PTC Therapeutics Q3 2023 Earnings Call Transcript

Quartr
Provided by Quartr
October 26, 2023

There are 15 speakers on the call.

Operator

Thank you for standing by and welcome to the PTC Therapeutics Third Quarter 2023 Financial Results Conference Call. At this time, all participants are in a listen only mode. After the speakers' presentations, there will be a question and answer session. Please be advised today's call is being recorded. I would now like to turn the conference over to your host, Jane Hanlon, Associate Director of Investor Relations.

Operator

Please go ahead.

Speaker 1

Good afternoon and thank you for joining us today to discuss PCC Therapeutics' 3rd Quarter 2023 Corporate Update and Financial Results. I'm joined today by our Chief Executive Officer, Doctor. Matthew Klein Our Chief Business Officer, Eric Powells our Chief Commercial Officer, Kiley O'Keefe and our Chief Financial Officer, Pierre Gravier. Today's call will include forward looking statements based on our current expectations. Please take a moment to review the slide posted on our Investor Relations website in conjunction with the call, which contains our forward looking statements.

Speaker 1

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 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 10 ks filed with the Securities and Exchange Commission as well as the company's other SEC filings. We will disclose certain non GAAP information during this call. Information regarding our use of GAAP to non GAAP financial measures and a reconciliation of GAAP to non GAAP are available in today's earnings release. With that, let me pass the call over to our CEO, Matthew Klein.

Speaker 1

Matt?

Speaker 2

Thank you, Jane. Good afternoon and thank you all for joining the call. I'm pleased to share our Q3 results I will begin with the recent announcement of our agreement with Royalty Pharma To monetize up to $1,500,000,000 of the Agrisby 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 2 years.

Speaker 2

Notably, PTC maintained its rights to the remaining $250,000,000 of milestones related to Avrisete Global Mints sales. The royalty 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 and D programs and robust global commercial infrastructure. Now, I'll turn to our Q3 results. We had another solid quarter with total revenue of $197,000,000 which keeps us on target for meeting our 2023 total revenue guidance of $940,000,000 to $1,000,000,000 Our DMD franchise revenue in the quarter totaled $136,000,000 This strong performance allows us to update our 2023 DMD revenue guidance To between $565,000,000 $595,000,000 from between $545,000,000 $575,000,000 Eric and Kiley 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.

Speaker 2

Let me begin with an update on Translarna. Following the negative opinion from the CHMP on the conversion of the conditional marketing authorization the full marketing authorization and on the renewal of the conditional authorization, CHMP gave us the option to request reexamination of both opinions Or only one opinion. We decided to pursue reexamination of the 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 Translarna in Europe. We remain optimistic that we can address key concerns raised by the CHMP on the evidence of benefit in the Translarna clinical trials as well as concerns raised on the methodological robustness of the STRIDE data analyses.

Speaker 2

As previously discussed, in accordance with EMA 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 cepiaterin, we held a pre NDA meeting in the Q3 with FDA to discuss the NDA submission. At the meeting, FDA stated that the cepiaterin clinical safety and efficacy data supported NDA submission for the treatment of pediatric and adult PKU patients.

Speaker 2

However, they requested that we complete 26 week non clinical mouse study to assess potential carcinogenicity risk of sepia terran prior to submission. This non clinical study was initially not required when cephalterin was acquired from Censa as the NDA submission was planned under the Section 505(2) pathway. With our decision to file under the 505(1) 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 MAU study results during the NDA review process. We now expect NDA submission to occur no later than the Q3 of 2024.

Speaker 2

This submission could occur in the Q2 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 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 $1,000,000,000 plus global commercial opportunity for cepiaterin. Moving to the PTC-five eighteen Huntington's disease program, Enrollment is ongoing in the PIVOT HD study for both the Stage 2 and early Stage 3 cohorts. We expect the next data update to occur in the first half of This update will include 12 month data on the initial group of subjects on whom we reported data in June of this year.

Speaker 2

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 3 months of Safety data could support 12 week dosing at 5 milligrams and 10 milligram dose levels and at 6 months of clinical safety data Demonstrating a similar favorable safety profile could support 12 month dosing in the PIVOT HD trial. This is very good news as it suggests that the safety data being generated from TIVOT HD should be sufficient to lift a partial hold in the United States.

Speaker 2

Turning to betiquinone. The data in the MOVE. FA study demonstrated betiquinone's treatment benefit across several disease Including favorable effects on the upright stability subscale of the mFARS assessment, which is predictive of time to loss of ambulation. We had a Type C written response only meeting with FDA in the Q3 to determine whether the data from LUBFA would be sufficient to support In the written response, the FDA stated that while they see the value of upright stability As a clinically meaningful endpoint, they 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.

Speaker 2

In parallel, we are participating in a scientific advice procedure with the EMA to determine if the Move FA data Could support a conditional marketing authorization application in the EU. We expect to have the outcome of this procedure in the Q1 of 2024. Turning to OXTAZA, we had an informal meeting with FDA in the Q3, 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. 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. FDA suggested that we conduct a pre BLA meeting to review the contents of the planned BLA.

Speaker 2

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 position 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 and Kiley to discuss our strong commercial performance in the quarter. Eric?

Speaker 3

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 our commercial portfolio of 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 expansion. Let me focus on our 2 key products in the DMD franchise. Translarna and Emflaza continue to be important growth drivers, Delivering $136,000,000 in net revenue for the 3rd quarter, which is 4% compared growth compared to the Q3 of 2020 With strong year to date performance, we are raising our DMD revenue guidance from $545,000,000 to $575,000,000 to $565,000,000 to $595,000,000 For Translarna, we achieved $69,000,000 in quarterly revenue.

Speaker 3

Year to date sales were $281,000,000 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 healthcare providers the totality of data and real world evidence supporting the efficacy of Translarna And reemphasizing the significant life changing impact this treatment has on young boys suffering from this devastating disease, For whom Translarna 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 Translarna And its continued availability for all new and existing patients. Now turning to Emflaza. The Emflaza business continues to be solid.

Speaker 3

Quarterly net revenues was $67,000,000 which is 23% Growth over the prior year quarter. We have had $188,000,000 in year to date sales. We continue to see strong trends in the new patient start forms and high compliance. The continued Emflaza 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 Emflaza brand ahead of loss of exclusivity next year. Now, I will ask Kiley to update the progress of our current and future new product launches.

Speaker 3

Kiley?

Speaker 4

Thanks, Eric. Let me begin with UPSTASA, the 1st 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 U. K.

Speaker 4

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 with a patient from the Middle East Also receiving treatment in France this quarter. Moving to TEGSEDI and WAYLIVRA in Latin America. We continue to grow our franchise in the region with recent MAA approval for TEGSEDI in Argentina and WAYLIVRA in Mexico.

Speaker 4

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 TEGSEDI and WAYLIVRA before the end of this year, which is in recognition of the increased number of patients who rely on these life changing treatments. Lastly, as Matt mentioned, we are extremely excited about the cepiaterin opportunity. The APHINITY Phase 3 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.

Speaker 4

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, the team is actively working on launch activities to ensure a fast uptake upon approval. The potential market opportunity for sepia Karen is composed of a number of key PKU patient segments, all of which our APHINITY data suggests we can address. First, patients who have not been trialed on Kuvan or are considered therapy naive. This includes many of the classical PKU patients where we have demonstrated benefit in both the Phase 2 study and the APHINITY study. 2nd, patients who have not responded to Kuvan.

Speaker 4

3rd, patients who have achieved some level of blood fee reduction from Kuvan, but are not well controlled and for whom cepiaterin may deliver a better reduction in blood fee levels. For these patients, a reduction in blood fee To target Phe 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 APHINITY study And from their understanding of the mechanistic benefits of sepiateran, all interested patients should be trialing sepiateran. With an expected addressable population of approximately 15% to 30% of the overall global PKU population, This would put us above $1,000,000,000 market opportunity. In conclusion, our 3rd quarter builds on an excellent first half of twenty twenty three With significant progress across all of our commercial products and across all geographies, our customer facing team is set to have A very strong closeout 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 strategies for our future product pipeline.

Speaker 4

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

Speaker 5

Thank you, Kylie. I would like to begin by discussing the financing with royalty format as we announced last week. That deal, together with the pipeline reprioritizations and OpEx reductions that we announced in May September, Puts PTC in a very strong financial position. We are pleased to work again with Royalty Pharma on this win win transaction. The non dilutive financing provides PTC with the capital to support operations and allows For increased operational and financial flexibility by removing the Blackstone debt obligation from our balance sheet.

Speaker 5

In addition, the deal structure provides the potential for additional non dilutive capital over the next 2 years. To recap the details of the deal, PTC monetized up to $1,500,000,000 of the equity royalty stream. Royalty Pharma acquired additional royalties on Aprize for $1,000,000,000 upfront. The agreements included options for PTC to sell up to an additional $500,000,000 or For Royalty Pharma to acquire half of such retained royalties for up to $250,000,000 at a later date, Last royalties received by PTC. PTC maintains all economics associated with up to $250,000,000 The remaining commercial sales milestone associated with Everdige Global Net Sales.

Speaker 5

The agreement builds on the Previous strategic partnership established with Royalty Pharma in 2020. The initial agreement was for the monetization of approximately 43% As a result of the current agreement, PTC will maintain ownership of approximately 19 of the total Eberty royalty stream, pending any exercise of future options by PTC or Royalty Pharma All the achievements of the cap from the 2020 royalty agreement. I'll now share the financial highlights of our Q3 2023. Please refer to the 3rd quarter earnings press release issued this afternoon for additional details. Beginning with top line results.

Speaker 5

Total revenue for the Q3 was $197,000,000 This consisted of DMD franchise revenue of $136,000,000 and other revenue of $61,000,000 Starting with the DMD franchise. Translarna net product revenue in the quarter was $69,000,000 with Emflaza net product revenue of $67,000,000 Moving to AVD. 3rd quarter global revenue of CHF 360,000,000, which equates To over US400 $1,000,000 was achieved by Roche, earning royalty revenue of $50,000,000 for PTC. As Matt mentioned, the 3rd quarter performance puts us in a strong position to achieve 2023 total revenue guidance Of $940,000,000 to $1,000,000,000 including an expected $100,000,000 milestones when Energia surpasses $1,500,000,000 in annual net sales. Non GAAP R and D expenses were $150,000,000 for the Q3 of 2023, Excluding $14,000,000 in non cash stock based compensation expense compared to $150,000,000 for the Q3 of 2022, excluding $15,000,000 in non cash stock based compensation expense.

Speaker 5

Non GAAP SG and A expenses Were $16,000,000 for the Q3 of 2023, excluding $13,000,000 in non cash stock based comp expense Compared to $67,000,000 for the Q3 of 2022, excluding $14,000,000 in non cash stock based compensation expense. Cash, cash equivalents and marketable securities totaled approximately $295,000,000 As of September 30, 2023, compared to $411,000,000 as of December 31, 2022. I will now turn the call over to the operator for Q and A. Operator?

Operator

Thank you. One moment for our first question. Our first question comes from the line of Eric Joseph of JPMorgan. Your line is open.

Speaker 6

Hi, good afternoon. Thanks for taking the question. Just a couple on PKU from us. Really, just around this regulatory path here, I guess, can you just clarify when the decision was made to pursue a 505(1) Pat, for sepsis after it over 505(2) and maybe what prompted that decision? And then I guess in electing to go with the 50 5b1, was it not clear the carcinogenicity study would be needed, would likely be a requirement?

Speaker 6

And really, ultimately, I guess, just Looking forward, what should give investors confidence that assuming that the carcinogenicity study Turns out nothing that the NDA submission and review cycles and other ones to be straightforward. Thank you.

Speaker 2

Thanks for the questions, Eric. So Let me just first start with a little bit about 505(1) versus 505(2). The 505(2) pathway is typically used For me too compounds where there's already been and there's an existing approval for the active ingredient in the compound for which one seeks approval. Alternatively, the 505(1) pathways for innovative therapies, which is much more appropriate for something like sepia terran, which while Its active ingredient is DH4, which is basically the active component of Kuvan. It has many factors that make it different, Which underlies the superior efficacy we've observed to date and why this is such a promising therapy.

Speaker 2

Since we initially wasn't thinking about the 505(2) pathway, that's where things were lined up when we acquired it. And after we did our own analysis and understanding of the Relative benefits of each pathway, it became clear that the 505(1) was much more appropriate. Now with the 505(2) pathway since here There is an active ingredient already approved. You can utilize the studies, not safety and efficacy studies, but other supportive studies like non clinical studies That were used to support that approval. With the 505(1) pathway, you don't have the ability to rely on those existing studies.

Speaker 2

The decision to switch was based on a couple of things. 1, C. P. Teran is quite differentiated in terms of its Efficacy profile from Kuvan. 2nd, if you go 505(2) pathway, the company's Product, the company whose product you refer 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 patent.

Speaker 2

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 innovative compound much more suited to the 505(1) pathway. We then obviously had interactions with the agency to understand what would be required under the 505(1) Pathway and that included things like juvenile toxicity and uproetox, all of which Studies will be conducted, including the NDA, no issues there. And then for carcinogenicity, what's typically required is that you Submit to the agency a weight of evidence request to request a waiver for carcinogenicity. Now obviously, we were quite confident in getting that waiver.

Speaker 2

One, there is no evidence of genotoxicity of cepiaterin. In the cepiaterin non clinical studies, the 6 month and 9 month studies, there was no evidence of secretarial related carcinogenicity, pre neoplastic lesions and neoplastic lesions. Furthermore, while we weren't referring to the Kuvan NDA, the clinical experience with Kuvan over many years clearly demonstrates There is no carcinogenicity risk associated with VH4. So we submitted all of that to the agency. Now the agency obviously came back and said That the 2 different there's 2 different carcinogen studies.

Speaker 2

1 is a 2 year rat study. They said, fine, do that post approval. No problem. But Since you're in the 505(1) pathway, they would want the 26 week mouse study to inform the label, In the label, they have to say whether or not there is a potential carcinogenicity risk. And while we were under 505(2) pathway, we could use the labeling In the Kuvan label, which referred to risk of adrenal tumors, which has never been seen 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.

Speaker 2

And since it's a standard part, would be considered a standard part of the 505(1) pathway, it would be something you would need to submit With the NDA. Now, I'll also say and address the other part of your question, in our discussions, they were it was Clearly stated that the safety and efficacy 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. Again, given the incredible strength of the efficacy data we have, the safety data we have, And obviously, far from ideal. The additional time you're going to have now is only going to build that dossier further with greater Length of exposure, greater ability to show more durability effect, the kinds of things we're seeing in the long term open label study.

Speaker 2

And obviously, we're going to have even more data showing C tolerance, we recently reported the latest update to C tolerance at the ATSIAM meeting in September, again showing that patients are able to tolerate Beyond the recommended daily allowance of protein and still have control of phenylalanine. So the strength of this data remains, it It is in no way impacted by the need to do this non clinical study. It is an unfortunate delay. We're going to continue discussions with the agency if we could submit The application is sooner, but the bottom line is this is a strong differentiated compound. The data we have to date, the studies we've done So there's no evidence of carcinogenicity risk according to the study reports we have, genotoxicity and the like.

Operator

Thank you. One moment please. Our next question comes from the line of Kristin Kluszka of Cantor Fitzgerald. Kristin Kluszka, your line is open.

Speaker 7

Hi, everyone. First, just wanted to congratulate you on the Royalty Pharma deal. And I had a question about Translarna, 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 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 8 years when they've given you the green light? Or will you be required to conduct Any type of work in the background?

Speaker 7

Thank you.

Speaker 2

Kristen, thank you very much for the question. So as we mentioned in our prepared comments, The previous procedure, there were 2 opinions. There's actually 2 procedures in 1. 1 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 2 opinions, but really get together.

Speaker 2

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 1 or both? Look, our priority here is to maintain make sure this drug stays on the market, stays available for the boys in Europe, when there's no other targeted therapies and non transplantation available. And we believe that best chance of doing that is to focus solely on maintenance of the conditional authorization for now. We also believe in a way That by not asking for a conversion to a full approval that the issues some of the issues they were used 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 data in Study 41, including in the ICT population where we have clear evidence of benefit over a number of different endpoints, As well as obviously the long term STRIDE data.

Speaker 2

So we really feel that by focusing this question on just renewal of the conditional authorization that we can provide the necessary evidence I can get this opinion from negative to positive. Now as you mentioned, what happens from the test as you asked 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 in STR1VE. While we've obviously Been able to show clear benefit in delaying time to loss of ambulation by 3.5 years in the most recent analysis and continue to show meaningful Multi year delay loss of pulmonary function as we continue to collect more data over time, there'll be even more patients informing the loss of ambulation now, Even more patients informing the pulmonary function analysis and hopefully ultimately cardiac function and mortality.

Speaker 2

So there's still a lot more meaningful data that Truly inform the long term benefit of TransAlta from Stride. There's also the possibility to talk about bolstering Stride either With additional analyses or a second registry, that's a possibility. 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 that the scientific experts gave in the scientific advice A portion of the procedure last time was that clinical studies for genetic directed therapies in DMD are really hard And really difficult to produce meaningful data. The experts have told CHMP 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.

Speaker 2

The short answer is, look, we'll have to collect additional data. We'll be Well positioned and quite honestly pleased to do so with the priority now to keep this therapy on the market in Europe and we believe by pursuing just the renewal of the condition

Speaker 7

Okay. Thanks. And just second part of that, I would imagine since you had the announcement that 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, And if they can be of any help ahead of this upcoming meeting and decision. Thanks again.

Speaker 7

Yes.

Speaker 2

Kristen, good question. I think needless to say that physicians and the patient community was Surprised, disappointed and quite honestly scared for the patients. I think this is the only therapy they have That is directed for nonsense mutation patients. 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 many have said they can't imagine Having to take patients off a drug that's safe and effective.

Speaker 2

The patients on their own have the ability on their own to reach out And let their voice be heard. I'm sure in many parts of Europe that will happen given the fear and concern they have. And I think similarly for the physician community, No want to speak up. Our sense here is that most people as we were never thought this fate 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.

Speaker 2

And importantly, as you say, share their story,

Operator

Thank you. One moment please. Our next question comes from the line of Sami Corwin of William Blair. Your line is open.

Speaker 7

Great. Thanks so much. On the topic of Translarna, 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 does 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.

Speaker 2

Yes, Sandy, thank you for the question. Again, I think the in the physicians we've spoken with, the first response was Clarifying and reconfirm that in no way that things change, patients can stay on the drug, they can lighten prescriptions and obviously everyone's going to do everything they can to Sure. Patients stay on therapies, but let me kick it over to Eric. I don't know if you want to give some more detail on prescriptions.

Speaker 8

Yes. Thanks for the question, Sami. First of all, we haven't actually seen an impact since CHMP has issued their opinion. In fact, we've seen physicians Who have actually 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.

Speaker 8

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. And we've been reaffirming that Translarna It's not only just available, it's available for existing patients, but it's also we've seen new prescriptions as well.

Speaker 8

The fundamentals that we see, Sami, 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 even patients that have gone from ambulatory to non ambulatory and 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 healthcare providers in other parts of the world and still continue to generate and see growth from Translarna in the quarter.

Speaker 8

So, the simple answer of course is that, we have not seen any discontinuations and the fundamentals remain strong. And we're as I mentioned earlier in my talk, we're not only very confident in what we did this quarter, We're very confident in how we'll finish 2023 and we've actually raised guidance and our DMD guidance is now $565,000,000 to 5.95 Which includes, Translarna growth in the 4th quarter and combined that would equal about 11% to 17% year over year growth For the DNB franchise compared to last year.

Speaker 7

Great. Thank you.

Operator

Thank you. One moment please. Our next question comes from the line of David Lebowitz Citi, your line is open.

Speaker 2

David Lebowood?

Speaker 9

Thank you for taking my question. When looking at the Translarna European sales, could you please Overseas 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?

Speaker 2

David, thank you for the question. Let me start with your second part first. As we've talked about in the past, many of our largest markets 5 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 the European authorization. In terms of revenue, we have In the past that while many years ago, Europe would have been the primary source of our TransAlarm revenue. We've done a lot of work over the past year Past years to diversify our business.

Speaker 2

I know Kylie, do you want to go into a little bit more detail about the breakdown of revenue?

Speaker 4

Yes, absolutely. As Matt was just saying, we spent Essential effort and time over 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 to total Translarna 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

Speaker 9

Sure. I mean, is there any way you can let us, I guess, 0 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?

Speaker 4

Yes. So 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 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% currently, You wouldn't expect that number to remain flat over the coming years.

Speaker 9

Got it. And with respect to expenses going forward, Is there any way you can give us, I guess, some level of bandwidth on what to expect for 2024 and beyond when The restructuring is in full place.

Speaker 2

Yes. So David, we announced the I revised our OpEx guidance previously to 8.10 to 8.60 and also we then announced the subsequent cuts and how that would have an impact of additionally another Approximately 20% in run rate 2024. Obviously, we'll give the updated OpEx guidance at JP Morgan in January.

Speaker 9

Thank you for taking my questions.

Operator

Thank you. One moment please. Our next question comes from the line of Kelly Hsieh of Jefferies. Your line is open.

Speaker 10

Hi. This is Yoon for Kelly. Thanks very much for taking the question. So the first question on Translarna. 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.

Speaker 10

And then on the pre BLA meeting for AADC deficiency, On the comparability, in terms of manufacturing, are there any specific assays that you have to develop before the meeting?

Speaker 2

Yes. Thank you very much for the question. So on your first question regarding the positive opinion, We're able to convert that to a positive opinion, the continued conditional marketing authorization in Europe. 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.

Speaker 2

And that specific obligation is typically It's a requirement to collect additional data to support the benefit risk profile of the therapy. So there's no timeline per se, but there will be a specific obligation that would require us 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 condition marketing authorization, as we've done for years, requires an 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 in STRIDE as well as benefit that we've seen in STRIDE.

Speaker 2

There are therapies that have been Have had conditional marketing authorization status for decade, 2 decades. So this would not be the first time that a therapy continued in the conditional frame for a bit more time. On your second question regarding the PDLA 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 Intent to use commercially and usually 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 the commercial process is Over a decade old. Those are clinical studies that were started in the early 2010s and there simply is not enough of that Your clinical supply available to provide the additional replicates and additional data that the agency wanted us to have To finalize the comparability analysis, we obviously had data across all the assays that we believe show that the process is comparable.

Speaker 2

We've asked for some additional analyses, It's a bit challenging to get that material given the age of the material. Now importantly, we're 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. So it is the commercial like material for which there was no comparability assay And what we're able to show in AADC, which is a genetic disease of dopamine deficiency, is that when we give the drug, we're able to measure increases in dopamine. Obviously, that's a reliable, quantifiable biomarker that's not only incredibly important to the disease cytology, but also logically We'll proceed the subsequent development of dopamine related motor function, which is exactly what we observed in the clinical study.

Speaker 2

So that fits squarely in the framework of accelerated approval. And I think everyone has seen lately in CBER, there has been increasing Interest, Peter Mark has talked about this ahead of CBER, of using the accelerated pathway for rare disease gene therapies as a way to quickly get these therapies Two patients. So we're looking forward to a pre BLA meeting in December. 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'd expect this to be a BIA shortly thereafter.

Operator

Thank you. One moment please. Our next question comes from the line of Brian Abrahams of RBC Capital Markets. Brian Abrahams, your line is open.

Speaker 11

Hey, good afternoon. Thanks for taking my questions. As you prepare for the MAA filing for ceftiaparin 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 U. S, 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?

Speaker 11

Will it 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.

Speaker 2

Thanks for the questions, Brian. So on the question regarding the NA in Europe, I think this is another example of how regulatory authorities Tend to look at things differently. The feedback we have gotten from Europe regarding carcinogenicity is they understand very well That the active metabolite for cephalterin is BH4 and They understand that BH4 and CPFTRN are both naturally occurring co factors. They understand the data we've collected to date in terms of carcinogenicity risk 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 Kuvan Health. For many years, There's a knowledge base that exists that there's no carcinogenicity risk associated with B4 used clinically for many years.

Speaker 2

So we don't believe the issue we have at FDA will be an issue with Europe for that region. So again, just Different authorities 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 twenty twenty four. On your question regarding the Type C meeting for Translarna, the purpose of the meeting is really to focus on the Evidence that we have, the many sources of evidence we have showing that not only there's clear evidence of benefit in In studies such as Study 41, but that could be confirmed in a number of ways, including meta analysis, the long term RAN-one STRIDE registry. And so really working constructively with the division to say what are the components we need and how do we formulate them in order to support We end the resubmission.

Speaker 2

As we typically do, once we have clarity in the outcome of the meeting, sometimes that can come from the meeting itself, sometimes that 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, not the least of which are the boys with non sex mutation DMD in the U. S. Who have waited years for therapy and then also The large number of boys in the U.

Speaker 2

S. Who've been on TransAlarmNet for a number of years and their participation in clinical studies and beyond, all of whom are quite Interested in ensuring that this truck can be available in the U. S. For them.

Speaker 11

It's really helpful. Thanks for that.

Operator

Thank you. One moment please. Our next question comes from the line of Colin Bristow of UBS, your line is open.

Speaker 12

Hey, good afternoon. Thanks for taking the questions. On the cepiaterin NDA filing time line, I'm just curious, why is the latter end of your guidance 3Q 2024? I'm curious, can you confirm whether the study has started? And it just seems like a sort of extreme upper bound of this Time line if this study is all that's needed.

Speaker 12

And then on the AADC, could you just give us a little more detail On why FDA thinks the comparability data is still not sufficient? And then what are you sort of hoping or what will be discussed The pre BLA meeting in December. Thank you.

Speaker 2

Thanks for the questions, 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 the study, get the slot at the CRO, get the animals in order, Get the doses confirmed, get the protocol set, get the protocol agreed upon and start the study. We expect to begin dosing in the study, have all those things ready and dosing that Study to start in December. That's a 6 month study. So by the clock that all the animals get dosed in December, the in life portion should be done in June.

Speaker 2

Once the end life portion is done in June, they then have to sacrifice the animals, both through the histological studies, all the histological analysis and write their 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 audited draft report, which is necessary for submission. So that's where you get the 3Q time bound from is merely the realities of to do a 26 week study takes more than 26 weeks and that's We wanted to give a quick picture of what we think could be the longest possible date or the latest possible time for that submission. Obviously, as we mentioned, the bank team received, We're able to work out something with the agency where perhaps we could submit those data during the day 120 safety review and late 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.

Speaker 2

And as we indicated in our discussions with them, they see 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 not we had very limited supply of the clinical 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 Conducting the commercial material, they wanted additional data points, a greater number of samples that we simply couldn't provide Due to limited supply. In terms of 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're going to present their integrated safety summary from all the studies that have been done, How are we going to present the efficacy data? How are we going to include other components of the regulatory studies in the package?

Speaker 2

They thought it would be very important to 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 So we believe the most prudent thing to do is to have that CLEBOLA meeting and then pending results be in a position to submit as quickly thereafter as possible.

Speaker 12

Great. Thank you for that.

Operator

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

Speaker 13

Question, in your discussions with the EMA on vatiquinone, what gives you confidence that it may accept Move FA for conditional market 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.

Speaker 2

Thanks, Jeff, for the question. So The frameworks in FDA, the EMEA site to differ and the discussions we're having with FDA are around the potential for accelerated approval based on upright Stability being an intermediate clinical endpoint. Obviously, upright stability, as we've talked about, is all the four sections of the mFARS, which The primary endpoint, the one 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, in future cataxia for ambulatory patients, the key thing for a therapy to do is to delay That time to loss of ambulation, delay loss of ambulation. And so to have an endpoint that can do it, we believe, meets that criteria for intermediate clinical endpoint.

Speaker 2

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 the analyses we have. And as you indicated, Could we provide some additional supportive analysis to Move FA, in particular the fact that we have a 6 month open label extension study during which all subjects are blinded, so that gives us an to look at changes in trajectory, for example, for the placebo conditions once we switched on to Aptiv. That's the U. S.

Speaker 2

In terms of Europe, The conditional marketing authorization, there's a number of criteria set out for a conditional marketing authorization. Do you have initial data that shows There's a favorable benefit risk of a therapy, are you being able to unmet medical need, getting is getting this therapy to patients sooner, potential public health benefits. And I think when you consider the ticlinone and the MOVE FA 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 NPAR score and there's a number of important sources of benefit in the move that they studied, not only in upright stability of the bolvar subscale also on fatigue, which is the number one symptom for patients. And then if you look at the Wellastat or safety profile of betikinol, particularly in pediatric patients, We can clearly demonstrate that this initial study has a favorable benefit risk profile.

Speaker 2

Obviously, it's unmet medical need not only Pediatric patients provision all approved therapies for FA in Europe for patients of any age. And obviously, given when you have a therapy that can potentially slow delay of loss of ambulation, That's an irreversible morbidity and those patients will therefore benefit from access to therapy sooner. The final point, Obviously, we know very well from the Translarna experience is to be able to demonstrate that you can collect more data on FA patients to support the Support the 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 for additional authorization and we look forward to discussions with the Great.

Speaker 2

Thank you.

Operator

Thank you. One moment please. Our next question comes from the line of Alexander Zaniak of Truist Securities. Your line is open.

Speaker 2

Hi. Thanks for taking my question. Congrats, first of all, on securing the royalty financing deal. That's great. Maybe 2 for me.

Speaker 2

1 on ceptiaparin, when might we see another cut of the OLE C tolerance data? And then one on Translarna, 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 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 Are you comfortable with sales or not? Thanks.

Speaker 2

Yes. Thanks for the questions, Alex. So first on the fee tolerance, As we shared, we gave an update on the C tolerance data at the SSI EM meeting in Israel in September. Those were 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 level of fee tolerance beyond the recommended daily allowance. And these are incredibly important data.

Speaker 2

As we said all along, The fee tolerance component is really not for regulatory purposes necessarily. We have the sufficient efficacy data for that and are 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 The tolerates are really quite important, one for differentiation is something KugaN was never able to demonstrate and for physician adoption and for payer discussions, particularly On the Translarna front, the look, again, we see the Ability to keep the conditional authorization has a big win, not only obviously for us, but really most importantly for the patients. I would turn it over to Kylie, if you want

Speaker 9

to comment Kylie on the what

Speaker 2

you think the global payer impact could be Fine. A conditional authorization?

Speaker 4

Yes. I think from a payer impact, I think it will be quite minimal, Alex. I think one of the The team has done an incredible job is with the conditional authorization that we've had over the last 9 years is being able to secure a favorable Pricing corridor and reimbursement, 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

Speaker 2

Definitely. Thanks for taking the questions.

Operator

Thank you. One moment, please. Our next question comes from the line of Joseph Schwartz of Leerink Partners. Your line is open.

Speaker 2

Great. Thanks very much. I was wondering if you could talk about your publication plans for the APHINITYCEPTIA APHTRO 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-five eighteen in PIVOT HD patients outside the U.

Speaker 2

S, so where do you stand on implementing that decision? Yes, absolutely. So maybe I'll take the I think let me take the second question first and then I'll let Kaj to answer the first question second. So on 518, so we as we talked about, we shared the results from the 5 10 milligram dose Groups, the 1st cohort of 33 patients in June, those data from our standpoint were 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 demonstrating a dose dependent lowering of pontucanet protein in the blood seeing the differential exposure of PTC-five eighteen in the CSF relative So plasma at that 10 milligram dose 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 lowering of Huntington mutant Huntington proteins in the brain, all of which was very, very important. And of course, the other key point is that we're doing all of the safety.

Speaker 2

The safety profile of the drug was quite strong in those 1st 12 weeks. We had no Hi, Jeremy. They had serious adverse events. There were no NFL spikes, all very, very important, particularly given concerns that were raised over other HCC lowering therapies that have drawbacks that we've talked a lot about in the past. We said based on those data, 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 Huntington protein levels 30% to 50%.

Speaker 2

And so with the decision with those early data, while we had the ability to go up to 20 milligrams, the DSMB has supported us Starting 20 milligram cohorts, the regulatory authorities and local ethics committees have approved us going to 2020. 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 510, because those very well may be sufficient To move forward, Geneseev, we haven't initiated those 20 milligram dosing yet. We're not sure we're going to need to and we want to better understand I know longer term biomarker effects of the current dose levels before revisiting that decision. Let me now turn it over to Kylie to answer your question around

Speaker 4

Yes. Thanks, Joe. We are absolutely getting the APHINITY study published in a peer reviewed journal, the team is working on that as we speak and is looking to target a high impact journal. And so the time lines for getting that published is obviously driven by the Journal of Choice. So we work this is work in progress.

Speaker 4

The team is moving through this and we expect it to be published During 2024, pending the journal chosen.

Speaker 2

Thank you.

Operator

Thank you. One moment, please. Our next question comes from the line of Gena Wang of Barclays. Your line is open.

Speaker 14

Hi. Thank you for taking my questions. So I do have, I think, Three quick questions. The first one is regarding the PKU program. Since initially was thinking about 505 2, is that because the lack of confidence of their IP position that this drug will be very different from Kuvan?

Speaker 14

That's the first question. And then related to how confident you are on the IP regarding this is a new composition of a matter? And then for the PIVOT HD, I don't know if I missed it. So have you mentioned Like exactly what kind of data you would need in order to remove FDA clinical hold? So based on I think in your prepared remarks, you did mention certain months of clinical safety data.

Speaker 14

When I look at the press release, it's a 6 months of clinical safety data demonstrates similar favorable safety profile could support 12 months dosing And what additional data that will require to can dose more than 12 months and what dose you can dose like beyond 10 milligram? So that's the second question. And a quickly last question regarding the Estrada in AADC. So if you are using current U. S.

Speaker 14

Data for accelerated approval, what additional study you will need to do in order to get a full approval in the future.

Speaker 2

Great. Thank you very much for the questions, Gina. The first question for Number 1, regarding PKU at Sensa. Look, I think that was really what more reflection of Sensa being 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 it's Not uncommon for a smaller company to think about the development path that way.

Speaker 2

I think from our standpoint, the It's very clear this is a highly differentiated therapy that is much more suited to the 505(1) pathway. Obviously, we're We're in a position to have the resources to do the necessary studies and not have to rely on another MDA and incur that risk Having to stay based on the launch of the therapy following approval. As we talked about, not only do we have a great deal of Confidence in how differentiated cepiaterin is and its ability to meet the persistent large unmet medical need for PKU patients. And as we've heard from physicians, including I'm going to go on a commercial deep dive this summer. Our desire for physicians to even switch patients who may be served to some extent We've been to see good care and because of what we've been able to show in terms of the large magnitude of clinical benefit.

Speaker 2

We've also talked about the P here, we obviously have orphan designation. We also have some potential patent extensions that we believe will extend the orphan exclusivity out Several years. Your second question on Pivot HD, as we had talked about in the past, in our discussions with the agency, they've said that Where they wanted to see additional evidence that we can dose at the dose levels we intended in PIVOT HD, those additional data Could take the form of non clinical data. Could 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.

Speaker 2

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 have them to FDA in order to fulfill that need of demonstrating that PTC-five eighteen can be demonstrated safely. So once we did these 3 months, we have the 12 week data, we took those data that we presented and obviously since all patients aren't Enrolled at the same time, we had some data beyond 12 weeks.

Speaker 2

We provided all of that to the agency and that was clinical data, including clinical laboratories, including the NFL levels That we had shared at the earnings adverse event reports, the lack of serious adverse events, the DSMB minutes, Letters from the DSMB 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 for 12 week dosing in 5 10 milligrams, 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 what they would like to see is data at the 6 month time point. So basically a little bit longer than 3 months to support the duration of dosing that we had proposed in PIVOT HD. So right now, quite simply doing the timing math is very possible by the time we got that data, sent it to the FDA, Got the review, got sites ready, up and running in the U.

Speaker 2

S. It might be that we'll be done with enrollment in PIVOT HD. We're Extremely close right now to completing enrollment in the Stage 2 patients and enrollment is little very quickly overall for the study, particularly after the gene data release When we were able to provide a lot of comfort to physicians and patients that unlike other Huntington's long therapies, we were able to 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.

Speaker 2

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 3 here and Be able to offer the opportunity for patients to participate in the PDC-five zero eight development. Your third question was regarding AUSTAZA and accelerated approval and confirmatory study. So we are using the existing clinical study 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.

Speaker 2

And 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. 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 a way that we've been able to show previously in the clinical studies of Apsdessa that were done previously, where over time we're able 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.

Speaker 4

Thank you.

Operator

Thank you. One moment please. Our next question comes from the line of Paul Choi of Goldman Sachs, your line is open.

Speaker 13

Good afternoon and thank you for taking our questions. Two questions for me. First On the commercial side, with the approval of vomerolone today, can you maybe just comment on how you're thinking about The impact to Enflaza and would you maybe consider pulling back on sales force 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 Intent to present in terms of your Pivot HD update next year. Should investors continue to expect Plasma Huntington updates and neurofilament changes or would you perhaps present some details on other endpoints Including clinical endpoints.

Speaker 13

Thank you very much.

Speaker 2

Thanks, Paul, for the question. Let me grab the second one first and then I'll turn the other question over To Eric or Kylie. So first, in terms of the 5.18 data. So the 12 month data that we Setting up a call that we would share in the 1st half of 2024, that will be data from the biomarker portion, right? We talked about PIVOT It's being a 12 month placebo controlled study in 2 parts.

Speaker 2

The first part, the 12 week focuses on pharmacodynamic and pharmacokinetics as well as safety. And then in that second portion at the 12 month time point, we would have data, further data on neurofilament levels now, less about safety, but maybe more about recording, Treatment benefit, CSF, mutant Huntington protein levels, volumetric changes on MRI. We also will have some Clinical data at that time, which are not main endpoints at the 12 months, but obviously we're collecting this data. I think We will certainly share the biomarker data, share what clinical data we have with the obvious caveat that even the 12 months, it's very hard I think it had interpretable clinical effect on things like the UHD RS scale or even The total motor score or single digit modalities test just given just the rate of progression in the disease And the sensitivity of those instruments to change over a short period of time. So the answers will have those data that being focused will be the biomarker data, obviously, continuing safety.

Speaker 2

We will also, when ready, have data on the additional subjects who are, I think, going to hit the 12 week time point and then ultimately 12 month time point. We haven't given a timeline for that. The timeline we've 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 the 12 week data. So in terms of your question on vamorilant and Emflaza, Alex, do you want to take that?

Speaker 8

Yes. Thanks for the question, Paul. I think with Emflaza, we know that Emflaza has been currently on the market for more than 6 years. It is currently the standard of care. We've established Emflaza as the standard of care because there's been a number of publications and there's also a lot of Scientific evidence that is actually preserved greater motor function than prednisone.

Speaker 8

And we know that the data has Continually support of 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. We understand that the community wants options, but we know that right now we have been focused 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 Emflaza than any other DMD treatment. 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.

Speaker 8

So while the Amoralone is an additional option, we also know that clinically it hasn't been differentiated like Emflaza And that we have a very strong and loyal customer base.

Speaker 13

Okay. Thank you for taking our questions.

Operator

Thank you. One moment please. Our next question comes from the line of Tazeen Ahmad Bank of America, your line is open.

Speaker 7

Okay. Thanks so much for taking my questions. A few quick ones from me, if I may. So To keep with the topic of the approval 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 Emflaza next year and beyond. And then second question, As it relates to, sepiastorin milestone agreements with Stensa, I believe you've already paid $30,000,000 for completing Phase III enrollment.

Speaker 7

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 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.

Speaker 2

Sure. Thanks for the question, Celine. Let me take the third one and then I'll Pass to the team for the other 2. So 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 have been therapies that have had conditional authorization for many, many years, even beyond a decade.

Speaker 2

So 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. 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, 1, 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, the safety story on Transvaro is quite Robust, and what we've clearly been able to show that is a therapy that is safe for the long term just as we've been able to show the benefit long term Through the STRIDE registry. In terms of your questions on Emflaza strategy and as well as milestone payments, Kylie, do you want Take Emflaza?

Speaker 4

Yes, absolutely. So on the Emflaza front, Tazeen, I think What we continue to do is see Emflaza as a standard of care across all DMD patients. And we have been able to Straight the benefit of Emflaza in a number of different milestones and we continue to believe 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 preserve the business. And again, that doesn't shift based on the Memorial loan approval.

Speaker 4

We have good strong relationships across our customer base and with patient advocacy groups, and we will continue to leverage On the milestone question,

Speaker 7

Are you able to provide any color on the specific strategies that you're going to use for Emflaza?

Speaker 4

Yes, absolutely. So there's 4 main pillars that we're focused on with regards to protecting the business. So one is ensuring that we have And 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 dispense is written program That the team is working on as we speak.

Speaker 7

Okay. Thank you.

Speaker 5

Thank you.

Speaker 2

And

Speaker 14

then in your

Speaker 4

just to answer the last question, Tazeen, around the milestones for Sensus. So you are Correct. We obviously had paid the $30,000,000 in equity in 2023. We don't expect any additional milestones For SENSAR in 2023, but we had shared in the Q that we expect $65,000,000 worth of Our regulatory success based milestone for SENSOR in the next 12 months, so in 2024 and we haven't broken out the specifics around that.

Operator

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

Speaker 2

Great. Thank you. Thank you all for joining the call today. We look forward to a strong closeout in 2023 as we 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. Thank you all again and have a good evening.

Operator

Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day.

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Earnings Conference Call
PTC Therapeutics Q3 2023
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