Q1 2024 PTC Therapeutics Inc Earnings Call

Okay.

Unknown Executive: Good day, and thank you for standing by. Welcome to PTC's first quarter 2024 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 11 on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star 11 again. 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.

Good day, and thank you for standing by.

Jane Hanlon: Welcome to PTC first quarter 'twenty 'twenty four financial results conference call. At this time, all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During this session you will need to press star one on your telephone you will then hear an automated message advising George.

Your question. Please press Star one again, 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 Hanlin Associate director of Investor Relations. Please go ahead.

Jane Hanlon: Good afternoon, and thank you for joining us today to discuss PTC Therapeutics' 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.

Jane Hanlon: Good afternoon, and thank you for joining us today to discuss P. T C Therapeutics first quarter 2024, corporate update and financial results.

Jane Hanlon: I'm joined today by our Chief Executive Officer, Dr. Matthew Klein, our Chief Business Officer, Eric <unk>, Our Chief Commercial Officer, Kylie O'keeffe, and our Chief Financial Officer P O Gracias.

Jane Hanlon: 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.

Jane Hanlon: 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.

Jane Hanlon: 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.

Jane Hanlon: 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. With that, let me pass the call over to our CEO, Dr. Matthew Klein. Thank you.

Matthew Klein: 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 claims that.

Matthew Klein: Thank you, Jane. 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 program. As we have discussed, 2024 will be a year of execution, with a number of important and value-inspiring 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.

Matthew: Thank you Jamie 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.

Matthew Klein: We have discussed 2024 will be a year of execution for PTC.

Matthew Klein: A number of important value inflection milestones throughout the year.

Matthew Klein: We are off to a great start with strong revenue and achievement of all of the planned first quarter regulatory and clinical milestones.

Matthew Klein: Starting with commercial performance, we had a great quarter driven by execution across the entire commercial portfolio.

Matthew Klein: First quarter revenue totaled $210 million and DMD franchise revenue was $161 million.

Matthew Klein: The 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 the CHMP opinion to withdraw TransLarna authorization, and thus, we will continue to commercialize TransLarna across Eric and Kylie will provide additional details on our commercial performance shortly. We had a number of important regulatory achievements.

Matthew Klein: Our first quarter DMT revenue, resulting from our team's efforts to ensure that we optimize revenue during the time that trends worn out remains authorized in Europe.

Matthew Klein: Good time, the European Commission has not yet adopted the HMP opinion to withdraw translarna authorization and that we will continue to commercialize trans lineup across Europe.

Matthew Klein: Eric and Carly will provide additional details on our commercial performance shortly.

Matthew Klein: We had a number of important regulatory achievements in the first quarter as planned we submitted the marketing authorization application for CP apparently yet.

Matthew Klein: As planned, we submitted the marketing authorization application for sepia tarin to the EMA, and we remain on schedule to submit the NDA for sepia tarin no later than the third quarter. The European MAA submission is an important step towards our planned global launch of Cepiaterin as we bring a potential new standard of care to DKU 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 therapies.

Matthew Klein: And we remain on schedule to submit the NDA for CPA, Karen No later than the third quarter.

Matthew Klein: The European MAA submission is an important step towards our planned global launch of CPA terror as we bring our potential new standard of care to PKU patients around the globe.

Matthew Klein: At Empathised recently by recent Milberg, the executive director of the National PKU Alliance. The vast majority of PKU patients are not served by the currently available PKU therapies and there was a great deal of enthusiasm in the PKU community Praesepe a turret based on the data generated to date.

Matthew Klein: And there is a great deal of enthusiasm in the PKU community for sepiateran based on the data generated to date, including the reported patient experience with diet liberalization. In the first quarter, we also submitted the BLA for Abstaza, and we aligned with the FDA on an NDA resubmission for Translarna and an NDA submission for Vitequinone for the treatment of Friedreich's attack. 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.

Matthew Klein: <unk> reported patient experience and diet liberalization.

Matthew Klein: In the first quarter. We also submitted the BLA for ups data and we are aligned with the FDA on an NDA resubmission per transport and an NDA submission for <unk> for treatment of Friedrich ataxia.

Matthew Klein: The NDA Resubmission for <unk> will be based on the placebo controlled results from study 41 and data from the stride registry, which confirm long term benefits of trans Lora and slowing time to loss of ambulation.

Matthew Klein: We expect to submit the NDA for vitiquinone in mid-2025. The vitiquinone NDA will include results from the 72-week placebo-controlled portion of the MOVE-FA trial, along with data from the trial's long-term open-label experiment. We expect to submit this NDA in late 2024. Turning to our development programs, we plan to share interim results from the Pivot HD study of PTC 518 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.

Matthew Klein: We expect to submit the NDA in mid 2024.

Matthew Klein: A particular note NDA will include results from the 72 week placebo controlled portion of the Bluebird trial, along with data from those trials long term open label extension, we expect to submit the NDA in late 2024.

Matthew Klein: Turning to our development programs, we plan to share interim results from the pivot HD study of PTC, five one and Huntington's disease patients in the second quarter.

Matthew Klein: <unk> update will include 12 month biomarker and clinical results from the initial cohort of approximately 30 subjects on whom we shared data last summer.

Matthew Klein: Specifically, we will share data on blood Huntington protein lowering, CSF mutant Huntington protein lowering, volumetric MRI changes, and SL levels, as well as data on several clinical scores, including the total motor score, total functional capacity, and the CUH DRS. These 12-month data will allow us to understand the longer-term safety and tolerability profile of PTC518, as well as to identify favorable early signals of CNS activity on disease The second quarter update will also include 12-week results for a larger number of Stage 2 and Stage 3 subjects, including blood Huntington protein. Lastly, we completed enrollment in the Cardinal Registration-Directed Trial of Utiloxostat in ALS and remain on schedule to report top-line results in the fourth quarter of this year.

Matthew Klein: Specifically, we will share data on blood Huntington protein Laurie CSF mutant Huntington protein lowering volumetric MRI changes and then fell level as well as data on several clinical scores, including the total motor score total functional capacity and C U H Vrs.

Matthew Klein: These 12 month data will allow us to understand the longer term safety and Tolerability profile of PTC 518, as well as to identify favorable early signals of CNS activity on disease Biomarkers for clinical end points.

Matthew Klein: The second quarter update will also include 12 week results for a larger number of stage, two and stage three subjects, including blood Huntington protein changes.

Matthew Klein: Lastly, we completed enrollment in the Cardinal registration directed trial of <unk> in ALS patients and remain on schedule to report top line results in the fourth quarter of this year.

Matthew Klein: Utiloxostat is the first compound being developed for ALS that specifically targets seroptosis. 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 eutroloxistat to address the significant unmet need of ALS patients.

Matthew Klein: Lots of that is the first compound being developed for Alice.

Matthew Klein: Typically targets therapy doses pathway of oxidative stress felt that demonstrated to be highly relevant to al's pathology.

Matthew Klein: Given the recent changes in the therapeutic landscape for Alice positive results from the Cardinal study could enable you to lots of Scott to address the significant unmet need of ALS patients.

Matthew Klein: 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 2020. I will now turn the call over to Eric and Kylie to discuss our commercial performance.

Speaker Change: 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 many important expected milestones in 2024.

Matthew Klein: 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 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 launch preparations for Abstaza in the U.S. and for Cepheap Terra and Global. Our global DMV 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.

Eric: Thanks, Matt.

Eric: Mobile customer facing team has kicked off 2024 on a strong footing and has delivered $178 million in revenue for our five marketed products.

Eric: Our team is focused on growth as well as diversification within our current commercial portfolio and on executing our launch preparations for <unk> stays in the U S and for shipyard Taryn globally.

Eric: Our global DMD franchise had a robust quarter well 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.

Eric Pauwels: We delivered revenue of $161 million, which resulted from our strategies to continue to maximize trans-LARNA revenue in Europe and to successfully protect the Implaza business in the U.S. For TransLarna, we achieved $104 million in revenue this quarter. The team continued to work to ensure that translarna patients in Europe continue to receive treatment. Evaluations of local country pathways and named patient sales for continued access to treatment are ongoing. Now turning to Implod.

Eric: We delivered revenue of $161 million, which resulted from our strategy is to continue to maximize trends larger revenue in Europe and to successfully protect the employer business in the U S.

Eric: Fortunately in Florida, we achieved $104 million in revenue this quarter.

Eric: <unk> continued to work to ensure that transplant patients in Europe continued to receive treatment.

Eric: Devaluations of local country pathways and named patient sales for continued access to treatment are ongoing.

Eric: Now turning to employers.

Eric Pauwels: Quarterly net revenue was $57 million, which reflects our strategy to protect the brand in the face of initial generic entry. Robust Implaza sales were driven by continued brand loyalty from health care providers and patients, with a significant number of new patients starting on Implaza. We continue to work closely with health care providers, payers, specialty pharmacies, and advocacy groups to reinforce the benefits and the value of EMPLASA while reemphasizing our exclusivity for 2- to 5-year-old DMD patients. Now, I will ask Kylie to update the progress of our current and future new product launches. Kylie? Thanks, Eric.

Eric: Quarterly net revenue was $57 million, which reflects our strategy to protect the brand in the face of initial generic entry.

Matthew Klein: Robust and Plaza sales were driven by continued brand loyalty from health care providers and patients with a significant number of new patient starts unemployed.

Matthew Klein: We continue to work closely with health care providers payers and specialty pharmacies and advocacy groups to reinforce the benefits and the value of employers.

Matthew Klein: I'll re emphasizing our exclusivity for two to five year old DMD patients now.

Highly: Now I will ask highly to update the progress of our current and future new product launches.

Matthew Klein: <unk>.

Kylie O'Keefe: We continue to plan for our global launch of Step Uterine following the recent submission of the MAA in the EU 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, dieticians, and PKU patients of the potential of sepiatarin to meet these significant unmet needs.

Kylie: Thanks, Eric.

Highly: We continue to plan for our global launch of Serbia Taryn. Following the recent submission of the MAA in the EU.

Highly: And the planned NDA submission to the FDA later this year as.

Matthew Klein: As well as additional regulatory submissions in Brazil, and Japan in 2024.

Matthew Klein: As Lisa Milberg, the executive director of the National PKU Alliance recently stated there is a significant unmet need for PKU patients.

Matthew Klein: There is widespread recognition amongst metabolic specialists geneticist dietitians and PKU patients of the potential of <unk> to meet the significant unmet need.

Kylie O'Keefe: As we saw for numerous patients in the AFFINITY trial, classical PKU patients, as well as those unresponsive to and poorly controlled on Cuvan, could potentially do significantly better on sepiaterans. Importantly, we continue to see durability of treatment effect and the ability for patients on sepiateran 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 PKU patient advocacy groups around the world have shared that PKU patients have been waiting for a therapy like sepiatarin that combines efficacy through fee reduction and a potential ability to liberalize their incredibly burdensome fee-restricted diet to improve their quality of life.

Matthew Klein: As we saw for numerous patients in the affinity trial classical PKU patients as well as those unresponsive and poorly controlled on Suzanne could potentially do significantly better onset Serbia karyn.

Matthew Klein: Importantly, we continue to see durability of treatment effect and the ability for patients on <unk> to increase the dietary protein intake beyond the recommended daily allowance, while still maintaining control of phenylalanine levels and the ongoing affinity long term extension study.

Kylie O'Keefe: PKU patient advocacy groups around the world have shed that PKU patients have been waiting for a therapy like Serbia, Karen that combines efficacy through fee reduction and the potential ability to liberalize, they're incredibly burdensome they restricted diet.

Matthew Klein: To improve the quality of life.

Kylie O'Keefe: We continue to believe in the potential $1 billion plus global opportunity. Now, turning to Apstazer, 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 U.S. are well underway, and the customer facing team is incredibly excited to bring this much needed treatment to AADC patients in the U.S.

Kylie O'Keefe: We continue to believe in the potential $1 billion plus global opportunity.

Matthew Klein: Now turning to ups data, the first and only approved gene therapy and feeds directly into the brain, where we continue to see transformative results.

As Matt mentioned, we submitted a BLA to the FDA in March and launch preparations in the U S are well underway and the customer facing team is incredibly excited to bring this much needed treatment to ADC patient in the U S.

Kylie O'Keefe: 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 GT-002 study was presented at the ISPMD Congress that showed significant uptake of CSF, HVA, and F-DOPA up to eight weeks after administration of Apsazer, translating into dopamine production and improvements in common symptoms such as hypotonia.

Kylie O'Keefe: In Europe, we traded new patients in France, and the UK as well as treating new cross border patients in the quarter.

Matthew Klein: In February data from the GT. Two study was presented at the ISP in the Congress that showed significant uptake of CSF HVA and F. Dopa. After eight weeks after administration of upsides are translating into dopamine production and improvements in common symptoms such as.

Matthew Klein: Hypotonia.

Pierre Gravier: 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 Tegcete and Huilebra 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 a new group purchase order for Weylivra and anticipate receiving a group purchase order for Tegceti shortly.

Matthew Klein: Globally patient identification treatment center readiness and access and reimbursement discussions continue to advance as we prepare for additional filings and regulatory approvals.

Pierre Gravier: Moving to take city in way Libra in Latin America.

Matthew Klein: We continue to make excellent progress across the franchise with growth in both patients identified and patients treated across the region.

Matthew Klein: In Brazil, we completed delivery of the new group purchase order for Wiley rock and anticipate receiving a great purchase order for take very shortly.

Pierre Gravier: Our strategy for geographical expansion continues, with additional regulatory filings planned and approvals anticipated for both products. In conclusion, coming off a robust 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 strategies for Sepia, Terran, and Upstaser. I will now turn the call over to Pierre for a financial update. Pierre?

Pierre Gravier: Our strategy for geographical expansion continues with additional regulatory filings planned and approvals anticipated.

Pierre Gravier: <unk> products.

Matthew Klein: In conclusion coming off for Bos 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 a global launch strategy to Serbia Taryn panel today, though.

Matthew Klein: I will now turn the call over to Pierre for a financial update.

Pierre: Thank you Kelly.

Pierre Gravier: I'll now share the financial highlights of our first quarter of 2020. Please refer to the earnings press release issued this afternoon for additional details. Beginning with top line results, total revenue for the first quarter was $210 million, including DMV franchise revenue of $161 million. Starting with the DMV franchise, Flanders Net Product Revenue in the quarter was $104 million, while Flanders Net Product revenue in the full year was $57 million. Moving to heavy.

Pierre: I'll now share the financial highlights of our first quarter of 2024.

Pierre: Please refer to the earnings press release issued this afternoon for additional details.

Pierre Gravier: Beginning with top line results.

Pierre: Total revenue for the first quarter was $210 million.

Pierre Gravier: Excluding DMD franchise revenue of $161 million.

Pierre: Starting with the DMD franchise.

Pierre: <unk> net product revenue in the quarter was $104 million, what Im Plaza net product revenue of $57 million.

Pierre Gravier: Moving to <unk>.

Pierre Gravier: First quarter global revenue of about $40 million was achieved by Roche, earning royalty revenue of $31 million for. Non-GAAP R&D expense was $107 million for the first quarter of 2024, excluding $9 million in non-cash, stock-based compensation expense, compared to $180 million for the first quarter of 2023, excluding $15 million in non-cash, 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 a differentiated, high-potential R&D program.

Pierre: First quarter global revenue of about $40 million with achieved by Walsh, earning royalty revenue of $31 million for PTC.

Pierre Gravier: 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 $118 million for the first quarter of 2023, excluding $15 million noncash stock based compensation expense.

Pierre: The year over year reduction in R&D expenses reflects our strategic portfolio prioritization of debt.

Pierre Gravier: Company continues to focus its resources on a differentiated high plex onshore R&D programs.

Pierre Gravier: Non-GAAP SG&E expense was $64 million for the first quarter of 2024, excluding $9 million in non-cash stock-based compensation expense, compared to $73 million for the first quarter of 2023, including $14 million in non-cash, stock-based compensation expenses. This expense reduction reflects lower employee costs as a result of the reduction in work. Cash equivalents and marketable securities totaled $885 million on March 31st, 2024, compared to $877 million on December 31st, 2021. 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 separation lock. And I will now turn the call over to the operator for Q&A. Operator? Thank you.

Pierre: non-GAAP SG&A expense was $64 million for the first quarter of 2024, excluding $9 million in noncash stock based compensation expense.

Pierre: Paired to $73 million for the first quarter of 2023, excluding $14 million in noncash stock based compensation expense.

Pierre Gravier: This expense reduction reflects lower employee cost as a result of the reduction in the workforce.

Pierre: Cash cash equivalence and marketable securities totaled $885 million as of March 31, 2024.

Pierre Gravier: Paired to $877 million as of December 31, 2023.

Pierre: 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 Catherine launch.

Speaker Change: And I will now turn the call over to the operator for Q&A operator.

Speaker Change: Thank you.

Unknown Executive: As a reminder, to ask a question, you'll need to press star 1-1 on your telephone. To withdraw your question, please press star 1-1 again. Please wait for your name to be announced. Please stand by while we compile the Q&A roster. One moment for our first question. Our first question comes from the line for Kristen Kluska.

Speaker Change: As a reminder to ask a question you will need to press star one on your telephone.

Speaker Change: Your question. Please press Star one again, please wait for your name to be announced please standby, while we compile the Q&A roster.

Speaker Change: Our first question.

Unknown Executive: Our first question comes from the line of Christian cluster.

Unknown Attendee: Hi everyone. Thanks for taking the question. On PKU, I know you've gone at length multiple times with us talking about the specific segments where the highest unmet need remains, but I'm wondering, initially, if there's a specific market segment where you'll see uptake being the strongest. So, you know, one thing we weren't appreciating that our checks are suggesting patients under 18, for example, is really a really good candidate.

Christian Cluster: <unk> with Cantor Fitzgerald. Your line is now open.

Christian Cluster: Hi, everyone. Thanks for taking the question.

Unknown Attendee: P. J you I know you've gone it multiple times with us talking about the fixed segment.

Christian Cluster: The highest unmet.

Unknown Attendee: Need remains well Im wondering initially if you think there is a specific market segment, where the update being the strongest so one thing we werent participating better sectors.

Unknown Attendee: Patients under 18 for example is a really critical market.

Matthew Klein: Kristen, thank you very much for the question. You know, we have talked a lot about how the strong data set, both from Affinity, as well as from the long-term extension, including the fee tolerance data, really positions us well to address all of those key market segments. And that's why we really see this as such a large opportunity, and we talked about it easily being a billion-dollar-plus opportunity. I'll let Kylie go into a little bit more detail about what we see as sort of the initial segments that we're positioned to cover.

Christian Cluster: Yeah.

Speaker Change: Okay, great. Thank you very much for the question.

Matthew Klein: We have talked a lot about how the strong data set.

Matthew Klein: From affinity as well as from the long term extension, including the few tolerance data really position us well to address all of those key market segments.

Kylie O'Keefe: And that's why we really see that.

Christian Cluster: Such a large opportunity.

Kylie O'Keefe: Keith or being a $1 billion plus opportunity I'll, let highly go into a little bit more detail about what we see as sort of the initial segments that we're positioned to penetrate.

Kylie O'Keefe: Yeah, thanks, Matt. And thanks, Kristen, for the question. I think, as Matt highlighted, there 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, is therapy nave. So that includes patients that have classical PKU, higher medical need, also those that have previously failed on Kuvan, and those that are poorly controlled.

Speaker Change: 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 with <unk>.

Kylie O'Keefe: ERP naive so that includes patients.

Kylie O'Keefe: That a class that have classical PKU high unmet medical need also those that have previously failed on cruzan and those that are poorly controlled and I think we've also talked about Christian in the past as Kols have highlighted we had annual <unk> highlight this on the deep dive we did last year, but since then we've had a number of.

Kylie O'Keefe: And I think we've also talked about, Kristen, in the past, as KOLs have highlighted. We heard Ania Muntau highlight this in the deep dive we did last year. But since then, we've heard a number of other KOLs also highlight this, the importance of even those on Kuvan that could have a deeper reduction in fee levels because that really means something to patients. And their ability to be able to deepen that fee reduction allows them to look at potentially liberalizing their diet.

Christian Cluster: Other Kols also highlights.

Kylie O'Keefe: The importance of even those onto then that could have.

Kylie O'Keefe: Deeper reduction in fee levels, because that really means something to patients and their ability to be able to deepen that fee reduction allows them to look at potentially liberalizing diet. That's truly important sorry, it's hard to sort of pinpoint a particular segment, where you will be looking at sort of those key segments in the near term and that's why we believe we're able to achieve gabelli.

Kylie O'Keefe: And 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're able to achieve stability dollars.

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

Kylie O'Keefe: With.

Speaker Change: Okay, Thanks, and I remember it your deep dive you had a nice map that talked about some of the key regions and where theres already patients identified that either don't respond to one of the available therapies or for whatever other reason they were available.

Kylie O'Keefe: Wondering what work you've done around Europe, as well as Japan, and Brazil, as you think about those filings and upcoming decision.

Kylie O'Keefe: Yeah, 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, visiting the Treatment Centers of Excellence, getting to know the patient communities, and upon launch, they'll be ready to execute on 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 are people coming to PTC, gearing up, and wanting the drug. So it's coming from from both directions.

Speaker Change: Yeah, absolutely we've done consistent work across all the different regions as we've talked about we have existing commercial infrastructure in place and the teams are ready to go so they're out there they're visiting the treatment centers of excellence to getting to know the patient communities and upon bullish they'll be ready to execute upon those patients.

Kylie O'Keefe: So we have similar information that's being collected across all of the different markets and that's what we're also collecting that in addition to that there is a substantial market pulp. So that's people coming to PTC gearing up and wanting to drug so it's coming from from both directions.

Speaker Change: Thank you.

Unknown Attendee: Thanks, Kristen. Thank you. One moment for our next question, please. Our next question comes from the line of Eric Joseph with JP Morgan. Your line is now open.

Speaker Change: Thanks Kristen.

Speaker Change: One moment for our next question please.

Unknown Attendee: Yes.

Speaker Change: Our next question comes from the line of Eric Joseph with Jpmorgan. Your line is now open.

Unknown Attendee: Hi, good evening. Thanks for taking the time to ask the question. Just picking up on your opening comments on the pending European Commission decision for TransLerna, I guess we were expecting a potential update earlier in the month. Do you have any visibility as to when the EC might come to with its decision and whether they're perhaps reconsidering CHMP's recommendation in light of regulatory progress with FDA, and then maybe just following up on that, if transplant remains authorized, how should we be thinking about sequential performance in the second quarter Thank you.

Eric William Joseph: Hi, good evening, Thanks for taking the question just picking up on your.

Eric William Joseph: Your opening comments on the pending European Commission decision for Translarna.

Unknown Attendee: We're expecting a potential update earlier in the month do you have any visibility as to when.

Unknown Attendee: Etsy might come to you with this decision and whether they are perhaps reconsidering.

Eric William Joseph: <unk> recommendation and lighter.

Unknown Attendee: Perhaps regulatory progress with FDA.

Unknown Attendee: And then maybe just following up on that.

Speaker Change: Hey, Glenn remains authorized how should we be thinking about sequential performance in the second quarter.

Unknown Attendee: To the extent you saw sort of advanced pull through.

Unknown Attendee: Last quarter. Thank you.

Matthew Klein: Thank you very much for the questions, Eric. You highlighted the obvious, right, with the CHMP opinion in January. Typically, it would be 67 days following that opinion that the European Commission would adopt that opinion and TransArna would have been withdrawn. That has not happened. We remain fully authorized, as we've talked about, it's business as usual, in terms of commercializing Transwarna in Europe.

Unknown Attendee: Okay.

Speaker Change: Thank you very much for the questions Eric.

Christian Cluster: Highlighted the obvious right with this the HMP opinion in January.

Matthew Klein: Typically it would be 67 days following that opinion that the European Commission.

Christian Cluster: Adopt that opinion in terms of order would have been withdrawn.

Matthew Klein: That has not happened.

Christian Cluster: We remain fully authorized as we've talked about some business as usual in terms of <unk>.

Matthew Klein: Commercializing.

Christian Cluster: And what I would say in Europe.

Matthew Klein: We have been notified by the Commission that they will be meeting this week to discuss the matter in a live meeting. Obviously, we're in a little bit of an unprecedented, actually a lot of an unprecedented situation here, but considering that TransLaurina has a strong data record of efficacy and safety, and considering the significant unmet medical need for non-sensitization patients in Europe, it's translargenly withdrawn The tremendous outcry from the patient and physician community. It may not be that surprising that the commission is looking into this very closely.

Christian Cluster: We have been notified by the commission.

Christian Cluster: They will be leading this week to discuss the matter.

Christian Cluster: <unk> meeting.

Matthew Klein: Obviously, we're going a little bit of an on premise.

Matthew Klein: So a lot of an unprecedented situation here.

Christian Cluster: But considering.

Christian Cluster: Trends line of housing strong data records.

Matthew Klein: Efficacy and safety.

Christian Cluster: Fiddling with significant unmet medical need for nonsense mutation patients.

Matthew Klein: In Europe, our Transalta, we withdrawn.

Christian Cluster: Normally our cloud from a patient and physician community.

Matthew Klein: It may not be that surprising that the commission is looking at this very closely.

Matthew Klein: Obviously, until we hear back, we'll wait for the update, and we'll continue to make translargen 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 this therapy to patients as long as we can. And in terms of your second question, which was about what we see in terms of impacts on revenue, look, revenue performance in the first quarter was expected based on what we've talked about, based on the fact that we said for TransLaura in Europe, it would be business as usual as long as it's authorized.

Christian Cluster: Obviously, we're all week further update until until we hear we'll continue again to make sure I want it available to as many patients as possible.

Matthew Klein: Okay.

Matthew Klein: Our teams are working to do that and we look forward to the opportunity to continue to bring the.

Christian Cluster: <unk> therapy to patients as long as we can.

Matthew Klein: In terms of your second question, which was on what we see in terms of impacts the revenue look revenue performance in the first quarter was expected based on what we've talked about based on the fact that we said per trend large in Europe. It will be business as usual as long as authorized as Eric mentioned on the call.

Matthew Klein: As Eric mentioned on the call, we have a number of strategies in place in the U.S. to protect the brand, protect the plaza, and protect that business. Those strategies will continue. The efforts for TransLaura will continue through this quarter, and if there's a need to update our revenue guidance, we will.

Christian Cluster: We had a number of strategies in place in the U S.

Matthew Klein: To protect the brand protection Plaza and protect that business those strategies, we'll continue the efforts for Translarna will continue.

Matthew Klein: Through this quarter and if there is a need.

Christian Cluster: Need to update our revenue guidance, we will.

Unknown Attendee: Thanks for taking the questions.

Speaker Change: Okay, great. Thanks for taking the question.

Christian Cluster: Sure.

Unknown Attendee: One moment for our next question, please. Our next question comes from the line of Kelly Shi with Jeffries. Your line is now open.

Speaker Change: Thank you.

Speaker Change: One moment for our next question please.

Christian Cluster: Okay.

Christian Cluster: Our next question comes from the line of Kelly <unk> with Jefferies. Your line is now open.

Matthew Klein: Thank you for taking my questions. I'm just curious, for the ALS trial, you mentioned the MOA of R2-loxostat is through inhibiting ferroptosis. I wonder what kind of genetic biomarker is associated with ferroptosis in ALS patients? And do you expect more prominent treatment outcomes in subgroups of ALS patients?

Christian Cluster: Sure.

Speaker Change: Thank you for taking my questions.

Kelly: Just curious for the AOS trial, you mentioned most of our.

Matthew Klein: Auction Luxor stature is true inhibiting.

Kelly: So Rob Ptosis wonder what kind of a genetic biomarker associated with for Rob Ptosis.

Matthew Klein: I'll ask patients and do you expect more prominent of treatment all com in subgroups of patients.

Matthew Klein: Kelly, thank you very much for the question. Therapeutics is a pathway, a relatively recently described pathway of inflammation, cell stress, and cell death that is increasingly being linked to neurodegenerative diseases, including ALS. And what is important about this is it's not related to any specific genetic abnormality; it's really a common response pathway in ALS, and that's why our trial with eutrologist 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 of ALS.

Matthew Klein: Patients.

Speaker Change: Okay. Thank you very much.

Speaker Change: Question third closeness as a pathway a relatively recently described pathway inflammation cell stress and cell death.

Matthew Klein: That is increasingly being linked to neurodegenerative diseases, including ALS.

Kelly: And what is important about this is it's not.

Matthew Klein: Related to any specific genetic asked about it's really a common response pathway in E. L F.

Kelly: Why our trial with each market that is in.

Matthew Klein: Enroll both genetic.

Matthew Klein: And idiopathic ALS patients. So this is one advantage of this approach is that we are targeting a pathway comment to any genetic or non genetic cause of ALS.

Kelly: Okay.

Speaker Change: Okay. Thank you.

Unknown Attendee: Thank you. One moment for our next question, please. Our next question comes from the line of Sammy Corwin with William Blair. The line is now open.

Speaker Change: Thank you one moment for our next question. Please.

Unknown Attendee: Right.

Kelly: Our next question comes from the line of Sami Corwin with William Blair. Your line is now open.

Unknown Attendee: Yes, Sammy, thank you very much for the questions. I'll just make a brief comment, then I'll turn it over to Kyle to give a little bit more detail.

Samantha Danielle Corwin: Hey, guys. Thanks for taking my question and congrats on the quarter.

Samantha Danielle Corwin: I was wondering if you could provide any additional color on how much the EU contributed to translate into revenue this quarter.

Matthew Klein: Certainly, on your second question, given the unmet need for non-sensitization DMD patients in the U.S. and what's known about transluonin, a number of patients have been on transluonin for years, there's a great amount of anticipation for the potential availability of transluonin once FDA approval. And similarly, for vatiquinone, for pediatric patients, there's a significant remaining unmet need, and it's now well appreciated in the physician expert community as well as the patient community that the data that we've collected in MOVE-FA demonstrating that important...

And then have you heard any feedback from U S physician patient.

Matthew Klein: Et cetera on their perception of the <unk> and the kit went out data and kind of what their view of what the commercial potential might be in the U S.

Matthew Klein: Okay.

Speaker Change: Yes, certainly thank you very much for the questions I'll take the.

Kelly: A brief comment and then I'll turn it over to Kyle to give a little bit more detail.

Matthew Klein: Certainly.

Your second question.

Matthew Klein: Given the unmet need pronounces mutation DMD patients in the U S and what's known about travel on a number of patients who've been on trend for years physically amounts of anticipation for the potential.

Kyle: Availability of transport to get FDA approval, and similarly for particular announced for pediatric patients business significant remaining unmet need.

Matthew Klein: Significant Effect on Upright Stability. And what that means in terms of delaying time and loss of ambulation is incredibly meaningful for patients. And therefore, there really is a significant amount of interest in the tachycardia in the FAA community. All right, I'll turn it over to you for one more call along with the other units.

Pierre Gravier: It's well appreciated in the physician expert community as well as the patient data.

Pierre Gravier: That we've collected to move ethane demonstrating that importantly.

Kyle: Significant effect, an 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.

Kylie O'Keefe: Yeah, thanks, Matt. And thanks, Sammy, for the question.

Speaker Change: More particularly island.

Speaker Change: <unk>, Alright, I will turn it over to you for more color on.

Unknown Attendee: Kevin.

Kylie O'Keefe: I think starting with your first question, Sammy, around the contribution from European revenue for TransLana, it's pretty consistent with the first quarter of last year. We've shared that, you know, it represents around 45% of total revenue, and it's pretty consistent when you look at Q1 of this year compared to Q1 of last year. So, as Matt said earlier and in his comments, the plan going into the quarter was to continue to ensure patients have access to TransLana while it remains on the market. And I think the team has done an incredible job executing on that plan.

Speaker Change: Okay.

Speaker Change: Yes, Thanks, Matt and thanks, Tony for the question I think starting with your first question for me around the contribution from <unk>.

European revenue for trends line, it's pretty consistent with the first quarter of last year, we've shared that.

Kylie O'Keefe: Present around 45% of total revenue and it's pretty consistent.

Kylie O'Keefe: When you look at Q1 of this year to Q1 of last year. So as Matt said earlier in his comments the plan going into the quarter was to continue to ensure patients have access to trends line of 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 you.

Kylie O'Keefe: So contribution is about consistency. And jumping to your second question about TransLana in the U.S. and perception there, and also for Tequanone and FA, I think what Matt said is absolutely accurate. I think starting with TransLana, there's still nothing available for nonsense mutation DMD patients, and so there's a higher medical need there. And then when you look at FA, there's nothing available for pediatric patients. And I think physicians are starting to understand how SkyClaris fits into the marketplace in older patients, and there's still a place for Tequanone in those older patients as well.

Speaker Change: Question around <unk> in the U S and perception, there and also the <unk> and <unk>.

I think I think what Matt said is absolutely accurate I think starting with translunar, there's still nothing.

Pierre Gravier: <unk> for nonsense mutation DMD patients and so there's a high unmet medical need there and then when you look at at Fe does nothing available for pediatric patients and I think physicians are starting to get to understand how Scott Scott <unk> fits into the marketplace in the older patients and there is still a place for the chicken I mean, those older patients as well.

Kylie O'Keefe: So across the board, we've seen very positive feedback. Physicians are very well versed in TransLana in the U.S., as Matt said, there are a number of patients that are on the drug. And then as we're engaging with the community on FA, there's positive feedback coming there too.

Kylie O'Keefe: So across the board, we've seen very positive feedback.

Kylie O'Keefe: Physicians are very well versed on trends later in the U S is that said that the number of patients that are on the drug and then as were engaging with the community on FY <unk>.

Speaker Change: Positive feedback coming that too.

Unknown Attendee: Thank you. One moment for our next question, please. Our next question comes from the line of Joseph Thome with TD Cowan. Your line is now open.

Speaker Change: Great. Thank you.

Speaker Change: Thank you one moment for our next question. Please.

Joseph Patrick Schwartz: Our next question comes from the line of Joseph <unk> with TD Cowen. Your line is now open.

Unknown Attendee: Hi there. Good afternoon.

Matthew Klein: Thank you for taking my questions. Maybe on the Huntington study, it looks like maybe this might be the first time we're really committing to some of those functional measures, the TMS, TFC, and CU-HDRS. What are your expectations for efficacy on those points? Is 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 see them? Maybe a second question, just on AADC gene therapy, can you talk a little bit about reimbursement progress in Europe, and maybe what you are learning there that you can apply to the U.S.? Thanks.

Joseph Patrick Schwartz: Hi, there good afternoon. Thank you for taking my questions maybe on the Huntington study.

Matthew Klein: It looks like maybe this might be the first time, we're really committing to some of those functional measures the Tms TFC in CAH Drs.

Joseph: Maybe what are your expectations for for efficacy on those points as the follow up time that we're seeing.

Matthew Klein: In the Q2 data going to be long enough to show a benefit on these measures do you think or how should we interpret those data when we when we see them and maybe second question just on the ADC 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 U S.

Matthew Klein: Thanks for the questions, Joe. We are very much looking forward to the HD 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, get a glimpse at the NF biomarker effect, including Huntington protein levels in the CSF, NFL levels, and brain volumes.

Speaker Change: Thanks for the question Joe.

Matthew Klein: We are very much looking forward to the HG 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 for whom we shared 12 week data last summer and this will allow us to for the first time yet.

Matthew Klein: A glimpse at CNS biomarker effects, including Huntington protein levels in the CSF NFL levels brand volumes and as Heath pointed out.

Kylie O'Keefe: And as you pointed out, the Clinical Scales, looking at the total motor score, CHU-BRS, and total functional capacity. I think from our standpoint, a home run on the data would be to be able to see continued safety and tolerability after 12 months and then be able to see some signal of CNS activity, whether that's on biomarkers or on any of the clinical scales. And given the small number of patients, I think we're really looking for a signal or a trend here, given the duration, 12 months, and as we said, this is approximately 30 patients.

Kylie O'Keefe: Clinical scale looking at the total motor score <unk> until the functional capacity.

Speaker Change: I think from our standpoint, a homerun on the data would be to be able to see continued safety and tolerability. After 12 months and then be able to see some signal of CNS activity, whether thats on biomarkers or off on any of the clinical scale and given the small number of patients I think we'd really looking for a signal or a trend here.

Kylie O'Keefe: Given.

Kylie O'Keefe: The duration of 12 months ago. When we say this is approximately 30 patients and so that's how we're really looking at success safety Tolerability at us signal either on biomarker and clinical studies that were having CNS activity I think patient.

Kylie O'Keefe: So that's how we're really looking at success here, safety, tolerability, and a signal either on biomarker or clinical scales that we have CNS activity in patients. And let me turn it over to my colleagues. Do you want to get some more color on A and C reimbursement and how that's setting the stage for me? Yeah, absolutely.

Kylie O'Keefe: Now, let me turn it over to Colin.

Colin: More color on the agency reimbursement and how that setting the stage for you.

Kylie O'Keefe: Yeah, absolutely. We continue to see progress with pricing and reimbursement negotiations across Europe. And we've continued to have favourable 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 through cross-border healthcare. And so that's continued success in this space. If you talk about learnings and how we sort of think about the US market, I think one of the things that we've walked away with from some of these discussions is that there is a recognition of high unmet need in AADC, and with the absence of standard of care from a disease-modifying point of view, there are no treatments available.

Speaker Change: Yeah, 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 trading patients in those additional countries as we talked about in the quarter, we treated additional patient in France in the UK and additional patients.

Kylie O'Keefe: And through cross border health care, and so that 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 from.

Kylie O'Keefe: From some of these discussions is that the recognition of high unmet need in ADC and then with the absence of standard of care from a disease modifying point of view, there's no treatment available that the recognition of a ultra orphan condition and therefore, a small budget impact and a recognition of the transformative results that come with it.

Kylie O'Keefe: There's a recognition of an ultra-orphan condition and, therefore, a small budget impact, and a recognition of the transformative results that come with the treatment of Upstazer. And so, together, this allows us to be able to move forward with favourable pricing and reimbursement negotiations. And we do expect that to carry across into the US upon launch.

Kylie O'Keefe: <unk> of upside, though 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.

Unknown Attendee: Thanks, Jeff. Thank you. One moment for our next question, please. Our next question will come from the line of Brian Abrahams with RBC. The line is now open.

Speaker Change: Great. Thank you very much.

Speaker Change: Thanks, Jay Thank you one moment for our next question. Please.

Unknown Attendee: Our next question will come from the line of Brian Abrahams with RBC. Your line is now open.

Unknown Attendee: Hi, this is Joan on behalf of Brian. Thanks for taking our question. So back on TransLarna, can you talk more about the buying pattern you've seen for TransLarna in Europe in recent weeks? If the European Commission does decide to follow the CHMP opinion, are you seeing anything on the ground that might suggest that withdrawal from the channels may be more gradual or, on the opposite side, even more rapid than you're expecting? Thanks.

Unknown Attendee: Hi, This is Joe on for Joe on for Brian. Thanks for taking my question.

Speaker Change: So back on track.

Unknown Attendee: Can you talk more about the buying pattern, you're seeing for Translarna in Europe.

Unknown Attendee: In recent weeks.

Unknown Attendee: If European Commission does decide to follow <unk> opinion are you seeing anything underground might suggest that could withdraw from the channels may be more gradual or yes.

Speaker Change: On the other side, even more rapid.

Matthew Klein: Yeah, thanks for the questions, Joe. Look, we are seeing, as I said, really business as usual. Their prescriptions and numbers are really unchanged, and it goes without saying that patients and physicians want to take advantage of every day that transluana is on the market, and we expect that fully to continue to be the case. Our teams, as Kylie pointed out, are focused on ensuring that happens, and we're ensuring that patients have access to therapy.

Unknown Attendee: And you're expecting thanks.

Speaker Change: Yes, thanks for the questions Joe.

Matthew Klein: Look we are seeing really business as usual.

Matthew Klein: Prescriptions in numbers are really unchanged here.

Matthew Klein: And it goes without saying that the patients added acquisitions want to take advantage of every day that trends Lora is on the market and we expect that fully to continue to be the case.

Matthew Klein: Kansas is probably quite that our focus on ensuring that happens that we're showing that patients have access to therapy of course, we've also been working in the background to put.

Matthew Klein: 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 transluana in the event that the EC Commission adopts the opinion in transluana.

Matthew Klein: Mechanisms in place to leverage mechanisms that might be available on a country by country basis to continue to provide trend water in the event that the EC Commission adopts the opinion trade one has a job.

Matthew Klein: Got it. Thank you. If I could squeeze in one more, are you scheduled to meet with the FDA regarding the uptrend filing anytime soon? I was wondering if you'll get any visibility on whether you can file in parallel to the carcinogen study.

Speaker Change: Got it. Thank you if I could squeeze in one more.

Matthew Klein: Are you scheduled to meet with the FDA regarding our <unk> filing anytime soon.

Matthew Klein: I'm just wondering if youll get a visibility on whether you can file in parallel to the extension study.

Matthew Klein: Yes, we had, Joe, we had the pre-NDA meeting last year with the agency last fall, and it was very clear that every other part of the package was there and in place, that safety and efficacy data would support our NDA and support approval upon review. And one outstanding matter was the completion of that Carson Agency study.

Matthew Klein: Alright.

Matthew Klein: Thank you, yes, we had Joe we had a pre NDA meeting last year with the agency last.

Matthew Klein: Paul and it was very clear that every other part of the package is there and in place.

Matthew Klein: Safety efficacy data would support.

Matthew Klein: NDA in support approval.

Matthew Klein: In our view and what outstanding matter was the completion of that Carcinogenicity study. We mentioned that we expect that study to be done in June we don't expect to ever for a meeting with the agency. We did say that we plan to contact them to discuss timing of the submission relative.

Matthew Klein: We 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, but maybe bring that in a little earlier to Q2 based on that correspondence. But we don't expect that it will be a formal meeting.

Matthew Klein: Relative to the completion of that study, we said that we still remain on track to submit in Q3, but for maybe bringing that in a little earlier into Q2 based on the correspondence, but we don't expect that will be a formal meeting.

Unknown Attendee: Operator Thank you. One moment for our next question. Our next question comes from the line of Jenna Wang with Barclays. Your line is now open.

Speaker Change: Got it thank you Matt.

Jenna Wang: Thank you one moment for our next question.

Unknown Attendee: The next question comes from the line of Gena Wang with Barclays. Your line is now open.

Unknown Attendee: Thank you. I just have a very quick question. The first one is regarding TransLana's status in Europe. Based on your discussion with EMA, when do you expect TransLana to be withdrawn in Europe?

Jenna Wang: Thank you I just have a very quick questions.

Jenna Wang: The first one is regarding translarna.

Unknown Attendee: Nope.

Unknown Attendee: Status.

Jenna Wang: Based on your discussion with <unk> when do you expect trends will.

Unknown Attendee: It will be withdrawn in Europe.

Matthew Klein: And then the second question is regarding sepatarians in PKU. I think you mentioned that you wanted to target the initial patient population. That could be one part of a classical PKU. Can you help us understand how, you know, our understanding that the sepatarian is a precursor of a co-factor and a classical PKU usually does not have any alanine hydroxylase, so basically does not have an enzyme, like how would the sepatarian be helpful in the classical PKU patient population? Thank you for the questions, Gene.

Matthew Klein: And then second question is regarding <unk>.

Matthew Klein: Materials in PKU.

Gene: I think you mentioned that you wanted to.

Matthew Klein: Target initial patient population that could be one part is a classical GPU can you help us understand how.

Matthew Klein: Understanding that the secretary is a precursor for coal sector and across your PKU, usually does not have any.

Gene: Hi, Hi, hydroxylase, so basically does not have enzymes like how would.

Speaker Change: The chairman will be helpful.

Matthew Klein: Thank you for your questions, Gina. As we discussed regarding your first question on the status of trans law in Europe, 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 the adoption of the opinion has not occurred. We had to notify that the Commission was planning to meet this week to discuss the matter.

Matthew Klein: So to your patient population.

Matthew Klein: Thank you for the question as Gina discussed regarding your first question.

Matthew Klein: On the status of Translarna in Europe.

Matthew Klein: Following the opinion in January typically the European Commission would have adopted that opinion within 67 days clearly we're sitting here in April and that adoption in your opinion has not occurred.

Matthew Klein: <unk> had to notify the commission was planning to meet this week.

Matthew Klein: To discuss the matter.

Matthew Klein: And I assume they're taking into consideration the current status in Europe, the lack of alternative therapies for patients with non-sense mutation BND, the data which supports the safety and efficacy of transluana, and the outpouring of support for the authorization remaining intact from the patient and physician community across Europe. So I think they're looking at the matter closely. We expect to have an update in the near future, and as we said, until that time, it's really business as usual.

Matthew Klein: I assume they are taken into consideration the current status in Europe. The lack of alternative therapies for patients with nonsense mutation DMD data, which support the safety and efficacy of transplant.

Matthew Klein: Portfolios.

Matthew Klein: Support for the authorization remaining intact from the patient and physician community across.

Matthew Klein: Across Europe, So I think I look at the matter closely we expect to have an update in the future and as we said until that time, it sort of business as usual using every day to continue to ensure that patients have access to translarna.

Matthew Klein: We use it every day to continue to ensure that patients have access to transluana. On your second question regarding classical PKU, I think there's sometimes a misunderstanding. The definition of classical PKU is basically patients, children, or adults who at some point in their life have a documented phenylalanine level of greater than 1200 micromolar per liter. And that could be at any point in time, or it could be lower if they get on the diet under control.

Matthew Klein: Your second question regarding classical continue I think there's sometimes a misunderstanding.

Matthew Klein: Definition of classical PKU is basically.

Matthew Klein: Patients children or adults so at some point and there might have a documented.

Matthew Klein: Phenylalanine levels of greater than 1200, micro molar per liter and that could be at any point in time or could they be lower they can out of the diet control.

Matthew Klein: A very small number of those patients have what's called homozygous null mutations. That means they have on both alleles a null mutation that prevents them from having the phenylalanine hydroxylase enzyme. But that is a very small minority of patients. Therefore, the remainder of the classical PKU patients have a functional enzyme. Obviously, it's severely affected by the mutation and has a low function. Cepiaterin is, as you pointed out, a precursor of BH4, which is the cofactor for the enzyme. It also has a second function, which is a chaperone function that stabilizes the conformation of the PAH enzyme.

Matthew Klein: There is small number of those patients have what is called homozygous normally patients that means they have on boats.

Matthew Klein: Unknown mutations that prevents them from having.

Matthew Klein: Federal Alley hydroxylase enzyme.

Matthew Klein: Very small minority of patients.

Matthew Klein: And therefore, the remainder of the classical PKU patients have functional antibody, obviously severely affected by the mutation in heart function CPA Taryn.

Matthew Klein: As you pointed out a precursor of BH for which he is the co packer cutting edge science. It also has the second function, which is a chaperone culture, which stabilizes the confirmation of the th environment 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.

Matthew Klein: 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 effect. In fact, in the INFINITY trial, in the subset of classical PKU patients, we had a mean generality reduction of 69%. That was actually a greater magnitude of reduction than was observed in the overall population, so it's certainly indicating that cepiaterin can play an important role for these patients. Similarly, as we've mentioned, we've seen patients go into the extension and participate in the tolerance protocol.

Matthew Klein: The affinity trial and the subset of classical PKU patients, we had a knee federal alanine reduction of 69% that was actually a greater magnitude of reduction that was observed in the overall population. So certainly signifies that <unk> can play an important role for these patients. Similarly, as we concluded that we have seen patients go into the open label.

Matthew Klein: Sanction and participating tolerance protocol, we are seeing classical PKU patients.

Matthew Klein: We are seeing classical PKU patients, which is defined as classical PKU patients being able to liberalize their diet and maintain control of phenylalanine. So all of that really speaks to the importance of cepiaterin and the potentially really important role it has for all patients with PKU, including those classical patients who tend to be the most

Matthew Klein: Defying the classical PKU patients being able to liberalized their diet and maintain control of NOL. So all of that really speaks to the importance of CPU taryn and potentially a really important role for all patients with PKU, including both classical patients who are tend to be the <unk>.

Matthew Klein: Cindy.

Matthew Klein: Yeah.

Unknown Attendee: Thank you. One moment for our next question. Our next question comes from the line of Jeff Hung with Morgan Stanley. The line is now open. Thanks for taking my questions.

Speaker Change: Thank you one moment for our next question.

Unknown Attendee: Our next question comes from the line of Jeff Hung with Morgan Stanley. Your line is now open.

Jeff Hung: Hey, Thanks for taking my questions Principia upturn can you just remind us of the data that's collected in patients under two years old and are there plans or timelines for starting that and then given the meaningful effect on book.

Matthew Klein: Thanks, Jeff. We did include patients under 2 in the Affinity study. Now, they went through the initial run-in phase, and we had patients who had a greater than 30% reduction in the run-in phase, but the regulatory authorities wanted those very young patients not to be randomized but to go directly into the Open Label Extension study, directly into long-term extensions. So we're getting data in a number of patients under the age of two.

Speaker Change: Like what would you give you give you confidence for results translated the younger patients.

Speaker Change: Thanks, Jeff.

Matthew Klein: We did include patients under two and the affinity study.

Matthew Klein: They went through the initial run NXP and we had patients who had a greater than 30% reduction in the launch phase, but the regulatory authorities wanted them barragan cases, not to be randomized, but to go directly into the open label extension study. So we have patients who started in <unk>.

Matthew Klein: Trinity who were under two and we've actually had additional patients that we've enrolled.

Matthew Klein: And what we're seeing is exactly what we're seeing in patients over the age of two. We're seeing safety and tolerability and also efficacy in terms of reducing fentanyl. So again, the data continue to support the potential benefit of CPTAN in the full range of PKU patients, both classical and non-classical, and in patients of all ages.

Matthew Klein: Directly into long term extension, so we're getting data in a number of patients under the age of two and what we're seeing is exactly what we're seeing in patients over the age of too we're seeing safety and Tolerability and also efficacy in terms of reducing federal Allomap. So again the data continue to support.

Matthew Klein: The potential benefit of secret there in the full range of PKU patients both classical nonclassical patient book all pages.

Unknown Attendee: Thank you. One moment for our next question, please. Our next question comes from the line of Joseph Schwartz with Lerig Partners. Your line is now open. Bye, everyone.

Speaker Change: Great. Thank you.

Joseph Patrick Schwartz: Thank you one moment for our next question. Please.

Unknown Attendee: Our next question comes from the line of Joseph Schwartz with Leerink Partners. Your line is now open.

Unknown Attendee: Hi, everyone. This is Danny on for Joe.

Unknown Attendee: Yes, thank you very much for the call. The question, rather, is rather. So we are, we designed the cardinal study to be, as you said, registration directly. And this came from our feedback with FDA, both in terms of the duration of the study being roughly a six month study, placebo control, and the endpoint strategy having the primary endpoint being the ALS-FRS scale. We would define success here as a statistically significant benefit on the primary endpoint, which on the ALS-FRS scale, that has traditionally been the threshold for agency approval.

Unknown Attendee: So I was wondering if you could just talk a little bit more about the <unk> readout for Alex I think you've said in the past that the study could be Registrational can you give us an idea of what regulators will be looking for.

Unknown Attendee: Uh huh.

Unknown Attendee: And can you kind of give us some insight into what a clinically meaningful change in ALS functional rating scale.

Speaker Change: Thank you.

Speaker Change: Yes, Jamie Thank you very much for the call.

Unknown Attendee: The question Robert So we are we designed the Cardinal study.

Unknown Attendee: As you said registration directly and this team from our feedback with FDA. Both in terms of the duration of the study being.

Unknown Attendee: Roughly six month study placebo control and the endpoint strategy, having the primary endpoint being the ALS FRS scale.

Unknown Attendee: We will define success here as a.

Unknown Attendee: Specifically significant benefit on the primary endpoint, which of the AOS.

Unknown Attendee: Stefan a sale that has traditionally been the threshold for agency approval. We powered the study to have what we believe would be a clinically meaningful.

Unknown Attendee: We powered the study to have what we believe would be a clinically meaningful effect, which is roughly a two and a half 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 ALS-FRS, we also, of course, have secondary endpoints capturing other important aspects of the disease, including mortality, and respiratory function, where we, of course, will look for supportive data on that ALS-FRS scale. We believe that would position us to advance Mutant Oxide for approval in the U.S.

Unknown Attendee: Clinically meaningful effect, which is roughly two five point difference between the treatment and.

Unknown Attendee: A placebo group.

Unknown Attendee: Thanks.

Unknown Attendee: We designed the study to be well powered to detect that so we believe if we were able to how statistical significance on the OSF RF. We also of course have secondary endpoints, capturing other important aspects of the disease, including mortality, including respiratory function.

Unknown Attendee: Where are we of course will look for supportive data of that.

Unknown Attendee: <unk>, we believe that would position us to.

Unknown Attendee: Advance each lifestyle for approval in the U S.

Speaker Change: Great. Thank you.

Speaker Change: Thank you one moment for our next question. Please.

Unknown Attendee: Okay.

Unknown Attendee: Our next question comes from the line of David Leibowitz with Citi. Your line is now open.

Matthew Klein: Thank you. One moment for our next question, please. Our next question comes from the line of David Lebowitz with Citi. Your line is now open.

David Neil Lebowitz: Thank you very much for taking my question.

David Neil Lebowitz: To this point have you really.

David Neil Lebowitz: Significantly felt the presence of generic Frazer.

Matthew Klein: Or.

Unknown Attendee: Thank you very much for the question. As we talked a bit on the call, we've put a lot of strategies in place to preserve the Enplaza market, even in the face of genetic competition. I'd like to talk a little bit more about what we're seeing in terms of that.

David Neil Lebowitz: Recently approved.

Unknown Attendee: Lamar alone.

Unknown Attendee: Okay.

Unknown Attendee: David Thank you very much for the question.

Unknown Attendee: We talked a bit about.

Unknown Attendee: Paul we put a lot of strategies in place to preserve.

Unknown Attendee: The plaza market, even in the face of generic competition.

Unknown Attendee: I talked a little bit more about what we're seeing in terms of dynamics.

Kylie O'Keefe: Yeah, absolutely. I think, David, the answer, the quick answer to that is no.

Speaker Change: Yes, absolutely I think David the answer the quick answer to that is no.

Kylie O'Keefe: And I think that's a testament to the strategies that the team has put in place to protect the business. And as we've said, in the first quarter, they've been executing on that. I think what's really been a strong message for us is the continued number of 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 Implaza and the continued benefits seen by both patients and physicians. Thanks for taking my question.

Kylie O'Keefe: That's a testament to the strategy that the team has put in place to protect the business and as we've said in the first quarter they've been executing upon that I think what's really been.

Kylie O'Keefe: 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 <unk> and the continued benefit seen by both patients and physicians.

Kylie O'Keefe: Thanks for taking my question.

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

Speaker Change: Thanks, David.

Danielle Brill: Thank you one moment for our next question. Please.

Unknown Attendee: Our next question comes from the line of Danielle Brill with Raymond James Your line is now open.

Unknown Attendee: Hi, guys. Good evening. Thanks for taking our questions. I have two brief ones.

Danielle Brill: Hi, guys. Good evening, thanks for taking our questions I have two brief ones.

Matthew Klein: First, to clarify the trans-LARNA 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 called because the EC is considering not ratifying the decision? And then the second question is about the particularly known sadness in the EMA. I believe EMA feedback on the feasibility of a conditional approval was expected at one cue. Any updates on that front? Thank you.

Matthew Klein: First to clarify on Translarna status in the EU is it possible that the delay in the EC ratification of the C. H M P.

Matthew Klein: On a procedural or was this meeting.

Matthew Klein: Weeks, specifically call because the ECP is considering not ratify the decision.

Matthew Klein: And then on the <unk>.

Matthew Klein: Question is about the checkpoint on sadness and the MAA I believe EMA feedback on the feasibility of a conditional approval is expected in <unk> any updates on that front. Thank you.

Matthew Klein: Thanks, Danielle, for the questions. For your first question, the typical procedure is 67 days. Usually, this is done in writing. It's usually a written agreement across the member states, and that then allows for ratification by the EC. That procedure, we know, was paused, and instead, a live meeting was called for discussion. What the exact nature of that discussion was, or what motivated that discussion, we can't say. What we can say is that the typical EC adoption occurs within 67 days or clearly beyond that time point. It's typically a written procedure. They're having a lot of meetings. So there are a lot of things that are going on now that are really atypical.

Speaker Change: Yes, Thanks, Danielle for the question on your first question.

Matthew Klein: The typical procedure is 67 days, usually this is done by writing.

Matthew Klein: Written.

Matthew Klein: Agreements across the member states.

Matthew Klein: It allows for the ratification by the AUC that procedure, we know was paused instead of like meeting was called for discussion.

Matthew Klein: The exact nature of that discussion was what motivated that discussion we can say.

Matthew Klein: What we can say is that typical.

Matthew Klein: You see adoption occurs within 67 days, we're clearly beyond that time point, it's typically a written procedure, they're having a lot of meetings. So theres a lot of things that are going on now.

Matthew Klein: Really atypical.

Matthew Klein: 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't say. But what we can say is we're far beyond what we had expected and what was typically observed, and the procedure has not gone according to what typically happens. In terms of your question regarding the ticker number, we had previously shared that we had gotten feedback from the EMA, and we had gone through the scientific advice procedure.

Matthew Klein: What that means in terms of the ultimate EC decision whether to adopt the opinion and the matter back to the CHP whatever the right side. We can say what we can say is we're far beyond what we had expected and what was typically observed and the procedure has not gone according to our typically.

Matthew Klein: Happens.

Matthew Klein: In in terms of your question regarding particularly on we had previously shared that we had gotten feedback from the EMA, we have gone through the scientific advice procedure.

Matthew Klein: They did not indicate that they thought that the MOVE-FA study could support 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 that recent meeting with the FDA in Q1, we are moving forward with the NDE based on the MOVE-FA study as well as open-label extension data, both from the older study performed a few years back as well as from the MOVE-FA long-term open label extension.

Matthew Klein: <unk> did not indicate that they thought that the move that phase study could support conditional authorization at this time, we're looking forward to further discussions with them and of course on the FTE side, we have a different experience. We're after we had there recently meeting with the FDA in Q1.

Matthew Klein: We are moving forward with ENB based on we'll move that they study as well as open label extension data both from the older setting perform a few years back as well as from the moves that they are long term open label extension.

Unknown Attendee: Thank you for the clarification.

Unknown Attendee: Okay.

Unknown Attendee: 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.

Unknown Attendee: Thank you for the clarification.

Tazeen Ahmad: Thank you one moment our next question please.

Tazeen Ahmad: Our next question comes from the line of <unk> Ahmad with Bank of America. Your line is now open.

Matthew Klein: Hi guys, thanks so much for taking my question. 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, what's your level of confidence that a biomarker can be used at least as an endpoint, maybe not the sole endpoint? Has that topic been brought up in recent discussions? Thanks.

Tazeen Ahmad: Hi, guys. Thanks, so much for taking my question.

Matthew Klein: One on the FAA.

Matthew Klein: Can you just talk to us about the patient population.

Matthew Klein: Different it might be in the U S versus EU in terms of sizing.

Matthew Klein: And then secondly for Huntington based on the conversations that you've been having so far with the agency what's your level of confidence that that a biomarker Kennedy used at least as an endpoint.

Matthew Klein: Maybe not the endpoint.

Matthew Klein: Endpoint.

Matthew Klein: On that topic.

Matthew Klein: It's been brought up in recent discussion.

Matthew Klein: Thank you very much for the questions, Tazeen. In terms of populations for FA, it's roughly a similar size population prevalence in the U.S. and in Europe. Clearly, in both territories, there's nothing indicated for patients under the age of 16, and we talked a lot about how the data from the FA really supports the important treatment effects in that population with regard to delay in time of loss of ambulation. Obviously, that has applicability beyond just the under 16-year-old patients; the effects we observed in upward stability are relevant to all ambulatory patients with freegic apaxia. Populations are roughly the same size.

Matthew Klein: Thank you very much for the question as to being in terms of populations for FAA is roughly similar sized population.

Matthew Klein: <unk> in the U S.

Matthew Klein: And in Europe.

Matthew Klein: 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.

Matthew Klein: The.

Matthew Klein: Data from Fei really supports.

Matthew Klein: B J.

Matthew Klein: Important treatment effect in a population with regard to delay title.

Matthew Klein: Lots of ambulation.

Matthew Klein: And obviously that has applicability beyond just the under 16 year old patients the effects, we observed in our part stability of element to all ambulatory patients with frequent attacks so part.

Matthew Klein: We see an ability to fill the unmet need in the pediatric population but also potentially have an important effect for all ambulatory patients regardless of their age. I believe your second question was on biomarkers and HD as an endpoint. Is that correct?

Matthew Klein: Population is roughly the same size, we see an ability to fill the unmet need in the pediatric population, but also potentially having important.

Matthew Klein: <unk> effects for all ambulatory patients regardless of their age I believe your second question was on biomarker in HD as an endpoint is that correct.

Matthew Klein: So, we have not had discussions yet with the agency regarding biomarker accelerated pathways and biomarkers' role in the endpoint strategy. But I think we've clearly seen that the agency, 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 that definitive efficacy data in a phase 2 trial takes many, many years. I think the challenge we have in HD, of course, is that there's no precedent yet for what that accelerated approval biomarker would be.

Speaker Change: That's great.

Speaker Change: Okay. So it would be.

Matthew Klein: Yeah.

Matthew Klein: We have not had discussions yet with the agency regarding biomarker accelerated pathways and biomarkers roll in and the endpoint strategy.

Matthew Klein: 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 you'd like Alzheimer's disease, we're collecting that definitive efficacy data in a phase II trial. It takes many many years I think the challenge we have in each key of course is there is no.

Matthew Klein: The precedent yet for what that accelerated approval biomarker would be.

Matthew Klein: We believe that the PIVOT-HD study offers several important biomarkers, including peripheral Huntington-Muller, particularly with a systemically administered drug. And obviously, we've talked a bit about the potential for NFL levels, which have been used in the case of Tefercin for ALS, and then also things like Huntington 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 of what a pathway using biomarker data would look like or what would be, as you asked, the role of biomarker data in establishing the efficacy of a therapy. But we think there certainly should be an appetite just based on the agency's recent activities.

Matthew Klein: We believe that the pivotal <unk> study offer several important biomarkers, including peripheral Huntington lowering particularly with a systemically administered drug and obviously you've talked a bit about the potential for NFL levels, which has been used in the case of to first improve and then also things like Huntington protein in the CSF. So what we plan to do it.

Matthew Klein: 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 or what would be.

Matthew Klein: The role of biomarker data in establishing efficacy of the therapy for Huntington's disease, but we think theres certainly should be an appetite just based army agencies' recent activity.

Unknown Attendee: 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.

Paul Choi: Okay. Thank you.

Paul Choi: Thank you one moment for our next question.

Unknown Attendee: Our next question comes from the line of Paul Cheng with Goldman Sachs. Your line is now open.

Unknown Attendee: Good afternoon, and thank you for taking my questions. I have two, and my first is just with regard to the Cardinals trial and ALS. In the wake of the recent Phoenix study results from AmLex, have you either implemented or contemplated any, you know, study design changes or changes to the statistical plan, just based on the recent Phoenix results, and just, you know, what your thoughts are there? And then, second, just to follow up on PIVOT HD and PTC 518, can you maybe just comment on, with regard to your regulatory discussions, just on the safety side for U. Thank you for taking my questions.

Speaker Change: Good afternoon, and thank you for taking my questions I have.

Unknown Attendee: And my first is just with regard to the.

Unknown Attendee: The Cardinal trial in <unk> in the wake of the recent.

Unknown Attendee: Phoenix study results from Amex have you either implemented or contemplated any study design changes or changes to the statistical plan just based on the recent Phoenix results and just what your thoughts are there and then second just to follow up also as well on pivot.

Unknown Attendee: And PTC 508 can you maybe just comment on that.

Unknown Attendee: With regards to your regulatory discussions just on the safety side for U S sites and any progress that may have been made there. Thank you for taking my questions.

Matthew Klein: Thank you very much, Paul, for the questions. Your first question regarding cardinals, when the FDA has been quite clear on what they want to see in terms of analytical approaches for the ALS FRS. They're very interested in understanding changes in score as a continuous variable. They've also been interested in understanding mortality and the time to death. And specifically, they 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 the ALS FRS score as well as patients who may have died and the information about their timing 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 wanted to see. And that doesn't change with anything regarding the Phoenix study.

Matthew Klein: Thank you very much Paul for the question. Your first question regarding Cardinal when we did the FDA has been quite clear on what they want to see in terms of analytical approaches for the ALS FRS there.

Matthew Klein: Interested in understanding changes in score as a continuous variable they've also been interested in understanding mortality and the time to mortality and specifically you talked about wanting to understand the difference in scores.

Matthew Klein: <unk> treatment in placebo and then also implementing something.

Matthew Klein: Called the joined rank test, which is a way of analyzing together both the change in <unk> as well as patients who may have died and the information at the time of death. Following enrollment. So we've of course taken the agency's guidance to ensure that our analysis plan with consistent with what they want to sleep.

Matthew Klein: And that doesn't change with anything regarding the Phoenix that we work closely with the agency in designing a study to ensure that it would be ledger.

Matthew Klein: We work closely with the agency in designing the study to ensure that it would be registration-directed and ensuring that we have the appropriate analysis plan so that when we get the results, if they're positive, we'd be well positioned to advance the drug towards approval. Regarding your question on safety data from PIVOT-HD and discussions with the agency, as we prepare for the second quarter data disclosure, we will then have the safety data that the agency has asked us to review in order to lift the partial hold.

Matthew Klein: Registration directed in ensuring that we have the appropriate analysis plan. So that when we get the results. If they are positive that we'd be well positioned to advance the drug towards approval regarding your question on.

Matthew Klein: Safety data contributing <unk> in discussions with the agency as we prepare for the second quarter data disclosure, we will have that have the safety data that the agency has asked to review in order to lift the partial hold so we look forward to submitting those data to the agency when available.

Matthew Klein: So we look forward to submitting those data to the agency when they are available. Just as a reminder, they had asked us, following the last data review of 12-week data, to provide them with 6-month data on a sufficient number of subjects that would confirm what we've seen at 12 weeks. Well, clearly, we're going to be in a position to provide the agency not only 6-month data but 12-month data on a number of patients. And, as we've shared, we're continuing to see the drug being well tolerated. So we look forward to putting that data package together, submitting it to the agency, and hopefully lifting that partial hold requirement.

Matthew Klein: Just as a reminder, they had asked US following the last data review of 12 week data to provide them with six months data on a sufficient number of subjects that would confirm what we've seen at 12 weeks, while clearly we're going to be in a position to provide the agency not only six months data with 12 months data on a number of patients and as we've shared we're continuing.

Matthew Klein: To see the drug to be well tolerated. So we look forward to putting that data package together are submitting it to the agency.

Matthew Klein: Hopefully two lifting a partial hold in near future.

Unknown Attendee: Great. Thanks for taking my questions.

Speaker Change: Great. Thanks for taking my questions.

Matthew Klein: 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.

Speaker Change: Thank you.

Speaker Change: 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.

Matthew Klein: Well, thank you all for joining the call today. 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. We are well positioned to continue this success throughout the remainder of the year and look forward to updating you all as we move forward. So, thank you all, and have a good evening.

Matthew Klein: Well. Thank you all for joining the call today 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.

Matthew Klein: We are well positioned to continue.

Matthew Klein: Our success throughout the remainder of the year and look forward to updating you all as we move forward. So thank you all and have a good evening.

Unknown Executive: This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone have a wonderful day.

Unknown Executive: This concludes today's conference call. Thank you for your participation you may now disconnect everyone have a wonderful day.

Unknown Executive: Great.

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