Q1 2025 PTC Therapeutics Inc Earnings Call
Speaker Change: Ladies and gentlemen, thank you for standing by. Welcome to PTC Therapeutics First Quarter 2025
Speaker Change: 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.
Speaker Change: 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.
Speaker Change: Today's call will include forward-looking statements based on our current expectations.
Speaker Change: These statements are subject to certain risks and uncertainties and actual results may differ materially [inaudible]
Speaker Change: These reviews slide posted on our investor relations website in conjunction with the call, which contains information about our forward-looking statements
Speaker Change: and our most recent quarterly report on Form 10Q, an annual report on Form 10K, filed with the SEC.
Speaker Change: 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 four-looking statements
Additionally, we will disclose certain non-GAAP information during this call.
Speaker Change: Information regarding our use of gap-to- non-GAAP financial measures and a reconciliation of gap-to-non-gap are available in today's earnings release. I will now pass the call over to our CEO , Dr. Matthew Klein.
Speaker Change: Thank you all for joining today. Following the year about standing execution across every part of the company we're off to a great start in 2025.
Speaker Change: We achieved 190 million of revenue in the first quarter, made great progress on our preparations for the anticipated global launch of suffiance, and continued to work with regulatory authorities on our several pending approval applications.
Speaker Change: 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 flowbreak even
Let me begin with our revenue performance.
Speaker Change: We closed the quarter with 190 million in total product and royalty revenue with continued strong contributions from the DMD franchise.
Speaker Change: With this revenue performance, we are narrowing our 2025 full-year revenue guidance to 650 to 800 million. We expect a further narrow guidance pending regulatory actions and additional clarity upon and flaws of performance for the remainder of 2025.
Speaker Change: 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
Speaker Change: 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 name-patient programs.
Speaker Change: In the first quarter, we shared updated data from the ongoing suffiance long-term studies that continue to support the ability of suffiance to address all key patient-market segments and provide patients the ability to liberalize their diet
Speaker Change: The most recent analysis of affinity long-term extension data demonstrates that 97% of participants in the fee-tolerance study were able to increase their dietary fae intake.
Speaker Change: 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. [inaudible]
Speaker Change: We also shared results of the genetic variant analysis of the phase 3 affinity trial which demonstrated meaningful treatment effect in classical PKU subjects with non-BH4 responsive genotypes.
Speaker Change: Providing further evidence that suffiance can provide benefit to all disease sometimes.
Speaker Change: Discussions with the FDA on the Defiance 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 Defiance NDA review.
Speaker Change: As we have discussed, we believe we can achieve over 1 billion in revenue from suffiance, a significant revenue opportunity that will provide the foundation for PTC's future growth.
Speaker Change: Similar to the Suffcience NDA review, we have not seen any impact of recent FDA changes on our other approval applications [inaudible]
Speaker Change: FDA Review of the Ptikwanone NDA for the Treatment of Children and Adults of Fritrix and Taxi is progressing at the typical cadence for an application under priority review. The FDA is in the process conducting inspections, and we have been told that FDA does not plan to hold an ad comm meeting.
Speaker Change: For the Translana MBA, we have been receiving information requests and clinical site inspections have already been conducted [inaudible]
Turning to the PTC 518 Huntington Institute's program
Speaker Change: Yesterday, we announced positive top-line results for the Pivot HT Phase 2 study.
Speaker Change: The study met its primary endpoints of blood HCT lowering and safety.
Speaker Change: and the results on the full study population are consistent with the previously reported evidence of dose-dependent HCT lowering, favorable safety profile, and early signals of dose-dependent clinical effect at 12 months in stage 2 patients [inaudible]
Speaker Change: 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.
Speaker Change: Supporting that over a longer treatment period, we are seeing effects of HTTP lowering on multiple aspects of disease.
Speaker Change: We plan to complete additional analyses and look forward to discussing next development and regulatory steps, including the potential for accelerated approval.
Speaker Change: Finally, I want to highlight our strong catch position. We close Q1 with over 2 billion on our balance sheet.
Speaker Change: 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 flowbreak even without the need to access additional capital.
Speaker Change: 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 the Tiquinone and TransLarna. In addition, this cash position provides us with insulation from global macro uncertainties.
Speaker Change: 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: 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.
Eric Pauwels: 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. [inaudible]
Eric Pauwels: We delivered strong first quarter revenue of 134 million for our global DMD franchise, which resulted from our defense strategies to maximize trans-larter revenue in Europe and to successfully protect the inflows of business in the US.
Eric Pauwels: While we remain disappointed with the EC decision to withdraw Translarnas' marketing authorization in Europe , we have planned for the scenario for many months by working at a country level in Europe to identify pathways to continue to commercialize Translarnas.
Eric Pauwels: In fact, we already have confirmation from many countries in the EU seeking continued access to Translana via local reimbursement mechanisms. [inaudible]
Eric Pauwels: 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.
Eric Pauwels: In markets outside of Europe , we continue to receive orders in Latin America, Commonwealth of Independence States [inaudible]
Eric Pauwels: and the Middle East and North Africa regions. And we expect to see continued access to transplant therapy moving forward for both new and existing non-sensitization DMD patients.
Eric Pauwels: As Matt mentioned, the Translona NDA is currently under review by the FDA, and if approved, our experienced US team is prepared for a rapid and effective launch.
Eric Pauwels: As for influenza, quarterly net revenue remained 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.
Eric Pauwels: Moving to TechSetty, Enway Libra, we continue to grow these franchises in Latin America through patient identification efforts as well as geographic expansion in the region.
Eric Pauwels: For Abstaza and Cability, we continue to focus our commercial efforts in countries where patients are identified, including those countries with AADC deficiency founder effects.
Eric Pauwels: Now, turning to suffice, 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.
Eric Pauwels: 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 .
Eric Pauwels: Worldwide, there are approximately 58,000 addressable patients with PKU in markets where the clients could be reimbursed.
Eric Pauwels: We expect to roll out the global launches in 25 markets over the next 12 months, prioritizing the launches in Germany, the US, and Japan.
Eric Pauwels: Defiance is a highly differentiated therapy that we believe will deliver transformative outcomes for patients living with PKU.
Eric Pauwels: Our data have consistently demonstrated the significant and meaningful efficacy of surveillance in both classical and non-classical PKU patients, underscoring its broad commercial potential across the full spectrum of patients.
Eric Pauwels: Our research and in-person meetings with key healthcare providers indicate their understanding of the potential of suffiance to help more patients reach their dietary goals.
Eric Pauwels: Diet liberalization is a critical factor for PKU patients, physicians and pairs and is expected to drive early adoption of suffiance.
Eric Pauwels: Patients with PKU are often connected through social media when we see posts suggesting they are well informed about the benefits of suffice [inaudible]
Eric Pauwels: Now, moving to Vitykronone for Frederick's attack here, there remains a significant unmet need for children as well as adults with FA
Eric Pauwels: The ticklenones 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.
Eric Pauwels: In preparation for a potential launch, our team has worked to understand the different dynamics of the pediatric and adult patient markets.
Eric Pauwels: In the US, the estimated prevalence is approximately 6,000 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. [inaudible]
Eric Pauwels: Many other centers of excellence in the US also treat adult FAA 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. [inaudible]
David Lebowitz, David Lebowitz, David Lebowitz, David Lebowitz Inc
Pierre Gravier: With that, I will now turn the call over to Pierre for a financial update.
Pierre?
Thank you, Eric.
Speaker Change: I now share the financial highlights of our first quarter of 2025 .
Pierre Gravier: Beginning with Stopline Results Total products and royalty revenue for the first quarter was 190 million including DMD franchise revenue of 134 million [inaudible]
Starting with the DMB franchise.
Pierre Gravier: Translona, net product revenue in the quarter was 86 million, and then Plaza net product revenue was 48 million
Pierre Gravier: Boy Vizdi, Rocha Cheat, first-quarter global revenue of approximately $470 million dollars, resulting in royalty revenue of $36 million for PTC
Pierre Gravier: For the first quarter of 2025, non-GAAP R&D expense was 100 million excluding 9 million in non-cash stock based composition expense compared to 107 million for the first quarter of 2024, excluding 9 million in non-cash stock based composition expense
Pierre Gravier: Nonggap as DNA expands with 72 million for the first quarter of 2025
Pierre Gravier: Excluding 9 million in non-cash stock-based composition expense compared to 64 million for the first quarter of 2024, excluding 9 million in non-cash stock-based composition expense [inaudible]
Pierre Gravier: Cash, Cash's equivalent for marketable securities total, 2027 million as of March 31st, 2025, compared to 1,014 million as of December 31st, 2024.
Pierre Gravier: The 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 early efforts and explore business development opportunities to augment our commercial portfolio and pipeline.
Speaker Change: and then we now turn the call-over to the operator for Q&A. Operator? Hello?
Thank you for joining us.
[inaudible]
Speaker Change: Thank you. At this time we will conduct the question and answer session. As a reminder to ask a question you will need to press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question please press star 1-1 again.
David Lebowitz, John Bohnsack, John Bohnsack, John Bohnsack
Our first question comes from Kristen, 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 to science, 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 months away from the PEDUFA. 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? We've heard these.
Kristen Kluska: 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.
Eric Pauwels: 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 Scum [inaudible]
Speaker Change: Several rounds of label negotiations. We believe we're near the end. We buy through package.
Speaker Change: Insert Discussions, Cartoon Create, Patient Information, Lebowitz. So as you pointed out, things that are pretty far along in the review process. So, that gives us a great deal of confidence that one, the review was on track. I know there's been a lot of concerns with changes in FDA that could be an impact.
Speaker Change: 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 would typically not be done based on the Purdue for date, but we remain confident that... [inaudible]
Speaker Change: One of the approval and two, they're 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 seeder and the teams that we've been working with for all of our NDAs have appeared to be intact. Thank you very much.
Speaker Change: that contact people are saying the teams do the same. So, overall, no impact on the supply and send aid or any of other applications nor do we anticipate a technique. In terms of the second question before turn of the Eric, I'll just say this is just spinning the...
Eric Pauwels: 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 patient communicating from all different types. Those are on therapies those from therapy naive sharing their experiences and a lot of social media activity that I think is driving a lot of 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 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 re imagines PKU basically disease web site, where a lot of the patients health care providers families are engaging ville enroll in the program.
Eric Pauwels: And we see a very steady cadence of every week every month that number increasing.
Speaker Change: And as Matt said, there's really been no specific patient type that had been all patients there've been younger patients there has been a health care providers with.
Speaker Change: A bolus of patients that already ready to go and some of them are just really interested not only in sharing the information, but getting updates about the status of.
Speaker Change: Suffice ultimately when that will be approved so we're very pleased right now that a lot of the activity is going through social media and then channeling that through our disease awareness site. So we anticipate that that will continue and of course publications scientific information and all of that is shared widely as well.
Speaker Change: Thank you.
Speaker Change: Our next question comes from Eric Joseph at J P. Morgan.
Speaker Change: Hi.
Speaker Change: Good afternoon, thanks for taking the questions.
Speaker Change: Just on.
Speaker Change: Cepheid in Europe.
Speaker Change: Wondering if.
Speaker Change: Whether it's reasonable to expect any contribution to topline sales performance in 2025.
Speaker Change: And that you might actually see some pull through.
Speaker Change: Through named patient access programs, beginning in Germany, and then secondly.
Speaker Change: Now that you have obviously, a lots going on with <unk> with multiple new product launches.
Speaker Change: Our focus on cash flow breakeven that said just given the balance sheet I'm wondering whether.
Speaker Change: You can talk a little bit about sort of your.
Speaker Change: Appetite for a business development perspective areas that you might be focused it and whether it's sort of the broader pressure that we're seeing on valuations Mike.
Speaker Change: Kind of spur that activity, alright that interest a little bit.
Speaker Change: Further thank you.
Eric Pauwels: And thank you for the question Eric.
Speaker Change: On the first one yes, we absolutely expect to revenue in 2025 from Europe.
Speaker Change: As Eric alluded to we'll be ready to launch in Germany. Once we have the adoption of the opinion and we will also be leveraging other early access programs to garner revenue and 25 and as soon as possible I think this is.
Speaker Change: For us we have a well established global commercial infrastructure, including in Europe. Our teams are very well.
Speaker Change: Versed in launching products launching rare disease products and also understanding the country by country nuances in the country by country programs that enable us to accelerate revenue opportunities in cases, where we can ahead of formal pricing and reimbursement discussions.
Speaker Change: In terms of business development, let me turn it over and appear to talk a little bit how we're thinking about potential opportunities as we turn some cards over the rest of the year.
Speaker Change: Yes first of all we're very happy with our strong financial position of our <unk> in this environment WC gives us the flexibility to continue all our activities and not to worry about cash anytime soon Furthermore, in terms of BD, we're absolutely looking at business development opportunities both commercial.
And pipeline assets PTC has done historically.
Speaker Change: And obviously, we'll horning, one way or the other as we get further clarity on our portfolio.
Speaker Change: Great. Thanks for taking the questions.
Speaker Change: Our next question comes from Judah Frommer at Morgan Stanley.
Judah Frommer: Hi, Thanks for taking my questions guys.
Speaker Change: Maybe just following up on <unk>.
Speaker Change: Is there any indication you can give us of I guess relatively recent interest from the nutritionists community.
Speaker Change: Then are you able to delineate between commercialization efforts and ramp in Europe versus.
In the U S and what's being done differently in each thank you.
Speaker Change: Yes, thank you for the questions.
Speaker Change: Let me just start by saying that our entire launch plan, how does the pad nutritionists and dietitians intimately involved.
Speaker Change: I appreciate that patient centers of excellence have physicians.
Speaker Change: Clearly important role for patient management, but sodium nurse practitioners and nurses and dietitians are off on the frontline of contact with patients who aren't on a therapy diet management is such a key part of the PKU piece.
Speaker Change: Patient daily life. So we've done a lot of work to make sure that we understand.
Speaker Change: The needs of nutritious hear from them.
Speaker Change: 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.
Speaker Change: The commercialization of suppliers.
Eric Pauwels: Yes, interestingly enough, we will be launching both in Germany, and the U S. In a very similar timeframe and 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 two centers have opted in to our disease webs.
Eric Pauwels: This 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 and these patients will be available at commercial law.
Eric Pauwels: Launch.
Eric Pauwels: Immediately once we ended up launching in pricing the product in Germany. So we believe that the U S and Germany will be very significant contributors to revenue in the second half of 2025.
Eric Pauwels: Thanks.
Eric Pauwels: Yeah.
Eric Pauwels: <unk>.
Eric Pauwels: Our next question comes from Brian Abrahams at RBC.
Speaker Change: Hi, This is Joe on for Brian Thanks for taking my question.
Eric Pauwels: Just wanted to ask on Huntington's.
Eric Pauwels: You've had a little more time to look at the data and do you have any updated thoughts on how to best balance accelerating potential approval timeline and maximizing the chances of demonstrating drug benefits clearly any thoughts on how you could potentially shorten the approval timeline like interim read at a certain percentage of patients.
Eric Pauwels: I would be very helpful. Thank you.
Eric Pauwels: Yeah, Okay. Thanks.
Speaker Change: Thanks, Joe for the question is where it hasnt been that much time, we have been a little busy but I will say that our impressions of the data from yesterday remain very similar.
Speaker Change: We were very pleased with the results. When you look at this in terms of the phase III 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 in 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 free drug exposure.
Speaker Change: <unk> in the plasma.
Speaker Change: The job, it's demonstrating itself to be safe and well tolerated and we're seeing signals. Both are important clinical and biomarker effect over at 12 months added 24 months that confirm that things are moving in the exact direction they need to and finally I'll add.
Speaker Change: A lot of questions about the <unk> pacings and what does that do to our thoughts about the program that was incredibly important learning to make one of the important hypothesis of the pivotal <unk> trial is that stage two patients may be optimal clinical trial population. So let me just make clear clinical trial population is different than that.
Speaker Change: Patient population, who will drug may ultimately benefit, it's a population in whom over the.
Speaker Change: Typical length of a clinical trial, you are well positioned to show that you are modifying disease progression.
Speaker Change: And strong enough way that you can meet and <unk>.
Speaker Change: I can see endpoint and we've talked a lot about being concerned that seems to patients may be so advanced.
Speaker Change: Very difficult to capture modification in a population that was our hypothesis going into pivotal HD and that was proven out. So that's a very important learning as we think about the next stage in development now that that stage. Two population is likely the optimal one and can we can establish efficacy in terms of accelerated the task.
Speaker Change: We continue to believe that.
Speaker Change: We've demonstrated that we are lowering http levels and our discussions with the agency.
Speaker Change: Indicating that theyre aligned scientifically that HTC lowering its likely to predict clinical benefit and 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 things in stage two that they should be driven by.
Speaker Change: Tms S TMT and as we moved up to 24 months, we're now able to show additional associations with significant effect relative to natural history of disease rating scale and the dose dependent lowering of Nfl's, which now provides biological evidence of potential neural protection, which really again supplements. This concept that hcg.
Speaker Change: Laura is associated with favorable things that in the long term can result in.
Speaker Change: And efficacy in an efficacious therapy for Huntington disease patients. So again, we're we're very much where we were yesterday and our view of the data and look forward to discussions with Novartis as we chart additional steps.
Speaker Change: In terms of its regulatory discussions and further development plans I would say the only thing thats come between yesterday and today is a lot of outreach from patients and kols during their enthusiasm for the data, including experts like Dr. Ed Wild is probably one of the main experts and Biomarkers of <unk>, who is incredibly enthusiastic about the NFL data in <unk>.
Speaker Change: Lowering in the safety and Tolerability. So if anything what we've heard from outside has increased our belief of the strength of this data set for this disease.
Speaker Change: Our next question comes from Kelly She at Jefferies.
Speaker Change: Currencies are there for Kelly I have a question about <unk>, specifically on dial liberalization Portsmouth volumes.
Speaker Change: I Wonder if you could please remind us how you can leverage your findings for payer reimbursement purposes, especially with where patients who respond to generic standard of care in other words whats the clinical utility and your view of even higher Dio liberalization of that could support reimbursement in this segment with minimal payer pushback.
Speaker Change: Okay. Thank you very much for the question Jose Let me, let me just give a overview.
Eric Pauwels: One quick overview, and then I'll, let Eric go into detail of it about the Payor dynamics and the importance of <unk>.
Speaker Change: The tolerance.
Speaker Change: David I think the tolerance is something that's very important to patients is incredibly important for patient uptake physician updating and as you pointed out as a role.
I think one of the things to point out is that the data our data have shown in the clinical studies and it's also based on mechanism that patients who may be enjoying.
Speaker Change: Benefits of.
Speaker Change: <unk> four therapy branded or generic.
Speaker Change: Going to have a greater amount of lowering with secret Teri that's something we saw in our clinical trial would be 27 subjects, who came into the trial.
Speaker Change: Separate taryn.
Speaker Change: And again, it's it makes sense mechanistically when you consider that we're able to get much greater intracellular concentrations.
Speaker Change: BH for CPA Taryn administration, and SAP are tailoring administration, and then of course for those who are not considered to be BH for responsive or have mutations that are considered to be not meeting for responsive we've been able to show that we have been able to have a significant effect not only in terms of phenylalanine lowering.
Speaker Change: But also in terms of your ability to allow patients to have that liberalization and that includes the more severe classical PKU patients and in a lot of the patients who are in that therapy naive bucket Eric.
Eric Pauwels: Eric do you want to talk a little bit how we're thinking about.
Speaker Change: The few tolerance data in terms of the.
Speaker Change: And discussions indices.
Speaker Change: Yes, thanks for the question and in fact, we actually have presented.
Speaker Change: AMC, we don't see it but we also presented all the data lives and we've also tested in market research with a number of key U S payers, both commercial and government.
Speaker Change: The first thing we 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 for each ingalls is in <unk>.
Speaker Change: Presses and in addition to that the diet liberalization is one of the things that really triggers there.
Speaker Change: Appetite, if you will to say that the product is highly differentiated and superior too.
Speaker Change: Kuban as it stands.
Speaker Change: And we've actually press and looked at the various things in terms of potential steps or prior authorizations, we believe there'll be prior authorizations to label and only naive patients might be going through steps because the vast majority of patients and 90% of the patients in the U S are not on any kind of current medical.
Speaker Change: Treatment, which means more than more than half or more have actually tried and failed. So we'll be able to avoid many of those because dolby prior the prior authorizations will allow for clinical information on the patient and if we have to go through step edits theyre very short so so far the payers.
Speaker Change: The dynamics have been very favorable and we will continue to test that.
Speaker Change: We engaged and become closer to the launch.
Speaker Change: Very helpful. Thank you.
Eliana Merle: Our next question comes from Eliana Merle at UBS.
Speaker Change: Jackman time for Ellie. Thanks, so much for taking our questions and congratulations on the progress.
Speaker Change: Let's talk about on <unk> Plaza. So what have you been seeing in terms of volume growth.
The generic approval opened but do you expect to see here going forward. This year and can you talk about some of your strategy to defend the brand against generic erosion. Thank you.
Eric Pauwels: Thanks for the question. Thanks for the question, Jonathan Let me just turn it over to Eric.
Speaker Change: We're very proud of the continued and plaza.
Eric Pauwels: Performance through the first quarter and really a testament to terrific efforts by our teams Eric.
Eric Pauwels: The teams have continued to if you will garner brand loyalty from the Duchenne community I mean, I think the secret sauces, we've been with them for the last eight years.
Eric Pauwels: 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 do same patients that while we have seen some generics come in.
Eric Pauwels: 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 because it's unclear for us whether the generics are rebating at a higher rate.
Eric Pauwels: We do expect some erosion will continue to expect the erosion is more generic entrants come in but 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.
Eric Pauwels: 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 patients and thats been the secret sauce.
Eric Pauwels: Great. Thank you.
Eric Pauwels: Okay.
Our next question comes from Geoff Meacham of Citigroup.
Eric Pauwels: Alright.
Eric Pauwels: Thanks.
Speaker Change: Just had another one on the diet liberalization in PKU I guess more of a commercial one though.
Speaker Change: How rapidly do you think real world use could reflect this I wasn't sure what what success looks like in the U S.
Speaker Change: And then are there differences when you think commercially between the European and Japanese market.
Speaker Change: Just on this topic. Thank you.
Speaker Change: Thanks very much for the question.
Speaker Change: And when you think about it.
Speaker Change: Commercially you mean, instead of a real lifecycle drug is out there and being taken by my 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 liberalized their diet, whether it's a small amount of liberalization.
Speaker Change: Complete liberalization OE from the diet.
Speaker Change: <unk> is not has not only.
Speaker Change: Benefits to them in terms of daily life, but also.
Speaker Change: Have other important benefits, especially the kids in school in terms of socialization.
Speaker Change: And peer to peer interactions. So I think this plays out very well.
Speaker Change: Not something that is actively monitored in the commercial setting, but it is something that we know.
Speaker Change: That is going to be important for patients to try it and this is part of the reason for the earlier question. We've been working so closely with dietitians and nutrition.
Speaker Change: Yourself therapists to help manage things appropriately so patients can liberalized their diet and are very thoughtful rational way. So they are set up for success and congratulate do so so.
Speaker Change: Those that can get to a full liberalization relabel get there those that can get some liberalization and do that and help understand if it's the case that they can have their lunch at school now in state with the other kids and have a typical luncheon and maybe have less protein that other meal. So all of that are things that will play out in a commercial setting and is why we see.
Speaker Change: Staffed our medical team and are working so closely with nutritionists and the expert centers.
Speaker Change: If you have any additional comment on differences in Japan or <unk>.
Speaker Change: Sure.
Speaker Change: No we haven't actually seen any differences and in fact, I think guy's liberalization of you've been well embraced by our health care providers, obviously are Europe and Japan. There is patient information that is out there on PKU, but physicians really drive a lot of that education, they're incredibly impressed with diet liberalization and dieticians have embraced.
<unk> is one of the reasons to really revolutionize or really transform the way patients not only socialized lives, but importantly, they have to change their diet. It from for a 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.
Speaker Change: Presses.
Speaker Change: Our next question comes from <unk> Ahmad Bank of America.
Ahmad: Good afternoon, guys. Thanks for taking my question.
Ahmad: For me I just wanted to ask another question on free drugs can you just clarify for us.
Ahmad: What doctor feedback is on the under Matt need. So if you are able to get approved in this indication what would prevent let's say every person from being put on it and then secondly on your comments about FCA coming back and saying that.
Ahmad: You should not expect to have an ad com.
Ahmad: Is that based on discussions you've had specifically with the agency and agency.
Ahmad: Data itself, it's clear enough or is there a different reason why at the time, they're not planning on holding an AD com. Thanks.
Speaker Change: Thank you very much for the questions. Let me start with the second one.
The communication of that not having an AD comm was something that was raised by the agency at our mid cycle meeting.
Speaker Change: That was held.
Speaker Change: Last month.
Speaker Change: And at this point in the review they don't see a need.
Speaker Change: I expect to hold the icon meeting they didn't give any further detail on that and as we've said all along we believe the agency understands the disease understands the endpoints both from their experience with the squad Claris review as well as a number of other.
Speaker Change: <unk> active therapies in development. So I think they are very long conversations and in our discussions regarding a particular packages become very clear that they understand the <unk> endpoint. They understand the dynamics involved with upright stability. They understand the long term registry that was an important part of our confirmatory evidence. So we were not surprised by.
Speaker Change: The decision to not hold the AD com.
Speaker Change: In terms of accessing populations I think look credit.
Speaker Change: There is nothing available for patients under the age of 16, and Thats certainly a population where we've been able to show benefit as well as safety and the trials, we have safety data with particular now going down to <unk>.
Speaker Change: Children less than one year of age and we haven't been experiencing adult populations as well and so I believe that we have the opportunity to be.
Speaker Change: Therapy, not only for for children, who don't have alternatives now, but also to be a safe and additional.
Speaker Change: Essential synchrony, well tolerated and effective therapy for adults, Eric I don't know if you.
Speaker Change: Once you can provide any more color on what we can.
Speaker Change: The work that your team has been doing in terms of understanding yes.
Speaker Change: Yes. Thanks for the question to the <unk> I mean, our teams have been very active we've been in pediatric neurology now for over eight years, we understand the dynamics in these children's hospitals, where the vast majority of patients are either diagnosed are treated.
Speaker Change: Feedback is obviously, great a very high unmet need the burden of illness. The disability of the Comorbidities in children is very very high there's no approved therapy and when physicians in particular, particularly the pediatric neurologist see the profile very convinced and we believe there'll be a rapid uptake, but in addition, a lot of them are.
Speaker Change: Treating adults.
Speaker Change: That said, we believe that this is going to be a broad use especially for patients who are naive and not have been on <unk> therapy, or those who are poorly controlled or dropped out. So the opportunity is very large and the first thing that our health care provider C is the efficacy and efficacy that is at least as good or currently over there with the current treatment available.
Speaker Change: But the safety profile is the big winner here, because it's very safe and there is very limited or no monitoring involve particularly for children and they all recognize that there is 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.
Speaker Change: And 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 in preparing the market for the launch of a particular loan.
Gena Wang: Our next question comes from Gena Wang of Barclays.
Speaker Change: Hi, This is <unk>. Thanks for taking our question. So I have a question for Translarna. We know about you have agreements with ex EU countries based on the EU approvals. So in light of the EC withdraw decision.
Speaker Change: You could you share with us the status and the expectation in ex EU countries and the houses tenable the revenue would it be.
Eric Pauwels: Thank you very much for the question Eric.
Speaker Change: Erik pointed out.
Eric Pauwels: Even in EU.
Speaker Change: The European commissions.
Speaker Change: Hi.
Directive.
Speaker Change: To use articles one seven an article five for individual countries in Europe to continue to make commercial product available. We are still able to generate revenue is in Europe. So I just wanted to emphasize that as Eric said in his presentation.
John: And then John.
Speaker Change: I want to talk about what we're seeing outside Europe, which has been virtually no impact.
John: Yes, theres been absolutely no disruption.
John: Especially in Latin America, we've already negotiated a contract with Brazil, we've begun shipping product in Brazil.
John: These are group purchase orders that we'll be shipping the natural cadence over the course of the year.
Speaker Change: Mahler, Matt Latin American markets as well.
Speaker Change: 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 reimburse trans lineup within Europe.
Speaker Change: Yes. Thanks for that is really helpful and the last one we also want to go back to Huntington's disease State. How you reported yesterday. So in 24 months data you compare to the results with our natural history controls, but we noticed that to use that to defend the references so in the functional.
Speaker Change: Outcome compared to that of your data with you roll HD disease registry at for El Nino Raw filament light you compare to the data with <unk>.
Speaker Change: Lancet publication, so could you share with us what's the rationale when selecting the natural history controls and why do you use different referenced datasets.
Speaker Change: Yeah. So let me 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 20000 entrance and allowed us to get a robust <unk>.
Speaker Change: <unk> matched comparator population, so that we could really understand the benefit we were observing with with PTC 500 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 Laurie.
Speaker Change: NFL and referred made reference to and that the.
Speaker Change: The most recent natural history publication from parking in the group in London, showing that in stage two patients.
Speaker Change: <unk> tends to be an increase an increase in NFL of about 12, 5% per year.
Speaker Change: There is there are registries that have.
Speaker Change: <unk> data such as track HD and others and we will go ahead and look at that but we wanted to just <unk>.
Speaker Change: Communicate the concept, which has been consistently shown at every study that over the course of time NFL increases in HD patients and we wanted to give a reference to the magnitude as most recently reported that the state specific patients, but the only direct matched comparison was done for the functional outcomes that generated the comparative values and the P value.
Speaker Change: Showing no evidence of significant stock relative to that matched natural history on the on the sea.
Speaker Change: <unk> T.
Speaker Change: TFC as well as the DMT scales.
Speaker Change: That's all really helpful. Thanks, so much.
Speaker Change: Okay.
Speaker Change: Our next question comes from Peyton Brown sack at TD Colin.
Peyton Brown: Hi, guys. Good afternoon, thanks for taking our questions.
Speaker Change: I guess kind of in a more broad sense can you talk about any impacts of the global macro factors, we've been seeing over the past couple of weeks would influence your financial guidance.
Speaker Change: Such things as like tariffs will be magnet manufacturing executive order yesterday or most favored nation and then how that would impact your decision to conduct business development going forward. Thank you.
Peyton Brown: Thanks for the question Peyton.
Speaker Change: Look I well none.
Speaker Change: 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.
Speaker Change: So that was the most favorite nation.
Speaker Change: So far I've been around maybe Medicaid there is a bill that Holly and others are Greenfield car. So we don't have a crystal ball, but let's just start with the tariffs we expect to have minimal impact.
Speaker Change: On our business for a number of reasons, particularly for our U S products. The IP is domiciled in the U S. So it's there's no transfer pricing is the product remains.
Speaker Change: All of them throughout so any potential tariff would be on cost of goods it would be quite quite minimal impact to our business.
Speaker Change: Similarly on most favored nation as Eric alluded to we're very thoughtful about establishing our pricing corridor, that's something we do.
Speaker Change: Independent of MFN situation to ensure that we're getting the maximum value.
Speaker Change: 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, we've got.
Speaker Change: The recent changes in <unk> all of our applications are in Cedar all of our pending applications and relying on clinical efficacy from a clinical trials both.
Speaker Change: Placebo controlled as well as in.
Speaker Change: In each case longer term studies that confirm the benefit we saw in the placebo controlled studies. So I think we're sitting in a position that is not would not be affected good or bad by element changes going items can seeber and as I mentioned, despite all the changes at FDA everything remains on schedule for us and what we've observed.
Speaker Change: So no impact so I would say there's been a great deal of macro.
Speaker Change: Things, a great deal of anxiety and uncertainties, but we.
Speaker Change: We're pretty well insulated from from each of them.
Speaker Change: Maybe if I could just ask a quick follow up on that.
Karen has has your pricing strategy changed at all due to macro updates or is everything stayed about the same.
Speaker Change: No we have no changes in our strategy again.
Speaker Change: Our strategy anticipates a lot of these things prior to even the introduction of <unk>.
A discussion of legislation on orders or anything like that.
Speaker Change: Great. Thank you guys.
Speaker Change: Our next question comes from Joel Beatty at Baird.
Speaker Change: Hi, This is Chris on for Joel Thanks for taking our question.
Speaker Change: Regarding particular, now and just getting maybe a little deeper into the patient breakdown.
Speaker Change: Are you able to provide.
Speaker Change: Some general color on the percentage of patients Youre anticipating will come from that that pediatric 16 and under population versus adults.
Speaker Change: Yeah.
Speaker Change: Yes.
Speaker Change: Thanks for the questions Chris.
Speaker Change: Talked about that.
Speaker Change: 6000 patients in the U S with Friedrich.
Speaker Change: <unk> ataxia, and we said about a third of them, we believe we'd be in that pediatric bucket.
Speaker Change: Our next question comes from Joseph Schwartz Leerink partners.
Speaker Change: Hi, guys. This is Jenny I think Joe Thank you for taking our question.
Speaker Change: The majority of your products and candidates are either approved or other regulatory approval of stage of development with Sanchez PTC 518.
Speaker Change: I'll just say that.
Speaker Change: And that pipeline gap and a little less going on in terms of earlier stage development at least your 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. You have cash on hand that could be deployed 58 for BD are there any opportunities that you are actively pursuing.
Speaker Change: Our general areas you might be interested in thank you.
Speaker Change: Thanks for the question Jami so.
Speaker Change: The answer to both is yes.
Speaker Change: We do have.
Speaker Change: Pipeline programs and working with that we've been working on we disclosed some of them at the Jpmorgan discussion. So we 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.
Speaker Change: Programs to ensure that we're leveraging our unique scientific platforms, including splicing.
Speaker Change: Our fab business inflammation platforms, I think the experience of PTC five eight following on the heels of a <unk> 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.
Speaker Change: Favorably affect splicing.
Speaker Change: Are those basically.
Speaker Change: So we have a number of splicing programs that we're working on.
Speaker Change: That are at various stages of preclinical development that we look forward to moving into the clinic very soon it will be detailing them soon.
Speaker Change: Sure.
At the Jpmorgan conference that we have a program with a <unk> inhibitor that we expected. These phase two ready by the end of the year that we're looking at for a number of different neuro inflammatory.
Speaker Change: Indications given the importance of <unk> two.
Speaker Change: Pharma Tory response, and we also have we shared NLP three inhibitor program Thats peripherally base that we're looking at for a number of potential indications, where the NLRB III and swam ozone has been intimately linked to disease pathology, but but more to come at all that in.
Speaker Change: In addition.
Speaker Change: RF looking at peer set and business development opportunities.
Speaker Change: Things that we think that can complement our existing R&D portfolio and as you know business development is not.
Speaker Change: It is just sort of a long term proposition. So we've been working on us for a while we have a number of different potential things that we're looking at that if some are earlier stage, some or even commercial stage summer.
Speaker Change: 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 <unk>.
Speaker Change: Translarna from particularly on the U S that will also help direct where we might move but.
Speaker Change: The key part is we're looking at about a number of different opportunities and as we always have we will continue to be very strategic and how we think about utilizing business development to supplement the R&D and our commercial portfolios.
Speaker Change: Thank you.
Speaker Change: Our last question comes from Paul Choi at Ges.
Speaker Change: Hi, This is Daniel on for Paul. Thank you for clarifying that you're mainly looking with cedar, but we still have a question regarding <unk> could.
Speaker Change: Could 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 the move up a thank you very much.
Speaker Change: Thanks for the question Danielle.
Speaker Change: So as we've talked about the comparison of our long term data following move FAA with so.
The robust <unk> homes. Its natural history database is an important part of our confirmatory evidence. We in fact, providing a comparison with the move FAA data long term data to the <unk> database, where we were able to show a 50% slowing.
Speaker Change: In disease progression over three years, and then we did a similar comparative analysis.
Speaker Change: From a long term study of a previously conducted placebo controlled study in adult spoke.
Speaker Change: Ambulatory and non ambulatory, where we again, we demonstrated a significant multiple.
Speaker Change: Multi point slowing and.
Speaker Change: Disease progression in that case over 24 months.
Speaker Change: I'll point out that the Facs registry is probably one of the most robust rare disease registries by this has been established by Farah and they've done an incredible job of ensuring a reliable.
Speaker Change: <unk> network of centers that contribute high quality data to.
Speaker Change: This registry.
Speaker Change: With frequent assessments that allow for a gradual or comparison with data that we would collect in our clinical studies. The FDA of course is familiar with the FAA Crs registry because that was used as the confirmatory evidence as Scott Claris authorization.
Speaker Change: In 2023, so it's something they know well and it's something that I think many have called out the stakeholders registry is the type of natural history database that can support regulatory decision making.
Speaker Change: We're happy to do that.
Speaker Change: In April to the deferral of the FAA community and the patients who contributed their data to that registry because it really.
Speaker Change: It allows us to inform a really important.
Speaker Change: Really important data point, which is the long term benefit we see with particularly on in both children and adults with <unk> ataxia.
Speaker Change: Very helpful. Thank you.
Speaker Change: This concludes the question and answer session I would now like to turn it back to Dr. Matthew Klein for closing remarks.
Speaker Change: 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 our continued successes in 2025 and beyond Thank you again.
Speaker Change: Thank you for your participation in today's conference. This does conclude the program you may now disconnect.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Yes.