Q1 2024 PTC Therapeutics Inc Earnings Call

Participants

Jane Hanlon; Associate Director, Investor Relations; PTC Therapeutics Inc

Matthew Klein; Independent Director; PTC Therapeutics Inc

Eric Pauwels; Chief Business Officer; PTC Therapeutics Inc

Kylie O'Keefe; Chief Commercial Officer; PTC Therapeutics Inc

Pierre Gravier; Chief Financial Officer; PTC Therapeutics Inc

Christian Donado; Analyst; Cantor Fitzgerald

Eric Joseph; Analyst; JPMorgan Chase & Co

Kelly Shi; Analyst; Jefferies LLC

Sami Corwin; Analyst; William Blair

Presentation

Operator

Good day, and thank you for standing by, and welcome to PTC's first-quarter 2024 financial results conference call. (Operator Instructions)
Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Jane Hanlon, Associate Director of Investor Relations. Please go ahead.

Jane Hanlon

Good afternoon, and thank you for joining us today to discuss PTC Therapeutics's first-quarter 2024 corporate update and financial results. I am joined today by our Chief Executive Officer, Dr. Matthew Klein; our Chief Business Officer, Eric Pauwels; our Chief Commercial Officer, Kylie O'Keefe; and our Chief Financial Officer, Pierre Gravier.
Today's call will include forward-looking statements based on our current expectations. Please take a moment to review the slide posted on our Investor Relations website in conjunction with the call, which contains our forward-looking statements. Our actual results could materially differ from these forward-looking statements. As such, statements are subject to risks that can materially and adversely affect our business and results of operations.
For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10-Q, and annual report on Form 10-K filed with the Securities and Exchange Commission, as well as the company's other SEC filings. We will disclose certain non-GAAP information during this call. Information regarding our use of GAAP to non-GAAP financial measures and a reconciliation of GAAP to non-GAAP are available in today's earnings release.
With that, let me pass the call over to our CEO, Dr. Matthew Klein. Matt?

Matthew Klein

Thank you, Jane, and good afternoon and thank you all for joining the call. I'm pleased to share with you our first-quarter 2024 financial results and to provide an update on the progress of our development programs. As we have discussed, 2024 will be a year of execution for PTC, with a number of important and value inflection milestones throughout the year. We are off to a great start with strong revenue and achievement of all of the planned first-quarter regulatory and clinical milestones.
Starting with commercial performance, we had a great quarter driven by execution across the entire commercial portfolio. First-quarter revenue totaled 210 million, and DMD franchise revenue was $161 million first quarter DMD revenue resulted from our team's efforts to ensure that we optimize revenue during the time that Translarna remains authorized in Europe. At this time, the European Commission has not yet adopted a CHMP opinion to withdraw Translarna authorization, and thus we will continue to commercialize Translarna across Europe. Eric and Kylie will provide additional details on our commercial performance shortly, we had a number of important regulatory achievements in the first quarter as planned, we submitted the marketing authorization application for CP adherent to the EMA, and we remain on schedule to submit the NDA for CP apparent no later than the third quarter. European MAA submission is an important step towards our planned global launch of CP. tariffs as we bring a potential new standard of care to PKU patients around the globe.
As emphasized recently by Lisa Milberg, the Executive Director of the National PKU alliance, the vast majority of PKU patients are not served by the currently available PKU therapy. And there was a great deal of enthusiasm in the PKU community for CP at Heron based on the data generated to date, including the reported patient experience in diet liberalization in the first quarter, we also submitted the BLA for data and we aligned with the FDA on an NDA resubmission for Translarna and an NDA submission for a particular note for treatment of Friedreich's ataxia. The NDA resubmission for Translarna will be based on the placebo-controlled results from Study 41 and data from the STRIDE registry, which confirm long-term benefits of Translarna in slowing time to loss of ambulation, we expect to submit the NDA in mid 2024, of particular note NDA will include results from the 72 week placebo-controlled portion of the move FA trial, along with data from those trials long-term open-label extension. We expect to submit this NDA in late 2024.
Turning to our development programs, we plan to share interim results from the pivotal HD. study of PTC. five iA in Huntington's disease patients in the second quarter. This data update will include 12 month biomarker and clinical results from the initial cohort of approximately 30 subjects on whom we shared data last summer. Specifically, we will share data on blood Huntington protein, lowering CSF mutant Huntington protein, lowering volumetric MRI changes and NfL levels, as well as data on several clinical scores, including the Total Motor Score, total functional capacity and CUHDR. These 12-month data will allow us to understand the longer-term safety and tolerability profile of PTC. five one eight as well as to identify favorable early signals of CNS activity on disease biomarkers or clinical endpoints.
Second quarter update will also include 12 week results for a larger number of Stage two and Stage three subjects, including blood Huntington protein change. Lastly, we completed enrollment in the Cardinal registration directed trial of future losses that in ALS patients and remain on schedule to report top line results in the fourth quarter of this year due to losses. That is the first compound being developed for ALS that specifically target therapy, ptosis pathway of oxidative stress and cell death demonstrated to be highly relevant to ALS pathology. Given the recent changes in the therapeutic landscape for ALS, positive results from the CARDINAL study could enable mutual access that to address the significant unmet need of ALS patients.
In closing, I am proud of our team's execution in the first quarter. We achieved all of our planned objectives and remain on schedule to achieve the many important expected milestones in 2024.
I will now turn the call over to Eric and Kylie to discuss our commercial performance.
Eric?

Eric Pauwels

Thanks, Matt. Our global customer facing team has kicked off 2024 on a strong footing and has delivered $178 million in revenue for our five marketed products. Our team is focused on growth as well as diversification within our current commercial portfolio and on executing the launch preparations for it stays in the U. S and for safety at Terra and globally, our global DMD franchise had a robust quarter, while our geographic expansion continues to progress in Latin America and the Middle East and North Africa and our future growth markets in the Asia Pacific region, we delivered revenue of $161 million, which resulted from our strategies to continue to maximize Translarna revenue in Europe and to successfully protect the Emflaza business in the US for Translarna, we achieved 104 million in revenue this quarter. The team continues to work to ensure that Translarna patients in Europe continued to receive treatment evaluations of local country pathways and named-patient sales for continued access to treatment are ongoing.
Now turning to Emflaza. Quarterly net revenue was $57 million, which reflects our strategy to protect the brand in the face of initial generic entry. Robust Emflaza sales were driven by continued brand loyalty from health care providers and patients with a significant number of new patient starts on implants. We continue to work closely with health care providers, payers, specialty pharmacies and advocacy groups to reinforce the benefits and the value of Emflaza while reemphasizing our exclusivity for two to five year old DMD patients.
Now I will ask Kylie to update the progress of our current and future new product launches filing.

Kylie O'Keefe

Thanks, Eric. We continue to plan for our global launch, except the apparent following the recent submission of the NDA in the U.S. and the planned NDA submission to the FDA later this year, as well as additional regulatory submissions in Brazil and Japan in 2024. As Lisa Milberg, the Executive Director of the National PKU alliance recently stated there is a significant unmet need for PKU patients there is widespread recognition amongst metabolic specialists, geneticists dietitians and PKU patients of the potential of Serbia Taryn to meet the significant unmet need as we saw for numerous patients in the AFFINITY trial, classical PKU patients as well as those unresponsive to and poorly controlled on Kuvan could potentially do significantly better onset diabetes care. And importantly, we continue to see durability of treatment effect and the ability for patients on therapy adherence to increase their dietary protein intake beyond the recommended daily allowance, while still maintaining control of phenylalanine levels in the ongoing AFFINITY long-term extension study, PKU patient advocacy groups around the world have shed that PKU patients have been waiting for a therapy like that. The apparent that combines efficacy through fee reduction and a potential ability to liberalize their incredibly burdensome. They restricted diet to improve their quality of life. We continue to believe in the potential $1 billion plus global opportunity.
Now turning to UPS data, the first and only approved gene therapy infused directly into the brain where we continue to see transformative results.
As Matt mentioned, we submitted our BLA to the FDA in March and launch. Preparations in the US are well underway, and the customer-facing team is incredibly excited to bring this much-needed treatment to AADC patients in the US.
In Europe, we treated new patients in France and the UK as well as treating new cross border patients in the quarter. In February, data from the GTO. two study was presented at the ISPMD. Congress that showed significant uptake of CSFHBA. and F. data after eight weeks after administration of UPS data translating into dopamine production and improvements in common symptoms such as hypotension globally, patient identification, treatment center readiness and access and reimbursement discussions continue to advance as we prepare for additional filings and regulatory approvals. Moving to Texas City and Waylivra in Latin America. We continue to make excellent progress across this franchise with growth in both patients identified and patients treated across the region. In Brazil, we completed delivery of the new group purchase order for Waylivra and anticipate receiving a group purchase order for take study shortly. Our strategy for geographical expansion continues with additional regulatory filings planned and approvals anticipated for both products.
In conclusion coming offer BOSS first quarter, we have set a strong trajectory for 2024 and are well positioned to continue to deliver and diversify our portfolio across our geographies as well as to execute our global launch strategy for SAP at Heron point-of-sale.
I will now turn the call over to Pierre for a financial update. Pierre?

Pierre Gravier

Thank you. Kindly are now share the financial highlights of our first quarter of 2024. Please refer to the earnings press release issued this afternoon for additional detail beginning with top-line results. Total revenue for the first quarter was 210 million, including DMD franchise revenue of 161 million. Starting with the DMD franchise. Translarna net product revenue in the quarter was 104 million for Emflaza net product revenue of $57 million.
Moving to heavy first quarter global revenue of about USD14 billion was achieved by was earning royalty revenue of $31 million for PTT, non-GAAP R&D expense was $107 million for the first quarter of 2024, excluding $9 million in noncash stock-based compensation expense compared to $180 million for the first quarter of 2023, excluding $15 million in noncash stock-based compensation expense. The year-over-year reduction in R&D expenses reflects our strategic portfolio prioritization as the Company continues to focus its resources on its differentiated, high-potential R&D programs, non-GAAP SG&A expense was $64 million for the first quarter of 2024, excluding $9 million in noncash stock-based compensation expense compared to $73 million for the first quarter of 2023, excluding $14 million in noncash stock-based compensation expense. This expense reduction reflects lower employee cost as a result of the reduction in the workforce. Cash cash equivalents and marketable securities totaled $885 million as of March 31st, 2024, compared to $877 million as of December 31st, 2023. The strong balance sheet provides PTC with the resources to execute on our strategy and to achieve our milestones over the next several years, including the anticipated to Catarina, and I will now turn the call over to the operator for Q&A. Operator?

Question and Answer Session

Operator

(Operator Instructions) Christian cost cluster, Cantor Fitzgerald.

Christian Donado

Your line is now open by everyone.
Thanks for taking the product there. On PKU. I know you've gone at Layne's multiple times with us talking about this segment of where the highest unmet need we need remains. But I'm wondering initially if you think there is a specific market segment where you'll see the uptake being the strongest. So one thing we weren't up indicating that our tax rate ticked up, I think basins under 18 for example, is a really critical market in the Gulf.

Kylie O'Keefe

Christian, thank you very much for the question. We have talked a lot about how a strong data set, both from affinity as well as from the long-term extension, including the Phe tolerance data, really position us well to address all of those key market segments. And that's why we really see this as such a large opportunity from the topline even being a $1 billion plus opportunity.
Let's highly go into a little bit more detail about what we see is sort of the initial segments that we're positioned to penetrate.

Pierre Gravier

Yes.
Thanks, Matt. And thanks, Kristen, for the question. I think as Matt highlighted, that truly is an opportunity across all the different segments and I think in the near term immediately post launch, I think we are going to be looking at a number of key segments to penetrate quickly. I think one of the opportunities as we've talked about in the past therapy naive, that includes patients that have class that have classical PKU, high unmet medical need. Also those that have previously failed on Kuvan and those that are poorly controlled. And I think we've also talked about Chrysalin in the past, as KOLs have highlighted, we had annual one cow highlight this on the deep dive. We did last year. But since then, we've had a number of other KOLs also highlight this the importance of even those on Kuvan that could have a deeper reduction in Phe levels because that really means something to patients and their ability to be able to deepen that Phe reduction allows them to look at potentially liberalizing their diet. That's truly important. So it's hard to sort of pinpoint a particular segment, but we will be looking at sort of those key segments in the near term. And that's why we believe we were able to achieve stability.

Christian Donado

Okay, thanks. And I remember at your deep dive, you had a nice map that talked about some of the key regions where there's already patients identified that either don't respond to one of the available therapies or for whatever other reason they were available. But I'm wondering what work you've done around Europe as well as Japan and Brazil as you think about those on filings and upcoming visits?

Pierre Gravier

Yes, absolutely. We've done consistent work across all the different regions. As we've talked about. We have existing commercial infrastructure in place and those teams are ready to go. So they're out there. They're visiting the treatment centers of excellence, the getting to know the patient communities and upon launch, they'll be ready to execute upon those patient segments. So we have similar information that's being collected across all of the different markets, and that's what we're also collecting. But in addition to that, there's a substantial market pull. So there's people coming to PTC gearing up and wanting the drug. So it's coming from both directions.

Christian Donado

Yes.

Matthew Klein

Thanks, Kristen.

Operator

Eric Joseph, JPMorgan.

Eric Joseph

So high that even maybe second question, just picking up on your your opening comments on the pending European Commission decision for Translarna, I guess we were expecting a potential update earlier in the month. Do you have any visibility as to when the EC. might come through with his decision and whether they're perhaps reconsidering CHMP's recommendation and one of them and perhaps regulatory progress with FDA? And then maybe just following up on that, if that kind of weather remains authorized. How should we be thinking about sequential performance in second quarter to the extent you saw sort of advanced pull through last quarter?
Thank you.

Eric Pauwels

Thanks very much.
For the questions. Eric, you highlighted the obvious right. And with the CHMP opinion in January, typically it would be 67 days. Following that opinion that the European Commission would adopt that opinion and Translarna would have been withdrawn. That has not happened. We remain fully authorized, as I talked about it, some business as usual in terms of commercializing at 21 a year. We have been notified by the commission that they will be meeting this week to discuss the matter in a live meeting. Obviously reeling a little bit of an unprecedented change a lot of an unprecedented situation here, but yet, but considering that Translarna has a strong data record of efficacy and safety and considering the significant unmet medical need for nonsense mutation patients in Europe of transborder, the withdrawn, the tremendous outcry from the patient and physician community. It may not be that surprising that the commission is looking at this very closely obviously, will we further update until until we hear we'll continue again to make Translarna available to as many patients as possible. And our teams are working to do that. And we look forward to the opportunity to continue to bring the therapy to patients as long as we can.
And in terms of your second question, which was on what we see in terms of impact to the revenue outlook of revenue performance in the first quarter, it was expected based on what we talked about based on the fact that we said for Translarna in Europe, it could be business as usual was authorized. As Eric mentioned on the call, we had a number of strategies in place in the U.S. to protect the brand protect and Plaza and protect our business by those strategies will continue. The efforts for Translarna will continue on to this quarter. And if there's a need to update our revenue guidance, we will.
Okay, great. Thanks for taking the question.

Operator

Kelly Shi, Jefferies.

Kelly Shi

Your line is now open and thank you for taking my questions. I'm just curious for the ALS trial. You mentioned IMOA. as actually roxadustat is through inhibiting for apoptosis. I wonder what kind of a genetic biomarker associated with for Aptose's EALS. patients? And do you expect more prominent treatment all com, a subgroup of AR patients?

Kylie O'Keefe

Kelly, thank you.
Very much for the question, Sarah post. This is a pathway and a relatively recently described pathway of inflammation, cell stress and cell death. And that is increasingly being linked to neurodegenerative diseases, including ALS. And what is important about this is it's not a related to any specific genetic us about what's really a common response pathway in ALS. And that's why our trial with huge losses that has enrolled both genetic and idiopathic ALS patients. So this is one advantage of this approach is that we're targeting a pathway common to any genetic or non genetic cause are they aligned?

Kelly Shi

Thank you.

Operator

Sami Corwin, William Blair.

Sami Corwin

Hey, guys.
Thanks for taking my question and congrats on the quarter. I was wondering if you could provide any additional color on how much you contributed to Translarna revenue this quarter? And then have you heard any feedback from US physician patients and et cetera, on their perception of the Translarna and the check went out data and kind of what their view of what the commercial potential might be in the U.S. banks?

Matthew Klein

Yes.
Certainly, thank you very much for the questions. I'll just make a brief comment then I'll turn it over to Karl to give a little bit more detail, certainly on on your second question, does it given the unmet need for nonsense mutation DMD patients in the U.S. and what's known about Translarna and number of patients who've been on Translarna for years, there's a great amount of anticipation for the potential availability of Translarna can FDA approval. And similarly, for particular announcer for pediatric patients. There's a significant remaining unmet need, and it's not well appreciated in the physician expert community as well as depreciation and the type of data that we've collected and move FA, demonstrating that important significant effect in upright stability. And what that means in terms of delaying time to loss of ambulation is incredibly meaningful for patients and therefore, there really is a significant amount of interest for particularly on the F-18. And I'll turn it over to you for more color on the revenue.

Sami Corwin

Yes.

Pierre Gravier

Thanks, Matt, and thanks Jamie, for the question. I think starting with your first question, Simon, around the contribution from and European revenue for Translarna, it's pretty consistent with first quarter of last year as we've shared that represents around 45% of total revenue. And it's pretty consistent when you look at Q1 of this year to Q1 of last year.
So as Matt said earlier, in his comments planned going into the quarter was to continue to ensure patients have access to Translarna while it remains on the market. And I think the team has done an incredible job in executing upon that plan. So contribution is about consistent.
Jumping to your second question around Translarna in the US in perception there and also in particular. And as I think I think what Matt said is absolutely accurate. I think starting with Translarna, there's still nothing available for nonsense mutation. Dmd patients enter this high unmet medical need there. And then when you look at FA, there's nothing available for pediatric patients. And I think physicians are starting to get to understand how Scott Scott Clark fits into the marketplace in the older patients, and there's still a place for the equipment in those older patients as well. So across the board, we've seen very positive feedback from physicians are very well versed on Translarna in the US is that said, there's a number of patients they are on the drug. And then as we're engaging with the community on FA, there's positive feedback on the matter Great.

Kylie O'Keefe

Thank you.

Matthew Klein

Thank you. One moment for our next question, please.
Question comes from the line of Joseph Tung with TD. Cowan. Your line is now open for further.

Kylie O'Keefe

Good afternoon. Thank you for taking my questions. Maybe on the Huntington study, looks like maybe this might be the first time we're really committing to some of those functional measures. The TMSTFC. and CUHDRS.? And maybe what are your expectations for efficacy on those points as the follow-up time that we're seeing in the Q2 data going to be long enough to show benefit on these measures, do you think or how should we interpret those data when we when we see them? And maybe on second question, just on the AADC gene therapy. Can you talk a little bit about reimbursement progress in Europe? And maybe what are you learning there that you can apply to the US. six. Thanks for the questions, Joe. We are very much looking forward to the VHT. data readout later in the second quarter. As we talked about, this will be our opportunity to share 12-month data from that initial group of patients on whom we shared 12 week data last summer. And this will allow us to for the first time yet to get a glimpse at CNS biomarker effect, including huntingtin protein levels in the CSF NfL levels, brain volumes. And as you pointed out, clinical scales, looking at the total motor score C2B lasts until the functional capacity. I think from our standpoint on a home run on the data would be to be able to see continued safety and tolerability up to 12 months and then be able to see some signal of CNS activity, whether that's on biomarkers or on on any of the clinical scales. And given the small number of patients I think we're really looking for a signal or trend here. I've given the duration 12 months and I get and we said this is approximately 30 patients. And so that's how we're really looking at success here, safety, tolerability at US signal, either on biomarker and or clinical studies that we're having CNS activity. I think patients and let me turn it over to colleagues want to give some more color on AC. reimbursement and how that's setting the stage for the U.S.?

Pierre Gravier

Yes, absolutely. So we continue to see progress with pricing and reimbursement negotiations across Europe. And we've continued to have favorable agreements come into place and we'll be shortly treating patients in those additional countries.
As we talked about in the quarter, we treated additional patients in France in the UK and additional patients in and through cross border health care. And so that's continued success in this space.
If you talk about learnings and how we sort of think to the U.S. market. I think one of the things that we've walked away with some from some of these discussions is that recognition of high unmet need in a DC. And with the absence of standard of care from a disease modifying point of view, there's no treatments available that the recognition of a ultra-orphan condition. And therefore small budget impact and a recognition of the transformative results that come with the treatment of upsized. And so put together, this allows us to be able to move forward with favorable pricing and reimbursement negotiations, and we do expect that to carry across into the U.S. upon launch.

Christian Donado

Great.

Kylie O'Keefe

Thank you very much.

Pierre Gravier

Thanks, Tarek.

Matthew Klein

Thank you. One moment for our next question our next question will come from the line of Brian Abrahams with RBC. Your line is now open.

Pierre Gravier

Guy, this is Joe on for John for Ryan and thanks for taking a question. So back on Translarna, can you talk more about the buying pattern you're seeing for Translarna in Europe in recent weeks? And if European Commission does decide to follow a CHMP opinion, are you seeing anything on the ground that might suggest that we draw from channels may be more gradual or on the other side, even more rapid than that than you're expecting CapEx for the questions?

Kylie O'Keefe

Joe, look, we are seeing as really business as usual, their prescriptions and numbers are really unchanged here. And it goes without saying that the patients and the physicians want to take advantage of every day that Translarna is on the market, and we expect that fully to continue to be the case. Our teams is probably quite that are focused on ensuring that happens that we're ensuring that patients have access to therapy. Of course, we've also been working in the background to put mechanisms in place to leverage mechanisms that might be available on a country-by-country basis to continue to provide Translarna in the event that the EC commission adopt the opinion trend one as of June.
Yes.

Eric Pauwels

Thank you.

Pierre Gravier

And if I could squeeze in one more or are you scheduled to meet with the FDA regarding asked the ATryn filing anytime soon? And I'm just wondering if you're get a visibility on whether you can file in parallel to the carcinogens study?

Eric Pauwels

Yes, we had, Joe.

Kylie O'Keefe

We had a pre-NDA meeting last year with the agency last fall, and it was very clear that every other part of the package there and in place of safety, efficacy data would support our NDA and support approval, our view and what outstanding matter, what was the completion of that carcinogenicity study. We've mentioned that we expect that study to be done in June. We don't expect to have a formal meeting with the agency. We did say that we plan to contact them to discuss timing of the submission relative to the completion of that study, we said that we still remain on track to submit in Q3 or can even bring that in a little earlier into Q2 based on that correspond. But we don't expect that will be extraordinary.
Got it.

Christian Donado

Thank you.

Matthew Klein

And thank you for a moment for our next question.
Our next question comes from the line of Gena Wang with Barclays. Your line is now open.

Pierre Gravier

And I thank you.

Jane Hanlon

I just was very quick questions. The first one is regarding Translarna Europe status on based on your discussion with EMA, when do you expect Trans Mountain will be withdrawn in Europe?
And then second question is regarding asset materials in PKU, I think you mentioned that you wanted to target initial patient population that could be one part is a classical PKU. Can you help us understand how our understanding that the secretary is a precursor for coal sector and across APK. usually does not have any and filling at L&E type hydroxylase. So basically does not have an enzyme like how would the secretary and will be helpful in classic PKU patient population?

Eric Pauwels

Thank you for the questions.

Kylie O'Keefe

Gena, as we've discussed regarding your first question on the status of Translarna in Europe, of the following the opinion in January. Typically, the European Commission would have adopted that opinion within 67 days. Clearly, we're sitting here late in April and that adoption of the opinion has not occurred, and we have been notified that the commission was planning to meet this week to discuss the matter of biosimilar taking into consideration the current status in Europe a lack of alternative therapies for patients with nonsense mutation DMD, the data which supports safety and efficacy of Translarna for the outpouring of support for the authorization remaining intact from the patients physician community across across Europe. So I think they're looking at the data closely. We expect to have an update in the near future. And as we said, until that time and it's really business as usual, the usual we're using every day to continue to ensure that patients have access to Translarna.
On your second question regarding Glasgow, Kentucky, I think there's sometimes a misunderstanding because the definition of classical PKU is basically patients, children or adults who at some point in their life have a documented of phenylalanine level of greater than 1,200 micromolar per liter that could be at any point in time or could they be lower because the diet control a very small number of those patients have what's called homozygous known mutation. That means they have on both a real unknown mutation that prevents them from having parallelly hydroxylase enzyme, but as a very small minority of patients and therefore, the remainder to classical PKU patients have functional enzyme, obviously severely affected by the mutation and has more functions. Cp at Heron is, as you pointed out, a precursor of BH4, which is a cofactor for the enzyme. That also has a second function, which is a chaperone culture, which stabilizes the confirmation of the PAH enzyme. And therefore, we believe that's why we're seeing what we've seen in classical PKU patients in our studies, which is a significant factor affecting the AFFINITY trial in the subset of classical PKU patients. We had a nice phenylalanine reduction of 69%. That's actually a greater magnitude of reduction that was observed in the overall population. So certainly signifies a CP. Karen can play an important role for these patients.
Similarly, as we've included, we've seen patients go into the open-label extension and participating tolerance protocol. We are seeing classical PKU patients. It is defined with classical PKU patients are being able to liberalize their diet and maintain control of mental health. So all of that, it really speaks to the importance of CP, Terran and potentially a really important role for all patients with PKU, including both classical patients and who are tend to be the most severe.

Matthew Klein

Thank you. One moment for our next question.
Our next question comes from the line of Jeff Hung with Morgan Stanley. Your line is now open.

Eric Pauwels

Thanks for taking my questions. On for semi upturn. Can you just remind us of the data that was collected in patients under two years old?

Kylie O'Keefe

And are there plans or timelines for starting that?

Eric Pauwels

And then given the meaningful effects on booking on it, like what would you give you give you confidence for results translating the younger patients?

Christian Donado

Yes.

Eric Pauwels

Thanks, Jeff. We did include patients under two in the AFFINITY study.

Kylie O'Keefe

Now they went through the initial one in Spain and we had patients who had a greater than 30% reduction in the run-in phase. But the regulatory authorities wanted then those very young patients not to be randomized, but to go directly into the open-label extension study. So we have patients who started in AFFINITY who were under two, and we've actually had additional patients that we've enrolled directly into long-term extension. So we're getting data in that number, a number of patients under the age of two. And what we're seeing is exactly what we're seeing in patients over the Agento. We're seeing safety and tolerability and also efficacy in terms of reducing Panorama. So again, the data continue to support the potential benefit of CP parent and the full range of PKU patients, both classical non-class VO. and then patients of all ages for.
Thank you.

Matthew Klein

One moment for our next question, please.
Our next question comes from the line of Joseph Schwartz with Leerink Partners. Your line is now open.

Jane Hanlon

Hi, everyone. This is Jenny on for Joe. Thanks for taking our question. So I was wondering if you could just talk a little bit more about the 4Q readout for ALS I think you've said in the past that the study could be registrational. Can you give us an idea of what regulators would be looking for and to split that and can you kind of give us some insight into what a clinically meaningful change in ALS functional rating scale would be thinking, if to.

Kylie O'Keefe

Thank you very much for the call. The question rather. So we are how we designed the CARDINAL study to be, as you said, registration directly. And this came from our feedback with FDA, both in terms of relation of the study being and roughly six month study, placebo control and the endpoint strategy having the primary endpoint being the ALSFRS. scale, we would define success here as a statistically significant benefit on the primary endpoint, which we isolate on the ALSFRI. sale that has traditionally been the threshold for agency approval. We powered the study to have what we believe would be a clinically meaningful and clinically meaningful effect, which is roughly 2.5 point difference between the treatment and the placebo group. And we designed the study to be well powered to detect that. So we believe if we were able to have statistical significance on the ALSFRS, we also, of course, have secondary endpoints, capturing other important aspects of the disease, including mortality, including respiratory function. And that's where we of course, will look for supportive data of that tied to the ALSFRS scale. We will better position us to advance Interlott set for approval in the EU.

Christian Donado

Great.

Kylie O'Keefe

Thank you.

Matthew Klein

Thank you. One moment for me question, please.
Our next question comes from the line of David Lee with Citi. Your line is now open.

Kylie O'Keefe

Thank you very much for taking my question. At this point, have you really it significantly felt the presence of generic Emflaza or that recently approved of tomorrow alone.
David, thank you very much for the question. We talked a bit about on the call. We put a lot of strategies in place to preserve the inflows and market, even in the face of generic competition estimate the higher they're talking a bit more about in terms of Dynepo?

Pierre Gravier

Yes, absolutely. I think, David, the answer the quick answer to that is no. And I think that's a testament to the strategy that the team has put in place to protect the business. And as we said in the first quarter, they've been executing upon that. I think what's really been a strong message for us is the continued new patient starts, and we've seen an incredibly large number of new patient starts in the first quarter. And I think that's a testament to the loyalty to Emflaza and the continued benefit seen by both patients and physicians.

Eric Pauwels

Thanks for taking my question.

Pierre Gravier

Thanks, David.

Matthew Klein

Thank you. One moment for our next question, please.
And next question comes from the line of Danielle Brill with Raymond James. Your line is now open.

Pierre Gravier

Hey, Kevin, and thanks for taking our questions.

Jane Hanlon

I have two brief ones on.

Pierre Gravier

First to clarify on Translarna status in the EU, is it possible that the delay in the EC ratification of the CHMP opinion is procedural or was this meeting this week specifically calls because the ECB is considering not ratifying that decision?
And then on my second question is about the economic softness in the EMA, I believe EMA feedback on the feasibility of a conditional approval was expected in 1Q. Any updates on that front? Thank you.

Kylie O'Keefe

Yes, thanks, Daniel, for the questions. On your first question that the typical procedures, 67 days usually this is done by writing side is usually written agreement across the member states. And that then allows for the ratification by the EC that procedure we know was a pause and said a live meeting was called for discussion. What the exact nature of that discussion was, what motivated that discussion. We can't state what we can say is the typical ECIP. of adoption occurs within 67 days will clearly beyond that time point.

Eric Pauwels

It's typically written procedure.

Kylie O'Keefe

They're having a live meeting. So there's a lot of things that are going on now that are really a typical and what that means in terms of the ultimate EC decision, whether to adopt the opinion, send the matter back to the CHMP, whatever they decide. We can say what we can say is we're far beyond what we had expected. It was typically observed and the procedure has not gone according to what typically happens. But in terms of your question, regarding particular, dominant previously shared that we had gotten feedback from the EMA from we had gone through the scientific advice procedure. They did not indicate that they thought that the move that phase study could support five conditional authorization at this time. We're looking forward to further discussions with them. And of course, on the FDA side, we have a different experience where after we had a recent meeting with the FDA in Q1, we are moving forward with the NDA based on the move at a study as well as open-label extension data, both from the older setting performed a few years back as well as from the move FA on long term open label extension.

Pierre Gravier

Thank you for the clarification.

Matthew Klein

Thank you. One moment for our next question, please.
Our next question comes from the line of Tazeen Ahmad with Bank of America. Your line is now open.

Kylie O'Keefe

Hi, guys.

Jane Hanlon

Thanks so much for taking my question on one on FA., can you just talk to us about the patient population, how different it might be in the U.S. versus EU in terms of sizing?
And then secondly, for Huntington, you know, based on the conversations that you've been having so far with the agency with your level of confidence that that a biomarker can be used at least as an endpoint, maybe not the sole endpoints? And is that topic have been brought up in recent discussions.

Kylie O'Keefe

Thanks, but thank you very much for the question is in terms of populations for FH is roughly similar size population prevalence in the US and in Europe. Clearly in the in both territories. There is nothing indicated for patients under the age of 16, and we've talked a lot about how the data from move assay really supports the important treatment effect in that population with regard to delaying in time and lots of ambulation. And obviously that has applicability beyond just the under 16 year old patients to the effects we observed in upright stability development to haul ambulatory patients with Friedreich ataxia. So population is roughly the same size we see as ability to fill the unmet need in the pediatric population, but also potentially having important important effects for all ambulatory patients regardless of their age.
I believe your second question was on biomarker and HD. an as an endpoint.

Eric Pauwels

Is that correct?

Pierre Gravier

At that time.

Kylie O'Keefe

So we we can be we have not had discussions yet with the agency regarding biomarker accelerated pathways and biomarkers role in any endpoint strategy. And I think we've clearly seen that the agency is particularly the neurology division, has been looking to leverage the accelerated approval pathway for neurodegenerative diseases like Huntington's disease, like Alzheimer's disease, where collecting a definitive efficacy data in a Phase two trial takes many, many years. I think the challenge we have in each key, of course, is there's no precedent yet for what that accelerated approval biomarker will be. We believe that the pivotal two study offers several important biomarkers, including peripheral huntingtin lowering predict with a systemically administered targets. And obviously, we talked a bit about the potential for Nf-L levels, which is the news in the case of Jefferson for ALS and then also things like huntingtin protein in the CSF. So what we plan to do is collect data and begin to have discussions with the agency once we have data in hand in hand with what a pathway using biomarker data for what would be as you as you ask the role of biomarker data in establishing the efficacy of a therapy for Huntington's disease. But we think there's certainly should be an appetite just based on agency's recent activity.
Thank you.

Matthew Klein

Thank you. One moment for our next question. Our next question comes from the line of Paul Cho with Goldman Sachs. Your line is now open.

Kylie O'Keefe

Good afternoon, and thank you for taking my questions.

Eric Pauwels

I have two and My first is just with regard to the CARDINAL trial in ALS, in the wake of the recent arm PHOENIX study results from Alex have you either implemented or contemplated any study design changes or changes to the statistical plan, just based on the recent Phoenix results on and just what your thoughts are there and then second, just to follow up also as well on pivot HD. and PTC. five one eight. I'm can you maybe just comment on on the with regard to your regulatory discussions just on the safety side for U.S. sites and any progress that may have been made there.

Kylie O'Keefe

Thank you for taking my questions.

Eric Pauwels

Thank you very much, Paul, for the questions.

Kylie O'Keefe

On your first question regarding Cardinal, when we the FDA has been quite clear on what they want to see in terms of analytical approaches for the ALSFR., and they're very interested in understanding changes in score as a continuous variable have also been interested in understanding mortality and the time to mortality. Specifically, they've talked about wanting to understand the difference in scores between treatment and placebo and then also implementing something called a joint rank test, which is a way of analyzing together both the change in air et cetera, score as well as patients who may have died and the inflammation at the time of death following enrollment. So we've, of course, taken the agency's guidance to ensure that our analysis plan was consistent with what they want to see. And that doesn't change with anything regarding the Phoenix that we need more closely with the agency in designing the study to ensure that it would be a registration directed in ensuring that we have the appropriate analysis plan so that when we get the results, if they're positive, that we'd be well positioned to advance the drug towards approval.
Regarding your question on safety data and pivotal study and discussions with the agency as we prepare for the second quarter data disclosure, which we will have then have the safety data that the agency has asked us to review in order to lift the partial hold. So we look forward to submitting those data to the agency when available as just as a reminder, they had asked us following the last data review of 12 week data to provide them with six month data on a sufficient number of subjects, if that would confirm what we've seen it at 12 weeks?
Well, clearly we're going to be in a position to provide the agency, not only six month data, but 12 months data on a number of patients. And as we've shared, we're continuing to see the drug to be well tolerated. So we look forward to putting that data package together us submitting it to the agency and hopefully to lifting the partial hold in the near future.

Christian Donado

Great.

Kylie O'Keefe

Thanks for taking my questions.

Matthew Klein

Thank you.
And at this time, I'm showing no further questions, I'd like to hand the conference back to Dr. Matthew Klein for closing remarks.

Kylie O'Keefe

Well, thank you all for joining the call today are clearly we're very excited about the outstanding performance in the first quarter, both in terms of revenue and the execution across all of our programs of the acquirer are well positioned to continue this success throughout the remainder of the year and look forward to updating you all as we move out. So thank you all, and have a good day.

Matthew Klein

This concludes today's conference call. Thank you for your participation. You may now disconnect, and everyone have a wonderful day.