Q3 2023 PTC Therapeutics Inc Earnings Call

October 26, 2023

[music].

Okay.

Thank you for standing by and welcome to the PTC Therapeutics third quarter 'twenty train three financial results Conference call. At this time, all participants are in a listen only mode.

After the Speakers' presentation, there'll be a question and answer session.

To ask a question at that time, Please press star one on your telephone.

Please be advised today's call is being recorded.

I would now like turn the conference to your host Jane Hamlin Associate director of Investor Relations. Please go ahead.

Good afternoon, and thank you for joining us today to discuss P. C. P therapeutics third quarter 2023, corporate update and financial results.

I'm joined today by actually if executive officer, Dr. Matthew Klein, our Chief business Officer, Eric Pals.

Chief Commercial officer, Kylie O'keeffe, and our Chief financial Officer paragraph yet.

Today's call will include forward looking statements based on our current expectations.

Please take a moment to review the slides 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.

Such statements are subject to risks that can materially and adversely affect our business and the results of operations.

For a detailed description of applicable risks and uncertainties. We encourage you to review the company's most recent quarterly report on Form 10-Q, and annual report on Form 10-K filed with the Securities and Exchange Commission as well as the company's other SEC filings.

We will disclose certain non-GAAP information during this call.

Information regarding our use of GAAP to non-GAAP financial measures and a reconciliation of GAAP to non-GAAP are available in todays earning release.

With that let me pass the call over to our CEO Matthew Korn, Matt.

Thank you James Good afternoon, and thank you all for joining the call.

Just to share our third quarter results and outlook for the remainder of the year, including an update on our development program.

Ill begin with the recent announcement of our agreement with royalty pharma to monetize up to $1 5 billion of the Brisbane royalty stream.

Non dilutive financing provides PTC to capital to support planned operations and allowed us to retire the Blackstone debt obligations.

In addition, the deal structure includes flexibility for accessing additional capital over the next two years, notably PTC maintains its rights to the remaining $250 million of milestones related to a risky global net sales.

The royalty financing deal along with the operating expense reductions announced in September put PTC, our very strong financial footing as we continue to focus our resources on our differentiated high potential R&D programs and robust global commercial infrastructure.

Now I'll turn to our third quarter results, we had another solid quarter with total revenue of $197 million.

Which keeps us on target for meeting our 2023 total revenue guidance of $940 million to $1 billion.

Our DMD franchise revenue in the quarter totaled $136 million.

This strong performance allows us to update our 2023, and DMD revenue guidance to between $565 million and $595 million from between $545 million and $575 million, Eric Mccarthy, who will provide additional details on our commercial performance shortly.

I'd like to now provide an update on recent regulatory activities for several of our programs.

Let me begin with an update on <unk>.

Following a negative opinion from the <unk> on the conversion of the conditional marketing authorization to full marketing authorization and on the renewal of the conditional authorization.

<unk> gave us the option to request reexamination of both opinions or only one opinion we.

We decided to pursue reexamination of a negative opinion on renewal of the conditional authorization only.

As such the reexamination process will focus solely on the allowance of continued conditional authorization of trademark in Europe.

We remain optimistic that we can address key concerns raised by the <unk> on the evidence of benefit from the trend line of clinical trials as well as concerns raised on the methodology and robustness of the stride data analyses.

Previously discussed in accordance with <unk> guidelines, we expect the opinion from the reexamination procedure in late January with adoption of that opinion by the European Commission 67 days later.

The U S. A type C meeting with FDA to discuss the potential path to NDA Resubmission is scheduled for this quarter.

Turning to CPA Carol we held the pre NDA meeting in the third quarter with FDA to discuss the NDA submission at.

At the meeting FDA stated that the CPA Taryn clinical safety and efficacy data supported NDA submission for the treatment of pediatric and adult PKU patients.

However, they requested that we complete 26 week non clinical mouth study to assess potential carcinogenicity risk of CPO taryn prior to submission.

Operator: At this time, all participants are on a listen-only mode.

Operator: After to speak as presentations, there will be a question and answer session. To ask a question at that time, please press Star 11 on your telephone. Please be advised today's call is being recorded.

This non clinical study was initially not required from CPE carry was acquired from sensor is the NDA submission was planned under the section 500 <unk> pathway.

Jane Hanlon: I would now turn the conference to your host, Jane Hanlon, Associate Director of Investor Relations. Please go ahead.

With our decision to file under the 500 <unk> one pathway. The 26 week study is considered a required NDA components if needed to inform labeling.

Matthew Klein: Good afternoon, and thank you for joining us today to discuss PTC Therapeutics' third quarter, 2023 corporate update and financial results. I'm 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.

We will continue to discuss with FDA the potential to submit the mouse study results during the NDA review process.

We now expect NDA submission to occur no later than the third quarter of 2024.

Michigan could occur in the second quarter, if FDA allows submission of the non clinical study report during the review process.

Matthew Klein: Today's call will include forward-looking statements based on our current expectations. Please take a moment to review this 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 the results of operations.

For the EU, we expect to submit a marketing authorization application to EMA in the first half of 2024.

The delay in NDA submission in no way mitigates the strength of the affinity data given the highly meaningful clinical effects observed in the trial as well as the continued evidence of providing phenylalanine tolerance benefits to the full spectrum of PKU patient long term open label extension study, we remain incredibly enthusiastic.

Matthew Klein: For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report on Form 10Q, an annual report on Form 10K, filed with the Securities and Exchange Commission, as well as the company's other SEC filings.

About the potential of $1 billion, plus global commercial opportunity for <unk>.

Moving to the PTC 508, Huntington's disease program enrollment is ongoing in the pivot HD studies for both the stage two and early stage three cohorts. We expect the next data update to occur in the first half of 2020 for this update will include 12 month data on the initial group of subjects on whom we reported data.

Pierre Gravier: We will disclose certain non-GAP information during this call. Information regarding our use of GAP to non-GAP financial measures, and a reconciliation of GAP to non-GAP are available in today's earning release.

In June of this year.

Regarding the status of the trial in the United States, We had a type a meeting with FDA to discuss the clinical safety data needed to enable resumption of enrollment of the pivot HD trial at U S study sites.

Matthew Klein: With that, let me pass the call over to our CEO, Matthew Klein. Matt?

Matthew Klein: Thank you, Jane.

Matthew Klein: Good afternoon, and thank you all for joining the call. I'm pleased to share our third-quarter results in Outlook for the remainder of the year, including an update on our development program. I will begin with the recent announcement of our agreement with Ruralty Forma to monetize up to $1.5 billion of the RISD Ruralty Stream. This non-delutiful financing provides PTC the capital to support planned operations and allowed us to retire the Blackstone debt obligation.

At the meeting FDA stated at the existing three months of safety data could support 12 week dosing at five milligrams and 10 milligram dose levels and at six months of clinical safety data demonstrating a similar favorable safety profile could support 12 month dosing in the pivotal <unk> trial. This is very good news.

Matthew Klein: In addition, the deal structure includes flexibility for accessing additional capital over the next two years. Notably, PTC maintains its rights, remaining $250 million of milestones related to a RISD global midfail. The Ruralty financing deal, along with the operating expense reductions announced in September, put PTC on very strong financial footing as we continue to focus our resources on our differentiated, high potential R&D programs and robust global commercial infrastructure.

Just that the safety data being generated <unk> HD should be sufficient to lift the partial hold in the United States.

Turning to particularly the data and the movie based study demonstrated particularly on treatment benefit across several disease endpoints, including favorable effects on the upright stability subscale of the <unk> assessment, which is predictive of time to loss of ambulation.

Had a type C. Written response only meeting with FDA in the third quarter to determine whether the data from our <unk> assay would be sufficient to support an NDA for accelerated approval.

Matthew Klein: Now, I'll turn to our third-quarter results. We had another solid quarter with total revenue of $197 million, which keeps us on target for meaning our 2023 total revenue guidance of $940 million to $1 billion. Our DMV franchise revenue in the quarter totaled $136 million.

In response, the FDA stated that while they see the value of upright stability as a clinically meaningful endpoint. They believed a confirmatory study would likely be needed to support NDA submission.

As this was a written response only and we believe we can address the concerns raised by the FDA. We have requested a follow up <unk> meeting.

Matthew Klein: This strong performance allows us to update our 2023 DMV revenue guidance to between $565 million and $595 million from between $545 million and $570 million.

In parallel we are participating in a scientific advice procedure with the Eni to determine if they move up a data could support a conditional marketing authorization application in the EU.

We expect to have the outcome of this procedure in the first quarter of 2024.

Eric Pauwels: Eric and Kylie will provide additional details on our commercial performance shortly.

Turning to ups data, we had an informal meeting with FDA in the third quarter at which time. They said that the data we have provided to support comparability between the clinical drug product and the intended commercial drug product, we're still not sufficient.

Matthew Klein: I'd like to now provide an update on recent regulatory activities for several of our programs. Let me begin with an update on Translana. Following the negative opinion from the CHMP on the conversion of the conditional marketing authorization to full marketing authorization and on the renewal of the conditional authorization. CNP gave us the option to request three examination of both opinions. We decided to pursue re-examination of the negative opinion on renewal of the conditional authorization only.

In that meeting the FDA says that the available data from the clinical study in the United States assessing the safety of the drug delivery cannula could be used to support a BLA for accelerated approval based on biomarker data demonstrating a treatment related increase in de Novo dopamine production FTE.

Matthew Klein: As such, the re-examination process will focus solely on the allowance of continued conditional authorization of Translana in Europe. We remain optimistic that we can address key concerns raised by the CHMP on the evidence of benefits in Translana clinical trials, as well as concerns raised on the methodological robustness of the stride data analysis. As previously discussed in accordance with EMA guidelines, we expect the opinion from the re-examination procedure in late January with adoption of that opinion by the European Commission 67 days later.

FDA suggested that we conduct a pre BLA meeting to review the content of the planned BLA. This meeting has been scheduled for December and pending the outcome, we expect to submit the BLA shortly thereafter.

Let me conclude by saying I'm incredibly proud of our team's continued ability to execute on all fronts.

The recent royalty pharma financing deal along with our operating expense reductions positioned PTC as strongly as possible for future growth as we realize the potential of our many promising programs.

I will now turn the call over to Eric entirely to discuss our strong commercial performance in the quarter Eric.

Matthew Klein: The U.S., a type C meeting with FDA to discuss a potential path to NDA resubmissions is scheduled for this quarter.

Thanks, Matt.

We're proud of the accomplishments of our global customer facing team, which continues to deliver revenue growth and build on our success as we focus on a strong close to the year for our commercial portfolio of products.

Matthew Klein: Turning the CP attaring, we held a pre-NDA meeting in the third quarter with FDA to discuss the NDA submission. At the meeting, FDA stated that the CP attaring clinical safety and FFC data supported NDA submission for the treatment of pediatric and adult PKU patients. However, they requested that we complete 26-week non-clinical mouse study to assess potential carcinogenicity risk of CP attaring prior to submission. This non-clinical study was initially not required when CP attaring was acquired from Senza as the NDA submission was planned under the Section 505-B2 pathway.

Once again, our global DMD franchise delivered a strong quarter with continued growth from new patient starts high compliance low discontinuation dose adjustments and geographic expansion.

Let me focus on our two key products in the DMD franchise.

<unk> and in Florida continue to be important growth drivers delivering 136 million in net revenue for the third quarter, which is 4% compared growth compared to the third quarter of 2022.

Matthew Klein: With our decision to file under the 505-B1 pathway, the 26-week study is considered a required NDA component if needed to inform labeling. We will continue to discuss with FDA the potential to submit the mouse study results during the NDA review process. We now expect NDA submission to occur no later than the third quarter of 2024. This mission could occur in the second quarter if FDA allows submission of the non-clinical study report during the review process. For the EU, we expect to submit a marketing authorization application to EMA in the first half of 2024. The delay in NDA submission in no way mitigates the strength of the acidity data.

With strong year to date performance, we are raising our DMD revenue guidance from.

$545 million to $575 million.

Two 565 million to $595 million.

For <unk>, we achieved $69 million in quarterly revenue.

Year to date sales were $281 million.

The team has worked tirelessly to continue to bring this important treatment to existing as well as new patients in our markets around the world.

Matthew Klein: Given the highly meaningful clinical effects observed in the trial, as well as the continued evidence of providing central aligning tolerance benefits to the full spectrum of PKU patients in the long-term open label extension study, we remain incredibly enthusiastic about the potential billion-dollar plus global commercial opportunity for CP attaring.

The recently concluded World Muscle Society meeting with an opportunity to present and discuss with health care providers, the totality of data and real world evidence supporting the efficacy of trends larger and re emphasizing the significant life changing impact. This treatment has on young boys suffering from this devastating disease.

Matthew Klein: Moving to the PTC-518 Huntington's disease program, enrollment is ongoing in the pivot HD study for both the stage 2 and early stage 3 cohorts.

For whom trends lineup is there only therapy that specifically targets nonsense mutation DMD.

Matthew Klein: We expect the next data update to occur in the first half of 2024. This update will include 12 month data on the initial group of subjects on whom we reported data in June of this year.

Our customer facing teams have increased communications with health care providers in Europe, providing medical information on trends learner and it's continued availability for all new and existing patients.

Matthew Klein: Regarding the status of the trial in the United States, we had a type A meeting with FDA to discuss the clinical safety data needed to enable resumption of enrollment of the pivot HD trial at U.S, study sites. At the meeting, FDA stated that the existing three months of safety data could support 12 week dosing at five milligrams and 10 milligram dose levels. And at six months of clinical safety data, demonstrating a similar favorable safety profile could support 12 months of those things in the pivot HD trial. This is very good news as it suggests that the safety data being generated from pivot HD should be sufficient to lift the partial homes in the United States.

Now turning to Florida the.

The employer business continues to be solid.

Quarterly net revenues was $67 million, which is 23% growth over the prior year quarter.

We have had $188 million in year to date sales.

We continue to see strong trends in the new patient start forms and high compliance the.

The continued in Plaza growth is impressive and highlights the brand loyalty in the DMD community in the United States as our team is actively implementing plans to defend and protect the in Plaza breath ahead of loss of exclusivity next year.

Matthew Klein: Turning to the Tiquinone, the data in the moving phase study demonstrated the Tiquinone treatment benefit across several disease endpoints, including favorable effects on the upright stability subscale of the M-FAR's assessment, which is predictive of time to loss of ambulation.

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

Lee.

Thanks, Eric let me begin with ups data, the first and only approved gene therapy and feeds directly into the brain.

Matthew Klein: We had a type C written response only meeting with FDA in a third quarter to determine whether the data from the FAA would be sufficient to support an NDA for accelerated approval. In the written response, the FDA stated that while they see the value of upright stability as a clinically meaningful endpoint, they believed a confirmatory study would likely be needed to support NDA submission. As this was a written response only, and we believe we can address the concerns raised by the FDA, we have requested a follow-up live meeting.

We continue to see transformative results for the patients we have treated thus far.

Rollout across Europe is progressing well without first patient treated in the U K this quarter following the positive nice recommendation earlier in the year.

Patient identification treatment center readiness and access and reimbursement discussions continue to advance.

We also continue to leverage early access programs and cross border treatment opportunities.

A patient from the Middle East also receiving treatment in France this quarter.

Matthew Klein: In parallel, we are participating in a scientific advice procedure with the EMA to determine if the move FAA data could support a conditional marketing authorization application in the EU. We expect to have the outcome of this procedure in the first quarter of 2024.

Moving to take city in way Libre in Latin America.

We continue to grow our franchise in the region with recent MAA approvals for <unk> in Argentina and way Libre in Mexicali.

Patient identification is robust and patient on treatment continue to grow across the region.

Matthew Klein: Turning to obstetia, we had an informal meeting with FDA in the third quarter. At which time they said that the data we have provided to support comparability between the clinical drug product and the intended commercial drug product were still not sufficient. However, in that meeting, the FDA said that the available data from the clinical study in the United States assessing the safety of the drug delivery cannula could be used to support a BLA for accelerated approval based on biomarker data, demonstrating a treatment related increase in de novo dopamine production.

In Brazil, we anticipate receiving new group purchase orders for both <unk> and with Libre before the end of this year, which is in recognition of the increased number of patients who rely on these life changing treatment.

Lastly, as Matt mentioned, we are extremely excited about the <unk> opportunity.

The affinity phase III data and the long term extension study preliminary data were presented at the recent <unk> Congress.

And were very well received by physicians and the PK you community.

Matthew Klein: The FDA suggested that we conduct a pre-BLA meeting to review the contents of the plan BLA. This meeting has been scheduled for December, and pending the outcome we expect to submit to BLA shortly thereafter.

They are excited about the opportunity to bring a differentiated therapy to PKU patients in need.

With strong differentiation from the mechanism of action and the affinity results, coupled with our global commercial infrastructure and proven track record and commercializing rare diseases.

Matthew Klein: Let me conclude by saying I'm incredibly proud of our team's continued ability to execute on all fronts. The recent royalty farmer financing deal, along with our operating expense reductions, position PTC is strongly as possible for future growth as we realize the potential of our many promising programs. I will now turn the call over to Eric and Kylie to discuss that strong commercial performance in the quarter.

<unk> is actively working on launch activities to ensure a fast uptake upon approval.

The potential market opportunity for Cepheid Taryn is composed of a number of key PKU patient segments.

All of which our affinity data suggest we can address.

Eric Pauwels: Eric, thanks Matt. We are proud of the accomplishments of our global customer facing team, which continues to deliver revenue growth and build on our success as we focus on a strong close to the year for commercial portfolio products. Once again, our global DMD franchise delivered a strong quarter with continued growth from new patient starts, high compliance, low discontinuation, dose adjustment, and geographic expense.

First patients who have not been trialed on to that or are considered therapy naive.

This includes many of the classical PKU patients, where we have demonstrated benefit in both the phase III study and the affinity study.

Second patients who have not responded to Kevin.

Third patients who have achieved some level of blood fee reduction from Cleveland, but are not well controlled and for whom Cepheid taryn may deliver a better reduction in blood <unk> levels.

Eric Pauwels: Let me focus on our two key products in the DMD franchise. Translana and Inflaza continue to be important growth drivers delivering 136 million in net revenue for the third quarter, which is 4% compared growth compared to the third quarter of 2022. With strong year-to-date performance we are raising our DMD revenue guidance from 545 million to 575 million to 565 million to 595 million. For Translana, we achieved 69 million in quarterly revenue. Year-to-date sales were 281 million. The team has worked tirelessly to continue to bring this important treatment to existing as well as new patients in our markets around the world.

So these patients a reduction in blood fee.

Target fee levels is clinically meaningful potentially allowing them to substantially increase their protein intake and significantly enhance the quality of life.

Many experts who have treated patients with PKU across the world have indicated that based on the data they have seen from our affinity study and from the understanding of the mechanistic benefit to Cepheid Taryn all interested patients should be trials that the apparent.

With an expected addressable population of approximately 15% to 30% of the overall global PKU population. This would put us above $1 billion market opportunity.

In conclusion our.

Third quarter builds on an excellent first half of 2023.

With significant progress across all of our commercial products and across all geographies all customer facing team is set to have a very strong close to the year.

Set ourselves up for continued success in the future by continuing to build on our commercial capabilities and to execute prelaunch strategy trap feature product pipeline now.

Eric Pauwels: The recently concluded World Muscle Society meeting was an opportunity to present and discuss with healthcare providers the totality of data and real world evidence supporting the efficacy of Translana and re-emphasizing the significant life-changing impact this treatment has on young boys, suffering from this devastating disease for whom Translana is their only therapy that specifically targets nonsense mutation DMD. Our customer facing teams have increased communications with healthcare providers in Europe providing medical information on Translana and its continued availability for all new and existing patients.

Now, let me turn the call over to <unk> for a financial update.

Thank you Kelly.

I would like to begin by discussing the financing with royalty pharma that we announced last week.

Doug deal together was the pipeline re prioritization and Opex reductions that we announced in May and September puts PTC in a very strong financial position.

We are pleased to work again with royalty pharma on this win win transactions.

The non dilutive financing provides PTC was the capital to support operations and allows for increased operational and financial flexibility by removing the Blackstone debt obligation from our balance sheet.

In addition, the deal structure provides the potential for additional non diluted capital for the next two years.

To recap the details of the deal PTC.

PTC monetize up to $1 5 billion of the <unk> royalty stream.

Eric Pauwels: The continued influenza growth is impressive and highlights the brand loyalty in the DMD community in the United States as our team is actively implementing plans to defend and protect the influenza bread ahead of a loss of exclusivity next year.

Royalty pharma acquired additional royalties on April one.

$1 billion upfront.

The agreements included options for PTC to sell up to an additional $500 million.

Or <unk>.

Kylie O'Keefe: Now, I will ask Kylie to update the progress of our current and future new product launches.

For royalty pharma to acquired half of such we tend royalties up to $20 $50 million at the later date.

Kylie O'Keefe: Kylie.

Kylie O'Keefe: Thanks, Eric. Let me begin with upstairs. The first and only approved gene therapy infused directly into the brain. We continue to see transformative results for the patients we have treated thus far. Our rollout across Europe is progressing well with our first patient treated in the UK this quarter following the positive, nice recommendation earlier in the year. Patient identification, treatment and readiness and access and reimbursement discussions continue to advance. We also continue to leverage early access programs and cross-border treatment opportunities with a patient from the Middle East also receiving treatment in France this quarter.

Yes royalties received by PTC.

Did you see interim teams all economics associated with up to $250 million and the remaining commercial sales milestone associated with every gigabyte in itself.

The agreement builds on our previous strategic partnership established with royalty pharma in 2020.

The initial agreement west for the monetization of approximately 43% of the <unk>.

The royalty stream.

As a result of the current agreements.

PTC will maintain ownership of approximately 19% of the total EBITDA royalty stream.

Pending any exercise of future options by PTC royalty pharma all the achievements of the cap from the 2020 royalty agreements.

Kylie O'Keefe: Moving to take steady and wear lever in Latin America, we continue to grow our franchise in the region with recent MAA approvals. For take steady in Argentina and wear lever in Mexico. Patient identification is robust and patient on treatment continue to grow across the region. In Brazil, we anticipate receiving new group purchase orders for both TechSetti and Welebra before the end of this year, which is in recognition of the increased number of patients who rely on these life-changing treatments.

Yes.

I'll now share the financial highlights of our third quarter 2023.

Please refer to the third quarter earnings press release issued this afternoon for additional detail.

Beginning with top line results.

Total revenue for third quarter was $197 million.

This consisted of DMD franchise revenue of $136 million in other revenue of $61 million.

Starting with the DMD franchise.

Kylie O'Keefe: Lastly, as Matt mentioned, we are extremely excited about the sepia-terran opportunity. The affinity faced three data and the long-term extent of prevention study preliminary data were presented at the recent SSIEM Congress and were very well received by physicians and the PKU community. They are excited about the opportunity to bring a differentiated therapy to PKU patients in need, with strong differentiation from the mechanism of action and the affinity results, coupled with our global commercial infrastructure and proven track record in commercializing rare diseases.

So on slide on net product revenue in the quarter was $69 million, what im floods on net product revenue of $67 million.

Moving to.

Third quarter global revenue of 360 million Swiss francs, which equates to over 40 million U S. Dollars was achieved by Roche, earning royalty revenue of $50 million for PTC.

As Matt mentioned.

Third quarter performance puts us in a strong position to achieve 2023 total revenue guidance.

$940 million to $1 billion.

Kylie O'Keefe: The team is actively working on launch activities to ensure a fast uptake upon approval. The potential market opportunity for sepia-terran is composed of a number of key PKU patient segments, all of which our affinity data suggests we can address. First, patients who have not been trialled on KUVAN or are considered therapy nae. This includes many of the classical PKU patients where we have demonstrated benefit in both the phase two study and the affinity study.

Including an expected $100 million milestones whenever it is your capacity is $1 5 billion.

Yes.

Kylie O'Keefe: Second, patients who have not responded to KUVAN. Third, patients who have achieved some level of blood-free reduction from KUVAN but are not well controlled and for whom sepia-terran may deliver a better reduction in blood-free. For these patients, a reduction in blood-free to target fee levels is clinically meaningful, potentially allowing them to substantially increase their protein intake and significantly enhance their quality of life. Many experts who have treated patients with PKU across the world have indicated that based on the data they have seen from our affinity study and from their understanding of the mechanistic benefit to sepia-terran, all interested patients should be trialled in sepia-terran. With an expected addressable population of approximately 15-30% of the overall global PKU population, this would put us above a billion dollar market opportunity.

non-GAAP R&D expenses were $150 million for the third quarter of 2023, excluding $14 million in noncash stock based compensation expense compared.

Compared to our Huntington $50 million for the third quarter of 2022, excluding $15 million in noncash stock based compensation expense.

non-GAAP SG&A expenses were $16 million for the third quarter of 2023.

Excluding $13 million in noncash stock based comp expense compared to $67 million for the third quarter of 2022.

Excluding $14 million in noncash stock based compensation expense.

Cash cash equivalence and marketable securities totaled approximately $295 million as of September 32023, compared to <unk> $11 million as of December 31, 2022.

I will now turn the call over to the operator for Q&A.

Radar.

Thank you.

Again, ladies and gentlemen, if you'd like to ask a question. Please press star one on your Touchtone telephone again to ask a question. Please press star one one.

One moment for your first question.

Okay.

Kylie O'Keefe: In conclusion, our third quarter builds on an excellent first half of 2023, with significant progress across all of our commercial products and across all geographies.

Our first question comes from the line of Eric Joseph of JP Morgan Your line is open.

Hi, good afternoon, thanks for taking the question.

Kylie O'Keefe: Our customer-facing team is set to have a very strong closer to the year and set ourselves up for continued success in the future by continuing to build on our commercial capabilities and to execute pre-launch strategy throughout future product pipelines.

A couple on PKU from Us really just around this regulatory paths here I guess.

Can you just clarify when the decision was made to pursue a 551.

Specifics of the accurate over a 552 and maybe what prompted that decision and then I guess.

Pierre Gravier: Now let me turn the call over to P.F, for a financial update.

Pierre Gravier: P.F.? Thank you, Kylie.

We have elected to go with a final proposal might be one.

Pierre Gravier: I would like to begin by discussing the financing with work e-forma that we announced last week. That deal, together with the pipeline re-prioritizations and OPEX reductions that we announced in May and September, puts PTC in a very strong financial position. We are pleased to work again with royalty-forma on this win-win product. The non-value-tiff financing provides PTC with the capital to support operations and allows for increased operational and financial flexibility by removing the blackstone debt obligation from a balance sheet.

Was it not clear the carcinogenicity study would be needed would likely be a requirement.

And really ultimately I guess.

Looking forward.

Should give investors confidence that.

Assuming.

Our carcinogenicity studies in terms of nothing that the NDA submission and review cycles would otherwise be straightforward. Thank you.

Thanks for the questions Eric So let me just first start with a little bit at 591 versus 505 to the $505. Two pathway is typically used for need two compounds, where it has already been and then there is an existing approval for the active ingredient in the compound for which one seats.

Pierre Gravier: In addition, the deal structure provides the potential for additional non-value-tiff capital over the next two years. To recap the details of the deal, PTC monetized up to $1.5 billion of the everyday world for PTC stream. Royalty Pharma acquired additional royalties on every day for $1 billion a front. The agreements included options for PTC to sell up to an additional $500 million or for Royalty Pharma to require half of such written royalties for up to $250 million at a later date, less royalties received by PTC.

Approval.

Alternatively, the classified one pathways for innovative therapies, which is much more appropriate for something like CPU, taryn, which while it's active ingredient is DH four which is.

Which is basically a reactive component Kuban. It has many factors that make you differentiate which underlies the superior efficacy we've observed to date and why this is such a promising therapy.

Central initially was in thinking about the type of Abbvie two pathway, that's where things have lined up but we acquired it.

After we did our own analysis and understanding of the relative benefits of each pathway. It became clear that the final one was much more appropriate now with the 500 to $5 two pathways since here as an active ingredient already approved you can utilize the study not safety and efficacy studies, but other supportive studies like non clinical study.

Pierre Gravier: PTC maintains all economics associated with up to $250 million in the remaining commercial sales milestone associated with every global net sale. The agreement builds on the previous strategic partnership established with Royalty Pharma in 2020. The initial agreement was for the monetization of approximately 43% of the everyday world's stream. As a result of the current agreement, PTC will maintain ownership of approximately 19% of the total everyday world's stream, pending any exercise of future options by PTC or Royalty Pharma or the achievements of the cap from the 2020 Royalty Agreement.

That were used to support that approval with the 500 <unk> pathway. So you don't have the ability to rely on those existing study.

Susan just switch was based on a couple of things one.

<unk> is quite differentiated in terms of its efficacy profile from Kuban.

If you go to $505 two pathways the company's product the company, whose products you referred to to utilize their studies can actually block you from launching the therapy for up to 30 months. If they still have an orange book listed patents. So obviously, we did not want to be in a situation we would risk the loss of the compound and then again just really isn't.

Pierre Gravier: And now share the financial highlights of our third quarter of 2023. Please refer to the third quarter earnings press release issued this afternoon for additional details. Beginning with stop line results.

Pierre Gravier: Total revenue for third quarter was $197 million. This consisted of D&D franchise revenue of $136 million and other revenue of $61 million. Starting with the D&D franchise. Translala net product revenue in the quarter was $69 million, what inflows a net product revenue of $67 million. Moving to a release.

Have a compound much more suited to the 500 <unk> pathway.

We do.

Then obviously had interactions with the agency to understand what would be required under the 505 pathway and that included things like juvenile toxicity, a new CRO costs all of which.

The studies will be conducted including the NDA, which is there and then per carcinogenicity. What's typically required is that you submit to the agency a weight of evidence request to request a waiver for carcinogenicity, obviously, we were quite confident in getting that waiver.

Pierre Gravier: Third quarter global revenue of 360 million Swiss francs, which equals to over 40 million US dollars was achieved by Roche, earning Royalty revenue of $50 million for PTC. As Matt mentioned, the third quarter performance puts us in a strong position to achieve 2023 total revenue guidance of $940 million to $1 billion, including an expected $100 million milestones whenever it is your passes $1.5 billion in annual net sales. Non gap R&D expenses were $150 million for a third quarter of 2023, excluding $14 million in non cash stock based compensation expense compared to $150 million for a third quarter of 2022, excluding $15 million in non cash stock based compensation expense.

One there is no evidence of Gino toxicity, CPO terror and the CPA Taryn non clinical studies the six month to nine month studies. There was no evidence of secretly CTO can related.

Carpenter's NFC pre neoplastic lesions of neoplastic lesions. Furthermore, while we werent, referring to the <unk> NDA clinical experience with <unk>. Many years clearly demonstrates that there is no carcinogenicity risk associated with each quarter. So we've submitted all of that.

To the agency the agency obviously it came back and said that the two different there's two different cars interesting study was one of the two year Rat study. They said fine do that post approval no problem, but since you are in the 500 <unk> pathway. They would want the 26 week mouse study to inform the labor.

Pierre Gravier: Non gap R&D expenses were $16 million for a third quarter of 2023, excluding $13 million in non cash stock based expense compared to $67 million for a third quarter of 2022, excluding $14 million in non cash stock based, and Compensation Expo.

Because in the label they have to say whether or not there is a potential carcinogenicity risk and while we were under 500 <unk> two pathway. They could use the labeling in the Kuban label, which referred to the risk of adrenal tumors, which has never been seen clinically, but they said look we have nothing I referred to we have nothing to inform the label. So we need you to do this study.

Pierre Gravier: Cash, Cash E-Covidance and Marketable Securities Total Approximately, $295 million as of September 30, 2022, compared to $4 million, $11 million as of December 31, 2022.

And since it's a standard part will be considered a standard part of the 500 <unk> pathway would be something you would need to submit with the NDA now.

Operator: Now, we'll now turn the call over to the operator for Q&A. Operator?

Also say and just the other part of your question and are discussing they were it was clearly stated that the safety and efficacy data we have with CPA Sharon.

Operator: Thank you. Again, ladies and gentlemen, if you'd like to ask a question, please put a star, 1-1 on your touchtone, telephone. Again, to ask a question, please put a star, 1-1.

Could support the full spectrum of patients, which would be our desired label. So we fully expect that once you get the study results because it required to have the study report for the mouse study for submission. Once we have that we expect a very smooth path from there again, given the incredible strength of the efficacy data we have the safety data we have.

Operator: One moment for our first question.

Eric Joseph: Our first question comes from the line of Eric Joseph of J.P. Morgan, you want to know a little bit?

Obviously far from ideal the additional time, we're going to have now is only going to build that dossier programs greater length of exposure greater ability to show more durability of effect the kinds of things we're seeing in the long term open label study and obviously, we could have even more data showing <unk> tolerance. We recently reported the latest update on <unk>.

Eric Joseph: Hi, good afternoon. Thanks for taking the question. Just a couple on PKU from us, really just to run this regulatory path here.

Matthew Klein: Can you just clarify when the decision was made to pursue a 505P1 path for Cypiacs right over a 505P2 and maybe what prompted that decision? And then, I guess, an electing to go with a 505P1, was it not clear that a carcinogenicity study would be needed, would likely be a requirement? And really, ultimately, I guess just looking forward what should give investors confidence that, you know, assuming that a carcinogenicity study turns up nothing, that the NDA submission and reduced cycles should otherwise be straightforward. Thank you. Thanks for the question, Eric.

Siam meeting in September again, showing that patients are able to tolerate <unk>.

The recommended daily allowance of protein and still have control of federal element. So the strength of this data.

We named it is in no way impacted by the need to do this in a clinical study. It is an unfortunate delay we're going to continue to discussions with the agency. If we could submit the application sooner, but the bottom line is this is a strong differentiator compound. The data we have to date. The studies. We've done shows there has been no evidence of cartilage.

Matthew Klein: Let me just first start with a little bit about 505P1 versus 505P2. The 505P2 pathway is typically used for Me2 compounds, where there's already been an existing approval for the active ingredient in the compound for which one seeks approval. Alternatively, the 505P1 pathway is for innovative therapies, which is much more appropriate for something like keeping a carin, which, while its active ingredient is BH4, which is basically the active component of KUVA, it has many factors that make it different to you, which underlines the superior efficacy we observed to date and why this is such a common therapy.

Tennessee risk according.

According to a study reports we have genotoxic like and again this continues to be a very very strong package.

Okay.

Thank you.

One moment please.

Our next question comes from the line of.

Chris concludes Scott.

Oh Cantor Fitzgerald, Chris conclude Sir your line is open.

Hi, everyone first just wanted to congratulate you on the royalty pharma deal and I had a question about trends Laurence can you talk about why you're only pursuing reexamination of the conditional authorization I guess, what advantages do you see going this way versus both and it's.

Matthew Klein: Since the initially was thinking about the 505P2 pathway, that's where things were lined up, but we acquired it, and after we did our own analysis and understanding of the relative benefits of each pathway, it became clear that the 505P1 was much more appropriate. Now, with the 505P2 pathway, since you're in an active ingredient already approved, you can utilize the studies not facing efficacy studies, but other supportive studies like non-clinical studies that were used to support that approval. With the 505P1 pathway, you don't have that ability to rely on those existing studies.

Assuming that you do get the Green light how are things going to be moving forward will it be kind of similar like what we've seen over the last eight years when they've given.

Given you the green light or will you be required to conduct any type of work in the background. Thank you.

Kristin. Thank you very much for the question. So as we mentioned in our prepared comments.

The previous procedure there were two opinions there was actually two procedures in Hawaii. One was the conversion of the conditional marketing authorization to full marketing authorization and the other was continuation of the conditional authorization.

Matthew Klein: Now, the decision to switch was based on a couple of things. One, keeping a carin is quite differentiated in terms of its efficacy profile from KUVA. Second, if you go to 505P2 pathway, the company's product, the company whose product you refer to to utilize their studies, can actually block you from launching the therapy for up to 30 months that they still have an orange-book listed path. So, obviously, we did not want to be in a situation where we would risk the launch of the compound, and then again, this really is a novel kind of a compound much more suited to the 505P1 path.

Two nuances of the procedural elements in Europe. They had brought that together and said we're going to issue two opinions, but really get together. So when they went negative on the conversion to full authorization.

Elected to go negative as well for the renewal of the condition and they gave us the option to say do you want to pursue one or both.

We're already here is to maintain nature of this drug stays on the market sees available for the boys in Europe for whom there is no other targeted therapies for nonsense mutation available.

Matthew Klein: We then obviously had interactions with the agency to understand what would be required under the 505B1 pathway and that included things like juvenile toxicity and recrotox, all of which studies will be conducted, including the NDA, which is there and then for carcinogenicity, what's typically required is that you submit to the agency a weight of evidence to request to request a waiver for carcinogenicity. Obviously, we were quite confident in getting that waiver.

And we believe the best chance of doing that is to focus solely on maintenance of the conditional authorization for now.

We also believe in a way that I am not asking for a conversion to a full approval that.

The issues some of the issues with having a.

Negative primary analysis population.

<unk> and the 741.

May become less of an issue really we can focus on other important and strong data in study 401, including in the ITT population, where we have clear evidence of benefit over a number of different end points as well as obviously the long term stride data. So we really feel that by focusing this question on just renewal of the conditional authorization that we can provide the net.

Matthew Klein: One, there's no evidence of genotoxicity and secretarian in the secretarian non-clinical studies, six month and nine month studies. There was no evidence of secretarian related carcinogenicity, pre-neoplasic lesions and neoplasic lesions, furthermore, while we weren't referring to the Kuwait NDA, the clinical experience with Kuwait over many years clearly demonstrates that there's no carcinogenicity. So we submitted all of that to the agency. Now the agency obviously came back and said that there's two different carcinogenic studies.

Sorry second get this opinion from negative to positive now as you mentioned what happened.

As you ask what happens from there well if you have a conditional marketing authorization in Europe, you are required to conduct.

Or collect additional evidence to continue to support the benefit. We believe there are many potential sources of this including continuing to collect data and strike.

Matthew Klein: One is a two year rat study. They said, fine, do that close to approval, no problem, but since you're in the 505B1 pathway, they would want the 26 week mouse study to inform the label because in the label, they have to say whether or not there's a potential carcinogenic. And while we were under 505B2 pathway, they could use the labeling in the Kuwait NDA, which refer to the risk of adrenal tumors, which is never maintained clinically, but they said, look, we have nothing to refer to, we have nothing to inform the label, so we need you to do this study. And since it's a standard part, we'd be considered a standard part of the 505B1 pathway, it'd be something you would need to submit with the NDA.

<unk> been able to show a clear benefit in delaying time to loss of ambulation by three and a half years in the most recent analysis and continue to show meaningful multi year delay in lots of pulmonary function as we can continue to collect more data over time there'll be even more patients informing the loss of ambulation analysis, even more patients with <unk>.

<unk>, the pulmonary function analysis, and hopefully ultimately cardiac function and mortality. So theres still a lot more meaningful data that can truly informed the long term benefit of Transalta Armstrong.

There's also the possibility to talk about bolstering striving there with an additional analyses and second largest treated that's a possibility.

Matthew Klein: Now, I'll also say, and just the other part of the question, in our discussions, they were clearly stated that the safety of the agency data we have with CPA Karen could support the full spectrum of patients, which would be our desired label. So we fully expect that once we get the study results, if it's required to have the study report to the mouse study for submission, once we have that, we expect a very smooth path from there.

I think in the universe of possibilities could they ask us to do another clinical trial I think that's possible probably not likely given a lot of the feedback.

The scientific expertise in the scientific advice.

Portion of the procedure last time was that clinical studies for genetic directed therapies in DMD or really hard and really difficult to produce meaningful data the experts have told.

Matthew Klein: Again, to give any incredible strength of the efficacy data we have, the safety data we have, and obviously what far from ideal, the additional time we're going to have now is only going to build that dossier program with greater length of exposure, greater ability to show more durability and affect the kinds of things we're seeing in the long term open label study, and obviously we're going to have even more data showing fee tolerance, and we recently ported the latest update in the fee tolerance data. Yes, I am meeting in September, again, showing that patients are able to tolerate beyond the recommended daily allowance, the protein and still have control of that line.

They believe that these longer term data collection mechanisms that are really most useful for understanding the true benefit. So that's a long answer. The short answer is look we'll have to collect additional data will be well positioned and quite pleased to do so the priority now is to keep this therapy on the market in Europe, and we believe by pursuing just a renewal of the conditional.

This is in the strongest position to do that.

Okay. Thanks, and just second part of that I would imagine since you had the announcement that the community would probably it's pretty upset, especially the ones that have been on the therapy long term. So wondering if there's anything you can collect from them anecdotal stories et cetera, and if they can be.

Matthew Klein: So the strength of the data is remained. It is no way impacted by the need to do this nonclinical study. It is an unfortunate delay. We're going to continue discussions with the agency. We can submit the application sooner, but the bottom line is this is a strong differentiator compound. The data we have to date, the studies we've done show the, there's no evidence of parcel legitimacy risk. According to the study reports, we have geotoxicity in life, and again, this continues to be a very, this will be a very strong path. Thank you.

Operator: One moment, please.

Anyhow.

This upcoming meeting and decision thanks again.

Yes, Chris Good question, I think needless to say that physician and patient community was surprise disappointed in and quite honestly scared.

For the patient. So I think this is the only therapy they have.

Hi.

That is directed for nonsense mutation patients many of them like they don't have a therapy for years and observe the benefits that we've been reporting for physicians. They understand the context of the disease. They understand the strength of the data that we produced.

Kristen Kluska: Our next question comes from the line of Kristen Kluska, out Cantor Fitzgerald, Kristen Kluska.

And many of them said, they can't imagine having to take patients off of drug that states and effective.

Kristen Kluska: Your line is open. Hi, everyone.

Bill the patients on their own have the ability on their own to reach out at <unk> and their voices heard I'm sure in many parts of Europe that will happen given the fear and concern they have in us and similarly to the physician community.

Matthew Klein: First, just wanted to congratulate you on the royalty farm the deal. And I had a question about trans-larna. Can you talk about why you're only pursuing re-examination of the conditional authorization? I guess what advantages do you see going this way versus both? And assuming that you do get the green light, how are things going to be moving forward? Will it be kind of similar, like what we've seen over the last eight years when they've given you the green light, or will you be required to conduct any type of work in the background?

I don't want to speak up at our sense here is that.

People as we were never thought this state will come or the severe reality, so I think the.

This is a little bit for them.

Paul to speak up and let their voices heard and importantly, as you say share their soy share their experience, particularly the physicians who are experts and can truly articulate.

Matthew Klein: Thank you. Kristen, thank you very much for the question. So as we mentioned in our prepared comments, the previous procedure there were two opinions. There were actually two procedures in one. One was the conversion of the conditional marketing authorization to full marketing operation, and the other was continuation of the conditional operation. Through nuances of the procedural elements in Europe, they had brought them together and said, we're going to issue two opinions, but really get together.

The benefit stave observed and the importance of this therapy.

For patients with nonsense mutation DMD.

Yes.

Thank you.

<unk>.

Yeah.

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

Great. Thanks, so much.

Matthew Klein: So when they went negative on the conversion to full authorization, they elected to go negative as well for the renewal of the conditional conditions. Then they gave us the option to say, do you want to pursue one or both? Look, our priority here is to maintain, make sure this drug stays on the market, stays available for the boys in Europe, and there's no other targeted therapy for non-sentitation available. And we believe that best chance of doing that is to focus solely on maintenance of the conditional authorization for now.

On the topic of Translarna I guess since the negative opinion have you seen any change and how physicians are writing scripts or if patients are accumulating medication ahead of a potential of that in our.

Opinion does not reverse and then can you speak a little bit as to if you've increased your sales efforts and non EU areas since the negative opinion as well. Thank you.

Matthew Klein: We also believe in a way that by not asking for a conversion to a full approval that the issues, some of the issues that we use with having a negative primary analysis population analysis in study 41 may become less of an issue, really, you can focus on the other important and strong thing that in study 41, including in the ITT population where we have clear evidence of benefit over a number of different endpoints, as well as obviously the long-term stride data. So we really feel that by focusing this question on just renewal of the conditional authorization that we could provide the necessary evidence that can get this opinion from negative deposit.

Yes, Amy Thank you for the question again I think the.

And the physicians we've spoken with the first response was.

Yes.

Clarifying and reconfirm that in no way and as things change patients can stay on the drug they can write prescriptions and obviously everyone's going to do everything the cabinet make sure patients stay on therapy, but let me.

Kick it over to Eric I don't know if you want to give some.

For more detail on the con.

Prescriptions.

Yes. Thanks for the question Sami first of all we haven't actually seen an impact since <unk> has issued their opinion in fact, we've seen physicians who have actually been very very.

They've been very very supportive in fact, our customer facing team is actually stepped up their interactions with health care providers advocacy groups and others to emphasize that the drug is actually available and I think that's one of the most important things. We've made specific calls to every prescribing physicians and we've worked with them because we have.

Matthew Klein: Now, as you mentioned, what happens from the test? Yes, what happens from there? Well, if you have a conditional marketing authorization in Europe, you are required to conduct or collect additional evidence to continue to support the benefit. Now, we believe there's many potential sources of this, including continuing to collect data and stride. Well, we've obviously been able to show clear benefit in delaying time to loss of the F-function and mortality. So there's still a lot more meaningful data that can truly inform the long-term benefit of translogic from stride.

Have relationships now for many many years with many of these physicians.

They know about the treatment they've been treating patients for many years and we've been reaffirming that the trends Lana is not only just available is available for existing patients, but it's also we've seen new prescriptions as well the fundamentals that we see.

Tommy is basically <unk>.

A limited to no discontinuation because of the CHP information new patients continue to get scripts compliance has actually remained very high and we've been able to maintain dose adjustments we've had to getting patients that have gone from ambulatory to non ambulatory and been maintained as well and then to your question about.

Matthew Klein: There's also the possibility to talk about bolstering stride, either with additional analyses or a second registry that's the possibility. I think in the universe of possibilities, because they have to do another clinical trial, I think that's possible, probably not likely, given a lot of the feedback that the scientific experts gave in the scientific advice portion of the procedure last time was that clinical studies for genetic directed therapies and DMD are really hard and really difficult to produce meaningful data.

Geographic expansion and outside.

Well some of some of the information has gone out to other countries. We've actually been able to continue to work with health care providers in other parts of the world and still continue to generate and see growth from trends Lorena.

In the quarter. So the simple answer of course is that.

We have not seen any any discontinuation in the finals fundamentals remained strong.

Matthew Klein: The experts have told the HMP they believe that these long-term data collection mechanisms that are really most useful for understanding the treatment. So that's a long answer. The short answer is, well, we'll have to collect additional data. It will be well positioned and quite honestly pleased to do so. The priority now is to keep this therapy on the market in Europe. And we believe by pursuing just a renewal of the conditional footage in the strongest position. You can do that. Okay, thanks.

And as I mentioned earlier in my in my in my talk we're.

We're not only very confident in what we did this quarter, but we're very confident in how we will finish 2023, and we've actually raised guidance in our DMD guidance is now 565 to $5 95, which includes <unk>.

Trans Laurent a growth in the fourth quarter and combined that would equal about 11% to 17% year over year growth for the dnb franchise compared to last year.

Matthew Klein: And just second part of that, I would imagine since you had the announcement that as the community was probably pretty upset, especially the ones that have been on the therapy long term. So, wondering if there's anything you can collect from them, anecdotes, stories, et cetera, and if they can be of any help ahead of this upcoming meeting and decision. Thanks again.

Great. Thank you.

Thank you one moment please.

Yes.

Our next question comes from the line of David Lebowitz.

<unk> Your line is open.

David for taking.

Thank you for taking my question when looking at the trends learn our European sales could you. Please or overseas sales can you. Please give us a breakdown of.

Matthew Klein: Yeah, Kristen, good question. I think we look to say that the position and the patient community was surprised, disappointed, and quite honestly scared for the patient. So, this is the only therapy they have that is directed for non-synthetician patient. Many have been on the therapy for years and observed the benefits that we've been reporting for physicians. They understand the context of the disease. They understand the strength of the data that we produced.

What those sales are in Europe versus the rest of the world.

Also could you give us insight as to what other geographies might have their opinion affected by.

EU opinion.

David Thank you for the question.

<unk>.

Sorry to your second part first.

Matthew Klein: And they can't, as many as said, they can't imagine having to take patients off a drug that's safe and effective. They'll, the patients on their own, you know, have a ability on their own to reach out and, and, and, and, but they've always be heard. I'm sure in many parts of Europe that will happen, given the, the fear of concern they have, and I can similarly for the physician community, they'll want to speak up.

As.

As we've talked about in the past.

Many of our largest markets outside of Europe have independent regulatory agencies that do their independent assessments.

And we will continue to make their independent regulatory decision independent of.

The CHP and <unk>.

The European authorization.

Matthew Klein: You know, I think here is that most people, as we were, would never thought this state would come in this would be a reality. So, I think the, this is a little bit for them, a call to speak up and let their voice be heard. And importantly, as you say, share their story, share their experience, particularly the positions who are experts and can truly articulate the benefits they've observed in the importance of the therapy for patients with non-synthetician DNA.

In terms of revenue.

We have said in the past that while many years ago Europe would have been the primary source of our trends on our revenue and we've done a lot of work over the past year past years to diversify the business on Ocado joins a little bit more detail about the breakdown.

Matthew Klein: Thank you.

Yes.

<unk>.

That was just saying we spent.

And at that time in the last couple of years to geographically diversify the business and this is the intent of evening out and sort of.

Ensuring that we have contribution from a number of regions titled trend line of revenue, So where we stand today, we have a number of growth markets that have continued to grow over the last couple of quarters and last year and this has allowed us to have a little less than half of.

Sammy Corwin: One moment, please. Our next question comes from the line of Sammy Corwin of William Blair, Sammy Corwin of William Blair, Elana's Open.

Sammy Corwin: Great. Thanks so much.

EU revenue contribution to total revenue and then the remainder being ex U S.

Eric Pauwels: On the topic of trans learner, I guess since the negative opinion, how do you see any change in how physicians are writing scripts? Or if patients are accumulating medication ahead of the potential that opinion is not reverse? And then can you speak a little bit as to if you've increased your sales efforts in non-EU areas since the negative opinion as well. Thank you. Yes, Sammy. Thank you for the question. Right. Again, I think the, in the positions we've spoken with, the first response was, you know, clarifying and you confirm that in no way that things change.

Sure I mean is there any way you can let us I guess zero in on what the particular number.

Might be in the range of that just just in case.

Things don't work out of Europe, we're trying to understand what.

What the implications might be going forward with respect to our projections.

Yes, David I think from that perspective, I think it's roughly around 45% to 48%, but the one thing I would say and what's important to know.

That was the European market some of that more mature market and so as you look out at the time you would expect that.

Eric Pauwels: And patients can stay on the drug. They can write any prescriptions. And obviously everyone's going to do everything the candidates for patients, the therapies, but let me kick it over to Eric and if you want to do someone detail on prescriptions. Yeah. Thanks for the question, Sammy. First of all, we haven't actually seen an impact since CHMP has issued their opinion. In fact, you know, we've seen physicians who have actually been very, very, they've been very, very supportive.

Total revenue for more mature market doesn't have the growth trajectory.

Some of that in <unk> and <unk> market.

While it currently sits around the 45% to 48% currently you wouldn't expect that number to remain flat over the coming years.

Got it and with respect to expenses going forward.

Eric Pauwels: In fact, our customer facing team has actually stepped up their interactions with healthcare providers, advocacy groups and others to emphasize that the drug is actually available. And I think that's one of the most important things. We've made specific calls to every prescribing physician and we've worked with them because we've had relationships now for many, many years with many of these physicians. They know about the treatment. They've been treating patients for many years.

Is there any way you can give us I guess some level of bandwidth on what you expect for 2024 and beyond when.

The restructuring is in full place.

Yes, David.

We announced the.

Revise our opex guidance.

Great.

Previously too.

A $10 16.

Eric Pauwels: And we've been reaffirming that the, the, that Translana is not only just available available for existing patients, but it's also we've seen new prescriptions as well. The fundamentals that we see, Sammy is basically, there's been limited to no discontinuations because of the CHMP information. New patients continue to get scripts. Compliance has actually remained very high and we've been able to maintain dose adjustments. We've had patients that have gone from ambulatory to non-ambulatory and been maintained as well.

And also we then announced the subsequent cuts.

And how that would have an impact of additional another approximately 20% and run rate 2024, obviously, we will give the updated opex guidance at Jpmorgan in January.

Thank you for taking my questions.

Thank you one moment please.

Our next question comes from the line of Kelly <unk> of Jefferies. Your line is open.

Eric Pauwels: And into your question about geographic expansion and outside. Well, that some of some of the information has gone out to other countries. We've actually been able to continue to work with healthcare providers in other parts of the world and still continue to generate and see growth from Translana in the quarter. So the simple answer, of course, is that we have not seen any, any discontinuations and the fundamentals remain strong. And we're, as I mentioned earlier in my, in my, in my talk, we're not only very confident in what we did this quarter, but we're very confident in how we'll finish 2023 and we've actually raised guidance and our DMD guidance is now 565 million to 595, which includes Translana growth in the fourth quarter and combined that would equal about 11 to 17% year over year growth for the DMB franchise compared to last year. Thank you.

Hi, This is <unk> for Kelly, Thanks, very much for taking my question.

So the first question on Translarna.

David Lebowitz: One moment, please.

Room that you're able to get the negative opinion reversed is there a deadline for you too.

Eventually have to convert that conditional approval to full approval and then on the pre BLA meeting for ADC deficiency.

On the comparability.

Manufacturing are there any specific assays that you have to develop before the meeting.

Yes. Thank you very much for the question. So on your first question regarding the.

The convert any positive opinion, if we're able to convert that to a positive opinion. The continued conditional marketing authorization here, there's typically not a fixed timeline to that typically what goes along with the conditional marketing authorization in Europe is something called a specific obligation and that specific obligation is typically.

Some requirements to collect additional data to support the benefit risk profile of the therapy. So there is no timeline per se, but there'll be there would be a specific obligation that require us to collect data and obviously the shape or form of that 10 design of that data collection.

David Lebowitz: Our next question comes from the line of David Lebowitz, a city.

Study would have some timeline likely tied to it also is part of the conditional marketing authorization as we've done for years requires.

David Lebowitz: Your line is open.

David Lebowitz: David Lebowitz. Thank you for taking my question. When looking at the trans line of European sales, could you please, or oversee sales, can you please give us a breakdown of what those sales are in Europe versus rest of the world? Also, could you give us insight as to what other geographies might have their opinion affected by the EU opinion? David, thank you for the question.

Annual renewal for the past several years, we've done that and that's a lot of that is relied on the continued evidence of safety, we're seeing Australia as well as benefit.

That we've seen in stripes near our therapies that have been have had conditional marketing authorization status for decade. Two decades. So this would not be the first time that <unk> therapy continued in the conditional frame a bit more time.

Eric Pauwels: Let me start with your second part first. As we've talked about in the past, the many of our largest markets outside of Europe have independent regulatory agencies that do their independent assessments and will continue to make their independent regulatory decisions independent of the CHMP and European authorization. In terms of revenue, we have seen the past that, well, many years ago, Europe would have been the primary source of our trans water revenue and done a lot of work over the past years, past years to diversify the business.

On your second question regarding the <unk> BLA meeting on the issue of comparability. So comparability analyses are done to show that the material that we used in the clinical studies and as similar as possible to the material.

<unk> commercially unusually that includes as you referred to a number of different analytical assays.

One of the challenges that we had is that the clinical trial material that we.

For which we had to establish comparability with our commercial process is.

Over a decade old.

Those are clinical studies that were started in the early 2010 and there simply is not enough of that residual clinical supply available to provide the additional replicates and additional data that the agency wanted us to have.

Eric Pauwels: As Matt was just saying, we spent substantial effort and time over the last couple of years to geographically diversify the business. And this was the intent of evening out and sort of ensuring that we have contribution from a number of regions to total trans water revenue. So, where we stand today, we have a number of growth markets that have continued to grow over the last couple of quarters and last year. And this has allowed us to have a little less than half of EU revenue contribution to total revenue and then the remainder being XUS.

To finalize the comparability analysis, obviously had data across all the assays that we believe show that the processes comparable due to ask for some additional analyses.

It's a bit challenging as you get that material given the age of that material now importantly.

It will to discuss with them the potential to leverage the accelerated approval pathway using our ongoing study in the U S, which is using material made with the commercial process.

The commercial like material for which there was no comparability assets and what we're able to show an ADC, which is a genetic disease and dopamine deficiency is that when we give the drug we're able to measure increases dopamine, obviously, that's a reliable quantifiable biomarker, that's not only incredibly important to the disease.

Eric Pauwels: Sure. I mean, is there any way you can let us, I guess, zero in on what the particular number might be in the range of just in case things don't work out in Europe. We're trying to understand what the implications might be going forward with respect to our projections. Yes, David, I think from that perspective, I think it's roughly around 45 to 48%. But the one thing I would say and what's important to know is those European markets are some of our more mature markets.

<unk> also logically will precede the subsequent development of dopamine related motor function, which is exactly what we observed in the clinical setting so that fits squarely in the framework of accelerated approval and I think everyone has seen lately in seeber, there has been increasing interest.

Eric Pauwels: And so as you look over time, you would expect that the contribution to total revenue for more mature markets doesn't have the growth trajectory as some of our newer and growth markets. And so while it currently sits around the 45 to 48% currently, you wouldn't expect that number to remain flat over the coming years. Got it.

Peter marks has talked about this ahead of siebert of using the accelerated pathway for rare disease gene therapies as a way to quickly get these therapies to patients. So we're looking forward to a pre BLA meeting in December so they asked us to do that to make sure. We're aligned on the contents of that accelerated approval BLA package and then pending the outcome of that meeting we expect to submit the.

Shortly thereafter.

Pierre Gravier: And with respect to expenses going forward, is there any way you can give us, I guess, some level of bandwidth, some what you expect for 2024 and beyond when the restructuring is in full place.

Thank you.

One moment please.

Our next question comes from the line of Brian Abrahams RBC capital markets, Brian Abrams Your line is open.

Operator: [inaudible] Thank you, one moment please.

Hey, good afternoon, thanks for taking my questions.

As you prepare for the MAA filing for separate App trend next year, what are your expectations for what the car study requirements will be.

For Europe.

And then secondarily.

I guess on Trans Lorena and the U S, where do you stand in terms of key discussion items.

And potential areas of focus that you are expecting for the type C meeting and when might we see an update from that will be shortly.

After the meeting or should we expect a little bit of a time gap to allow for the minutes to be collected.

Thanks for the question, Brian and so.

Brian Abrahams: Our next question comes to an line of Kelly Shi of Jeffries, Jelana's open.

On the question regarding the MAA in Europe.

I think this is another example of how regulatory authorities tend to look at things differently. The feedback we've gotten from Europe regarding carcinogenicity as they understand very well.

Brian Abrahams: Hi, this is Yun for Kelly. Thanks very much for taking the question. So the first question on Translana, assume that you are able to get the negative opinion reversed. Is there a deadline for you to eventually have to convert that conditional approval to full approval. And then on the pre-BLA meeting for ADC deficiency, on the comparability in terms of a manufacturing, are there any specific assays that you have to develop before the meeting?

Brian Abrahams: Yeah, thank you very much for the question. So on your first question regarding the convert the positive opinion or able to convert that to a positive opinion, the continued conditional marketing authorization, you're just typically not a fixed timeline to that, typically what goes along with the conditional marketing authorization, Europe is something called a specific obligation. And that specific obligation is typically some requirement to collect additional data to support the benefit and risk profile of the therapy.

The active metabolite of course <unk> is <unk> four.

And they understand that the four CPR training, both actually co factors.

They understand the data we've collected to date in terms of Carnival USD risks and they have said.

They would like us to not only have our own data, but that we can rely on the data and the experience of crew backhouse for many years.

There is a knowledge base that that exists that is.

Carson logistics risk associated with beach for used clinically for many years so.

We don't believe the <unk>.

We have at FCA will be an issue with Europe for that reason.

Again just.

He is looking at things differently and again, that's why we're able to move forward with that submission as we said in.

In the first half of 2024 on your question regarding the type C meeting per trans lineups.

Brian Abrahams: So there's no timeline for say, but there'll be a specific obligation that requires to collect data and obviously the shape or form of that and design of that data collection study would have some timeline likely tied to it. Also as part of a conditional authorization, as we've done for years requires an intangible renewal for the past several years we've done that and that's a lot of that is relied on the continued evidence of safety we're seeing in stride as conditional marketing authorization status for decade to decade.

Purposes, I mean, it's really to focus on the evidence that we have there are many sources of evidence we have shown that not only.

There is clear evidence of benefit change and studying such as spending 41, but that can be confirmed a number of ways, including meta analyses. The long term really won't stride registry and so really working constructively with the division is to say what are the components, we need and how do we formulate them in order to support the NDA.

Our resubmission.

We typically do once we have clarity in the outcome of the meeting sometimes that can come from the meeting itself, sometimes that requires minutes, sometimes that requires some back and forth. Afterwards as soon as we have clarity, we'll certainly share. It obviously, we know a lot of people are quite interested in the outcome of this meeting.

Brian Abrahams: So this would not be the first time that a therapy continued in the conditional frames for a bit more time. On your second question regarding the PBLA meeting and the issue of comparability. So comparability analyses are done to show that the material that we used in the clinical studies is as similar as possible to the material that we intend to use commercially and usually that includes as you referred to a number of different analytical assays.

And I believe simpler Chevy.

Boys with nonsense mutation DMD in the US who have waited years for therapy and then also the large number of boys in the U S who have been on trends behind us for a number of years and their participation.

In clinical studies and beyond all of whom are quite.

Interested in ensuring that this drug can be available in the U S for them.

Brian Abrahams: One of the challenges that we had is that the clinical trial material that we for which we had to establish comparability with a commercial process is over a decade old. Those are clinical studies that were started in early 2010s and there simply was not enough of that residual clinical supply available to provide the additional replicants and additional data that the agency wanted us to have to finalize the probability analysis. The obviously had data across all the assays that we believe show that the process of comparability that's just from the additional analyses is a bit challenging to get that material given the age of the material.

Yeah.

Really helpful. Thanks, Matt.

Thank you one moment please.

<unk>.

Our next question comes from the line of Colin Bristow of UBS. Your line is open.

Yeah.

Hey, good afternoon, thanks for taking the questions.

After an NDA filing timeline I'm just curious what is the latter end of your guidance three Q4.

I'm curious can you confirm whether the study has started and it just seems like a sort of extreme upper bound of this timeline. If this study is all that's needed.

And then on the ATC could you just put a little more detail on why FCA. The comparability data is still not sufficient and then what are you sort of hoping will be discussed.

Brian Abrahams: Now importantly we were able to discuss with them the potential to leverage the accelerated approval pathway using our ongoing study in the US which is using material made with the commercial process so it is the commercial like material for which there was no comparability assay and what we're able to show in ABC which is a genetic disease of dopamine deficiency is that when we give the drug or able to measure increases in dopamines. Obviously that's a reliable quantifiable biomarker that's not only incredibly important to the disease pathology but also logically will proceed to subsequent development of dopamine related motor function which is exactly what we deserve in the clinical study so that fits squarely in the framework of accelerated approval and I think everyone has seen lately in seabirds there has been increasing interest.

Pre BLA meeting in December.

Thanks for the question Colin so.

The if you just.

When you find out you have to do a study it takes a little bit of time to actually organize this study get the slot at the Kroger the animals in order to get the get the dosage confirmed the protocol say at the protocol agreed upon and start the study we expect to begin dosing in the study have all of those things right and dosing that study to start in December.

The six month study so by the clock that Ali I don't get dosed in December that's the in life portion should be done in Union. Once again my portion is done in June. They then have to sacrifice the animals both through the histological studies all the histological analysis like the reports, we're obviously going to work as quickly as we can to accelerate those timelines, obviously you can't shorten the 26.

Brian Abrahams: Peter Marx has talked about this ahead of seabirds of using the accelerated pathway for rare disease gene therapies is a way to quickly get these therapies to patients so we're looking forward to a pre-BLA meeting in December so they have to do that to make sure we're aligned on the contents of that accelerated approval BLA package and then pending the outcome of that meeting we just expected this BLA shortly Thank you.

Weeks, but we're doing everything we can to shorten the time for data analysis as well as getting the audited report, which is necessary for submission. So thats, where you get the three key time down from nearly the realities of the 26 week study takes more than 26 weeks and Thats and we wanted to get an accurate picture of what we think it could.

Colin Bristow: One moment, please. Our next question comes from a lot of Brian Abrams of RBC Capital Markets.

Be the longest possible date or the latest possible time for that submission obviously as we mentioned with their team to see if we're able to work out something with the agency, where perhaps we could submit those.

Colin Bristow: Brian Abrams, you're allowed to open. Hey, good afternoon. Thanks for taking my questions.

Data is during the day 120 safety review and Lee Senior deal, that's going to be the basis of our ongoing conversations because otherwise we believe we have a package that has every other component there and again as we indicated in our discussions with them.

Colin Bristow: As you prepare for the MAA filing for September after in next year, what are your expectations for what the car study requirements will be for Europe approval? And then, secondarily, I guess on Translana in the US, where do you stand in terms of key discussion items and potential areas of focus that you're expecting for the type C meeting? And when might we see an update from that? We'll be shortly after the meeting or should we expect a little bit of a time gap to allow for the minutes to be collected?

Our safety and efficacy data as being supportive of the NDA.

And so we look forward to being able to submit that as soon as possible in terms of comparability. This is simply a matter of we had very limited supply of the clinical materials. So there's only a certain number of assay runs we were able to do to provide data to compare to the assays that for <unk>.

Conducting the commercial material they want that additional data points, greater and a greater number of samples that we simply couldnt provide.

Colin Bristow: Thanks. Thanks for the questions, Brian. So on the question regarding the MAA in Europe, I think this is another example of how regulatory studies tend to look at things differently. To be back, we have gotten from Europe regarding car simplicity as they understand very well that the active metabolite for CPITaren in BH4, and they understand that BH4 and CPITaren are both naturally current co-factors. They understand the data we've collected to date in terms of car simplicity risks, and they have said they would like us to not only have our own data, but that we can rely on the data and experience the food band health for many years.

Due to limited supply in terms of the.

The pre BLA meeting it was suggested that we hold the pre BLA meeting.

Because they wanted to make sure that we're aligned on the contents of the package, how we better present their integrated safety summary from all the studies that are good about how we're going to prevent the efficacy data. How are we going to include other components of the regulatory studies in the package. They thought it would be very important to make sure as we.

We were told in the meeting it is not required but which are all companies. It's important to have this so we're sure that the file meets the format specifications, we want to avoid any filing issues. So we believe the most prudent thing to do is to have that pre BLA meeting and then pending the results to be in a position to submit as quickly thereafter as possible.

Colin Bristow: There's a knowledge-based evidence that there's no car simplicity risk associated with BH4 and these chronically from many years. So we don't believe that the issue we have at FCA will be an issue with Europe for that region.

Great. Thank you for that.

Yeah.

Colin Bristow: And so again, just different authorities looking at things differently, and again, that's why we're able to forward with that submission as we said in the first half of 2024. On your question regarding the type C meeting portrays lineup, the purpose of that being is really to focus on the evidence that we have, the many sources of evidence we have shown that not only there's clear evidence of benefit in studies that just study for the one, but that's to be confirmed in a number of ways, including that analysis of the long-term red one, stride registry, and so really working constructively with the divisions to say what are the components we need and how do we formulate them in order to support the end of the recent mission.

Thank you one moment please.

Our next question comes from the line of Jeff Hung of Morgan Stanley. Your line is open.

Question in your discussions with the EMA on particular known what gives you confidence that it makes that move that day for conditional marketing authorization is there anything that you can update in terms of analyses or presentation that would increase your confidence for a positive outcome on the conditional marketing authorization given the feedback you've received from FDA.

Okay.

Yeah, Thanks, Jeff for the question.

The frameworks in SBA in EMEA are slightly different in the discussions we're having with FCA around the potential for accelerated approval based on upright stability being an intermediate clinical endpoint, obviously upright stability as we've talked about is in all of the four sections of the employers which was the primary endpoint the one.

Colin Bristow: As we typically do, once we have clarity in the outcome of the meeting, sometimes that can come from the meeting itself, sometimes that requires minutes, sometimes that requires the back and forth afterwards, as soon as we have clarity to certainly share. And obviously, we know a lot of people are quite interested in the outcome of this meeting, not the least of which are the, you know, boys with non-transportation DNA in the US who have waited years for therapy, and then also the large number boys in the US who have been on a transporter for a number of years in their participation in clinical studies and beyond all of whom are quite interested in ensuring that this drug can be available in the US for them. It's really helpful. Thanks, that. Thank you. One moment, please.

That has been shown to be most important in pediatric and young adult patients, particularly ambulatory patients because it's been shown to be able to predict time to loss of ambulation.

Obviously I appreciate the ataxia for ambulatory patients the key thing for therapy to do is to delay that time to loss of ambulation delay loss of ambulation and so it didn't have an endpoint that can do it we believe meets that criteria for intermediate clinical endpoint, we look forward to continuing the discussions with the agency as is often necessary in rare diseases.

There's a lot of back and forth to talk about analyses, we have and as you indicated could we provide some additional support of analysis and move at Bay in particular, the fact that we have a six month open label extension study during which all subjects are blinded. So that gives us an opportunity to look at changes in trajectory for example for the placebo patients once we switched on basket that's.

Jeff Hung: Our next question comes from the line of Colin Bristow, of UBS, Elinus Open. Thank you for taking the questions.

Jeff Hung: On the set the Etterin NDA filing timelines, I'm just curious why is the lesser end of your guidance, 3Q24, and can you confirm whether the study has started? It just seems like a sort of extreme upper bound of this timeline, if this study is all that's needed.

That's the U S in terms of the Europe.

The conditional marketing authorization is a number of criteria set out for for a conditional marketing authorization do you have initial data that shows that there is a favorable benefit risk of a therapy are you beating of unmet medical need.

Matthew Klein: And then on the AADC, could you just put a little more detail on why FDA thinks the comparability data is still not sufficient?

Getting is getting this therapy to patients sooner potential.

Potential public health benefits and I think when you consider the.

It took went on and you move that phase <unk> study and the other data we have we clearly meet all of those criteria. While we didn't hit the primary endpoint of the overall at par score. There is a number of important sources of benefit in the move up a study not only in our price stability above our subscale also on T, which is in our blood center for patients and then if you look at the well.

Matthew Klein: And then what are you sort of hoping, or what will be discussed, the preview A meeting in December? Thank you. And thanks for the questions, Colin. So, if you just, you know, when you finally have to do a study, it takes a little bit of time to actually organize the study, get the slide as a CRO, get the animals order, get the doses confirmed, get the protocol set, get the protocol agreed upon and start the study.

Established safety profile in particular, particularly in pediatric patients. We can clearly demonstrate that this initial study has a favorable benefit risk profile, obviously its on that medical need not only for pediatric patients, but there is no approved therapies for <unk> in Europe for patients of any age and obviously given when you have a therapy that can potentially slow delay of loss of ambulation.

Matthew Klein: We expect to begin dozing in the study, have all those things ready and dozing at study to start in December. That's a six month study, so by the clock that all the animals get those in December, the in-life portion should be done in June. Once in-life portion is done in June, data at the sacrifice of the animal, both through the histological studies, all the histological outfits are right to report. We're obviously going to work as quickly as we can to accelerate those timelines, obviously we can't shorten the 26 weeks.

<unk> is an irreversible morbidity.

Those patients will therefore benefit from access to therapy sooner. The final point. So obviously, we know very well from the trend learner experience is to be able to.

Be able to demonstrate that you can collect more data on patients to support the.

Matthew Klein: But we're doing everything we can to shorten the time for data analysis as well as getting the audit of draft report, which is necessary for submission. So, that's where you get this week to time back from is merely the realities of to do a 26 week study, takes more than 26 weeks. And that's, and we wanted to give an accurate depiction of what we think could be the longest possible date for the latest possible time for that submission.

Condition worth a conditional approval and confirm that you have a favorable benefit risk balance. We obviously believe there's many sources of additional data that we could generate.

To confirm the benefit risk profile. So again, we believe we meet all of the necessary criteria from additional authorization and we'll look forward to discussions with the EMA to gain alignment with them on those points.

Matthew Klein: Obviously, as we mentioned, we're able to see if we're able to work out something with the agency where perhaps we could submit those data during the day 120 safety review and week-sage review. And that's going to be the basis of our ongoing conversations, because otherwise we believe we have a package that has every other component there. And again, it's being indicated in our sessions with them, they see our safety efficacy data as being supportive of the NBA.

Great. Thank you.

Okay.

Thank you one moment please.

Our next question comes from the line of Alexander Xanax of Truth Securities. Your line is open.

Hi, Thanks for taking my question and congrats on securing the royalty financing deal that's great.

Maybe two for me one on simply after and when might we see another cut of the OLED the tolerance data.

Matthew Klein: And so we look forward to being able to submit that as soon as possible. In terms of comparability, it's simply a matter of not, we had very limited supply of the clinical material. So, we're able, there's only certain number of assay runs we were able to do to provide data to compare to the assays that were conducted in the commercial material. They want the additional data points greater, a greater number of samples that we, we simply couldn't provide to do the limited supply.

And then one on <unk>.

Trends Lorena, if you are able to overturn the conditional marketing.

Ongoing conditional marketing authorization in at that ongoing study.

Have the official full marketing authorization have you done any market research to see how that would affect referencing countries worldwide and if they would be required.

Matthew Klein: In terms of the preview and meeting, it was suggested that we hold the preview and meeting because they wanted to make sure that we're aligned on the contents of the package, how we're going to present their integrated safety summary from all the studies that are going to, how we're going to present the efficacy data, how we're going to include other components of the regulatory studies in the package. They thought it would be very important to make sure, as we were told in the meeting, it's not required, but we tell all companies it's important to have this so we're sure that the file meets the format and specifications we want to avoid any violations.

Wholesales or not thanks.

Thanks for the question so first on the fee tolerance.

As we shared we gave an update on those two tolerance data at the Ssi one meeting in Israel in September those were getting really great data showing now with over 40 patients enrolled in that she tolerance protocol that we're seeing patients move through and get to levels.

Get to levels of fee tolerance beyond the recommended daily allowance and this is these are incredibly important data as we said all along the fee tolerance component is really not for regulatory purposes necessarily we have a sufficient efficacy data for that and are able to show in the long term extension that we're adding important durability CPR.

Matthew Klein: So, we believe the most prudent thing to do is to have that preview and meeting, and then Petty and Results to be in a position to submit as quickly there after as possible. Right, thank you for that. Thank you one moment, please.

Treatment effect as well as long term safety. This is really the fatality at a really quite important.

Alexander Xenakis: Our next question comes on a line of Jeff Hung, a Morgan family. Your line is open.

One for differentiation is something Cougar and was never able to demonstrate for physician adoption and for payer discussions, particularly outside of the U S on the.

Alexander Xenakis: Question, in your discussions with the EMA on particular known, what gives you confidence that it may accept move that they for conditional mark authorization? Is there anything that you can update in terms of analyses or presentation that would increase your confidence for positive outcome on the conditional marking authorization given the feedback you received from FDA. Yeah, thanks Jeff for the question. So, you know, the frameworks in FDA EMA are slightly different in the discussions we're having with FDA are around the potential for accelerated approval based on upright stability being an intermediate clinical end point.

<unk> one upfront.

Look again, we see the ability to keep the conditional authorization as a big win not only obviously across really most importantly for the patients.

Ill turn it over to Kelly, if you want to comment kind of on the what you think the global payer impact could be.

And conditional authorization.

Yes, I think from a paper impact I think it would be quite minimal and I think one of the things that the team has done an incredible job as with the conditional authorization that we've had.

Alexander Xenakis: Obviously upright stability we've talked about is in all the four sections of the MFARS, which was the primary endpoint, the one that has been shown to be most important in pediatric and adult patients particularly ambulatory patients because it's been shown to be able to predict time to loss of regulation. Obviously, in future, potassium for ambulatory patients, the key thing for therapy to do is to delay that time to loss of regulation, delay loss of regulation.

The law nine years is being able to secure a favorable pricing.

Pricing corridor, and reimbursement and being able to maintain that over the years. So I think at this stage, where we stand.

We don't see any sort of negative impact from <unk>.

Menuhin conditional authorization and of course, we'll continue to focus.

Yes.

Definitely thanks for taking the question.

Alexander Xenakis: And so to have an end point that can do it, we believe meets that criteria for intermediate clinical end point, we look forward to continuing the discussions with the agency as is often necessary and religious reasons a lot of back and forth to talk about the analyses we have. And as you indicate, could we provide some additional support of analyses to move FAA and particularly the fact that we have a six month open label extensions that are during which all subjects of blind is that gives us an opportunity to look at changes and trajectory for example for the placebo patients once we switched on to active.

Thank you one moment please.

Our next question comes from the line of Joseph Schwartz of Leerink Partners. Your line is open.

Great. Thanks, very much I was wondering if you could talk about your publication plans for the affinity stepping up to the data will we see that published in a peer reviewed journal anytime soon and then I believe you have the option to go up to a 20 milligram dose of PTC.

Pivot HD patients outside the U S. So where do you stand on implementing that decision.

Matthew Klein: That's the US in terms of the Europe. The conditional marketing authorization is number of criteria set out for for a conditional operation. Do you have initial data that shows that there's a favor of benefit risk of a therapy? Are you being in on that medical need? Getting is getting this therapy, the patients sooner potential public health benefits. And I think when you consider the tickling on and move FAA study and the other data we have, we clearly meet all of those criteria.

Yes, absolutely.

I'll take the.

I think let me take the second question first and then I'll kind of answer the first question.

So on.

So we as we talked about we shared the results from the five and 10 milligram dose groups. The first cohort of 32 patients in June those data from our standpoint, we're as good as they can be that we achieved that objective about 12 week portion of the study that first cohort of patients demonstrated a dose dependent lowering of Huntington.

Matthew Klein: While we didn't hit the primary end point of the overall at bar score, there's a number of important sources of benefit in the move FAA study, not only in our parts stability, mobile sub scale, all forms of teeth, which is in a bullet sentence for patients. And then if you look at the well established safety profile of the tickling on particular pediatric patients, we can clearly demonstrate that this initial study has a favorable benefit risk profile.

Protein in the blood seeing the differential exposure.

Could you just $5 eight in the CSF relative plasma at a 10 milligram dosing seeing that that ratio is one five to one suggesting that we're going to even greater exposure by one rig in the brain and even potentially higher levels or greater lowering of.

Matthew Klein: Obviously it's on that medical need, not only in pediatric patients, but there's no approved therapies for FAA in Europe for patients of any age. And obviously, given that you have a therapy that can potentially slow delay and loss of regulation, that's an irreversible morbidity. And in those patients with the appropriate benefit from access to therapy sooner. The final point, so obviously we know very well from the translonger experience is to be able to be able to demonstrate that you can collect more data on FAA patients to support the condition for the condition all approval and confirm that you have a favorable benefit.

Huntington mutant Huntington protein in the break all of which was very very important and that of course. The other key point is that we were doing all the safety the safety profile of the drug was quite strong in those first 12 weeks, we had no drug related serious adverse events. They were no NFL spikes, all very very important particularly given.

Matthew Klein: We obviously believe there's many sources in the additional data that we could generate to confirm the benefit is profile. So again, we believe we need all of the necessary criteria for additional authorization and look forward to discussions with the EMA to gain a line with them on those points.

Matthew Klein: Thank you.

Matthew Klein: One moment, please.

Concerns that were raised over others HCC lowering therapy.

Drawbacks that we've talked a lot about in the past we've said based on those data. We believe we may have a dose levels, we need right now to get us where we want to be in terms of the ultimate goal of the program, which is being able to lower brain cell Huntington protein levels, 30% to 50% and so with the decision.

Those early data, while we have the ability to go up to 20 milligrams with the SMB supported us starting 20 milligram cohorts the regulatory authorities and local ethics committees have approved us going into 'twenty, we're still in a holding pattern, we want to understand a little bit more with the biomarker effects are with the dose levels. We have now five and tenants because those very well may be.

Alexander Xenakis: Our next question comes from the line of Alexander Xenakis of Truist Security, Jalana Sultans. Hi, thanks for taking my question.

Sufficient to move forward and get us where they want to be so.

Alexander Xenakis: Congrats.

Haven't undershooting, those 20 milligram dosing, yet I'm not sure we're going to need to and we want to better understand the longer term bile.

Matthew Klein: First of all, I'm securing the World Bank of the United States. It's great. Maybe two for me. One lot of the OLE speed tolerance data. And then one on Translana. And if you are able to overturn the conditional marketing, the ongoing conditional marketing authorization and have that ongoing study, but you don't have the official soul marketing authorization.

Locker effects of the current dose levels before revisiting that decision.

Let me now turn it over to Tyler to answer your question around publication strategy for PKU.

Yes, Thanks, Joe we are absolutely.

Getting the affinity study published in a peer reviewed journal. The team is working on that as we speak and is looking to target a high impact.

Matthew Klein: Have you done any market research to see how that would affect referencing countries worldwide and if they would be required to hold sales or not? Thanks.

Hi High impact journal and it did.

Timeline for getting that publish is obviously driven by the channel of choice.

Matthew Klein: Thanks to the questions out. So first on the fee tolerance. As we shared, we gave an update on the fee tolerance data at the SSIDAM meeting in Israel in September. Those were again really great data showing now with over 40 patients enrolled in that fee tolerance protocol that we're seeing patients move through and get to levels. Get to level of fee tolerance beyond the recommended daily allowance. This is these incredibly important data.

What this is work in progress the team is moving through this and we expect it to be published during 2024 pending the channels.

Thank you.

Thank you one moment please.

Okay.

Our next question comes from the line of Gena Wang of Barclays. Your line is open.

Okay.

Hi, Thank you for taking my questions.

So I do have I think three quick questions at the first one is.

Matthew Klein: As we said all along, the fee tolerance component is really not for regulatory purposes. And so we had the sufficient efficacy data for that and I'm able to show in the long term extension that we're having important durability of CP action treatment effect as well as long term safety. This is really, the fee tolerance data is really quite important. One for differentiation is something Kugan is never able to demonstrate and for physician adoption and for payer discussions, particularly outside of the U.S. On the translaw and upfront, the look again, you know, we see the ability to keep the conditional authorization as a big win. Not only, obviously, for us, but really most importantly for the patients.

Regarding the PKU program.

Since initially with thinking about 505 B two is that because the lack of confidence of the IP position that this drug will be very different from <unk>. That's the first question.

Relatedly, how confident you are on the item regarding <unk>.

New composition of matter and then for the pivot HD I don't know if I missed it.

So have you.

Exactly what kind of data you would need in order to remove FTE clinical hold.

So based on.

Matthew Klein: When we start over to Kylie, if you want to comment, Kylie, on what you think the bill will pay her impact could be and find a conditional authorization. Yeah, I think from a paper impact, I think it would be quite minimal, Alex. I think one of the things that the team has done an incredible job is with the conditional authorization that we've had over the last nine years is being able to secure a favorable pricing corridor and reimbursement and being able to maintain that over the years. So I think at this stage, where we stand, we don't see any sort of negative impact from continuing conditional authorization. And of course, we'll continue to focus on that. Thanks for taking the question. Thank you.

Your prepared remarks, you did mention certain months clinical safety data when I look at the press releases of six months or a clinical safety data demonstrate similar favorable safety profile support 12 months dosing.

Matthew Klein: One moment, please.

Additional data that will be quite you can dose more than 12 months and what dose you can dose.

Beyond 10 milligram. So thats the second question and a quick weight loss last question.

Got it.

In ADC, so if youre using current U S data for accelerated approval, what additional studies would need to do.

In order to.

Uh huh.

To get a full approval in the future.

Great. Thank you very much for the questions. The first question for number one regarding PKU incentive to look I think that was really what.

Joseph Schwartz: Our next question comes from a line of Joseph Swartz of Lievering Partners, Your line of focus.

More reflection of sensor being a very small virtual company and probably looking for what they bought at the time would be the quickest and least expensive development path forward.

Joseph Schwartz: Great. Thanks very much.

Joseph Schwartz: I was wondering if you could talk about your publication plans for the affinity set the up for data. Will we see that published in a peer review journal anytime soon? And then I believe you have the option to go up to a 20 milligram dose of PPC 518 in pivot HD patients outside the US. So where do you stand on implementing that decision? Yeah, absolutely.

I think.

It's not uncommon for a smaller company to think about the development path that way.

I think from our standpoint.

The.

Very clear this is a highly differentiated therapy that is much more suited to the 500 <unk> pathway obviously.

Matthew Klein: So I'll take the, I think let me take the second question first and then I'll, I'll, like I answered the first question second. So I'm on 518. So we, as we talked about, we share the results from the five and 10 milligrams of those groups, the first cohort of 32 patients in June, you know, those data from our standpoint, where as good as they can be, we achieved every objective of that 12-week portion of study in that first cohort of patients, demonstrating the dose-dependent low and a pontuitinet protein in the blood, seeing the differential exposure of the G518 in the CFS relative to plasma, as I tend to remember and just seeing that that ratio is 1.5 to 1, suggesting that we're getting even greater exposure, 518 in the brain, and potentially higher levels, or greater low range of, you can, you can, you can, you can protein in the brain, all of which was very, very important.

We're in a position to have the resources to do the necessary studies and not have to rely on a leather NBA and incur that risk.

The state based on the launch of a therapy following approval as we've talked about not only do you have a great deal of confidence in how differentiated CPO Terra is in its ability to meet the persistent large unmet medical need for PKU patients some physicians, including under the mental on a commercial lead time this summer.

XIAFLEX physicians deepen switch patients who may be served to some extent include then to see good tailwind because of what we've been able to show in terms of the large magnitude of clinical benefit.

You also talked about the IP here, we obviously have orphan designation. We also have some potential patent extensions that we believe will extend the orphan exclusivity out several years.

Matthew Klein: And of course, the energy point is that we were doing all the safety, the safety profile of the drug was quite strong in those first 12 weeks. We had no germinated seriously worse events, they were no NFL spikes, all very, very important, particularly given concerns that were raised over other HCT low and therapies that have drawbacks that we, we talked a lot about in the past, we said this in those data, we believe we may have the dose levels we need right now to get us really want to be in terms of the ultimate goal of the program, which is being able to lower brain cell Huntington protein levels 30 to 50%.

Question on ticket HD as we had talked about in the past in a recession with the agency they have said that.

What they wanted to see additional evidence that we can dose at the dose levels.

<unk> activity <unk> those additional data could take the form of non clinical data can also take the form of clinical data and so we had made the decision since we were able to conduct this trial.

Many countries outside of the U S and enroll the study outside the U S that we would conduct the study collect the clinical data in the study and then provide those data as we had them to FDA.

Matthew Klein: And so with the decision, with those early data, while we have the ability to go up to 20 milligrams, with the S&B has supported us starting 20 milligrams cohorts, the regulatory authorities and local ethics committees have approved us going to 20. We're still in a holding pattern, we want to understand a little bit more what the biomarker effects are with the dose levels we have now 5 and 10, because those very well may be sufficient to the program.

In order to fulfill that need of demonstrating that <unk> can be demonstrated safely. So once we did the extreme up once we have the 12 week data. We took those data that we presented it obviously since all patients are enrolled at the same time, we had some data beyond 12 weeks, we provided all of that to the agency and that was clinical data.

Matthew Klein: So we are, we haven't understood those, the 20 milligram dose and yet we're not sure we're going to need to and we want to better understand the longer term bio marker effects of the current just moments before we visiting that decision.

Included clinical laboratories included the NFL levels.

We had shared at the earnings adverse event reports of a lack of serious adverse events. The SMB minutes letters from the F&B chair all of which were shared with FDA as I mentioned in the prepared remarks during our discussion in the meeting the FDA indicated that those data that we had at that point could be sufficient.

Kylie O'Keefe: Let me return to the other entirely to answer your question on publication strategy for PK. Yeah, thanks, Joe. We are absolutely getting the affinity study published in a peer review journal. The team is working on that as we speak and is looking to target a high impact, high impact journal. And so the timeline for getting that published is obviously driven by this journal of choice. So where we work, this is work of progress, the team is moving through this and we expect it to be published during 2024 pending the journal chosen. Thank you.

Operator: One moment, please.

For 12 week dosing in five and 10 milligrams. If that's what we wanted to start out but obviously the goal here is to think about longer term dosing as your question suggested and they say okay. We'd like to see is data at the six month time point, so basically a little bit longer than three months to support the duration of dosing that we had proposed and pivoting HD.

But right now quite simply doing the timing mass.

Very possible by the time, we got that data center to the FDA that the review sites ready up and running in the U S. If I say it will be that can be done with enrollment.

Gina Wang: Our next question comes in a lot of Gina Wang or Barclays, a lot of open.

Pivotal HD.

Extremely close right now to completing enrollment in the stage two patients that enrollment is moving very quickly to overall for the study, particularly after the June data release, when we were able to provide a lot of comfort to physicians and patients.

Gina Wang: Thank you for taking my questions.

Gina Wang: So I do have, I think, a three quick questions. The first one is regarding the PTU program. Since since initially we're thinking about 505 B2, is that because the lack of confidence of their IP position that this drug will be very different from KUVET. That's the first question. And then, you know, later on how confident you are on the IP regarding this is a new composition or a matter.

Unlike.

Other Huntington lowering therapies, and we're able to.

Our objectives and do so safely theres been a lot of interest in that study. There's obviously a lot of interest in the United States for patients and physicians.

We'd love to be able to open sites here, but if the study is fully enrolled and we'll look to start a phase III here and be able to offer the opportunity for patients to participate in.

Matthew Klein: And then for the pivot HD, I don't know if I missed it. So have you like exactly what kind of data you would need in order to remove FDA clinical hold. So based on, you know, I think your prepared remark, you did mention certain months of clinical safety data. When I look at the press releases in six months of a clinical safety data, demonstrate similar favorite safety profile could support 12 months dosing and additional data that will require to can dose more than 12 months and what dose you can dose, like a beyond 10 milligram.

The pit and the PTC 500 development.

Your third question was regarding up stays at an accelerated approval and confirmatory study. So we are using the existing clinical setting now in the U S and we have the endpoint that we're using to support the accelerated approval is an early endpoint of biochemical changes and you'll have a longer term extension component of that study.

Which will collect long term clinical data to provide the clinical evidence necessarily.

To support the full approval. So this is really an example, where we will have the study ongoing it's going to be a long term study that's going to look at the acquisition of motor developmental milestones over time much in the way that we've been able to show previously in the clinical studies that were done previously we're all the time when it was to show that these children develop the <unk>.

Matthew Klein: So that's the second question and a quickly last last question regarding the app stars are in AADC. So if you are using current US data for accelerators, what additional study you need to do in order to to get a full approval in the future.

Ability to first of their head and be able to sit crawl walk independently that obviously it takes many years, which is why in many ways. This is a very good setup for an accelerated approval, where we have biomarker evidence dopamine increases, which is obviously likely to predict long term clinical benefit of the acquisition of dopamine related motor.

Matthew Klein: Great. Thank you very much for the question, Zina. The first question, for number one, we've already piqued you a sense of, look, I think that was really what more reflection of sensing a very small virtual company and probably looking for what they thought at the time would be the quickest and least expensive development path forward. I think, you know, it's not uncommon for a smaller company to think about the development path that way.

Milestones.

Thank you.

One moment please.

Yeah.

Our next question comes from the line of Paul Choi of Goldman Sachs. Your line is open.

Good afternoon, and thank you for taking my questions two questions from me first on the commercial side with the approval of all of them are alone. Today can you maybe just comment on how youre thinking about the impact to in place and would you maybe consider pulling back on Salesforce resource resourcing for that product.

Matthew Klein: You know, I think from our standpoint, the, you know, it's very clear that this is a highly differentiated therapy that is much more soon to the 505B1 pathway. Obviously, we were in a position to have the resources to do the necessary studies and not have to rely on another MBA and incur that risk of having to stay placed on the launch of a therapy following approval. As we talked about, not only have a great deal of confidence in how differentiated CPTaren is and its ability to meet the persistent large mathematical need for PKU patients.

Starting next year ahead of your expected loss of exclusivity.

And then on the pipeline side can you maybe comment on what you would intend to present in terms of your pivot HD update next year.

Should investors continue to expect plasma.

Plasma Huntington updates on neuro if element.

Matthew Klein: And as we've heard from physicians, including Ivan Munteu on a commercial heat time this summer, I desire for physicians to even switch patients who may be served to some extent, improve them to CPTaren because of what we've been able to show in terms of the large magnitude of clinical benefits. We've also talked about the IP here. We obviously have orphaned designation. We also have some potential patent extensions that we believe will extend the whole of the exclusivity out to several years.

Okay, and just or would you perhaps presents some details on other other endpoints, including clinical endpoints. Thank you very much.

Thanks, Paul quick question, let me, let me grab the second one first and then I'll turn the other question over to two pilots.

So first in terms of.

The <unk> data. So the 12 month data that we said in the call that we would share in the first half of 2024 that will be data from the biomarker portion you talked about <unk> being a 12 month placebo controlled study in two parts. The first part for 12 weeks focuses on pharmacodynamics and pharmacokinetics as well as safety and then.

Matthew Klein: Your second question on CIVIT HD, as we had talked about in the past, the accessions with the agency, they said that whether they wanted to see additional evidence that we can dose at the dose levels, we intended in CIVIT HD. Those additional data could take the form of non-clinical data. It could also take the form of clinical data. And so we had made the decision since we were able to conduct this trial in many countries outside of the US and enroll the study outside the US, that we would conduct the study, collect the clinical data in the study, and then provide those data as we had them to FDA in order to put so that data demonstrating that PDC 5.8 can be demonstrated safely.

And that second portion of the 12 month time point, you would have data further data on their or filament levels now with us about safety, but maybe more about recording.

Benefit.

CSS Huntington protein mutant Huntington protein levels volumetric changes on MRI. We also will have some clinical data at that time point, which are not main endpoints at the 12 months, but obviously, we're collecting this data I think.

We would certainly share the biomarker data share where clinical data, we have with the obvious caveat that even with 12 months, it's very hard.

Matthew Klein: So once we did the screen month, once we had this 12-week data, we took those data that we presented. It obviously, since all patients aren't enrolled at the same time, we had some data beyond 12 weeks. We provided all of that to the agency and that was clinical data, including clinical laboratories, included the NFL levels that we had shared at the earnings and adverse event reports, the lack of serious adverse events, the DSNB minutes, letters from the DSNB chair, all of which were shared with FDA.

Interpretable click.

Clinical.

<unk> done things like the UHD Rs gala events.

Total motor score or single digit modalities tests, just given just the rate of progression of disease.

The sensitivity to those instruments to change over a short period of time.

The answers we'll have those data domain focus there'll be the biomarker data. Obviously continued safety. We will also when ready have data on the additional.

Matthew Klein: As I mentioned in the prepared remarks during our discussion in the meeting, the FDA indicated that those data that we had, at that point, could be sufficient for 12-week dose in 5.10 milligrams if that's what we wanted to start now. But obviously the goal here is to think about longer-term dosing as your question suggested, and they said everybody would like to see those data at the six-month time point. So basically, a little bit longer than three months to support the duration of those things that we had proposed in COVID-19.

Subjects, who are they kind of hit the 12 week time point and then ultimately hit the 12 month time point, we haven't given a timeline for that at the time I mean, given obviously the data point I think most are interested in which is that 12 month data point for the initial cohort of subjects on whom we shared.

When we shared the 12 week data.

To your question on for more alone and Plaza.

Eric do you want to take that yeah. Thanks for the question Paul I think within Faas, we know that some flaws has been currently on the market for more than six years. It is currently the standard of care.

Matthew Klein: But right now quite simply doing the timing mask is very possible. By the time we got that data, essentially, the FDA got the review, got sites ready, up and running in the US. It might very well be that could be done with enrollment in COVID-19. We're extremely close right now to completing enrollment in the stage two patients, and enrollment is very quickly overall for the study, particularly active at the June data release, when we were able to provide a lot of comfort to physicians and patients that, unlike other hospital-loan therapies, we were able to see our objectives and do so safely.

Established in Plaza as the standard of care, because theres been a number of publications and Theres also a lot of science scientific evidence that is actually preserved greater motor function than than prednisone.

And we know that the data has continually supported that and we have very very strong relationships with each one of the health care providers.

In terms of showing them the evidence, but also providing patient support.

We understand that the community wants options.

Matthew Klein: There's been a lot of interest in that study. There's obviously a lot of interest in the United States for patients and physicians. So we would love to be able to open sites here, but if the study is fully enrolled, then we'll look to start phase three here, and be able to offer the opportunity for patients to participate in the PDT-5-5-1-8-4-0.

But we know that right now we have been focused on and we are our field force has been focused on not only growing the brand. This year, but also we have a number of strategies that will also protect the brand.

Following the loss of exclusivity because we don't necessarily see this as being a fall off.

Matthew Klein: Your third question was regarding upstate and accelerated approval and confirmatory study. So we are using the existing clinical study now in the US, and we have the end point that we're using to support the accelerated approval is an early end point of biochemical changes, then you'll have a longer term extension component of that study, which will collect long term clinical data to provide the clinical evidence necessary to support the full approval.

Because of a generic or even a competitor and we have a number of key strategies right now and a lot of them are centered around leveraging our patient support programs because we have that direct line with patients and we have more patients on <unk> than any other DMD treatment.

We can continue to leverage that support.

And through that process, we will continue to work with our specialty pharmacies will be targeting key relationships with payers.

Matthew Klein: So this is your really an example where we will have the study ongoing. It's going to be a long term study that's going to look at the acquisition of development motor development milestones over time, much in a way that we've been able to show previously in the clinical studies of data that were done previously, where all the time we're going to show that these children develop the ability to first look their head and be able to sit, crawl and walk independent.

Two obviously continue to if you will foster brand loyalty. So all the more along as an additional option. We also know that clinically and it hasnt been differentiated like in Plaza and that we have a very strong and loyal customer base.

Okay. Thank you for taking our questions.

Yes.

Matthew Klein: We've got obviously takes many years, which is why in many ways, this is a very good setup for an accelerated approval where we have biomarker evidence, dopamine increases, which is obviously likely to be a long term clinical benefit of the acquisition of dopamine related motor milestones.

Thank you one moment please.

Our next question comes from the line of <unk> Ahmad Bank.

Bank of America. Your line is open.

Okay. Thanks, so much for taking my questions.

One from me if I may so.

Matthew Klein: Thank you.

So keep it the topic.

Peripheral for catalyst pharma, how if in any way does that change your strategy for how you might want to look.

Matthew Klein: One moment, please.

Paul Choi: Our next question comes online of Paul Choi of Goldman Sachs.

Beyond the loss of exclusivity for <unk> next year and beyond.

Paul Choi: Elias Open.

Paul Choi: Good afternoon, and thank you for taking our questions. Two questions for me. First on the commercial side. With the approval of the ever alone today, can you maybe just comment on how you're thinking about the impact to inflase and would you maybe consider pulling back on Salesforce resource, resourcing for that product, starting next year ahead of your expected loss of exclusivity. And then on the pipeline side, can you maybe comment on what you would intend to present in terms of your pivot HD update next year should investors continue to expect plasma hunting 10 updates and neurofilament changes, or would you perhaps present some details on other other endpoints, including clinical endpoints.

Matthew Klein: Thank you very much.

And then second question.

Matthew Klein: Thanks, Paul, for the question.

As it relates to set the aster and milestone agreements with FEMSA I believe you've already paid.

$30 million for completing phase three enrollment I guess, what other milestones should we anticipate either this year or next and then lastly to clarify on the conditional approval for Translarna and <unk>.

I'm sorry, if it was answered earlier is there a set amount of time.

For which a conditional approval would need to be renewed on a go forward basis. Thanks.

Okay.

Great. Thanks for the questions Suzanne Let me take let me take the third one and then I'll pass to the team and the other two so be it.

Matthew Klein: Let me grab the second one first, and then I'll turn the other question over to Eric and Kylie. So first, in terms of the 518 data. So the 121 data that we said, look, call that we would share in the first effort 2024. That will be data from the biomarker portion that each activity is being a 12 month of people control study into parts. The first part of 12 weeks focuses on some of the dynamic and formal kinetics as well as safety.

Additional authorization, obviously theres always comes with a specific obligation to collect additional data. So that's less of a time based.

Specific time based element, but rather at the time if necessary for that data collection effort, obviously, they've been therapies that have had conditional authorization for many many years say even beyond a decade.

Matthew Klein: And then in that second portion at the 12 one time point, we would have data further data on neurofilament levels now less about safety, but maybe more much recording. And then in terms of training, training benefit, CFS, hundreds and curting, hundreds and curting levels, volumetric changes on MRI. We also will have some clinical data at that time point, which are not main endpoints at the 12 months, but obviously we're collecting data.

So for US what we would do is look forward to the opportunity to keep the therapy on the market and then continuing to collect the data necessary. We do also have the obligation to submit for annual renewals, which we've been through before that's what we've done for the past several years to show that we're one collecting the data that we've agreed to as part of a specific obligation.

And then also providing any necessary updates, particularly around safety to the therapy that might emerge obviously that the safety story on trend walnuts quite.

Matthew Klein: I think we would certainly share the biomarker data share what clinical data we have with the obvious caveat that even the 12 months is very hard. I think I have interpretable clinical effect on things like the UHD RS scale and even the total motor score or same to different talents that just didn't just the latest progression. And the sensitivity of those instruments to change over a short period of time. The answers will have those data that being focused will be the biomarker data obviously can come to safety.

Robust and what we do.

Clearly been able to show that as a therapy than say for the long term just as we've been able to show that the benefit long term to the to the stride registry.

In terms of your questions on.

In Florida, the strategy and as well as milestone his courage you on that.

Taking plaza.

Yes, absolutely unnamed.

On the impasse of front to Dana I think what we continue to do with the implied there is the standard of care across all DMD patients and.

Matthew Klein: We will also when ready have data on the additional. Subjects who are, I think, going to hit the 12-week time point and that ultimately hit the 12-month time point. We haven't given any time lines for that. The time on the given obviously is the data point. I think most are interested in which is that 12-month data point to the initial cohort of subjects on whom we shared the 12-week data.

And we have been able to demonstrate the benefit of implied there in a number of different milestones and we continue to believe that that that's not going to shift in the near term I think from a loss of exclusivity perspective, we have a number of strategies that we're looking at to be able to present, the business and again that doesn't shift based on that the moral and appraisal.

We have good strong relationships across our customer base and with patient advocacy groups and we will continue to leverage that relationship as they move forward.

Matthew Klein: So in terms of your question on the law and the laws, Eric, do you want to take that?

Matthew Klein: Yeah, thanks for the question, Paul. I think within the flaws, we know that from flaws, has been currently on the market for more than six years. It is currently the standard of care. We've established in flaws as a standard of care because there's been a number of publications and there's also a lot of times with a scientific evidence that is actually preserved greater motor function than then prednisome. And we know that the data has continually supported that and we have very, very strong relationships with each one of the health care providers in terms of showing them the evidence, but also providing patient support.

On the milestone question to Jim.

Are you able to provide any color on specific strategies that you're going to you.

Huh.

Yeah, absolutely. So that's that's four main pillars that we're focused on with regard to protecting the business. So one is ensuring that we have and enhance patient support program, which is really really important for particularly DMD patients in Medicaid as an example.

And then also partnering with specialty pharmacy, partnering with Payors and partnering with manufacturers to be able to ensure that we're doing the best for the patient and protecting the business. So that some of the key strategies that we're looking at as well as a defense as written program that the team is working on as we speak.

Matthew Klein: We understand that the community wants options, but we know that right now we have been focused on, and our field force has been focused on, not only growing the brand this year, but also we have a number of strategies that will also protect the brand, following the loss of exclusivity. Because we don't necessarily see this as being a fall off. Because of a generic or even a competitor, and we have a number of key strategies right now, and a lot of them are centered around leveraging our patient support programs because we have that direct line with patients and we have more patients on and flaws than any other DMD treatment.

Okay. Thank you.

Thank you and then.

And just to answer the last question today around the milestones for sensor, but you are correct. We obviously had paper 30 million in equity in 2020, right don't expect any additional milestones.

Sent that in 2023.

<unk> said in the Q that we expect 60.

Matthew Klein: We can continue to leverage that support. And through that process, we'll continue to work with our specialty pharmacies will be targeting key relationships with payers to obviously continue to, if you will, foster brand loyalty. So all the more alone is an additional option. We also know that clinically, it hasn't been differentiated like in Plaza, and that we have a very strong and loyal customer base.

$65 million.

Our regulatory success based milestone.

Sure in the next 12 months so impactful.

We haven't broken out the specifics around that.

Thank you I'm showing no further questions at this time I'd like to turn the call back over to Dr. Matthew Klein, Chief Executive Officer for any closing remarks.

Great. Thank you and thank you all for joining the call today, we look forward to a strong close out into 2023 as we get ready for what is clearly also going to be a busy 2024, and we look forward to sharing updates with you as they become available. Thank you all again and have a good evening.

Matthew Klein: Okay, thank you for taking our questions.

Matthew Klein: Thank you.

Matthew Klein: One moment, please. Our next question comes from a line of Pazin Amad, a Bank of America line is open.

Pazine Ahmad: Okay, thanks so much for taking my questions. A few quick ones from me, if I may.

Thank you ladies and gentlemen, this does conclude today's conference. Thank you all participating you may now disconnect have a great day.

Pazine Ahmad: So to keep with the topic of the approval for Catalyst Forma, how is it in any way does that change your strategy for how you might want to look beyond the loss of exclusivity for inflow the next year and beyond. And then second question, as it relates to sepiaptorin milestone agreements with Venza, I believe you've already paid them 30 million for completing these three enrollment. I guess what other milestones should we anticipate either this year or next?

Yeah.

[music].

Okay.

[music].

Matthew Klein: And then lastly, to clarify on the conditional approval for trans Blarna, and I'm sorry if it was answered earlier, is there a set amount of time for which a conditional approval would need to be renewed on a go forward. Thanks for the questions. Let me take the third one and then I'll pass to the team for the other two. So for the conditional authorization, obviously there's always comes with a specific obligation to collect additional data.

Matthew Klein: So that's less of a time-based specific time-based element, but rather the time is necessary for that data collection effort. Obviously, there's been therapies that have had conditional authorization for many, many years, even beyond a decade. So, you know, for us, what we would do is look forward to you to keep the therapy on the market and then continuing to collect the data necessary. We do also have the obligation to submit for annual renewals, which we've been through before.

Matthew Klein: That's what we've done for the past several years to show that we're one collecting the data that we've agreed to as part of the specific obligation and then also providing any necessary updates, particularly right now. So, I think it's a little bit more about safety to the therapy that might emerge. Obviously, the safety story on Tranwara is quite robust, and we've clearly been able to show that it is a therapy that is safe in long-term, just as we've been able to show the benefit long-term to the stride registry.

Matthew Klein: In terms of your questions on influenza strategy and as well as mild symptoms, Kylie, do you want to take some poison? Yeah, absolutely. So, on the influenza front to zine, I think what we continue to do is the influenza has extended the care across all DMD patients, and we have been able to demonstrate the benefit of influenza in a number of different milestones, and we continue to believe that that's not going to shift in the near term.

Matthew Klein: I think from a loss of exclusivity perspective, we have a number of strategies that we're looking at to be able to preserve the business, and again, that doesn't shift based on the immoral approval. We have good, strong relationships across our customer base and with patient advocacy groups, and we will continue to leverage those relationships as we move forward.

Matthew Klein: On the milestone question to zine, are you able to provide any color on the specific strategies that you're going to use for influenza? Yeah, absolutely. So, there's this full main pillars that we're focused on with regards to protecting the business. So, one is ensuring that we have an enhanced patient support program, which is really, really important for particularly DMD patients and those in Medicaid as an example, and then also partnering with specialty pharmacies, partnering with payers, and partnering with manufacturers to be able to ensure that we're doing the best for the patients and protecting the business. So, there are some of the key strategies that we're looking at as well as a distance is written program that the team is working on as we speak.

Pierre Gravier: Okay, thank you. Thank you. And then in your, just to answer the last question to zine, around the milestones for census, so you are correct, we obviously had paid the 30 million in equity in 2023. Don't expect any additional milestone for census in 2023, but we had shared in the queue that we expect 65 million dollars worth of regulatory success based milestone for sensor in the next 12 months. So, in principle, and we haven't broken out the specifics around that. Thank you.

[music].

Thank you for standing by and welcome to the PTC Therapeutics third quarter 'twenty train three financial results Conference call. At this time all participants are in a listen only mode. After the speaker's presentation there'll be a question and answer session.

I ask a question at that time, Please press star one on your telephone.

Please be advised today's call is being recorded.

Now I'll turn the conference to your host Jean Hanlon Associate director of Investor Relations. Please go ahead.

Good afternoon, and thank you for joining us today to discuss P. C. P therapeutics third quarter 2023, corporate update and financial results.

I'm joined today by our Chief Executive Officer, Dr. Matthew Klein, our Chief Business Officer, Eric Powell our.

Our chief commercial officer, Kylie O'keeffe, and our Chief Financial Officer, Pierre grab yet.

Today's call will include forward looking statements based on our current expectations.

Please take a moment to review the slides 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.

Such statements are subject to risks that can materially and adversely affect our business and the results of operations.

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 todays earning release.

With that let me pass the call over to our CEO Matthew crime Matt.

Thank you Jamie good afternoon, and thank you all for joining the call.

Pleased to share our third quarter results and outlook for the remainder of the year, including an update on our development programs.

I will begin with the recent announcement of our agreement with royalty pharma to monetize up to $1 5 billion of the Brisbane royalty stream.

This non dilutive financing provides PTC the capital to support planned operations and allowed us to retire the Blackstone debt obligations. In addition, the deal structure includes flexibility for accessing additional capital over the next two years, notably PTC maintains its rights to the remaining $250 million of milestones.

Related to a risky global net sales.

Now I'll turn to our third quarter results, we had another solid quarter with total revenue of $197 million, which keeps us on target for meeting our 2023 total revenue guidance of $940 million to $1 billion.

Our DMD franchise revenue in the quarter totaled $136 million.

This strong performance allows us to update our 2023, DMD revenue guidance to between $565 million and $595 million from between $545 million and $575 million, Eric <unk>, who will provide additional details on our commercial performance shortly.

I'd like to now provide an update on recent regulatory activities for several of our programs. Let me begin with an update on <unk>.

Following a negative opinion from the <unk> on the conversion of the conditional marketing authorization to full marketing authorization and on the renewal of the conditional authorization.

<unk> gave us the option to request reexamination of both opinions or only one opinion we.

We decided to pursue reexamination of a negative opinion on renewal of the conditional authorization only.

As such the reexamination process will focus solely on the allowance of continued conditional authorization of trend line I think Europe.

As previously discussed in accordance with <unk> guidelines, we expect the opinion from the reexamination procedure in late January with adoption of that opinion by the European Commission 67 days later.

The U S. A type C meeting with FDA to discuss the potential path to NDA Resubmission is scheduled for this quarter.

Turning to CPA Carol we held the pre NDA meeting in the third quarter with FDA to discuss the NDA submission at.

At the meeting FDA stated that the CPA Taryn clinical safety and efficacy data supported NDA submission for the treatment of pediatric and adult PKU patients.

However, they requested that we complete 26 week non clinical mouse study to assess potential carcinogenicity risk of CPO taryn prior to submission.

This non clinical study was initially not required from CPE carry was acquired from sensor as the NDA submission was planned under the section 500 <unk> pathway with.

With our decision to file under the 500 <unk> one pathway. The 26 week study is considered a required NDA components if needed to inform labeling.

Matthew Klein: I'm sure no further questions at this panel. Let's turn the call back over to Dr. Matthew Klein, Chief Executive Officer for any closing remarks.

Matthew Klein: Great. Thank you.

We will continue to discuss with FDA the potential to submit the mouse study results during the NDA review process.

We now expect NDA submission to occur no later than the third quarter of 2024 transmission could occur in the second quarter. If FDA allows submission of the non clinical study report during the review process.

For the EU, we expect to submit a marketing authorization application to EMA in the first half of 2024.

The delay in NDA submission in no way mitigates the strength of the affinity data.

Given the highly meaningful clinical effects observed in the trial as well as the continued evidence of providing phenylalanine tolerance benefits to the full spectrum of PKU patients in the long term open label extension study, we remain incredibly enthusiastic about the potential of $1 billion plus global commercial opportunity for <unk>.

Moving to the PTC 508, Huntington's disease program enrollment is ongoing in the pivot HD study for both the stage two and early stage three cohorts. We expect the next data update to occur in the first half of 2024.

This update will include 12 month data on the initial group of subjects on whom we reported data in June of this year.

Matthew Klein: Thank you all for joining the call today. We look forward to a strong close down to 2023. If you get ready for what's clearly also going to be a busy 2024, and we look forward to sharing up to you as they become available.

Operator: Thank you all again and have a good evening. Thank you.

At the meeting FDA stated that the existing three months of safety data could support 12 week dosing at five milligrams and 10 milligram dose levels and at six months of clinical safety data demonstrating a similar favorable safety profile could support 12 month dosing in the pivotal <unk> trial. This is very good news as it some.

Operator: Ladies and gentlemen, this does include today's conference. Thank you all for participating.

Just that the safety data being generated <unk> HD should be sufficient to lift the partial hold in the United States.

Operator: You may now disconnect. Have a great day. Thank you all for joining us today. Thank you. [inaudible] David Lebowitz, Brian Abrahams, David Lebowitz, David Lebowitz[inaudible] Brian Abrahams, David Lebowitz, Brian[inaudible] Abrahams, David Lebowitz, Brian Abrahams, David Lebowitz[inaudible] That's a question at that time.

Operator: Please press Star 11 on your telephone. Please be advised today's call is being recorded.

Jane Hanlon: I would now turn the conference to your host, Jane Hanlon, Associate Director of Investor Relations. Please go ahead.

Type C. Written response, only meeting with FDA in the third quarter to determine whether the data from our <unk> assay would be sufficient to support an NDA for accelerated approval.

Matthew Klein: Good afternoon, and thank you for joining us today to discuss PTC Therapeutics Third Quarter 2023 Corporate Update and Financial Results. I'm joined today by our Chief Executive Officer, Dr. Matthew Klein. Our Chief Business Officer, Eric Powell, our Chief Commercial Officer, Kylee O'Keefe, and our Chief Financial Officer, Pierre Gravier.

In the written response, the FDA stated that they while they see the value of upright stability as a clinically meaningful endpoint.

Matthew Klein: 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 couldn't materially differ from these forward-looking statements. As such statements are subject to risks that can materially and adversely affect our business and the results of operations.

Believe the confirmatory study would likely be needed to support NDA submission.

As this was a written response only and we believe we can address the concerns raised by the FDA. We have requested a follow up live meeting.

Pierre Gravier: Yes, we will disclose certain non-GAP information during this call. Information regarding our use of GAP to non-GAP financial measures and a reconciliation of GAP to non-GAP are available in today's earning release.

In parallel we are participating in a scientific advice procedure with the Eni to determine if they move up a data could support a conditional marketing authorization application in the EU.

We expect to have the outcome of this procedure in the first quarter of 2024.

Matthew Klein: With that, let me pass the call over to our CEO, Matthew Klein. Matt?

Turning to abstain there we had an informal meeting with FDA in the third quarter at which time. They said that the data we have provided to support comparability between the clinical drug product and the intended commercial drug product, we're still not sufficient.

Matthew Klein: Thank you, Jane.

In that meeting the FDA said that the available data from the clinical study in the United States assessing the safety of the drug delivery cannula could be used to support a BLA for accelerated approval based on biomarker data demonstrating a treatment related increase in de Novo dopamine production FTE.

Let me conclude by saying I'm incredibly proud of our team's continued ability to execute on all fronts.

I will now turn the call over to Eric and Kylie to discuss our strong commercial performance in the quarter Eric.

Thanks, Matt.

Once again, our global DMD franchise delivered a strong quarter with continued growth from new patient starts high compliance low discontinuation dose adjustments and geographic expansion.

Let me focus on our two key products in the DMD franchise.

<unk> and in Florida continue to be important growth drivers delivering 136 million in net revenue for the third quarter, which is 4% compared growth compared to the third quarter of 2022.

With strong year to date performance, we are raising our DMD revenue guidance from.

545 million to $575 million.

Two 565 million to $595 million.

Core trends Lorna, we achieved $69 million in quarterly revenue.

Year to date sales were $281 million.

The team has worked tirelessly to continue to bring this important treatment to existing as well as new patients in our markets around the world.

The recently concluded World Muscle Society meeting with an opportunity to present and discuss with health care providers, the totality of data and real world evidence supporting the efficacy of trends Lauren and re emphasizing the significant life changing impact. This treatment has on young boys suffering from this devastating disease.

For whom trends <unk> is their only therapy that specifically targets nonsense mutation DMD.

Now turning to the Plaza the employers the business continues to be solid.

Quarterly net revenues was $67 million, which is 23% growth over the prior year quarter.

We have had $188 million in year to date sales.

We continue to see strong trends in the new patient start forms and high compliance.

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

Ali.

Thanks, Eric let me begin with ups data, the first and only approved gene therapy and feeds directly into the brain.

We continue to see transformative results for the patients we have treated thus far.

A rollout across Europe is progressing well without first patient treated in the U K. This quarter following the positive nice recommendation earlier in the year.

Patient identification treatment center readiness and access and reimbursement discussions continue to advance.

We also continue to leverage early access programs and cross border treatment opportunities.

A patient from the Middle East also receiving treatment in France this quarter.

Moving to take steady and way Libre in Latin America.

We continue to grow our franchise in the region with recent MAA approvals for <unk> in Argentina and way Libre in Mexico.

Patient identification is robust and patients on treatment continue to grow across the region.

In Brazil, we anticipate receiving new group purchase orders for both takes Eddy and Lea Libre before the end of this year, which is in recognition of the increased number of patients who rely on these life changing treatment.

Lastly, as Matt mentioned, we are extremely excited about the <unk> opportunity.

The affinity phase III data and the long term extension study preliminary data with <unk>.

<unk> at the recent S. S. IEM Congress and were very well received by physicians and the PK you community.

They are excited about the opportunity to bring a differentiated therapy to PKU patients in need.

With strong differentiation from the mechanism of action and the affinity results.

Without global commercial infrastructure and proven track record and commercializing rare diseases. The team is actively working on launch activities to ensure a fast uptake upon approval.

Matthew Klein: Good afternoon, and thank you all for joining the call. I'm pleased to share our third quarter results and outlook for the remainder of the year, including an update on our development programs. I will begin with the recent announcement of our agreement with Ruralty Forma to monetize up to $1.5 billion of the abridged Ruralty Stream. This non-delutiful financing provides PTC the capital to support planned operations and allowed us to retire the Blackstone debt obligation.

The potential market opportunity for Cepheid Taryn is composed of a number of key PKU patient segments, all of which our affinity data suggest we can address.

Matthew Klein: In addition, the deal structure includes flexibility for accessing additional capital over the next two years. Notably, PTC maintains its rights to remaining $250 million of milestones related to a risky global net sales. The Ruralty financing deal, along with the operating expense reductions announced in September, put PTC on very strong financial footing as we continue to focus our resources on our differentiated high potential R&D programs and robust global commercial infrastructure.

Matthew Klein: Now, I'll turn to our third quarter results. We had another solid quarter with total revenue of $197 million, which keeps us on target for meaning our 2023 total revenue guidance of $940 million to $1 billion. Our DMV franchise revenue in the quarter told $136 million. This strong performance allows us to update our 2023 DMV revenue guidance to between $565 million and $595 million from between $545 million and $575 million.

First patients who have not been trialed on to that or are considered therapy naive.

This includes many of the classical PKU patients, where we have demonstrated benefit in both the phase III study and the affinity study.

Second patients who have not responded to Kevin.

Third patients who have achieved some level of blood fee reduction from Cleveland, but are not well controlled and for whom Cepheid Taryn maker live a better reduction in blood <unk> levels.

So these patients a reduction in blood fee to target fee levels is clinically meaningful potentially allowing them to substantially increase their protein intake and significantly enhance the quality of life.

Many experts who have treated patients with PKU across the world have indicated that based on the data they have seen per MAU affinity study and from the understanding of the mechanistic benefit to Cepheid Taryn all interested patients should be trials that the apparent.

With an expected addressable population of approximately 15% to 30% of the overall global PKU population. This would put us above a $1 billion market opportunity.

In conclusion, our third quarter builds on an excellent first half of 2023 with.

With significant progress across all of our commercial products and across all geographies all customer facing team is set to have a very strong close to the year.

And set ourselves up for continued success in the future by continuing to build on our commercial capabilities and to execute prelaunch strategy trap feature product pipeline.

Now, let me turn the call over to Pierre for a financial update.

Thank you Kelly.

I would like to begin by discussing the financing with royalty pharma that we announced last week.

That deal together was the pipeline re prioritization and Opex reductions that we announced in May and September puts PTC in a very strong financial position.

We are pleased to work again with royalty pharma on this win win transactions.

In addition, the deal structure provides the potential for additional non.

Non diluted capital for the next two years.

To recap the details of the deal.

PTC monetize up to $1 $5 billion of the <unk> royalty stream.

Royalty pharma acquired additional royalties on April one.

$1 billion upfront.

The agreements included options for PTC to sell up to an additional $500 million.

Or.

Eric Pauwels: Eric and Kylie will provide additional details on our commercial performance.

For royalty pharma to acquired half of such we tend royalties up to $20 $50 million at the later date.

Matthew Klein: shortly.

Less royalties received by PTC.

Matthew Klein: I'd like to now provide an update on recent regulatory activities for several of our programs. Let me begin with an update on Translana. Following the negative opinion of the CHMP on the conversion of the conditional marketing authorization to full marketing authorization and on the renewal of the conditional authorization, CNP gave us the option to request three examinations both opinions or only one opinion. We decided to pursue re-examination of the negative opinion on the renewal of the conditional authorization only.

Did you see him on teams all economics associated with up to $250 million and the remaining commercial sales milestone associated with every global net sales.

Matthew Klein: As such, the re-examination process will focus solely on the allowance of continued conditional authorization of Translana in Europe. We remain optimistic that we can address key concerns raised by the CHMP on the evidence of benefits in the Translana clinical trials as well as concerns raised on the methodological robustness of the stride data analysis. As previously discussed, in accordance with EMA guidelines, we expect the opinion from the re-examination procedure in late January, with adoption of that opinion by the European Commission 67 days later.

Matthew Klein: The US, a type C meeting with FDA to discuss the potential path to NDA resubmissions is scheduled for this quarter.

Matthew Klein: Turning the CPU Tarrin, we held a pre-NDA meeting in the third quarter with FDA to discuss the NDA submission. At the meeting, FDA stated that the CPU Tarrin clinical safety and efficacy data supported NDA submission for the treatment of pediatric and adult PKU patients. However, they requested that we complete 26-week non-clinical mouse study to assess potential carcinogenicity risk of CPU Tarrin prior to submission. This non-clinical study was initially not required, when CPU Tarrin was acquired from Senza, as the NDA submission was planned under the Section 505-B2 pathway.

The agreement builds on the previous strategic partnership established with royalty pharma in 2020.

The initial agreement west for the monetization of approximately 43% of the.

Matthew Klein: With our decision to file under the 505-B1 pathway, the 26-week study is considered a required NDA component, if needed, to inform lately. We will continue to discuss with FDA the potential to submit the mouse study results during the NDA review process. We now expect NDA submission to occur no later than the third quarter of 2024. This submission could occur in the second quarter, if FDA allows submission of the non-clinical study report during the review process. For the EU, we expect to submit a marketing authorization application to EMA in the first half of 2024.

The royalty stream.

As a result of the current agreements PTC.

PTC will maintain ownership of approximately 19% of the total EBITDA royalty stream.

Pending any exercise of future options by PTC royalty pharma all the achievements of the cap from the 2020 royalty agreements.

Okay.

I'll now share the financial highlights of our third quarter 2022.

Please refer to the third quarter earnings press release issued this afternoon for additional detail.

Beginning with top line results.

Total revenue for third quarter was $197 million.

This consisted of DMD franchise revenue of $136 million in other revenue of $61 million.

Starting with the DMD franchise.

Tom Sloan on net product revenue in the quarter was $69 million, what im floods on net product revenue of $67 million.

Matthew Klein: The delay in NDA submission in no way mitigates the strength of the acidity data, given the highly meaningful clinical effects observed in the trial, as well as the continued evidence of providing phenylalanine tolerance benefits to the full spectrum of PKU patients in the long-term open label extension study, we remain incredibly enthusiastic about the potential billion-dollar plus global commercial opportunity for CPU Tarrin.

Moving to a week.

Third quarter global revenue of 360 million Swiss francs, which equates to over 40 million U S. Dollars was achieved by Roche, earning royalty revenue of $50 million for PTC.

Matthew Klein: Moving to the PTC-518 hunting services program, enrollment is ongoing in the pivot HD study for both the stage two and early stage three cohorts.

As Mark mentioned, the third quarter performance puts us in a strong position to achieve 2023 total revenue guidance.

$940 million to $1 billion, including an expected $100 million milestones whenever you surpassed $1 5 billion.

Yes.

non-GAAP R&D expenses were $115 million for the third quarter of 2023, excluding $14 million in noncash stock based compensation expense.

Matthew Klein: Turning to the Tiquinone, the data in the movie of a study demonstrated the Tiquinone treatment benefit across several disease endpoints, including favorable effects on the upright stability subscale of the M-FAR's assessment, which is predictive of time to loss of ambulation.

<unk> to our Huntington $50 million for the third quarter of 2022, excluding $15 million in noncash stock based compensation expense.

Matthew Klein: We had a type C written response only meeting with FDA in a third quarter to determine whether the data from the FAA would be sufficient to support an NDA for accelerated approval. In the written response, the FDA stated that while they see the value of upright stability as a clinically meaningful end point, they believed a confirmatory study would likely be needed to support NDA submission. As this was a written response only, and we believe we can address the concerns raised by the FDA, we have requested a follow-up live meeting.

non-GAAP SG&A expenses were $16 million for the third quarter of 2023, excluding $13 million in noncash stock based comp expense compared to $67 million for the third quarter of 2022.

Excluding $14 million in noncash stock based compensation expense.

Cash.

Cash equivalents in marketable securities totaled approximately $295 million as of September 32023, compared to <unk> $11 million as of December 31, 2022.

I will now turn the call over to the operator for Q&A.

Radar.

Yes.

Thank you.

Again, ladies and gentlemen, if you'd like to ask a question. Please press star one one on you touched on telephone again to ask a question. Please press star one one.

One moment for your first question.

Okay.

Our first question comes from the line of Eric Joseph of Jpmorgan. Your line is open.

Hi, good afternoon, thanks for taking the question.

Matthew Klein: Turning to Obstetina, we had an informal meeting with FDA in the third quarter, at which time they said that the data we have provided to support comparability between the clinical drug product and the intended commercial drug product were still not sufficient. However, in that meeting, the FDA said that the available data from the clinical study in the United States, assessing the safety of the drug delivery cannula, could be used to support a BLA for accelerated approval, based on biomarker data, demonstrating a treatment-related increase in de novo dopamine production.

A couple on PKU from Us really just around this regulatory path here I guess can.

Can you just clarify when the decision was made to pursue a 551.

Specifics of the accurate over a 505, two and maybe what prompted that decision and then I guess.

Matthew Klein: FDA suggested that we conduct a pre-BLA meeting to review the contents of the plan BLA. This meeting has been scheduled for December, and pending the outcome we expect to submit to BLA shortly thereafter.

It could have elected to go with a final proposal might be one.

Matthew Klein: Let me conclude by saying I'm incredibly proud of our team's continued ability to execute on all fronts. The recent royalty-former financing deal, along with our operating expense reductions, position PTC is strongly as possible for future growth as we realize the potential of our many promising programs. I will now turn the call over to Eric and Kylie to discuss our strong commercial performance in the quarter.

Was it not clear the carcinogenicity study would be needed would likely be a requirement.

And really ultimately I guess just.

Looking forward.

What should give investors confidence that.

Assuming the.

The carcinogenicity studies in terms of nothing that the NDA submission and review cycle should otherwise be straightforward. Thank you.

Approval.

Alternatively, the classified one pathways for innovative therapies, which is much more appropriate for something like CPU, taryn, which while it's active ingredient is DH four which is.

Which is basically a reactive component Kuban. It has many factors that make you differentiate which underlies the superior efficacy we've observed to date and why this is such a promising therapy.

Central initially with thinking about the five with Abbvie two pathway, that's where things will end up but we acquired it and after we did our own analysis and understanding of the relative benefits of each pathway. It became clear that the final one was much more appropriate now with a $505 two pathways since here as an active ingredient already.

Approved you can utilize this study not safety and efficacy studies, but other supportive studies like non clinical studies that were used to support that approval with the 500 <unk> pathway. So you don't have the ability to rely on those existing study.

Susan just sweeps was based on a couple of things one.

CPE, Kevin is quite differentiated in terms of its efficacy profile from Kuban.

If you go to $505 two pathways the company's product the company, whose products you referred to to utilize their studies can actually block you from launching the therapy for up to 30 months. If they still have an orange book listed patents. So obviously, we did not want to be able situation, we would risk the launch of the compound and then again that's really isn't.

Eric Pauwels: Eric, thanks Matt. We are proud of the accomplishments of our global customer-facing team, which continues to deliver revenue growth and build on our success as we focus on a strong close to the year for commercial portfolio products. Once again, our global DMD franchise delivered a strong quarter with continued growth from new patient starts, high compliance, low discontinuation, dose adjustments, and geographic expense.

I'll have a compound much more suited to the 500 <unk> pathway.

We do.

Then obviously had interactions with the agency to understand what would be required under the 505 pathway and that included things like juvenile toxicity, a new CRO costs all of which.

Eric Pauwels: Let me focus on our two key products in the DMD franchise. Translana and Inflata continue to be important growth drivers delivering 136 million in net revenue for the third quarter, which is 4% compared growth compared to the third quarter of 2022. With strong year-to-date performance, we are raising our DMD revenue guidance from 545 million to 575 million to 565 million to 595 million. For Translana, we achieved 69 million in quarterly revenue.

Eric Pauwels: Year-to-date sales were 281 million. The team has worked tirelessly to continue to bring this important treatment to existing as well as new patients in our markets around the world. The recently concluded world muscle society meeting was an opportunity to present and discuss with healthcare providers, the totality of data and real world evidence supporting the efficacy of Translana. And re-emphasizing the significant life-changing impact this treatment has on young boys suffering from this devastating disease, for whom Translana is their only therapy that specifically targets nonsense mutation DMD. Our customer facing teams have increased communications with healthcare providers in Europe, providing medical information on Translana and its continued availability for all new and existing patients.

The studies will be conducted including Anda, which is fair and then per carcinogenicity. What's typically required is that you submitted to the agency a weight of evidence request to request a waiver for carcinogenicity, obviously, we were quite confident in getting that labor.

Eric Pauwels: Now, turning to influenza. The influenza business continues to be solid. Quarterly net revenues was 67 million, which is 23% growth over the prior year quarter. We have had 188 million in year-to-date sales. We continue to see strong trends in the new patient's start forms and high compliance. The continued influenza growth is impressive and highlights the brand loyalty in the DMD community in the United States as our team is actively implementing plans to defend and protect the influenza brand ahead of a loss of exclusivity next year.

Kylie O'Keefe: Now, I will ask Kylie to update the progress of our current and future new product launches.

One there is no evidence of Hino toxicity, CPO terror and the CPA Taryn non clinical studies see six months nine months studies. There was no evidence of secretly CPO 10 related.

Kylie O'Keefe: Kylie.

Kylie O'Keefe: Thanks, Eric.

To the agency and that the agency obviously it came back and said that the two different two different cars interesting study was one of the two year Rat study. They said fine do that post approval no problem, but since you are in the 500 <unk> pathway. They would want the 26 week study to inform the labor.

Kylie O'Keefe: Let me begin with up stanza. The first and only approved gene therapy infused directly into the brain. We continue to see transformative results for the patients we have treated thus far. Our rollout across Europe is progressing well with our first patient treated in the UK this quarter following the positive, nice recommendation earlier in the year. Patient identification, treatments and readiness and access and reimbursement discussions continue to advance. We also continue to leverage early access programs and cross-border treatment opportunities with a patient from the Middle East also receiving treatment in France this quarter.

Because in the label they have to say whether or not there is a potential carcinogenicity risk and while we were under 500 <unk> two pathway. They can use the labeling in the Kuban label, which referred to the risk.

Kylie O'Keefe: Moving to take steady and way lever in Latin America. We continue to grow our franchise in the region with recent MAA approvals for take steady in Argentina and way lever in Mexico. Patient identification is robust, and patients on treatment continue to grow across the region. In Brazil, we anticipate receiving new group purchase orders for both TechSetti and Welebra before the end of this year, which is in recognition of the increased number of patients who rely on these life-changing treatments.

Risk of adrenal tumors, which has never been seen clinically, but they said look we have nothing we referred to we have nothing to inform the label. So we need you to do this study.

Yes.

Standard part will be considered a standard part of the 500 <unk> pathway would be something you would need to submit with the NDA now.

I would also say and just the other part of your question.

<unk>. They were it was clearly stated that the safety and efficacy data, we have with CPA Sharon.

Could support the full spectrum of patients, which would be our desired label. So we fully expect that once we get the study results. If it's required to have the study report for the mouse study for submission. Once we have that we expect a very smooth path from there again, given the incredible strength of the efficacy data we have the safety data we have and.

Obviously far from ideal the additional time, we're going to have now is only going to build that dossier program with greater length of exposure greater ability to show more durability of effect the kinds of things we're seeing in the long term open label study and obviously, we could have even more data showing <unk> tolerance. We recently reported the latest update on <unk>.

Kylie O'Keefe: Lastly, as Matt mentioned, we are extremely excited about the sepia-terran opportunity. The affinity phase three data and the long-term extension study preliminary data were presented at the recent SSIEM Congress, and were very well received by physicians and the PKU community. They are excited about the opportunity to bring a differentiated therapy to PKU patients in need, with strong differentiation from the mechanism of action and the affinity results, coupled with our global commercial infrastructure and proven track record in commercializing rare diseases.

Siam meeting in September again, showing that patients are able to tolerate.

The recommended daily allowance of protein and still have control of federal I mean, so the strength of this data.

It remains it is in no way impacted by the need to do this clinical study. It is an unfortunate delay and we're going to continue to discussions with the agency. If we could submit the application sooner, but the bottom line is this is a strong differentiator compound. The data we have to date. The studies. We've done shows there has been no evidence of Carthage.

Tennessee risk according.

According to the study reports, we have genotoxic life and again this continues to be a very.

We have very strong package.

Thank you.

One moment please.

Kylie O'Keefe: Second, patients who have not responded to KUVAN. Third, patients who have achieved some level of blood-free reduction from KUVAN, but are not well controlled, and for whom sepia-terran may deliver a better reduction in blood-free. For these patients, a reduction in blood-free to target fee levels is clinically meaningful, potentially allowing them to substantially increase their protein intake and significantly enhance their quality of life. Many experts who have treated patients with PKU across the world have indicated that based on the data they have seen from our affinity study and from their understanding of the mechanistic benefit to sepia-terran, all interested patients should be trialled on sepia-terran. With an expected addressable population of approximately 15% to 30% of the overall global PKU population, this would put us above a billion dollar market opportunity.

Our next question comes from the line of.

Chris concludes Scott.

Cantor Fitzgerald Christa includes Sir your line is open.

Kylie O'Keefe: In conclusion, our third quarter builds on an excellent first half of 2023, with significant progress across all of our commercial products and across all geographies.

Assuming that you do get the Green light how are things going to be moving forward will it be kind of similar like what we've seen over the last eight years when names.

Kylie O'Keefe: Our customer facing team is set to have a very strong closer to the year, and set ourselves up for continued success in the future by continuing to build on our commercial capabilities and to execute pre-launch strategy for our future product pipeline.

I'm, giving you the green light or will you be required to conduct any type of work in the background. Thank you.

Kristin. Thank you very much for the question so as we mentioned in the in our.

<unk> comments.

The previous procedure there were two opinions there was actually two procedures in one one was the conversion of the conditional marketing authorization to full marketing authorization and the other was continuation of the conditional authorization.

Pierre Gravier: Now let me turn the call over to P.F, for a financial update.

Pierre Gravier: P.F.? Thank you, Kylie.

Pierre Gravier: Finally, I would like to begin by discussing the financing with Warty Pharma that we announced last week. That deal, together with the pipeline re-prioritizations and OPEX reductions that we announced in May and September, puts PTC in a very strong financial position. We are pleased to work again with Warty Pharma on this win-win project. The non-value-tiff financing provides PTC with the capital to support operations and allows for increased operational and financial flexibility by removing the blackstone debt obligation from a balance sheet.

Nuances of the procedural elements in Europe. They had brought that together and said we're going to issue two opinions, but really get together. So when they went negative on the conversion to full authorization.

<unk> elected to go negative as well for the renewal of the condition and they gave us the option to say do you want to pursue one or both.

Priority here is to maintain nature of this drug stays on the market sees available for the boys in Europe. There is no other targeted therapies for nonsense mutation available.

And we believe the best chance of doing that is to focus solely on maintenance of the conditional authorization for now we also believe in a way that I am not asking for a conversion to a full approval.

The issues some of the issues with having a.

Negative primary analysis population.

Analysis in the 741.

May become less of an issue really we can focus on other important and strong data in study 401, including in the ITT population, where we have clear evidence of benefit over a number of different endpoints as well as obviously the long term strive data. So we really feel that by focusing this question on just renewal of the conditional authorization that we can provide them.

Sorry second get this opinion from negative to positive now as you mentioned what happened to some tests.

What happens from there well if you have a conditional marketing authorization in Europe, you are required to conduct.

Or collect additional evidence to continue to support the benefit. We believe there are many potential sources of this including continuing to collect data and strive while we've obviously been able to show a clear benefit in delaying time to loss of ambulation by three five years in the most recent analysis and continue to show meaningful multi year delay.

Lots of pulmonary function as we can continue to collect more data over time there'll be even more patients informing the loss of ambulation analysis, even more patients and points the pulmonary function analysis, and hopefully ultimately cardiac function and mortality. So theres still a lot more meaningful data that can truly informed the long term benefit of translarna.

Armstrong.

There's also the possibility to talk about bolstering striving there with an additional analyses and second largest treating that as a possibility.

I think in the universe of possibilities could they ask us to do another clinical trial, I think thats possible, probably not likely given a lot of the feedback.

The scientific experts gains in the scientific advice.

Portion of the procedure last time was that clinical studies for genetic directed therapies in DMD or really hard and really difficult to produce meaningful data the experts have told.

The HMP. They believe that these longer term data collection mechanisms that are really most useful for understanding the true benefit. So that's a long answer. The short answer is look we'll have to collect additional data will be well positioned and quite pleased to do so the priority now is to keep this therapy on the market in Europe, and we believe by pursuing just renewal of the conditional.

This is in the strongest position to do that.

Great. Thanks, and just second part of that I would imagine since you had the announcement that the community would probably it's pretty upset, especially the ones that have been on the therapy long term. So wondering if there's anything you can collect from them anecdotal stories et cetera, and if they can be.

Anyhow.

This upcoming meeting and decision thanks again.

Yes, Chris Good question, I think needless to say that physician.

The patient community was surprises disappointed in and quite honestly scared.

For the patient. So I think this is the only therapy they have.

That is directed for nonsense mutation patients many of them, but almost therapies for years and observe the benefits that we've been reporting for physicians. They understand the context of the disease. They understand the strength of the data that we've produced.

Kent and many of them said, they can't imagine having to take patients off of drug that safe and effective.

Pierre Gravier: In addition, the deal structure provides the potential for additional non-value-tiff capital over the next two years. To recap the details of the deal, PTC monetized up to $1.5 billion of the everyday work for PTC stream. Royalty Pharma acquired additional workies on every day for $1 billion upfront. The agreements included options for PTC to sell up to an additional $500 million, or for Royalty Pharma to require half of such written workies for up to $250 million at a later date, less workies received by PTC.

Bill the patients on their own have the ability to on their own to reach out at <unk> and their voices heard I'm sure in many parts of Europe that will happen given the fear and concern they have in us and similarly for the physician community.

Pierre Gravier: PTC maintains all economics associated with up to $250 million in the remaining commercial sales milestone associated with everyday global net sales. The agreement builds on the previous strategic partnership established with Royalty Pharma in 2020. The initial agreement was for the monetization of approximately 43% of the everyday workies stream. As a result of the current agreement, PTC will maintain ownership of approximately 19% of the total everyday workies stream, pending any exercise of future options by PTC or Royalty Pharma or the achievements of the cap from the 2020 Royalty agreement.

Pierre Gravier: I now share the financial highlights of a third quarter 2023. Please refer to the third quarter earnings press release issued this afternoon for additional details. Beginning with stop line results.

They'll want us to pick up but our sense here is that.

People as we were never thought this state will come or this will be a reality so I think the.

Pierre Gravier: Total revenue for third quarter was $197 million. This consisted of the D&D franchise revenue of $136 million and other revenue of $61 million. Starting with the D&D franchise. Translada net product revenue in the quarter was $69 million, what and flasas are net product revenue of $67 million. Moving to a video.

Pierre Gravier: Third quarter global revenue of 360 million Swiss francs, which equals to other following million US dollars was achieved by Roche, earning Royalty revenue of $50 million for PTC. As Matt mentioned, the third quarter performance puts us in a strong position to achieve 2023 total revenue guidance of $940 million to $1 billion, including unexpected $100 million milestones whenever these are passes $1.5 billion in annual net sales. Non gap R&D expenses were $150 million for the third quarter of 2023 excluding $14 million in non cash stock based compensation expense compared to $150 million for the third quarter of 2022, excluding $15 million in non cash stock based compensation expense.

This is a little bit for them or call to speak up and let their voices heard and importantly, as you say share their story share their experience, particularly the physicians who are experts and can truly articulate.

Pierre Gravier: Non gap R&D expenses were $16 million for the third quarter of 2023 excluding $13 million in non cash stock based compensation compared to $67 million for the third quarter of 2022, excluding $14 million in non cash stock based, and Compensation Expo.

Pierre Gravier: Cash, Cash Econvenants and Marketable Securities Total Approximately $295 million as of September 30, 2023, compared to $4 million, $11 million as of December 31, 2022.

The benefits, Dave observed and the importance of this therapy.

Operator: Now, we'll now turn the call over to the operator for Q&A. Operator?

For patients with nonsense mutation DMD.

Operator: Thank you. Again, ladies and gentlemen, if you'd like to ask a question, please press star 111 on your touch count. Again, to ask a question, please press star 111.

Yes.

Operator: One moment for our first question.

Yes.

Thank you.

Thanks.

Yes.

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

Eric Joseph: Our first question comes from the line of Eric Joseph of J.P.

Great. Thanks, so much.

Eric Joseph: Morton, you want to know this?

On the topic of Translarna I guess since the negative opinion have you seen any change and how physicians are writing script or patients.

Eric Joseph: Hi, good afternoon. Thanks for taking the question. Just a couple on PKU from us, really just to run this regulatory path here.

Patients are accumulating medication ahead of a potential of that.

Eric Joseph: Can you just clarify when the decision was made to pursue a 505P1 path for separate 50x right over a 505P2 and maybe what prompted that decision? And then I guess in a way to go with a 505P1, was it not clear that a carcinogenicity study would be needed, would likely be a requirement? And really, ultimately, I guess just looking forward what should give investors confidence that assuming that a carcinogenicity study turns up nothing that the NDA submission and reduce cycles should otherwise be straightforward. Thank you.

Opinion does not reverse and then can you speak a little bit as to if you've increased your sales effort and non EU areas since the negative opinion as well. Thank you.

Matthew Klein: Thanks for the question, Eric. Let me just first start with a little bit about 505P1 versus 505P2. The 505P2 pathway is typically used for knee-tooth compounds where it has already been an existing approval for the active ingredient in the compound for which one seeks approval.

Yes, Amy Thank you for the question again I think the.

And the physicians we've spoken with the first response was.

Matthew Klein: Alternatively, the 505P1 pathway is for innovative therapies, which is much more appropriate for something like seeking a term, which while its active ingredient is DH4, which is basically the active component of KUVA, it has many factors that make it different to you, which underlines the superior efficacy we observed to date and why this is such a promise in therapy. Since the initially was thinking about the 505P2 pathway, that's where things were lined up, but we acquired it, and after we did our own analysis and understanding of the relative benefits of each pathway, it became clear that the 505P1 was much more appropriate.

Yes.

Clarifying and reconfirm that no willingness things change patients can stay on the drug they can write prescriptions and obviously everyone's going to do everything Academy for patients stay on therapy, but let me.

Kick it over to Eric I don't know if you want to give some more detail on the con.

Matthew Klein: Now, with the 505P2 pathway since here in an active ingredient already approved, you can utilize the studies not facing efficacy studies, but other supportive studies like nonclinical studies that were used to support that approval with the 505P1 pathway that you don't have that ability to rely on those existing studies.

Descriptions.

Yes. Thanks for the question Sami first of all we haven't actually seen an impact since <unk> has issued their opinion in fact, we've seen physicians who have actually been very.

Matthew Klein: The decision to switch was based on a couple of things. One, Stephen Karen is quite differentiated in terms of its efficacy profile from KUVA. Second, if you go 505P2 pathway, the company's product, the company whose product you refer to to utilize their studies, can actually block you from launching the therapy for up to 30 months that they still haven't launched the tested path. So obviously, you did not want to be in a situation where you would risk the launch of the compound, and then again, this really is a novel kind of a compound much more suited to the 505P1 path.

Very good.

<unk> been very very supportive in fact, our customer facing team is actually stepped up their interactions with health care providers advocacy groups and others to emphasize that the drug is actually available and I think that's one of the most important things. We've made specific call to every prescribing physicians and we've worked with them because we have had relationship.

Matthew Klein: We then obviously had interactions with the agency to understand what would be required under the 505B1 pathway, and that included things like juvenile toxicity and recrotox, all of which studies will be conducted, including the FDA know what she's there, and then for carcinogenicity, what's typically required is that you submit to the agency a weight of evidence to request to request a waiver for carcinogenicity. Now, obviously we were quite confident in getting that waiver.

Matthew Klein: One, there's no evidence of genotoxicity of secretarian in the secretarian nonclinical studies, six month and nine month studies, there was no evidence of secretarian related carcinogenicity, pre-neoplasic lesions and neoplasic lesions, furthermore, while we weren't referring to the coup d'un NDA, the clinical experience with coup d'un over many years clearly demonstrates that there's no carcinogenicity. So we submitted all of that to the agency, and now the agency obviously came back and said that there's two different carcinogenic studies.

Matthew Klein: One is a two-year rat study, they said, fine, do that close to approval, no problem, but since you're in the 505B1 pathway, they would want the 26-week mouse study to inform the label, because in the label they have to say whether or not there's a potential carcinogenicity. And while we were under 505B2 pathway, they could use the labeling in the coup d'un label, which referred to a risk of adrenal tumors, which is never maintained clinically, but they said, look, we have nothing to refer to, we have nothing to inform the label, so we need you to do this study. And since it's a standard part, it would be considered a standard part of the 505B1 pathway, it would be something you would need to submit with the NDA.

Now for many many years with many of these physicians.

They know about the treatment they have been treating patients for many years and we've been reaffirming that the trend is not only just available its available for existing patients, but it's also we've seen new prescriptions as well the fundamentals that we see Jimmy.

Jimmy is basically <unk>.

Emitted to no discontinuation because of the <unk> information new patients continue to get scripts compliance has actually remained very high and we've been able to maintain dose adjustments we've had to getting patients that have gone from ambulatory to non ambulatory and been maintained as well and then to your question about.

Geographic expansion and outside.

Well.

Some of the information has gone out to other countries, we've actually been able to continue to work with health care providers and other parts of the world and still continue to generate and see growth from trends Lorena.

In the quarter. So the simple answer of course is that.

We have not seen any any discontinuation in the funnel fundamentals remains strong.

And as I mentioned earlier in my in my in my talk.

Not only very confident in what we did this quarter, but we're very confident in how we will finish 2023, and we've actually raised guidance in our DMD guidance is now 565 to $5 95, which includes.

Trans Laurent a growth in the fourth quarter and combined that would equal about 11% to 17% year over year growth for the dnb franchise compared to last year.

Yeah.

Great. Thank you.

Thank you one moment please.

Our next question comes from the line of David Lebowitz.

Citi. Your line is open.

David for taking so thank you for taking my question when looking at the trends learn our European sales could you. Please for overseas sales can you. Please give us a breakdown of.

Matthew Klein: Now, I'll also say, and just the other part of the question, in our discussions, they were clearly stated that the safety and efficacy data we have with CPAPA Karen could support the full spectrum of patients, which would be our desired label. So we fully expect that once we get the study results, if it's required to have the study report for the mouse study for submission, once we have that, we expect a very smooth path from there.

What those sales are in Europe versus the rest of the world.

Also could you give us insight as to what other geographies might have their opinion affected by.

EU opinion.

David Thank you for the question, let me start.

I'll start with your second part first.

Matthew Klein: Again, given the incredible strength of the efficacy data we have, the safety data we have, and obviously what far from ideal, the additional time we're going to have now is only going to build that dossier program with greater length of exposure, greater ability to show more durability and affect the kinds of things we're seeing in the long term, open label study, and obviously we're going to have even more data showing efficacy tolerance.

Matthew Klein: We recently ported the latest update in the fee tolerance data. Yes, I am meeting in September against showing that patients are able to tolerate beyond the recommended daily allowance, the protein and still have control of that. So the strength of this data is remained. It is no way impacted by the need to do this on clinical study. It is an unfortunate delay. We're going to continue discussions with the agency quickly to submit the application sooner.

As.

As we've talked about in the past.

Many of our largest markets outside of Europe have independent regulatory agencies that do their independent assessments.

Matthew Klein: But the bottom line is, this is a strong differentiates compound. The data we have to date, the studies we've done show, there's no evidence of parsing the chance to risk according to the study reports we have. Thank you.

We will continue to make their independent regulatory decision independent of.

The CHP.

You are kind of the European authorization.

Operator: One moment please.

In terms of revenue.

Yes.

<unk>.

That was just saying we spent.

And so at that time in the last couple of years to geographically diversify the business and this is the intent of evening out and sort of.

Kristen Kluska: Our next question comes from the line of Kristen Kluska, out Cantor Fitzgerald, Kristen Klusper.

Kristen Kluska: Your line is open. Hi everyone, first just wanted to congratulate you on the royalty farm the deal and I had a question about trans larna. Can you talk about why you're only pursuing re-examination of the conditional authorization? I guess what advantages do you see going this way versus both and assuming that you do get the green light? How are things going to be moving forward? Will it be kind of similar like what we've seen over the last eight years when they've given you the green light or will you be required to conduct any type of work in the background?

EU revenue contribution to total revenue and then the remainder being ex U S.

Sure I mean is there any way you can let us I guess zero in on what the particular number.

Might be in the range of that just just in case.

Things don't work out of Europe, we're trying to understand what.

What the implications might be going forward with respect to our projections.

Kristen Kluska: Thank you. Kristen, thank you very much for the question. So as I mentioned in our prepared comments, the previous procedure there were two opinions. There were actually two procedures in one. One was the conversion of the conditional marketing authorization to full marketing authorization and the other was continuation of the conditional authorization. Through nuances of the procedural elements in Europe, they had brought them together and said, we're going to issue two opinions but really get together.

Kristen Kluska: So when they went negative on the conversion to full authorization, they elected to go negative as well for the renewal of the condition. Then they gave us the option to say, do you want to pursue one or both. Look, our priority here is to maintain, make sure this drug stays on the market, stays available for the boys in Europe, and there's no other targeted therapy for non-sentitation available. And we believe that best chance of doing that is to focus solely on maintenance of the conditional authorization for now.

Kristen Kluska: We also believe in a way that by not asking for a conversion to a full approval, that the issues, some of the issues that we use with having a negative primary analysis population analysis in study 41 may become less of an issue. We really can focus on the other important and strong data study for your one, including in the ITT population, where we have clear evidence of benefit over a number of different endpoints, as well as obviously the long-term stride data.

Yes, David I think from that perspective, I think it's roughly around 45% to 48%, but the one thing I would say and what's important to note.

That was the European market some of that more mature market and so as you look over time, you would expect that.

Kristen Kluska: So we really feel that by focusing this question on just renewal of the conditional authorization that we could provide the necessary evidence that can get this opinion from negative deposit. Now, as you mentioned, what happens from test? I guess what happens from there. Well, if you have a conditional marketing authorization in Europe, you are required to conduct or collect additional evidence to continue to support the benefit. Now, we believe there's many potential sources of this, including continuing to collect data and stride, while we've obviously been able to show clear benefits in delaying time-to-loss abandonation by three and a half years and most recent continue to show meaningful multi-year delay loss of pulmonary function.

Total revenue for more mature market doesn't have the growth trajectory.

Some of that in <unk>, and <unk> market and so.

Kristen Kluska: As we can continue to collect more data over time, there'll be even more patients informing the loss of amulation analysis, even more patients informing the pulmonary function analysis and hopefully ultimately cardiac function and mortality. So there's still a lot more meaningful data that can truly inform the long-term benefit of transatlantic development. There's also the possibility to talk about bolstering stride, either with additional analyses or a second registry that's the possibility. I think in the universe of possibilities because they have to do another clinical trial, I think that's possible, probably not likely, given a lot of the feedback that the scientific experts gave and the scientific advice portion of the procedure last time was that clinical studies for genetic directed therapies in DMB are really hard and really difficult to produce meaningful data.

While it currently sits around the 45% to 48% currently you wouldn't expect that number to remain flat over the coming years.

Kristen Kluska: The experts have told the HMP they believe that these long-term data collection mechanisms that are really both useful for understanding the treatment. So that's a long answer, the short answer is, we'll have to collect additional data, it will be well-positioned and quite honestly pleased to do so. The priority now is to keep this therapy on the market in Europe and we believe by pursuing just a renewal of the conditional pushes in the strongest position.

Kristen Kluska: You can do that. Okay, thanks. And just second part of that, I would imagine since you had the announcement that as the community was probably pretty upset, especially the ones that have been on the therapy long term. So, wondering if there's anything you can collect from them, anecdotes, stories, etc., and if they can be of any help ahead of this upcoming meeting and decision. Thanks again. Yeah, Kristen, good question. I think me look to say that position and the patient community was surprised, disappointed, and quite honestly scared for the patient.

Got it and with respect to expenses going forward.

Kristen Kluska: So this is the only therapy they have that is directed for non-sensitiation patient. Many have been on the therapy for years and observed the benefits that we've been reporting for physicians. They understand the context of the disease. They understand the strength of the data that we produced. And they can't, as many as said, they can't imagine having to take patients off a drug that's safe and effective. They'll, the patients on their own, you know, have a ability on their own to reach out and, and, and, and, like their voice be heard, I'm sure in many parts of Europe that will happen, given the, the fear of concern they have, and I can similarly for the physician community, they'll want to speak about that.

Is there any way you can give us I guess some level of bandwidth on what you expect for 2024 and beyond when.

Kristen Kluska: You know, our sense here is that most people, as we were, would never thought this state would come or this would be a reality. So I think the, this is a little bit for them, a call to speak up and let their voice be heard. And importantly, as you say, share their story, share their experience, particularly the positions who are experts and can truly articulate the benefits they've observed in the importance of the therapy for patients with non-sensitiation DNA. Thank you.

The restructuring is in full place.

Yes, David.

We announced the.

Our revise our opex guidance.

Great.

Matthew Klein: One moment, please. Our next question comes from the line of Sammy Corwin of William Blair.

Previously too.

Matthew Klein: Sammy Corwin of William Blair, your line is open. Great. Thanks so much.

A 10% to <unk> 16.

Matthew Klein: On the topic of trans learner, I guess since the negative opinion, have you seen any change in how physicians are writing scripts or if patients are accumulating medication ahead of the potential that opinion is not reverse? And then can you speak a little bit as to if you've increased your sales efforts in non-EU areas since the negative opinion as well? Thank you.

And also we then announced the subsequent cuts.

And how that would have an impact of additional another approximately 20% and runway 2024, obviously, we will give the updated opex guidance at Jpmorgan in January.

Matthew Klein: Yes, Sammy. Thank you for the question. Right. Again, I think the, in the physicians we've spoken with, the first response was, you know, clarifying and you confirm that in no way the things change patients can stay on the drug, they can write any prescriptions and obviously everyone's going to do everything they can to make sure patients stay on therapy. But let me kick it over to Eric and if you want to give someone detail on the description.

Thank you for taking my questions.

Thank you one moment please.

Our next question comes from the line of Kelly <unk> of Jefferies. Your line is open.

Hi, This is <unk> for Kelly, Thanks, very much for taking my questions. So the first question on Translarna.

That you are able to get the negative opinion reversed.

Is there a deadline for you too.

Eventually have to convert a conditional approval to full approval and then on the pre BLA meeting for ADC deficiency.

<unk>.

The comparability.

Manufacturing are there any specific capacities that you have to develop before the meeting.

Yes. Thank you very much for the question. So on your first question regarding the.

The convert any positive opinion of course able to convert that to a positive opinion. The continued conditional marketing authorization in Europe. There is typically not a fixed timeline to that typically what goes along the conditional marketing authorization in Europe is something called a specific obligation and that specific obligations typically.

Some requirement to collect additional data to support the benefit risk profile of the therapy. So there is no timeline per se, but there'll be they would be a specific obligation that require us to collect data and obviously the shape or form of that 10 design of that data collection.

<unk> study would have some timeline likely tied to it also is part of the conditional marketing authorization as we've done for years requires.

Annual renewal for the past several years, we've done that and that's a lot of that is relied on the continued evidence of safety, we're seeing Australia as well as benefit.

Matthew Klein: Yeah, thanks for the question, Sammy. First of all, we haven't actually seen an impact since CHMP has issued their opinion. In fact, you know, we've seen physicians who have actually been very, very, they've been very, very supportive. In fact, our customer facing team has actually stepped up their interactions with healthcare providers, advocacy groups and others to emphasize that the drug is actually available. And I think that's one of the most important things we've made specific calls to every prescribing physician and we've worked with them because we've have relationships now for many, many years with many of these physicians.

Matthew Klein: They know about the treatment. They've been treating patients for many years. And we've been reaffirming that the, the, that Translana is not only just available available for existing patients, but it's also we've seen new prescriptions as well. The fundamentals that we see, Sammy is basically, they've been limited to no discontinuations because of the CHMP information, new patients continue to get scripts. Compliance has actually remained very high and we've been able to maintain dose adjustment.

On your second question regarding the <unk> meeting in the issue of comparability. So comparability analyses are done to show that the material that we used in the clinical studies as similar as possible to the material.

Matthew Klein: We've had patients that have gone from ambulatory to non-ambulatory and been maintained as well. And then to your question about geographic expansion and outside while that some of some of the information has gone out to other countries, we've actually been able to continue to work with healthcare providers in other parts of the world and still continue to generate and see growth from Translana in the quarter.

We intend to use commercially unusually that includes <unk>.

Third to a number of different analytical assays.

One of the challenges that we had is that the clinical trial material.

We.

For which we had to establish comparability with our commercial process is.

Matthew Klein: So the simple answer, of course, is that we have not seen any, any discontinuations and the fundamentals remain strong in, and we're, as I mentioned earlier in my, in my, in my talk, we're not only very confident in what we did this quarter, but we're very confident in how will finish 2023 and we've actually raised guidance and our DMD guidance is now 565 million to 595, which includes Translana growth in the fourth quarter and combined that would equal about 11 to 17% year over year growth for the DMB franchise compared to last year. Thank you.

Over a decade old.

Those are clinical studies that were started in early 2010, and there simply is not enough of that residual clinical supply available to provide the additional replicates and additional data that the agency wanted us to have.

Matthew Klein: One moment please.

David Lebowitz: Our next question comes from a line of David Lebowitz, a city.

<unk> finalized the comparability analysis, you, obviously had data across all the assays that we believe show that the processes comparable due to ask for some additional analyses.

It's a bit challenging to get that material given the age of the material.

Importantly, we were able to discuss with them the potential to leverage the accelerated approval pathway using our ongoing study in the U S, which is using material made with the commercial process.

Peter Mark has talked about this ahead of siebert of using the accelerated pathway for rare disease gene therapies as a way to quickly get these therapies to patients. So we're looking forward to a pre BLA meeting in December so they asked us to do that to make sure. We're aligned on the contents of that accelerated approval BLA package and then pending the outcome of that meeting we expect to submit the.

Shortly thereafter.

Thank you.

One moment please.

Our next question comes from the line of Brian Abrahams RBC capital markets, Brian Abrams Your line is open.

David Lebowitz: Your line is open. David Lebowitz. Thank you for taking my question.

Hey, good afternoon, thanks for taking my questions.

As you prepare for the MAA filing for separate App trend next year.

Are your expectations for what the car study requirements will be.

For Europe.

And then secondarily.

I guess on Trans Lorna and the U S, where do you stand in terms of key discussion items.

And potential areas of focus that you are expecting for the type C meeting and when might we see an update from that will be shortly after the meeting or should we expect a little bit of a time gap to allow for the minutes to be collected.

Thanks for the questions, Brian and so.

On the question regarding the MAA in Europe.

I think this is another example of how regulatory authorities tend to look at things differently. The feedback we've gotten from Europe regarding carcinogenicity as they understand very well.

The active metabolite of course, Cps Chairman is beach for.

And they understand that be towards Cps herein are both can actually co factors. They understand the data we've collected to date in terms of carcinogenicity risks and they have said.

They would like us to not only have our own data, but that we can rely on the data and the experienced <unk> for many years.

There is a knowledge base that that exists.

Carson has used the risk associated with beach for these clinically for many years so.

We don't believe the issue we have at FCA will be an issue with Europe for that reason.

And then just.

He is looking at things differently.

That's why we're able to move forward with that submission.

Seven eight.

In the first half of 2024 on your question regarding the type C meeting per trans lineups.

The purpose of that meeting is really to focus on the evidence that we have there are many sources of evidence we have shown that not only.

There is clear evidence of benefit.

Studies, such as spending 41, because that can be confirmed a number of ways, including meta analysis. The long term really won't stride registry and so really working constructively with the division is to say what are the components, we need and how do we formulate them in order to support.

NDA Resubmission.

As we typically do it once we have clarity in the outcome of the meeting sometimes that can come from the meeting itself, sometimes that requires minutes, sometimes that requires some back and forth. Afterwards as soon as we have clarity, we'll certainly share. It obviously, we know a lot of people are quite interested in the outcome of this meeting I.

I believe you said with Cherokee.

Boys with nonsense mutation DMD in the US who have waited years for therapy and then also the large number of boys in the U S who have been on.

<unk> hundred for a number of years when their participation.

In clinical studies and beyond all of whom are quite.

Interested in ensuring that this drug can be available in the U S for them.

That's really helpful. Thanks, Matt.

Thank you one moment please.

Our next.

Question comes from the line of.

Colin Bristow of UBS Your line is open.

Hey, good afternoon, thanks for taking the questions.

Yes.

The filing timelines I'm just curious what is the latter end of your guidance three Q4.

I was curious can you confirm whether the study has started and it just seems like a sort of extreme upper bound of this timeline. If this study is all that's needed.

And then on the ATC could you just put a little more detail on.

Why FCA the compatibility data is still not sufficient.

Then what are you sort of hoping will be discussed.

At a meeting in December.

Yeah. Thanks for the question Colin so.

If you just when you find out you have to do a study it takes a little bit of time to actually organize the study to get the slot at the Kroger the animals in order to get the get the dosage confirmed the protocols set at the protocol agreed upon and start the study we expect to begin dosing in the study have all of those things ready and dosing that study to start in December.

That's a six month study so by the clock that Ali I don't get dosed in December.

Unlike portion should be done in union. Once again my portion is done in June may not have to sacrifice the animals. Both through the histological studies all of his histological analysis report, we're obviously going to work as quickly as we can to accelerate those timelines. Obviously you can't shorten the 26 weeks, but we're doing everything we can to shorten the time for data analysis.

As well as getting the audited report, which is about the third of course submission. So thats, where you get the three key time down from nearly the reality to deal with 26 week study takes more than 26 weeks and Thats and we wanted to give an accurate depiction of what we think could be the longest possible date or the latest possible time for that submission obviously as we know.

David Lebowitz: When looking at the trans line of European sales, could you please or oversee sales? Can you please give us a breakdown of what those sales are in Europe versus rest of the world?

David Lebowitz: Also, could you give us insight as to what other geographies might have their opinion affected by the EU opinion?

And with their team received we're able to work out something with the agency, where perhaps we could submit those.

Eric Pauwels: David, thank you for the question.

Data is during the day 120 safety review and lease senior deal and that's going to be the basis of our ongoing conversations because otherwise we believe we have a package that has every other component there and again as the agency indicated we are in discussions with them.

Our safety and efficacy data as being supportive of the NDA.

And so as we look forward to being able to submit that as soon as possible in terms of comparability.

A matter of we had very limited supply of the clinical materials. So there's only a certain number of assay runs we were able to do to provide data to compare to the assays that for <unk>.

Conducting the commercial material they want that additional data points, greater and a greater number of samples that we simply couldnt provide.

Eric Pauwels: Let me start with your second part first. As we've talked about in the past, the many of our largest markets outside of Europe have independent regulatory agencies that do their independent assessments, and we'll continue to make their independent regulatory decisions independent of the city and European authorization. In terms of revenue, we have seen the past that while many years ago, Europe would have been the primary source of our trans line of revenue, and we've done a lot of work over the past years to diversify the business.

Eric Pauwels: I know Kylie, do you want to remember a bit more detail about the breakdown of revenue? Absolutely. As Matt was just saying, we've spent the central effort and time of the last couple of years to geographically diversify the business, and this was the intent of evening out and ensuring that we have a contribution from a number of regions to total trans line of revenue. So where we stand today, we have a number of growth markets that have continued to grow over the last couple of quarters and last year, and this has allowed us to have a little less than half of EU revenue contribution to total revenue, and then the remainder being XUS.

Due to limited supply in terms of the pre BLA meeting. It was suggested that we hold the pre BLA meeting.

Eric Pauwels: Sure. I mean, is there any way you can let us, I guess, zero in on what the particular number might be in the range of just in case things don't work out in Europe, we're trying to understand what the implications might be going forward with respect to our projections. Yes, David, I think from that perspective, I think it's roughly around 45 to 48 percent, but the one thing I would say and what's important to note is those European markets are some of our more mature markets, and so as you look over time, you would expect that the contribution to total revenue for more mature markets doesn't have the growth trajectory as some of our newer and growth markets. And so while it currently sits around the 45 to 48 percent, currently, you wouldn't expect that number to remain flat over the coming years.

Because they wanted to make sure that we're aligned on the contents of the package, how we better present their integrated safety summary from all the studies that are good about how we're going to see efficacy data. How are we going to include other components of the regulatory studies in the package. They thought it would be very important to make sure.

We've told them the meeting it is not required but which are all companies. It's important to have this so we're sure that the file meets the format specifications, we want to avoid any filing issues. So we believe the most prudent thing to do is to have that pre BLA meeting and then pending the results to be in a position to submit as quickly thereafter as possible.

Great. Thank you for that.

Thank you one moment please.

Our next question comes from the line of Jeff Hung of Morgan Stanley. Your line is open.

Question in your discussions with the EMA on particular known what gives you confidence that it may accept move out date for conditional marketing authorization is there anything that you can update in terms of analyses or presentation that would increase your confidence for a positive outcome on the conditional marketing authorization given the feedback you've received from FDA.

Yeah, Thanks, Jeff for the question.

That has been shown to be most important in pediatric and young adult patients, particularly ambulatory patients because it's been shown to be able to predict time philosophy ambulation.

Obviously in future ataxia for ambulatory patients the key thing for a therapy to do is to delay that time philosophy ambulation delay loss of ambulation and so it didn't have an endpoint that can do it we believe meets that criteria for intermediate clinical endpoint, we look forward to continuing the discussions with the agency as is often necessary in rare disease.

Pierre Gravier: Got it. And with respect to expenses going forward, is there any way you can give us, I guess, some level of bandwidth, somewhat to expect for 2024 and beyond when the restructuring is in full place.

The U S in terms of the Europe.

Conditional marketing authorization is a number of criteria set out for for a conditional marketing authorization do you have initial data that shows that there is a favorable benefit risk of a therapy are you beating of unmet medical need.

Is getting this therapy to patients sooner.

Potential public health benefits and I think when you consider.

Particularly and you move that phase <unk> study and the other data we have we clearly meet all of those criteria. While we didn't hit the primary endpoint will be overall at par score. There is a number of important sources of benefit.

Operator: [inaudible] David Lebowitz, David Lebowitz David Lebowitz Thank you.

Brian Abrahams: One moment, please.

Brian Abrahams: Our next question comes from a lot of Brian Abrams of RBC Capital Markets.

I move that the study not only in a point of stability above our sub scale also on peak, which is in our blood center for patients and then if you look at the well established safety profile, particularly on particularly in pediatric patients. We can clearly demonstrate that this initial study has a favorable benefit risk profile, obviously its on that medical need not only for pediatric patients for <unk>.

Brian Abrahams: Brian Abrams, you're allowed to open. Hey, good afternoon. Thanks for taking my questions. As you prepare for the MAA filing, precipitate after in next year. What are your expectations for what the car study requirements will be for Europe approval? And then secondarily, I guess on Translarna in the US, where do you stand in terms of key discussion items and potential areas of focus that you're expecting for the type C meeting? And when might we see an update from that? We'll be shortly after the meeting or should we expect a little bit of a time gap to allow for the minutes to be collected. Thanks.

Proof therapies for <unk> in Europe for patients of any age.

Brian Abrahams: Thanks for the questions, Brian.

Obviously, given when you have a therapy that can potentially slow delay of loss of ambulation.

Reversible morbidity.

And those patients will benefit from access to therapy sooner.

Final point, so obviously, we know very well from the trends learner experience is to be able to.

Be.

Be able to demonstrate that you can collect more data on patients to support the.

<unk> worth a conditional approval and confirm that you have a favorable benefit risk balance. We obviously believe there's many sources of additional data that we could generate two to confirm the benefit risk profile. So again, we believe we meet all of the necessary criteria conditional authorization and we'll look forward to discussions with the EMA to gain a lie.

And at what time on those points.

Great. Thank you.

Thank you one moment please.

Yes.

Our next question comes from the line of Alexander Xanax of Truth Securities. Your line is open.

Hi, Thanks for taking my question and congrats on securing the royalty financing deal that's great.

Maybe two for me one on <unk> when might we see another cut of the OLED the tolerance data.

And then one on <unk>.

Trends Lorena, if you are able to overturn the conditional marketing.

Ongoing conditional marketing authorization and have that ongoing study, but you don't have the official full marketing authorization have you done any market research to see how that would affect referencing countries worldwide and if they would be required.

Sales or not thanks.

Thanks for the question so first on the fee tolerance.

As we shared we gave an update on those two tolerance data at the <unk> meeting in Israel.

In September those were again really great data showing now with over 40 patients enrolled in the <unk> tolerance protocol that we are seeing patients move through and get to levels.

Get to level of tolerance beyond the recommended daily allowance and this is these are incredibly important data as we said all along the fee tolerance component is really not for regulatory purposes. So that we have the sufficient efficacy data for that and we're able to show in the long term extension that we're adding important durability CPR.

Treatment effect as well as long term safety. This is really the <unk> are really quite important.

One for differentiation is something Cougar and was never able to demonstrate for physician adoption and for payer discussions, particularly outside of the U S on the.

Colin Bristow: So on the question regarding the MAA in Europe, I think this is another example of how regulatory studies tend to look at things differently. To see exactly what we have gotten from Europe regarding car study is they understand very well that the active metatolite for CPITaren in BH4. And they understand that BH4 and CPAT are both naturally current co-factors. They understand the data we collected to date in terms of car study with UNICEFRIES.

Laurent upfront.

Look again, we see the ability to keep the conditional authorization as a big win not only obviously across really most importantly for the patients.

Ill turn it over to Colleen seawater contact highly on the what you think the global payer impact could be.

Colin Bristow: And they have said they would like us to not only have our own data, but that we can rely on the data and experience the crew van health for many years. There's a knowledge base that exists that is in no car study juicy risk associated with BH4 and these chronically from many years. So we don't believe that the issue we have at FCA will be an issue with Europe for that reason.

On a conditional authorization.

Yes, I think from a type of impact I think it will be quite minimal and I think one of the things that the team has done an incredible job with the conditional authorization that we've had.

Colin Bristow: And so again, just different authorities looking at things differently. And again, that's why we're able to forward with that submission as we said in the first half of 2024.

The law nine years is being able to secure a favorable pricing corridor and reimbursement and being able to maintain that over the years.

Thank you.

At this stage, where we stand.

We don't see any sort of negative impact from continuing conditional authorization and of course, we'll continue to focus.

Definitely thanks for taking the question.

Thank you one moment please.

Colin Bristow: On your question regarding the type C meeting for China, why not? That the purpose of that meeting is really to focus on the evidence that we have, the many sources of evidence we have showing that not only is clear evidence of benefits in studies that just study for the one that that's to be confirmed in a number of ways, including that analysis of the long-term and well-described registry. And so really working constructively with the divisions to say what are the components we need and how do we formulate them in order to support the end of the recent mission.

Our next question comes from the line of Joseph Schwartz of Leerink Partners. Your line is open.

Great. Thanks, very much I was wondering if you could talk about your publication plans for the affinity stepping up to the data will we see that published in a peer reviewed journal anytime soon.

Colin Bristow: As we typically do, once we have clarity in the outcome of the meeting, sometimes that can come from the meeting itself, sometimes that requires minutes, sometimes that requires the back and forth. Afterwards, as soon as we have clarity, we'll certainly share it. Obviously, a lot of people are quite interested in the outcome of this meeting. Not the least it was Charlie, you know, boys with non-transportations, the end of the US who have waited years for therapy, and then also the large number boys in the US who have been on, transformed for a number of years from their participation in clinical studies and beyond all of whom are quite interested in ensuring that this drug can be available in the US for them. It's really helpful. Thanks, that. Thank you.

Jeff Hung: One moment, please. Our next question comes to the line of Colin Bristow, of UBS, Alanis Open.

Then I believe you have the option to go up to a 20 milligram dose of PTC.

Pivot HD patients outside the U S. So where do you stand on implementing that decision.

Jeff Hung: Thank you very much for taking the questions. On the sepiatrin NDA filing timeline, I'm just curious why is the latter end of your guidance 3Q24? Can you confirm whether the study has started?

Matthew Klein: It just seems like a sort of extreme upper bound of this timeline, if this study is all that's needed. And then on the AADC, could you just put a little more detail on why FCA thinks the comparability data is still not sufficient? And then what are you sort of hoping, or what will be discussed, the preview A meeting in December?

Yes, absolutely.

Matthew Klein: Thank you.

Take the.

I think let me take the second question first and then I'll, let <unk>.

Matthew Klein: And thanks for the questions, Colin. So the, if you just, you know, when you find out you have to do a study, it takes a little bit of time to actually organize the study, get the slot at the CRO, get the animals order, get the doses confirmed, get the protocol set, get the protocol agreed upon and start the study. Please expect to begin dosing in the study, have all those things ready and dosing that study to start in December.

To answer the first question.

Matthew Klein: That's a six month study, so by the clock that all the animals get those in December, the in-life portion should be done in June. Once in-life portion is done in June, they have the sacrifice of the animals, both through the histological studies, all the histological analysis right there, reports. We're obviously going to work as quickly as we can to accelerate those timelines, obviously we can't shorten the 26 weeks, but we're doing everything we can to shorten the time for data analysis, as well as getting the audit of traffic port, which is necessary for submission.

So on <unk>.

So we as we talked about we shared the results from the five to 10 milligram dose groups. The first cohort of patients in June those data from our standpoint, we're as good as they can be that we achieve that objective at 12 week portion of the study that first cohort of patients demonstrated a dose dependent lowering of Huntington protein.

Matthew Klein: So that's where you get this week-to-time bound from is merely the realities to do a 26 week study, it takes more than 26 weeks. And that's, and we wanted to give an accurate depiction of what these things could be the longest possible date or the latest possible time for that submission. Obviously, as we mentioned with our team, you see we're able to work out something with the agency where perhaps we could submit those data during the day 120 safety review or a late-sage review and that's going to be the basis of our ongoing conversations.

Matthew Klein: Because otherwise, we believe we have a package that has every other component there. And again, as we see indicated in our assessments within, they see our safety efficacy data as being supportive of the NBA. And so we look forward to being able to submit that as soon as possible. In terms of comparability, it's simply a matter of not, we had very limited supply of the clinical material. So we're only certain number of assay runs we were able to do to provide data to compare to the assays that were conducted in the commercial material.

Blood seeing the differential exposure.

Could you just $5 eight in the CSF relative plasma at a 10 milligram dose seeing that that ratio is one five to one suggesting that we're going to even greater exposure in the brain.

Potentially higher levels or greater lowering.

<unk>.

Huntington mutant Huntington protein in the break all of which was very very important.

Of course, the other key point is that we will do with all the safety the safety profile of the drug was quite strong in those first 12 weeks, we had no drug related serious adverse events. There was no NFL spikes, all very very important particularly given.

Matthew Klein: They want the additional data points greater, a greater number of samples that we, we simply couldn't provide due to limited supply. In terms of the preview and meeting, it was suggested that we hold the preview and meeting because they wanted to make sure that we're aligned on the contents of the package. How are we going to present their integrated safety summary from all the studies that are going to, how are we going to present the efficacy data, how are we going to include other components of the regulatory studies in the package.

Concerns that were raised over other HCC lowering therapies.

Matthew Klein: They thought it would be very important to make sure as we were told in the meeting, it's not required, but we tell all companies it's important to have this so we're sure that the file meets the format and specifications we want to avoid any violations. So we believe the most prudent thing to do is to have that preview and meeting, and then penning the results to be in a position just to make as quickly there after as possible.

Alexander Xenakis: Right, thank you for that.

Alexander Xenakis: Thank you one moment please.

Matthew Klein: Our next question comes from a line of Jeff Hung, a Morgan family.

Sufficient to move forward and get us where they want to be so.

Matthew Klein: Your line is open. In your discussions with the EMA on particular known, what gives you confidence that it makes that move up a conditional mark authorization? Is there anything that you can update?

Haven't initiating those 20 milligram dosing, yet I'm not sure we're going to need to and we want to better understand the longer term bile.

Matthew Klein: In terms of analyses or presentation that would increase your confidence for positive outcome on the conditional marking authorization? Given the feedback you've received from FDA. Thanks Jeff for the question. So, you know, the frameworks in FBA EMA are slightly different in the discussions we're having with FCA are around the potential for accelerated approval based on upright stability being an intermediate clinical endpoint. Obviously, upright stability we've talked about is in all the four sections of the MFARS, which was the primary employees.

Locker effects of the current dose levels before revisiting that decision.

Let me now turn it over to Tyler to answer your question one publication strategy for PKU.

Yes, Thanks, Chuck we're absolutely.

Getting the affinity study published in a peer reviewed journal the payments working on that as we speak and is looking to target a high impact.

Matthew Klein: The one that has been shown to be most important in pediatrician and adult patients particularly ambulatory patients because it's been shown to be able to predict time to loss of ambulation. Obviously in future attacks here for ambulatory patients, the key thing for therapy to do is to delay that time to loss of ambulation, delay loss of ambulation. So to have an endpoint that can do it, we believe meets that criteria for intermediate clinical endpoint.

Hi High impact Journal.

Timeline for getting that publish is obviously driven by the channel of choice.

Matthew Klein: We look forward to continuing the discussions with the agency as is often necessary and where diseases is a lot of back and forth to talk about the analyses we have. And as you indicate, could we provide some additional support of analyses to move FAA and particularly the fact that we have a six month open label of sanctions that are during which all subjects are blinded. So that gives us an opportunity to look at changes and trajectory for example for the placebo patients once we switched on to active.

Matthew Klein: That's the U.S, in terms of the euro, the condition marketing authorization is number criteria set out for for a condition marketing authorization. Do you have initial data that shows that there's a favor of benefit risk of a therapy? Are you being on that medical need? Getting is getting this therapy, the patient's senior potential public health benefit. And I think when you consider the tickling on and move FAA study and the other data we have, we clearly meet all of those criteria.

What this is work in progress the team is moving through this and we expect it to be published during 2024 pending the channels.

Matthew Klein: While we didn't hit the primary endpoint of the overall at far score, there's a number of important sources of benefit in the move FAA study, not only an upper instability, a bulgur subscale, also on teeth, which is an influenza for patients. And then if you look at the well established safety profile of the tickling on particular pediatric patients, we can clearly demonstrate that the initial study has a favor. That's an irreversible benefit risk profile.

Thank you.

Matthew Klein: Obviously it's on that medical need, not only pediatric patients, but there's no approved therapies for FAA in Europe for patients of any age. And obviously, given that you have a therapy that can potentially slow the way of loss of regulation, that's an irreversible morbidity. And in those patients would therefore benefit from access to therapy sooner. The final point, obviously we know very well from the translonger experience is to be able to be able to demonstrate that you can collect more data on FAA patients to support the condition for the condition all approval and confirm that you have a favorable benefit.

Thank you one moment please.

Okay.

Our next question comes from the line of Gena Wang of Barclays. Your line is open.

Okay.

Hi, Thank you for taking my questions.

Matthew Klein: We obviously believe there's many sources of additional data that we could generate to confirm the benefit risk profile. So again, we believe we follow necessary criteria, condition authorization, and we look forward to discussions with the EMA to gain a line with them on this point.

So I do have I think three quick questions at the first one is.

Matthew Klein: All right, thank you.

Regarding the PKU program.

Matthew Klein: Thank you, one moment please.

Since initially we're thinking about 505 B two is that because the lack of confidence of the IP position that this drug will be very different from <unk>. That's the first question.

Alexander Xenakis: Our next question comes from the line of Alexander Xenakis of Truist Security, Jalana Zilken.

Relatedly, how confident you are on the IP regarding distance.

New composition of matter and then for the pivot HD I don't know if I missed it.

So have you.

Exactly what kind of data you would need in order to remove FTE clinical hold.

So based on.

Additional data that will require two can dose more than 12 months and what dose you can dose.

Beyond 10 milligram. So thats the second question and a quick weight loss last question.

Got it.

So if you are using current U S data for accelerated approval.

<unk> steady you would need to do.

In order to.

Uh huh.

To get a full approval in the future.

Alexander Xenakis: Hi, Sam, for taking my question, congrats for sponsoring the World of the Pynons and the L, that's great. Maybe two for me, one, Anzaphi Aptarin, when might we see another cut of the OLA's futon and then one on Translana, if you are able to overturn the conditional market, the ongoing conditional market authorization and have that ongoing study, but you don't have the official full marketing authorization. Have you done any market research to see how that would affect referencing countries worldwide and if they would be required to hold sales or not?

Great. Thank you very much for the questions. The first question for number one regarding PKU incentive look I think that was really well.

Matthew Klein: Thanks.

Matthew Klein: Yes, thanks for the questions, Alex. Well, first on the C-toler, as we shared, we gave an update on the C-tolerance data at the SSIDAM meeting in Israel. In September, for those who are again really great data showing now with over 40 patients enrolled in that C-tolerance protocol that we're seeing patients move through and get to levels, get to levels of C-tolerance beyond the recommended daily allowance. This is these incredibly important data.

Matthew Klein: As we said all along, the C-tolerance component is really not for regulatory purposes. Instead, we have the sufficient efficacy data for that and are able to show in a long-term extension that we're having important durability of CP-action treatment effect as well as long-term safety. This is really the, the C-tolerance data really quite important.

More reflection of sense, giving a very small virtual company and probably looking for what they bought at the time would be the quickest and least expensive development path forward.

Matthew Klein: One for differentiation is something C-tolerance is never able to demonstrate and for physician adoption and for payer discussions, particularly outside of the U.S. On the translonger front, the look again, you know, we see the ability to keep the conditional authorization as a big win. Not only I was thinking for us, but really most supported for the patients. When we start over to pilot, if you want to pilot on me, what do you think the bill will pay or in fact could be paying on a conditional authorization?

Matthew Klein: Yeah, I think from a paper impact, I think it will be quite minimal, Alex. I think one of the things that the team has done an incredible job is with the conditional authorization that we've had over the last nine years is being able to secure a favorable pricing corridor and reimbursement and being able to maintain that over the years. So I think at this stage where we stand, we don't see any sort of negative impact from continuing conditional authorization, and of course we'll continue to focus on that.

Matthew Klein: Thanks for taking the questions. Thank you.

I think.

Matthew Klein: One moment please. Our next question comes from a line of Joseph Swartz of Leigh-Ring Partners.

It's not uncommon for a smaller company to think about the development path that way.

Joseph Schwartz: Your line is open. Great, thanks very much.

I think from our standpoint the.

Very clear this is a highly differentiated therapy that is much more suited to the 500 <unk> pathway obviously.

We're in a position to have the resources to do the necessary studies and not have to rely on a another NBA and incur that risk.

The state based on the launch of a therapy following approval as we've talked about not only do you have a great deal of confidence in how differentiated CPO Terra is in its ability to meet the persistent large unmet medical need for PKU patients and as we've heard from physicians, including under the <unk> on a commercial lead time this summer.

XIAFLEX physicians deepen switch patients who may be served to some extent include band to see good tailwind because of what we've been able to show in terms of the large magnitude of clinical benefit.

You also talked about the IP here, we obviously have orphan designation. We also have some potential patent extensions that we believe will extend the orphan exclusivity out several years.

Question on activity HD as we had talked about in the past in a recession with the agency they have said that.

What they wanted to see additional evidence that we can dose at the dose levels.

<unk> activity <unk> those additional data could take the form of non clinical data you can also take the cohort clinical data and so we had made the decision since we were able to conduct this trial.

Many countries outside of the U S and enroll the study outside the U S that we would conduct the study collect the clinical data in the study and then provide those data as we had them to FDA.

In order to fulfill that need of demonstrating that put PTC five eight can be demonstrated safely. So once we did the three once we have the 12 week data we took those data that we presented it obviously since all patients are enrolled at the same time, we had some data beyond 12 weeks, we provided all of that to the agency and that with clinical data.

Included clinical laboratories included the NFL levels.

We had shared at the earnings adverse event reports by the lack of serious adverse events. The SMB minutes letters from the DSV share all of which were shared with FDA as I mentioned in the prepared remarks during our discussion in the meeting the FDA indicated that those data that we had at that point could be sufficient.

Joseph Schwartz: I was wondering if you could talk about your publication plans for the affinity set the afternoon data. Will we see that published in a peer review journal anytime soon?

Joseph Schwartz: And then I believe you have the option to go up to a 20 milligram dose of PPC-518 in pivot HD patients outside the US. So where do you stand on implementing that decision?

But right now quite simply doing the timing mass.

Very possible by the time, we got that data center to the FCA review sites ready up and running in the U S. If I say it will be that will be done with enrollment.

Matthew Klein: Yeah, absolutely, so maybe I'll take the, I think let me take the second question first and then I'll, I'll, I'll, I'll kind of answer the first question second. So I'm on 518. So we, as we talked about, we share the results from the five and 10 milligrams of those groups, the first cohort of 32 patients in June, you know, those data from our standpoint, where as good as they can be, that we achieved every objective of that 12-week portion of the study in that first cohort of patients, demonstrated the most important low on the puntitina protein in the blood, seeing the differential exposure of the G518 in the CFS relative to plasma, as I tend to remember, and just seeing that that ratio is 1.5 to 1, suggesting that we're getting even greater exposure, 518 in the brain, and even potentially higher levels, or greater low range of puntitina, mutant hundreds of proteins in the brain, all of which was very, very important.

Pivoting HD.

Extremely close right now to completing enrollment in the stage two patients that enrollment is moving very quickly overall for the study, particularly after the June data release, when we were able to provide a lot of comfort to physicians and patients.

Matthew Klein: And of course, the other key point is that we were doing all this safely. The safety profile of the drug was quite strong in those first 12 weeks. We had no germinated seriously worse events. There were no NFL spikes, all very, very important, particularly given concerns that were raised over other HCC low and therapies that have drawbacks that we talked a lot about in the past. We said this in those data.

Matthew Klein: We believe we may have the dose levels we need right now to get us where we want to be in terms of the ultimate goal of the program, which is being able to lower brain cell hunting. The protein levels are either 50 percent. And so with the decision, with those early data while we have the ability to go up to 20 milligrams with the S&B has supported us starting 20 milligrams cohorts, the regulatory authorities and local ethics committees have approved us going to 20.

Matthew Klein: We're still in a holding pattern. We want to understand a little bit more what the biomarker effects are with the dose levels we have now, 5 and 10, because those very well may be sufficient to move forward in general. So we are we haven't as a shooting those the 20 milligram dose and yet I'm not sure we're going to need to and we want to better understand the longer term by all marker effects of the current dose levels before we visiting that decision.

Unlike.

Kylie O'Keefe: Let me return over to Thailand to answer a question on publication strategy for PT. Yeah, thanks Joe. We're absolutely getting the affinity study published in a peer review journal. The team is working on that as we speak and is looking to target a high impact high impact journal. And so the timeline for getting that published is obviously driven by the journal of choice. So we're we work, this is work of progress. The team is moving through this and we expect it to be published during 2024 pending the journal. Thank you.

Other Huntington lowering therapies, and we're able to.

Our objectives and do so safely so there's been a lot of interest in that study. There is obviously a lot of interest in the United States for patients and physicians.

We'd love to be able to open sites here, but if the study is fully enrolled and we'll look to start a phase III here and be able to offer the opportunity for patients to participate in.

Operator: One moment, please.

Gina Wang: Our next question comes from a lot of Gina Wang, a barclays, a lot of open. Thank you for taking my questions. So I do have I think a three quick questions.

The pit and the PTC five under development.

Your third question was regarding upstate and accelerated approval confirmatory study. So we are using the existing clinical setting now in the U S and we have the endpoint that we're using to support the accelerated approval is an early endpoint of biochemical changes then you'll have a longer term extension component of that study.

Which will collect long term clinical data to provide the clinical evidence necessarily.

To support the full approval. So this is really an example, where we will have the study ongoing it's going to be a long term study thats going to look at the acquisition of motor developmental milestones over time much in the way that we've been able to show previously in the clinical studies that were done previously where over time ratings show that these children develop the.

Ability took first of their head and be able to sit crawl walk independently that obviously it takes many years, which is why in many ways. This is a very good setup for an accelerated approval, where we have biomarker evidence dopamine increases, which is obviously likely to predict long term clinical benefit of the acquisition of dopamine related motor.

Gina Wang: The first one is a regarding the PQ program. Since since initially was thinking about 505 B2 is that because they are lack of confidence of their IP position that this drug will be very different from KUVET. That's the first question. And then you know, later on how confident you are on the IP regarding this is a new composition or a matter.

Milestones.

Thank you.

One moment please.

Yeah.

Our next question comes from the line of Paul Choi of Goldman Sachs. Your line is open.

Good afternoon, and thank you for taking our questions two questions from me first on the commercial side with the approval of all of them are alone. Today can you maybe just comment on how youre thinking about the impact to in place and would you maybe consider pulling back on Salesforce resource resourcing for that product.

Starting next year ahead of your expected loss of exclusivity.

And then on the pipeline side can you maybe comment on what you would intend to present in terms of your pivot HD update next year.

Should investors continue to expect plasma.

Plasma Huntington updates on neuro if element.

Changes or would you perhaps presents some details on other other endpoints, including clinical endpoints. Thank you very much.

Thanks, Paul quick question, let me, let me grab the second one first and then I'll turn the other question over to Eric.

Thanks.

So first in terms of.

The 500000 data so the 12 month data that we said in the call that we would share in the first half of 2024 that will be data from the biomarker portion you talked about <unk> being a 12 months placebo controlled study in two parts. The first part for 12 weeks focuses on pharma.

Matthew Klein: And then for the pivot HD, I don't know if I missed it. So have you like exactly what kind of data you would need in order to remove FDA clinical hold. So based on, you know, I think your prepare remark you did mention certain months of clinical safety data when I looked at the press releases a six months of a clinical safety data. Demonstration is similar for safety profile could support 12 months dosing and additional data that will require to can those more than 12 months and what dose you can dose like a beyond 10 milligram.

With the pharmacokinetics as well as safety and then in that second portion of the 12 month time point you would have data further data on their or filament levels now with us about safety, but maybe more about recording.

Benefit.

CSF Huntington protein mutant Huntington protein levels volumetric changes on MRI. We also will have some clinical data at that time point, which are not me.

Main endpoints at the 12 months, but obviously, we're collecting data I think.

We would certainly share the biomarker data share where clinical data we have with the obvious caveat that even with 12 months, it's very hard I think.

Interpretable.

Clinical.

Effect on things like the UHD IRS scale or even.

The total motor score or single digit more gallons tests just given the.

The rate of progression of disease.

Sensitivity to those instruments to change over a short period of time.

And so as we will have those data domain focus there'll be the biomarker data. Obviously continued safety. We will also when ready have data on the additional.

Subjects, who are going to hit the 12 week time point and then ultimately hit the 12 month time point, we haven't given a timeline for that at the time on the given obviously the data point I think most are interested in which is that 12 month data point for the initial cohort of subjects on whom we shared.

When we shared the 12 week data so in terms of your question on for more alone.

<unk>.

Eric do you want to take that yeah. Thanks for the question, Paul I think within Faas.

No. That's some flaws has been currently on the market for more than six years. It is currently the standard of care we've.

We've established and plaza as the standard of care, because theres been a number of publications and Theres also a lot of time with it.

<unk> evidence that is actually preserved greater motor function than than prednisone.

And we know that the data has continually supported that and we have very very strong relationships with each one of the health care providers.

In terms of showing them the evidence, but also providing patient support.

We understand that the community wants options, but we know that right now we have been focused on and we are our field force has been focused on not only growing the brand. This year, but also we have a number of strategies that will also protect the brand.

Following the loss of exclusivity because we don't necessarily see this as being a fall off.

Matthew Klein: So that's the second question and a quickly last last question regarding the app stars are in AADC. So if you are using current US data for accelerate approval, what additional study you need to do in order to to get a full approval in the future.

We can continue to leverage that support.

And through that process, we will continue to work with our specialty pharmacies will be targeting key relationships with payers.

Matthew Klein: Great. Thank you very much for the question, Zina. The first question for number one, we've already piqued you in censor.

Two obviously continue to if you will foster brand loyalty. So all the more alone as an additional option. We also know that clinically and it hasnt been differentiated like in Plaza and that we have a very strong and loyal customer base.

Okay. Thank you for taking our questions.

Yes.

Thank you one moment please.

Our next question comes from the line of <unk> Ahmad Bank.

Bank of America. Your line is open.

Okay. Thanks, so much for taking my questions.

One from me if I may so.

So keep it the topic.

Peripheral for catalyst pharma, how if in any way does that change your strategy for how you might want to.

Look beyond the loss of exclusivity for <unk> next year and beyond.

Matthew Klein: Look, I think that was really what more reflection of censoring a very small virtual company and probably looking for, but they thought at the time would be the quickest and least expensive development path forward. I think it's not uncommon for a smaller company to think about the development path that way. I think from our standpoint, it's very clear that this is a highly differentiated therapy that is much more suited to the 505B1 pathway.

Matthew Klein: Obviously, we're in a position to have the resources to do the necessary studies and not have to rely on another MBA and incur that risk of having a state based on the launch of a therapy following approval. As we talked about, not only do we have a great deal of confidence in how differentiated secret terrain is and its ability to meet the persistent large mathematical need for PKU patients. And as we've heard from physicians, including Ivan Munteu on a commercial D-time this summer, a desire for physicians to even switch patients who may be served to some extent include VanTube secret terrain because of what we've been able to show in terms of the large magnitude of clinical benefits. We've also talked about the IP here. We obviously have orphanage designation. We also have some potential patent extensions that we believe will extend the whole of the exclusivity out to several years.

And then second question.

Matthew Klein: Your second question on Civite HD. As we had talked about in the past, the accessibility of the agency, they said that when they wanted to see additional evidence that we can dose at the dose levels, we intended in Civite HD. Those additional data could take the form of non-clinical data. It could also take the form of clinical data. So we had made the decision since we were able to conduct this trial of many countries outside of the US and enroll the study outside the US that we would conduct a study, collect the clinical data in the study, and then provide those data as we had them to FDA in order to put that need of demonstrating that CT-C5-1-8 can be demonstrated safely.

As it relates to set the aster and milestone agreements with FEMSA I believe you've already paid.

$30 million for completing phase three enrollment.

What other milestones should we anticipate either this year or next and then lastly to clarify on the conditional approval for Translarna and <unk>.

Matthew Klein: So once we did these three months, once we had the 12-week data, we took those data that we presented. It obviously, since all patients aren't enrolled at the same time, we had some data beyond 12 weeks. We provided all of that to the agency and that was clinical data, included clinical laboratories, included the NFL level that we had shared at the earnings adverse event reports, the lack of serious adverse events, the DSNB minutes, letters from the DSNB chair, all of which were shared with FDA.

I'm sorry, if it was answered earlier is there a set.

Mountain time.

For which a conditional approval would need to be renewed on a go forward basis. Thanks.

Yes.

Sure. Thanks for the question. So let me take let me take the third one and then I'll pass to the team and the other two so the.

Matthew Klein: And I mentioned in the prepared remarks during our discussion in the meeting, the FDA indicated that those data that we had at that point could be sufficient for 12 weeks, doseing in five and 10 milligrams. That's what we wanted to start now. But obviously, the goal here is to think about long-return dosing as your question suggested, and they said we're going to like to see those data at the six-month time point.

Matthew Klein: So basically, a little bit longer than three months to support the duration of those things that we had proposed in pivoting HD. But right now, quite simply, doing the timing mask is very possible. By the time we got that data sent to the FDA, got the review, got size ready, up and running in the US, it might very well be done with enrollment in pivoting HD. We're extremely close right now in completing enrollment.

Matthew Klein: We received two patients, and enrollment is very quickly overall for the study, particularly active in the June data release, when we were able to provide a lot of comfort to physicians and patients that unlike other hospital and therapies, we were able to see our objectives and do so safely. There's been a lot of interest in that study. There's obviously a lot of interest in the United States for patients and physicians, so we would love to be able to open sites here.

Could a conditional authorization, obviously theres always comes with a specific obligation to collect additional data. So that's less of a time based.

Matthew Klein: But if the study is fully enrolled and we look to start, I'll say it's three here, and be able to offer the opportunity for patients to participate in the pivot in the PDT-5 You're a third question was regarding upstate and accelerated approval and confirmatory study. So we are using the existing clinical study now in the US, and we have the end point that we're using to support the accelerated approval is an early end point of biochemical changes, and you'll have a longer term extension component of that study, which will collect long term clinical data to provide the clinical evidence necessarily to support the full approval.

Specific time based element, but rather at the time if necessary for that data collection effort, obviously they've been.

Matthew Klein: So this is really an example where we will have the study ongoing, it's going to be a long term study that's going to look at the acquisition of developed motor development milestones over time, much in a way that we've been able to show previously in the clinical studies of stanza that were done previously, where all the time we're going to show that these children develop the ability to first look their head and be able to sit, crawl and walk independently that obviously takes many years, which is why in many ways this is a very good setup for an accelerated approval where we have biomarker evidence, dopamine increases, which is obviously likely to predict long-term clinical benefit of the acquisition of dopamine-related motor milestones.

Therapies that have had conditional authorization for many many years say even beyond the decade.

Matthew Klein: Thank you.

So for US what we would do is look forward to the opportunity to keep the SaaS market and then continuing to collect the data necessary. We do also have the obligation to submit for annual renewals, which we've been through before that's what we've done for the past several years to show that we are one collecting the data that we've agreed to as part of a specific obligation.

And then also providing any necessary updates, particularly around safety to the therapy.

Emerge obviously that the safety story on trend walnuts quite.

Robust and we've clearly been able to show that as a therapy than say for the long term just as we've been able to show the benefit long term to the to the stride registry.

In terms of your questions on the strategy and as well as milestone payments courage you on that.

<unk> Plaza.

Yes, absolutely.

<unk> Plaza front to Dana I think.

We continue to do with the implied there is the standard of care across all DMD patients and we have been able to demonstrate the benefit of implied there in a number of different milestones and we continue to believe that that's not going to shift.

Near term I think from a loss of exclusivity perspective, we have a number of strategies that we're looking at to be able to present, the business and again that doesn't shift based on that the moral and appraisal we.

We have good strong relationships across our customer base and with patient advocacy groups and we will continue to leverage that relationship as we move forward.

Paul Choi: One moment please. Our next question comes online of Paul Choi of Goldman Sachs.

Paul Choi: Elias Open. Good afternoon, and thank you for taking our questions. Two questions for me. First, on the commercial side, with the approval of Weber alone today, can you maybe just comment on how you're thinking about the impact to inflase, and would you maybe consider pulling back on Salesforce resource, resourcing for that product starting next year ahead of your expected loss of exclusivity. And then on the pipeline side, can you maybe comment on what you would intend to present in terms of your pivot HD update next year should investors continue to expect plasma hunting 10 updates and neurofilament changes, or would you perhaps present some details on other endpoints, including clinical endpoints? Thank you very much.

On the milestone question.

Yes.

Are you able to provide any color on specific strategies that you're going to you.

Paul Choi: Thanks, Paul, for the question.

Got that.

Yeah, absolutely. So this four main pillars that we're focused on with regard to protecting the business. So one is ensuring that we have and enhance patient support program, which is really really important for particularly DMD patients in Medicaid as an example.

Matthew Klein: Let me grab the second one first, and then I'll turn the other question over to Eric and Kylie. So first, in terms of the pipeline data, so the 12-1 data that we've said in a call that we would share in the first effort 2024, that will be data from the biomarker portion. And each activity HD is being a 12-month placebo control study into parts. The first part, the 12-weeks focus is on pharmacognomic and pharmacognetics as well as safety.

And then also partnering with specialty pharmacy, partnering with Payors and partnering with manufacturers.

Matthew Klein: And then in that second portion, at the 12-1 time point, we would have data further data on neurofilament levels now less about safety, but maybe more much recording treatment benefit. We also have some clinical data at that time point, which are not main endpoints at the 12-months, but obviously we're collecting these data. I think we would certainly share the biomarker data, share what clinical data we have with the obvious KBS at even the 12-months is very hard to have interpretable clinical effect on things like the UHDRS scale.

But to ensure that we're doing the best for the patients and protecting the business. So that some of the key strategies that we're looking at as well as dispenses written program that the team is working on as we speak.

Okay. Thank you.

Thank you and then.

And just to answer the last question today around the milestones for sensor you are correct. We obviously had paper 30 million in equity in 2020.

Matthew Klein: Or even the total motor score or similar dialing tests was given to the latest progression in the disease and the sensitivity of those instruments to change over a short period of time. The answers will have those data that being focused will be the biomarker data, obviously continuing safety. We will also, when ready, have data on the additional. Subjects who are, I think, going to hit the 12-week time point in the middle to really hit the 12-month time point.

Any additional milestones.

Sent that in 2023.

Had shed in the Q that we expect.

$65 million.

Our regulatory success based milestone.

Sure in the next 12 months so impactful.

We haven't broken out the specifics around that.

Yeah.

Thank you I'm showing no further questions at this time I'd like to turn the call back over to Dr. Matthew Klein, Chief Executive Officer for any closing remarks.

Thank you ladies and gentlemen, this does conclude today's conference. Thank you all participating you may now disconnect have a great day.

Matthew Klein: We haven't given a time on to that. The time on the given obviously is the data point. I think most are interested in which is that 12-month data point to be initial co-blur subject on whom we shared, I think we shared the 12-week data.

Matthew Klein: So in terms of your question on the law law and the laws, Eric, do you want to take it?

Matthew Klein: Yeah, thanks for the question, Paul. I think within flaws, you know, we know that from flaws has been currently on the market for more than six years, and it's currently the standard of care. We've established in flaws as a standard of care because there's been a number of publications, and there's also a lot of times with a scientific evidence that is actually preserved greater motor function than prednisone. And we know that the data has continually supported that, and we have very, very strong relationships with each one of the healthcare providers in terms of showing them the evidence, but also providing patient support.

Matthew Klein: We understand that the community wants options, but we know that right now we have been focused on, and our field force has been focused on, not only growing the brand this year, but also we have a number of strategies that will also protect the brand following the loss of exclusivity, because we don't necessarily see this as being a fall-off. Because of a generic or even a competitor, and we have a number of key strategies right now, and a lot of them are centered around leveraging our patient support programs, because we have that direct line with patients, and we have more patients on and flaws than any other DMD treatment.

Matthew Klein: We can continue to leverage that support. And through that process, we'll continue to work with our specialty pharmacies, we'll be targeting key relationships with payers. To obviously continue to, if you will, foster brand loyalty. So all the more alone is an additional option. We also know that clinically, it hasn't been differentiated like in Plaza, and that we have a very strong loyal customer base.

Matthew Klein: Okay, thank you for taking our questions.

Matthew Klein: Thank you.

Matthew Klein: One moment, please.

Pazine Ahmad: Our next question comes from a line of Pazine Ahmad, a Bank of America line is open. Okay, thanks so much for taking my questions. A few quick ones from me, if I may.

Pazine Ahmad: So to keep up the topic of the approval for catalyst pharma, how is it in any ways that that change your strategy for how you might want to look beyond the loss of exclusivity for inflow the next year and beyond. And then second question, as it relates to sepiaptor and milestone agreements with Sesa, I believe you've already paid them 30 million for completing these three enrollment. I guess what other milestones should we anticipate either this year or next?

Matthew Klein: And then lastly, to clarify on the conditional approval for trans blarna. And I'm sorry if it was answered earlier. Is there a set amount of time for which a conditional approval would need to be renewed on a go forward? Thanks for the questions.

Matthew Klein: Let me take this third one and then I'll pass to the team for the other two. So for the conditional authorization, obviously there's always comes with a specific obligation to collect additional data. So that's less of a time-based specific time-based element, but rather the time is necessary for that data collection effort. Obviously there's been therapies that have had conditional authorization for many, many years, even beyond a decade. So, you know, for us what we would do is look forward to the opportunity to keep the therapy on the market, and then continue to collect the data necessary.

Matthew Klein: We do also have the obligation to submit for annual renewals, which we've been through before. That's what we've done for the past several years to show that we're one collecting the data that we've agreed to as part of the specific obligation, and then also providing any necessary updates, particularly when we're doing this. So, I think it's a little bit more about safety to the therapy, that might emerge. Obviously, the safety story on Tranwala is quite robust, and we've clearly been able to show that it's a therapy that is safe in long-term, just as we've been able to show the benefit long-term to the stride registry.

Matthew Klein: In terms of your questions on influenza strategy, and as well as mild symptoms, Kylie, do you want to take some pleasure? Yeah, absolutely. So, on the influenza front to Zine, I think what we continue to do is the influenza has extended the care across all DMD patients, and we have been able to demonstrate the benefit of influenza in a number of different milestones, and we continue to believe that that's not going to shift in the near term.

Matthew Klein: I think from a loss of exclusivity perspective, we have a number of strategies that we're looking at to be able to preserve the business, and again, that doesn't shift based on the memorial approval. We have good, strong relationships across our customer base, and with patient advocacy groups, and we will continue to leverage those relationships as we move forward. On the milestone question to Zine, are you able to provide any color on the specific strategies that you're going to use for influenza?

Matthew Klein: Yeah, absolutely. So, there's four main pillars that we're focused on with regards to protecting the business. So, one is ensuring that we have an enhanced patient support program, which is really, really important for particularly DMD patients and those in Medicaid as an example, and then also partnering with specialty pharmacies, partnering with payers, and partnering with manufacturers to be able to ensure that we're doing the best for the patients and protecting the business.

Matthew Klein: So, there are some of the key strategies that we're looking at as well as a distance is written program, because the team is working on as we speak. Okay, thank you. Thank you. And then in your, just to answer the last question to Zine, around the milestone for Census, so you are correctly, obviously, had paid the $30 million in equity in 2023. Don't expect any additional milestone for Census in 2023, but we had shared in the queue that we expect $65 million worth of regulatory success based milestone for Census in the next 12 months. So, in principle, and we haven't broken out the specifics around that. Thank you.

Matthew Klein: I'm sure no further questions at this panel. Let's turn the call back over to Dr. Matthew Klein, Chief Executive Officer for any closing remarks.

Matthew Klein: Great. Thank you.

Matthew Klein: Thank you all for joining the call today. We look forward to a strong close out of the 2023. If you get ready for what's clearly also going to be a busy 2024, and we look forward to sharing updates with you as they become available.

Operator: Thank you all again and have a good evening. Thank you.

Operator: Ladies and gentlemen, this does include today's conference. Thank you. We're all participating.

Operator: You may now disconnect. Have a great day. Thank you all for joining the call.

Q3 2023 PTC Therapeutics Inc Earnings Call

Request a DemoDemo

PTCT

PTC Therapeutics

Earnings