that you have an agreement with x EU countries based on the EU approvals. So in light of the EC with decision in EU, could you share with us the status and the expected EU countries and how sustainable the revenue would be?

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

Eric Pauwels: Yeah. There's been actually no disruption, you know, 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 will be shipping the natural cadence over the course of the year. In other smaller Latin America markets as well. Know, we can see that we see that the UK license is still in place, and we can continue to work through that. And, we've had orders in the Middle East and Northern Africa. So very little disruption outside of Europe. And as Matt said, we are working country by country. And to find the right mechanisms for reimbursed Translarna within Europe.

Han Hu: Yeah. Thanks for that. Really helpful.

Matthew Klein: The last one, we also want to go back to Huntington's disease data you reported yesterday. In twenty-four months data, you compared the results with natural history controls, but we noticed that you used the two different references. So in the functional outcome, you compared that your data with enroll HDD registry. But for an FL neural filament light, you compare the data with a Lancet publication. So 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: Yes, So Han. Let me clarify that. The only comparative analysis performed that we reported yesterday was a comparison of the treated patients for twenty-four 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 PTC518 treatment, on those different scales.

We did not perform a comparative analysis of the NFL data, but we did show was that we have the dose-dependent lowering of NFL and referred made reference to the most recent natural history publication from Parkin and the group in London showing that in stage two patients, theirs tends to be an increase in NFL of about twelve point five percent per year. There are registries that have NFL data such as Track HD and others, and we'll go ahead and look at that.

But 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, and we wanted to give a reference to the magnitude that's most recently reported for the stage-specific patients. But 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 scale.

Han Hu: That's really helpful. Thanks so much.

Operator: Our next question comes from Peyton Bohnsack at TD Cowen.

Peyton Bohnsack: Hi, guys. Good afternoon. Thanks for taking our questions. I guess kind of in a more broad sense, can you talk about any impacts from the global macro factors we've been seeing over the past couple of weeks, would influence your financial guidance. Like, maybe such things as, like, tariffs with the manufacturing executive order yesterday or most favored nation. And then how that would impact your decision to conduct business development going forward. Thank you.

Matthew Klein: Thanks for the questions, Peyton. Look, none of us have a crystal ball to predict exactly what's gonna happen in terms of tariffs, what's going to happen in terms of most favored nation, and, you know, the discussion so far has been around in maybe Medicaid. There's a bill that Holly and others are putting through a car. So 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 US products. The IP is domiciled in the US, so there's no transfer pricing as the product remains. US owned throughout.

So any potential tariff would be on the cost of goods and would be quite minimal impact on our business. Similarly, our most favored 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. So, again, I think we'd be very well positioned. And then in terms of other macro things going on, as I mentioned, the recent changes in CBER, all of our applications are in CBER. 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 saw in the placebo-controlled study. So I think we're sitting in a position that would not be affected good or bad by any of the changes going on in CBER. And as I mentioned, despite all the changes in FDA, everything remains on schedule for us, and we've observed no impact. I would say, well, there 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: Maybe if I could just ask a quick follow-up on that, this Cemetery. Has your pricing strategy changed at all due to any of the macro updates, or is everything stayed about the same?

Matthew Klein: 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: Great. Thank you, guys.

Operator: Our next question comes from Joel Beatty at Baird.

Chris: Hi. This is Chris on for Joel. Thanks for taking our question. Regarding betiquinone, 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: Yep. Thanks for the questions, Chris. I think we've talked about that there's about six thousand patients in the US with Friedreich ataxia, and we said about a third of them we believe would be in that pediatric bucket.

Operator: Our next question comes from Joseph Schwartz at Leerink Partners.

Jenny: Hi, guys. This is Jenny 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 to? Additionally, this market environment could be advantageous for companies like you guys who have cash on hand that could be deployed for the for BD. Are there any opportunities that you're actively pursuing or general areas might be interested in?

Thank you.

Matthew Klein: Thanks for the questions, Jenny. So answer to both is yes. We do have pipeline programs work that we've been working on. We disclosed some of them at the JPMorgan discussion, and we put a lot of effort just as we 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 our unique scientific platforms, including splicing, and our pherocytosis inflammation platform.

I think the experience with PTC 518 following on the heels of ARISD 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 slicing and do so safely. So we have a number of slicing programs that we're working on. That are at various stages of preclinical development that we're forward to moving into the clinic very soon, and we'll be detailing that soon.

We shared it at the JPMorgan conference that we have a program with a DOGDH inhibitor that we expect to be phase two 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, and we also have we shared an NLRP three, inhibitor program peripherally based that we're looking at for a number of potential indications where the NLRP three inflammasome has been intimately linked to disease pathology, more to come on all of that.

In addition, we are looking, as Pierre said, in business development opportunities and with things that we think that can complement our existing R&D portfolio and, as you know, business development is not a is sort of long-term proposition. So we've been working on it for a while. We have a number of different potential things that we're 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. And as we understand better our commercial portfolio later this year pending the regulatory decisions for Translarna for vutiquinone in the US. That will also help direct where we might move.

But know, the key part is we're looking at a number of different opportunities. And 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 portfolio.

Jenny: Thank you.

Operator: Our last question comes from Paul Choi at GS.

Daniel: Hi, this is Daniel on for Paul. Thank you for clarifying that you are mainly working with Cedar. But we still have a question regarding vadiquinone. You share any colors or feedback from the agency regarding the utilization for natural history for the approval, especially the long-term open label start part for MoveUpA. Thank you very much.

Matthew Klein: Thanks for the question, Daniel. As we've talked about, the comparison of our long-term data following Move FA with the robust Epic CMS of Fay Combs natural history databases as an important part of our confirmatory evidence. We, in fact, provided a comparison with the Move FA data long-term data to the FateCombs database where we were able to show a 50% slowing in disease progression over three years, then 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 significant multipoint slowing in disease progression, in that case over twenty-four months.

The I'll point out that the FACRS 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. FDA, of course, is familiar with the FA CMS registry because that was used as the confirmatory evidence as in the Scott Claris authorization back in 2023. So it's something they know well. And it's something that, I think many have called out.

So the State Homes registry as the type of natural history database that can support regulatory decision-making. So we're happy that it's we're grateful to the to FARA and the FA community and the patients who 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 etiquinone in both children and adults with Friedreich ataxia.

Daniel: Very helpful. Thank you.

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

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

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