Ptc Therapeutics, Inc. Q3 FY2020 Earnings Call

Ladies and gentlemen, thank you for standing by and welcome to PTC Therapeutics Third Quarter Corporate Update and Financial Results Call. At this time all participants are in listen-only mode. I would now like to hand the conference over to your speaker Miss Lisa Hayes, Vice President of investor relations. Please go ahead, ma'am.

Good afternoon. Thank you for joining us to discuss the PTC Therapeutics third quarter 2020 corporate update and financial results. Joining me on today's call are our chief executive officer, Stuart Peltz; our chief financial officer, Emily Hill; our chief development officer, Matthew Klein; and our Chief Business Officer, Eric Pauwels. Before we start, let me remind you that today's call will include forward-looking statements based on current expectations. Please take a moment to review the slide posted on our Investor Relations website in conjunction with the call, which contains our forward-looking statements. Our actual results could materially differ from these forward-looking statements as any such risks can materially and adversely affect our business and results of operation. For a detailed description of applicable risks and uncertainties, we encourage you to review the company's most recent quarterly report Form 10-Q and annual report 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 is available in today's earnings release. With that, let me pass the call over to our CEO, Stuart Peltz.

Thanks, Lisa. And thank you for joining the call today. We have made significant progress this quarter with our R&D pipeline as well as our commercial business, so we've continued growth. We've built PTC to create value for all stakeholders by discovering and developing novel therapeutics for patients with medical needs, and increasing revenue by bringing these products to patients through our global commercial engine. Our strong cash position allows us to continue to deliver on the promise of a pipeline to bring more therapies to patients and to grow further the company. Let me go through some of the achievements this quarter. Starting with Evrysdi for the treatment of SMA. We are very excited about the strong launch of Evrysdi in the U.S., not only for its efficacy and safety profile, but also its convenience as a first at-home orally administered treatment for SMA patients two months and older. The ease of administration and access to a home-delivered therapy is particularly important to patients, especially during the COVID-19 pandemic. Evrysdi showed clinically meaningful improvement in motor function and developmental milestone achievement across a broad range of ages and functional abilities of SMA patients. The Evrysdi launch has had a very positive response from physicians, payers and the whole SMA community. As a reminder, there is high unmet medical need in the SMA community with patients who are treatment-naive and patients who have concerns with durability or the administration burden of current therapies. Our partner Roche has reported that two-thirds of the initial patients on Evrysdi were previously treated with Spinraza or a similar therapy. We are seeing uptake across all types of SMA patients. To date, 25% of patients treated have been type one, with the remaining 75% classified as type two and three. There continues to be excellent progress in bringing Evrysdi to SMA patients globally, with approvals already obtained in Brazil, Ukraine and Chile. In addition, an NDA for Evrysdi was filed in Japan, which triggered a $7.5 million milestone payment to PTC. Evrysdi is also under review with the FDA, with a decision expected in April 2021. We appreciate the strong effort made by our partner Roche. Let me comment on our commercial progress this quarter. Across our commercial portfolio, we saw increased patient uptake and associated revenue. Our net revenue increased 66% year-over-year and net product revenue increased 16%. We're very pleased that we've continued to grow globally despite the COVID-19 challenges, including securing a purchase agreement with Brazil's Ministry of Health for Translarna. You can see we've made considerable progress on our commercial products, but I'm equally excited about the progress we've made in R&D programs and the value they will create. Let's start with our splicing platform. PTC was the pioneer in discovering and developing a selective small molecule for splicing with Evrysdi as the first product approved from this platform. We have a number of exciting polio splicing programs that are moving forward. Our plan is to create value by continually developing these products and to bring them to patients globally. After Evrysdi, the next most advanced compound from our splicing platform is PTC 518, which has been developed for Huntington's disease. I'm excited to report that PTC 518 will enter the clinic this quarter. Analogous to how we discovered Evrysdi, PTC 518 was constructed to be an orally bioavailable molecule that distributes to all tissues in the body. It is very effective in crossing the blood-brain barrier and is highly selective. We've learned that these elements of selectivity, biodistribution and pharmaceutical properties are critical to successfully developing differentiated splicing molecules. The Phase 1 trial will be performed in healthy volunteers, with results expected in the first half of next year. Similar to the SMA program, and because there was a direct correlation of blood and brain levels in preclinical studies, the results from the Phase 1 healthy volunteer study should allow us to demonstrate targeted engagement and proof of concept of the reduction of HTT mRNA. This will allow us to select doses for the subsequent study in Huntington's disease patients. Now, let me turn the attention to our late-stage clinical programs. From our binary platform, we recently announced that enrollment has begun in a registration-directed trial called Mighty with our compound Vatiquinone for the treatment of mitochondrial epilepsy. As a reminder, about half of all children with inherited mitochondrial disease suffer from refractory seizures. These seizures result from dysregulation of the electron transfer process, leading to oxidative stress and inflammation, particularly targeting the enzyme 15-lipoxygenase, which is a key regulator of the neural inflammation and oxidative stress response. We estimate that there are approximately 12,000 commercially addressable mitochondrial epilepsy patients globally. An additional registration-directed trial with Vatiquinone is also planned to initiate by year-end. FA disease pathology results from high levels of oxidative stress, which induces neural inflammation, known to be important in FA disease pathology and progression. Our program specifically aims to modulate these pathways to reduce inflammation. Previous Phase 2 results showed that our approach could alter the course of FA disease, and we are excited to initiate the registration-directed study this year. Our third late-stage program is PTC923 for the treatment of PKU; we expect to initiate a pivotal Phase 3 study in mid-2021. With an estimated 20,000 PKU patients in the U.S. alone, there continues to be high medical need, as the majority did not initially respond or are not adequately controlled on Kuvan. Results from previous studies demonstrated that approximately 50% more patients responded to PTC923 when compared to Kuvan. Furthermore, these studies demonstrated that PTC923 resulted in more than double the reduction in blood phenylalanine levels compared to Kuvan. We are currently conducting non-clinical studies to support the long-term dosing for the planned Phase 3 trial. I want to turn now to the Translarna dystrophin study, study 045. You may recall that this was the outcome of our discussion with the FDA about potentially securing accelerated approval for Translarna in the U.S., allowing these patients to receive the therapy. I'm very happy to report that with a very strong effort by the team, despite the challenges of COVID-19, the final muscle biopsy from the patient in study 045 has just been completed. Preparation and analysis of the samples according to our protocol are now underway, and we look forward to sharing top-line data in the first quarter of 2021. We are excited that PTC has the potential to accelerate access to Translarna for U.S. patients. We are also continuing to make progress with our gene therapy platform. The gene therapy manufacturing facility in Hopewell is occupied and ready for production. As we have discussed previously, our most advanced program is to treat AADC deficiency, where we have observed transformational and durable results in AADC deficient patients that have been treated for almost a decade. An application has been submitted and is under review by the CHMP. Due to COVID-19 related delays, PTC now expects the CHMP final opinion for AADC deficiency application in the first half of 2021. For the VLA, PTC expects submission to the FDA will also be in the first half of 2021. We also recently initiated a phase 2/3 trial for PTC299 for COVID-19 called Fight-19. We recognize that PTC299 has a unique dual mechanism that is potentially effective against both stages of the viral infection, including viral replication and an enhanced immune response. The combination of the mechanism, the preclinical data, the well-established safety profile, and the compound's oral bioavailability gives us great confidence in PTC299's potential as a treatment for COVID-19. We anticipate reporting top-line results in the first half of 2021. With that, I'll now turn the call over to Matt Klein for key updates in our clinical program, Matt.

Thank you, Stu. We've had a very productive quarter as we continue to advance innovative therapies from all of our R&D platforms. Our development teams have been working tirelessly throughout this COVID-19 pandemic to minimize the impact on ongoing trials and ensure that our next set of trials initiates without delay. As Stu mentioned, we are excited to report that we have now completed the final muscle biopsies for the dystrophin study. Analysis of the biopsy samples is now underway, and in accordance with the protocol, we remain blinded to study results until all biopsy analyses are completed. As a reminder, the primary outcome of this study is an increase in dystrophin expression over baseline, as assessed by an electrochemiluminescence assay that we developed in collaboration with the FDA. We expect to have top-line data from the over five dystrophin study in Q1 2021. Turning to our bioheat platform, we have initiated enrollment in the Mighty trial, the registration-directed trial of Vatiquinone in children with mitochondrial epilepsy. This phase 2/3 trial will enroll approximately 60 children with genetically confirmed mitochondrial disease and associated refractory seizures. The study design includes a one-to-one front-end period to ensure that all eligible subjects have a minimum number of seizures, followed by a six-month parallel arm phase in which subjects will receive either Vatiquinone or a placebo. The primary outcome of the trial is reduction in observed motor seizures, with secondary outcomes related to other aspects of seizure burden, as well as disease morbidity. The FDA has granted Vatiquinone orphan designation and rare pediatric designation for the treatment of mitochondrial epilepsy. The phase 3 Vatiquinone Friedrich Ataxia trial remains on schedule to initiate enrollment by year-end. This trial will enroll approximately 110 children and young adults with Friedrich Ataxia. The study design includes an 18-month parallel arm placebo-controlled phase, during which subjects will receive either Vatiquinone or a placebo. Primary endpoints for this study include a modified Friedrich Ataxia rating scale, with key secondary endpoints assessing ambulation and activities of daily living. This endpoint strategy was developed in collaboration with both the FDA and EMA. There are approximately 25,000 patients worldwide with Friedrich Ataxia. The second compound from our Bioheat platform, PTC857, has completed the phase 1 single ascending dose study as planned, and we expect to complete dosing in the MAD study by year-end 2020. Turning to our splicing platform, the PTC518 Huntington disease program remains on schedule with the phase 1 trial in healthy volunteers set to initiate this quarter. This phase 1 study includes both single and multiple ascending dose regimens to inform safety and pharmacologic parameters, as well as to guide dose selection for subsequent registration trials. Importantly, we're also planning to measure HTT mRNA levels in healthy volunteers to gain early proof of splicing mechanism, as was done in the SMA development program. We expect to have data from the phase 1 PTC518 study in the first half of 2021. Next, I'll provide an update on our PTC923 PKU program. We have initiated the long-term toxicology study needed to support the initiation of the phase 3 PKU trial that is scheduled to begin in mid-2021. This registration-directed trial will be a double-blind, placebo-controlled study that will include both children and adults with PKU. PTC923 is an oral formulation of synthetic, highly bioavailable precursor to BH4, the critical cofactor for phenylalanine hydroxylase, the enzyme that is effective in PKU. There are an estimated 50,000 PKU patients globally and 20,000 patients in the U.S., as Stu mentioned, there remains a significant unmet medical need for PKU patients. Turning to our gene therapy platform, through the COVID-19 related delays, PTC expects the final CHMP opinion on the AADC MA in the first half of 2021. The treatment procedures for the AADC deficiency patients with commercial tangler will be completed by year-end 2020, and the submission of the BLA to the FDA is expected in the first half of 2021. Finally, I want to provide an update on our Fight-19 trial. This study of PTC299, our orally bioavailable DHODH inhibitor being developed for the treatment of COVID-19, targets both key aspects of COVID-19 viral replication and the cytokine storm leading to lung disease. The trial consists of two stages with a planned interim analysis focused on safety at the completion of stage one. Enrollment is ongoing and remains on schedule to complete the first stage of the trial by year-end, and the second stage in H1 2021. I'll now pass the call over to Eric to provide a commercial update.

Thanks, Matt. Our customer-facing team at PTC delivered a strong quarter across the franchise with 16% growth year-over-year from our inline commercial products. We continue to accelerate growth within Emflaza, with product revenues increasing 68% year-over-year, and we continue to see newly prescribed patients and a reduction in the time from prescription to commercially reimbursed therapy. Also, some U.S. payers have lenient access restrictions to Emflaza, and importantly, the current base of DMD patients have maintained high compliance, with very few patient discontinuations, demonstrating the long-term therapeutic benefits of Emflaza. We continue bringing awareness to the importance of Emflaza as the standard of care for all DMD patients, with compelling real-world evidence demonstrating clinical benefit over practical treatment. Translarna continues to exceed our expectations in all regions outside of Brazil, where we were impacted by the timing of a group purchase order. We are pleased that in October, we entered a purchase agreement with Brazil's Ministry of Health to supply Translarna for both new and existing patients. The PTC Brazil team, DMD advocacy groups, and key opinion leaders all worked together to raise awareness of this important therapy, and we were ultimately successful in securing the order with Brazil's Minister of Health, ensuring continuity of treatment for DMD patients. This order is important, given the governmental administrative delays in Brazil, which has been exceptionally hard hit by the pandemic. The agreement specifies two shipments, one of which was received this quarter, and the subsequent one is expected in the first half of 2021. Now switching to Tegsedi; we continue to engage in pricing discussions for Tegsedi in Brazil and expect to finalize the public price by the end of the year. For both Tegsedi and Waylivra, we continue to engage in patient-finding in Latin America and are seeing success in these programs. We also continue to engage in early access programs in Latin America, as we await a decision on our Waylivra filing in Brazil. Now moving on to AADC; we continue to aggressively pursue patient-finding activities in preparation for potential launches in Europe next year. We have expanded our geographical reach to over 17 countries and have implemented 60 screening programs focused on enriched high-risk populations, particularly in cerebral palsy and epilepsy clinics. New programs, such as PTC Pinpoint, were launched; it is a single source that healthcare providers can access to screen potential AADC patients. These targeted genetic panels are provided at no cost. We're also adapting to local country needs by leveraging local diagnostic labs in key markets. Lastly, we are partnering with key Centers of Excellence globally to develop algorithms to execute patient finding against existing high-risk patient databases. We are also actively working with these key treatment centers to ensure that they are ready to treat AADC patients. In addition, we accelerated our digital presence with healthcare professionals through continued virtual masterclasses and supported AADC Awareness Day, along with informational content at ABC Family Network.com. These initiatives have proven useful in education and awareness about AADC, facilitating earlier diagnosis of patients. I will now turn the call over to Emily.

Thanks, Eric. PTC continues to deliver strong growth in our business while maintaining a robust balance sheet. As Stu shared, we are very pleased with the multiple international approvals of Evrysdi and the strong launch results. In the third quarter, we received a total of $35 million in milestones, along with the first commercial sale in the U.S. and the filing of the MAA with the EMA. Additionally, in the fourth quarter, we received $7.5 million from Roche for the CMA Japan submission. On October 15, Roche reported initial overseas sales of approximately 8 million Swiss francs. As a reminder, PTC retains approximately 57% of Evrysdi royalties until royalty pharma receives a return of $1.3 billion, after which 100% of the royalties revert to PTC. Now, I will highlight the third quarter 2020 financial results, which are summarized in the press release issued earlier today. Starting with our top-line results, we reported $118.4 million in total revenues in the third quarter of 2020, a 66% increase year-over-year. This includes $82.7 million of net product revenue and $35.7 million of collaboration and royalty revenue. Emflaza and Translarna continued to show growth, with the exception of the delay in timing of the Brazil order for Translarna. We are pleased that we have now secured that order. As Eric mentioned, the first segment of the order was received in the fourth quarter. Translarna net product revenues were $43.4 million for the quarter compared to $48.3 million in the third quarter of 2019. Again, the delay of the Brazil group purchase orders was the primary driver of this year-over-year decrease. Translarna continues to exceed our expectations outside of Brazil, and we are seeing continued global growth. For Emflaza, we reported net product revenues of $38.5 million for the third quarter of 2020 compared to $22.9 million reported for the third quarter of 2019. Growth in net product sales is driven by new patient prescriptions and continued operational improvements and efficiencies in our commercial business. Non-GAAP R&D expenses were $83.8 million for the third quarter of 2020, excluding $9.2 million in non-cash stock-based compensation expense, compared to $58.1 million for the third quarter of 2019, excluding $5 million in non-cash stock-based compensation expense. This year-over-year increase in R&D expenses reflects costs associated with advancing the gene therapy and bioheat platform, increased investment in research programs, and the advancement of the clinical pipeline. Non-GAAP SG&A expenses were $50.2 million for the third quarter of 2020, excluding $7.6 million in non-cash stock-based compensation expense, compared to $43.8 million for the third quarter of 2019, excluding $5.5 million in non-cash stock-based compensation expense. The increase in SG&A was due to continued investment in our commercial activities and manufacturing operations to expand our portfolio. Net loss was $69.7 million for the third quarter of 2020 compared to a net loss of $60 million for the third quarter of 2019. Cash, cash equivalents, and marketable securities totaled approximately $1.14 billion as of September 30, 2020, compared to $686.6 million as of December 31, 2019. This balance includes the $650 million in cash received by PTC in July upon the closing of the royalty pharma monetization deal. I will now hand the call over to the operator to start the question and answer section. Operator.

First question comes from Eric Joseph with JP Morgan. Your line is open.

Hi, good evening. You can hear me? Thanks for taking the questions. I just have a couple on PTC518 for Huntington's if I could. First, could you I guess, confirm that you filed the IND at this point? And I'm just also wondering, based on your dose-ranging findings studies what sense do you have right now of sort of the starting? What's the biologically effective dose might be in humans? And do you have a sense of how many dose cohorts you would anticipate escalating through in the phase 1 setting?

Sure. Maybe we'll start with the Huntington, right. So we're actually pretty excited about this. It'll be the first in human study of PTC 518, which is a splicing molecule that reduces the level of both the Huntington messenger RNA and Huntington protein. We've shown that it's the only available molecule that passes the blood-brain barrier and effectively reduces those levels. To that extent, we've shown that the levels observed in blood correlate with levels seen in the brain. So we feel pretty good that by being able to look at the PK levels within the healthy volunteers, we'll be able to identify the exposures that we want to achieve in patients. I'll let Matt talk a little bit about the phase 1 study for PTC 518.

Hi, Matt here. So we are on track to start the phase 1 before the end of the year. We are conducting it outside of the U.S., so there was a CTA obtained, and all the regulatory and ethics documents needed for approval have been successfully completed. We're very excited about having this opportunity to gather important proof of splicing mechanism in the phase 1 study of healthy volunteers, analogous to what we did with the SMA development program.

Got it. And as far as tracking or collecting samples in the periphery to look at mRNA downregulation of Huntington, is that something you expect to be tracking as early as the single ascending dose portion? Or would that happen more on the multiple ascending dose portion of that?

The nice thing about the design of this trial is that we will look for changes in both the single ascending dose as well as the multiple-dose phases. And we'll share relevant data as it becomes available.

Our next question comes from Danielle Brill with Raymond James. Your line is open.

Hi, guys. Good afternoon. Thanks so much for the question. So I guess a couple first, I'd be curious to hear what your thoughts were on the Scholar Rock data and SMA that were announced this week? And do you have any thoughts on how that might ultimately fit into the treatment landscape in the long term? And then a couple of follow up on your mitochondrial epilepsy trial?

Sure, obviously, when you think about the underlying cause of the disease, like in SMA, the original plan really treats the underlying cause and produces the amount of protein, which is quite important. We've seen that it helps SMA patients achieve developmental milestones and functional improvements. Now, when you think about other things that could be improved in terms of therapy, combination therapies that can help muscle growth and degeneration, in concert with SMA protein therapeutics can also be quite useful. So, we're excited about those developments and will continue to consider what are the next steps in terms of our program for the benefit of patients.

Understood. Thanks for that. And then, just now that the mitochondrial epilepsy trial is up and enrolling, do you have any rough idea of what timelines might look like for enrollment? And can you provide a little more color? Just remind us as to what you saw in the expanded access program, in terms of seizure benefits that gave you confidence in this indication? Thanks.

Sure. So just to remind everybody, we're doing a mitochondrial epilepsy refractory epilepsy trial. This trial is aimed to reduce the effects of oxidative stress and inflammation due to zebrafish responses. We have a unique 15-lipoxygenase inhibitor that is a key regulator and controlling these aspects. We have certainly early data showing that this compound has shown improvements in seizure frequency and other qualities. We think the enrollment could be completed by the end of 2022.

Yeah, absolutely. Danielle, thanks for the question. As Stuart mentioned, we're expecting data by the end of 2022. We're working closely with patient foundations and networks to have study sites enrolled as efficiently as possible. Additionally, we’ve incorporated remote assessments into our protocol to ensure minimal impact from COVID.

Great, thanks so much, Matt. For all those details, appreciate it.

Our next question comes from an unidentified analyst with Bank of America. Your line is open.

Hi, good evening, thanks for taking my questions. Wanted to get a little bit of color if I could about what our expectations should be for the Translarna data? You know, how much dystrophin production do you think is needed? Have you had any preliminary discussions with the agency on this point? And if they do give you the go ahead, can you talk us through timelines for what would need to happen in order for you to get a formal approval for the drug in the U.S.?

Sure. So we're very excited that we were able to complete this trial and get all 20 patient samples to generate the data. We have discussed with the FDA that we need to show a statistically significant increase in dystrophin levels over baseline. Based on our findings, if we meet this threshold, we expect to pursue accelerated approval in the U.S. We will analyze the data and, once it’s finalized, submit the NDA in the first half of the year.

Okay. And then of course on AADC, how is the patient identification process going for that indication? And can you give us a little bit of color on what the rate-limiting factors are right now to get the BLA?

Eric, do you want to go through a little bit on the patient identification work that you and your team are doing?

Sure. Hi, we've been actively working to identify patients for AADC, and this is an ultra-rare disease with approximately 5,000 patients worldwide. We've actually increased patient education and have launched a number of initiatives, including the masterclass program with healthcare providers. We've expanded our geographical reach to over 17 countries, and we’ve implemented 60 screening programs focused on high-risk patients.

And you're about to give us an update on how many have actually been identified, I think you have started to in the early stages?

We continue to focus on identifying around 300 or more addressable patients. We are looking globally, where there is access to high-cost rare disease medicines. We want to ensure these patients are ready by the time we have a first commercial launch.

Our next question comes from Vincent Chin with Bernstein. Your line is open.

Thank you very much for taking my questions and congrats on your progress. A couple of them; one on PTC 518 and then one on the AADC gene therapy. So starting with PTC 518, I was wondering if you could provide us with some additional color on the initial trial in healthy volunteers, specifically about the endpoints of the study beyond peripheral Huntington knockdown? What level peripheral Huntington knockdown you're looking for? And how do you measure it? And I guess, just timing-wise, what's your kind of thinking for when you would have readouts to support moving into interventions?

Yes, sure. We are focused on measuring both the Huntington protein and mRNA levels in the blood and determining how those correlate with levels in the brain. Our goal is to demonstrate a clear reduction of approximately 50% in Huntington levels, based on preclinical data. The phase 1 study is designed to guide dosing for subsequent registration trials, and we plan to have data from the phase 1 study in the first half of 2021.

I see. And then maybe a second one on the AADC gene therapy. So if there's a delay in the CHMP measures related to COVID, can you provide a little color on the questions from the EMA, and how they compare to what the FDA has asked?

Yes, you're right. And of course, we're pushing forward. There have been standard questions that arose during regulatory review, asking for additional details around some of our assays and other aspects of the data. The key timing issue was also due to contract organizations working on COVID-related activities, which has caused some delays.

Very helpful. Thank you very much and congrats again on all the progress.

Our next question comes from an unidentified analyst. Your line is open.

Hi, thanks for taking the questions. I'm curious about the controlled, blinded study for the initial trial in Huntington's, which was suggested by the FDA. Can you share your thoughts on why a controlled study is not being done for earlier approval? Also, what are your thoughts on the timeline for the AADC trial?

Sure. The phase 1 study will indeed be a placebo-controlled trial. The advantage of starting with healthy volunteers is we can quickly gauge the safety and efficacy without the variability that comes from treating patients with the disease. This initial study will help us define the optimal dosing to bring to patient populations.

Okay, great. Thank you.

Our next question comes from Alethia Young with Cantor. Your line is now open.

Hi. This is Li on for Alethia. Thanks for taking the call. I just want to follow up on AADC; curious about your perspective on the launch activity, especially in Europe. Are the early trends supporting your confidence in the product? And I have a follow-up.

Sure. I think in terms of our efforts to get ready for launch, there's a lot happening. Eric and his team have worked hard on this front.

Yes, definitely. We feel very confident about AADC. We have activated key sites in Europe and made significant adaptations to local activities to ensure that screening is efficient and effective. We are well-positioned for the launch in these markets.

Got it, that's helpful. And then on the U.S. dystrophin study; we are starting to see the regulatory environment become a bit more conservative. Do you think that dystrophin will still be an approvable endpoint? Or do you think the FDA might want to see functional data as well?

Our discussions with the FDA have offered us a clear understanding. The key metric is that dystrophin levels need to be statistically significant over baseline. If we can show that alongside robust clinical and safety data, we believe we can pursue accelerated approval.

Thank you very much.

Thank you. Our next question comes from Joel Beatty with Citi. Your line is now open.

Hi, thanks for taking the questions. The first one is on Translarna in Brazil. Could you characterize how the pricing and volume compares to the previous bulk orders from Brazil?

Yes, sure. The Brazil team has done an extraordinary job dealing with challenges. We worked closely with advocacy groups and key opinion leaders to ensure patients remain in treatment, which resulted in a substantial order. While specifics are hard to disclose, we are pleased that we've secured orders that cover not just existing patients but also new patients that have been diagnosed.

Thanks for that one. And one other question on AADC. Can you help characterize what needs to be completed between now and the NDA filing? And part of the reason I ask is that it seems like recently, there's some hope that the filing could be by the end of this year, and now that seems to be in the first half of next year.

Sure, I'd be happy to provide more detail. The ongoing impact of the pandemic has delayed some procedures, which are now rescheduled for the fourth quarter. We're also being meticulous in gathering the necessary data to align with the FDA regarding our submission strategy.

Hi there. Thank you for taking my questions. On a vertical note in Friedrich ataxia, is there a reduction in the FAR Score that physicians highlight as clinically meaningful around that 72 week timeframe that you're looking at, and are you making consideration regarding patient enrollment depending on disease severity?

Yes. The feedback we received from physicians suggests that improvements are indeed clinically meaningful, and we will be considering severity during enrollment.

Great, thank you. And the second part was just on the IND for the Friedrich ataxia gene therapy. Does bringing Hopewell online give more clarity on when that can be submitted?

Yes, we're making good progress on that front, and we’ll be able to provide a more precise update on timing soon.

Thanks for taking the question. Just a follow up on some of the comments made on the dystrophin study. What kind of delta versus background do you expect for the study?

We need to show a statistically significant improvement over baseline to pursue approval. Our assay development has focused on high sensitivity to capture these levels accurately.

Great. And on the commercial franchise, obviously, COVID is spiking again going into Q4.

Despite challenges, we're seeing continued growth for Emflaza and great performance from our portfolio overall. Emflaza remains a strong therapeutic option, and we believe we'll see sustained growth through to Q4.

I appreciate the additional color. Thank you.

Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is now open.

Hi, this is Steve, I'm for Brian Abrahams. Thank you for taking my question. On PTC 518, you touched on this. But do you anticipate the one-to-one blood-brain diffusion ratio will extend to deep brain structures? And given the progressive nature of Huntington's, how early do you think you'll have to start treating patients to see clinical gains?

Yes, the design of our drug allows for good distribution within all tissues and effectively within the brain. We believe treating patients earlier will yield the best outcomes, although timelines are difficult to determine.

Our next question comes from Gina Wang with Barclays. Your line is open.

I think it's settling our questions. This is David on for Gina. On CHMP opinion, will be in the first half of next year. What has been the reimbursement discussion with payers? What's the current consideration for pricing?

We emphasize the high unmet need for AADC treatment and the durability of our results. Pricing will reflect those factors, as well as considerations for reimbursement in different regions.

Got it, that's helpful. So just on the PK profile of the drug, what's the pure burden like, and can you provide some more color on the half-life, Tmax and also any effect?

Yes, the pharmacokinetics of our molecules are well understood, and we expect favorable absorption and distribution in human studies. Our studies suggest a half-life that allows effective dosing schedules for optimal therapies.

I'd like to turn the call back over to Stuart Peltz for closing remarks.

Thank you all for calling in today. Despite the challenges presented by the COVID pandemic, I'm proud of how our team has performed. We think about the approval process as the culmination of many years of discovery and development by our teams. We're excited about what lies ahead for PTC and all the patients we serve. We look forward to keeping everyone updated on our progress in the coming months.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.