Ladies and gentlemen, thank you for standing by, and welcome to the PTC Therapeutics Second Quarter 2020 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen only mode. I will now turn the conference over to your host, Mr. Alice King, Head of Investor Relations at PTC. Sir, please go ahead.
Thank you. Good afternoon and thank you for joining us to discuss the BTC Therapeutics second quarter 2020 corporate updates and financial results. Joining me on today's call is our Chief Executive Officer, Stuart Peltz, our Chief Financial Officer, Emily Hill, our Chief Development Officer, Matthew Klein, and our Chief Business Office are Eric Powell. 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 this live 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 and 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. 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.
Looking back at the second quarter, I'm proud of the continued strong commercial performance in our Duchenne franchise. With nearly 20% growth year over year, excluding Brazil. In Plaza had an outstanding quarter, with greater than 30% year over year growth. If you'll hear throughout the remainder of the call, despite the challenging environment through the global pandemic. PPC has continued to execute in our commercial business and advanced key platforms and programs in our pipeline.
1 of these key platforms is our validated small molecule splicing platforms. As many of you know, the most advanced splicing program has rinsed the plant for the treatment of spinal muscular atrophy or SMA with the PDUFA date on August 24, which is rapidly approaching. We believe there is a plan which would be the 1st and only oral treatment for SLA as the potential to be the most competitive commercial product for this devastating rare disorder. Risdiplan validates our splicing platform and represents how innovation can generate substantial value for Orlog stakeholders. When we started the SMA Slicing program, over a decade ago, it was considered a moonshot.
The dominant belief at the time of that while slicing as a great target in principle. It is a mechanism that occurs with most all RNAs and cannot be selectively modulated with small molecules. Because of our deep understanding and expertise in RNA biology, we knew that RNAs were actually the first enzymes that can form unique structures or catalytic function that could be targeted. We also knew that if successful, targeting RNA would lead to a new platform to discover compounds that could lead to multiple new treatment options for patients living with rare disorders. It represents a new paradigm for drug discovery.
Over the years, we've built the splicing technology that led to the discovery of Riza plant into a novel platform. As we highlighted recently in our splicing platform deep dive. TTC has unique expertise in our biology. We have constructed an ironing eccentric compound library propriety screening tool, a proven process to optimize compounds to bring them to clinic and a fully integrated global commercial infrastructure to bring rare disorder therapies to patients. As you may have heard on our recent brief dive, this is a platform that has a number of additional targets moving forward.
We anticipate 3 to 5 splicing development candidates over the next 3 to 5 years. The next splicing compound ends at the clinic is PTC-five eighteen, our development candidate for Huntington's disease, which is expected to be a 1st in human trial later this year. In addition to Huntington's disease, there are exciting new splicing programs emerging from our deep pipeline, including Scot3 and Naftop. We're also making progress in other platforms and programs in the second quarter. We strengthened our pipeline with the of PTC 923 for PKU.
PTC 923 expands our platform capabilities through the addition of the late stage program for inborn errors of metabolism, and we believe it has the potential to be the best in class treatment for PKU patients. We also recently initiated a phase twothree trial for PTC299 for COVID-nineteen. We recognize that PTC299 has a unique dual mechanism that is potentially effective against both stages of the viral infection. We worked with leading academic collaborators and quickly confirmed PTC299 anti viral activity against arthritis COVID-two and vitro, moving rapidly into the clinic for COVID-nineteen. The clinical trial is being conducted in 2 stage We expect stage 1 to be completed in the second half of twenty twenty and anticipate reporting top line results for both stages in the first half of twenty twenty one.
We have multiple sites in the United States, Brazil, Spain and Australia, with additional countries expected to initiate in the coming months. Ultimately, it's a combination of the mechanism the preclinical data, the well established safety profile and the compound oral bioavailability that gives us great confidence in PTC-two ninety nine potential as a treatment for COVID 19. One of the reasons that we took PDC-two thousand nine hundred and ninety four is because COVID 19 global pandemic requires our industry to work towards a solution. In addition to its obvious effect on the health of our individuals COVID-nineteen have impacted many industries, including our own. At PTC, we took early and aggressive steps to mitigate potential risks to our operations.
Importantly, despite the challenges presented by team, we have been able to execute on certain key programs and lessen the impact on others. As I mentioned earlier, we expect to initiate a first in human phase 1 trial with PTC-five eighteen for Huntington's Huntington's disease later this year in our IOE platform. The 2 potential registrational trials for the Ticquanone formerly known as PTC-seven forty three remain on track to initiate later this year. We're particularly excited about these upcoming trials. As a as they provide us for near term opportunities to address 2 rare disorders with a significant unmet medical need.
In addition, as we recently announced, we initiated the phase 1 study for PTC857. A second compound from our bioe platform has a schedule. Before I test the call over to the team, I want to touch on recent developments with Translarna for NAFSA mutation Duchenne muscular dystrophy. The first product we discovered developed in commercial by PTC. Importantly, the EMA confirm the risk benefit profile of Translarna with the 6 annual renewal of the conditional approval, which is the basis of our sales, outside the United States.
The CHMP recently recommended revision to the Translarna label removing the statement efficacy has not been demonstrated in non ambulatory patients. This change enables health care professionals to use their clinical judgment to make treatment decisions for their patients on Translarna with Los Angeles. It also supports our discussion with reimbursement authorities on continuing Translina treatment for patients who become non ambulatory. We have pioneered therapy for Duchenne muscular dystrophy and remain highly committed to the community. I'll now turn the call over to Matt.
For key updates on our clinical program. Matt?
Thanks, Duke. To start, I want to build on Steve's comments regarding our team's response to the COVID-nineteen pandemic. Despite the many challenges, we have worked hard to mitigate the impact on ongoing and planned studies. Let me begin with Study 045, the U. S.
Translarna Distance study. In developing the protocol for this study, we carefully considered every element of the design to minimize variability that could confound study results This included the decision to use a single site for the study at UCLA, the method of muscle biopsy collection, and the method of biopsy sample analysis. I want to highlight that the protocol specifies that sample analyses will not occur until the end of the study. PTC and study investigators will be blinded to the results until all analyses are complete. At this time, final study muscle biopsies have not yet been collected from 8 remaining boys in the whole 45 study Given the evolving COVID-nineteen landscape in Los Angeles and in other affected regions, where study patients reside, we are continuously monitoring the situation to determine when it will be possible to safely obtain the final biopsies.
We are also exploring all potential options in order to have a data readout by year end. Of course, we have ensured that all subjects remain on Transwana until they are able to complete the final study visit. Turning to our ILE platform. We remain on schedule to initiate potential registrational trials of etiquinone in refractory mitochondrial epilepsy in the 3rd quarter and in Friedreich's advocate in the 4th quarter. As we detailed in our BioE platform deep dives, the phase twothree mitochondrial epilepsy trial will enroll approximately 60 children with the most common mitochondrial disease subtypes that have refractory seizures as a key component of their pathology This trial will include a 1 month run-in period to ensure eligible subjects have a minimum frequency of observed motor seizures followed by a 6 month parallel arm phase in which subjects will receive either paticinoin or placebo.
We estimate that the refractory mitochondrial epilepsy market is approximately 11000 to 13000 patients in the U. S, EU, Latin America, and Japan. The phase 3 free drug testing trial will be a 48 week double blind placebo controlled trial and will enroll patients from the U. S, EU, Australia, and Latin America. Where we estimate the FA market size to be approximately 25,000 patients in aggregate.
We are working closely with site investigator teams and advocacy organizations to ensure that subjects for both of the Picranone potential registrational trials will be able to safely travel to and from study sites. In addition, we have adjusted certain elements of the study protocols to minimize that could occur in the event in the phase 1 trial for PTC0.05 dollars, the second compound from our bioree platform. This study is progressing well, and we look forward to having data from a single ascending dose and multiple ascending dose studies prior to the end of the year. Turning now to the splicing platform, our Huntington Disease Program remains on track to initiate 1st in human studies this year. These Phase 1 studies will include both single and multiple ascending dose regimens in order to inform safety and pharmacokinetic parameters and inform dose selection to achieve target Huntington MRNA level reduction in the range of 40% to 50%.
As you may recall, this strategy of validating target engagement and splicing activity in 1st in human studies was a key component of Rizdiplam development program. Moving on to our gene therapy platform. Due to COVID 19 related delays, we now expect to receive the final CHMP opinion or our AADC deficiency NAA in the first quarter of 2021. Analytical testing by our contract labs, which is needed to respond to standard review process inquiries, has been delayed as contract lab personnel and resources have been diverted to support their COVID-nineteen related efforts. Turning to the BLA submission for AADC deficiency, the key gating factor remains the study of the surgical use of the intended commercial cannula to deliver gene therapy product to young patients.
These treatment procedures have been delayed by hospital cancellations of elective surgeries due to COVID 19. These procedures are now scheduled to occur in Q3 and we still expect to be able to initiate the BLA submission for AADC deficiency to the FDA in the second half of twenty twenty in the absence of additional delays. Finally, I want to share that we have completed the integration of programs from the Censa acquisition. We are in the process of completing the necessary non clinical studies of PTC-nine twenty three to support the long term dosing plan for the phase 3 trial in PKU patients. Despite there being 2 marketed products, there remains a large unmet medical need globally.
For PKU patients. We look forward to providing additional insights into the PTC923 PKU program in a deep dive later this year. As you've heard, despite the impact of COVID-nineteen on certain clinical programs and regulatory timelines, We have been able to advance a number of key programs and in some cases, accelerate timeline. I will now pass the call to Eric to provide an update on the commercial business. Thanks, Matt.
As Stu highlighted, the DMD franchise had strong growth this quarter with both Emflaza and Translarna generating significant revenue in Q2. Outside of Brazil our DMD franchise had an outstanding quarter with revenue growth of nearly 20% year over year. We are exceeding expectations in key markets with the exception of Brazil, which is one of the countries most severely affected by COVID-nineteen. Importantly, we continue to find Additionally, as Stu noted, we believe that the revision of the language on the Translarna label will be a positive for patients. We see the update as an opportunity to and patients on the impressive real world results from the STRIDE Registry And Synergy DMD Natural History Study highlighting Translarna's long term efficacy.
Now let me provide an update on the group purchase order for Translarna in Brazil. As a reminder, in Brazil, the government is a central payer by which only a few large through the judicialization process. Due to centralized order. We remain highly engaged with Administrative Health and are working to ensure that Translarna patients will continue to receive this in in treatment. In addition to our ongoing meetings with the Brazilian government, the MD Advocacy Group's and KOLs are also making their voices heard to advocate for Translarna access in Brazil.
These stakeholders are critical to ensure that payers have the most recent information on new and existing patients. Notably We have seen a substantial increase in newly diagnosed patients in the second quarter. We anticipate an order later this year for both existing and new patients. Now turning to Emflaza. We are hitting our stride in the U.
S. By bringing awareness to the community on the critical importance of Inflaza treatment for all DMD patients. We continue to see ongoing improvements and greater efficiency supporting the business, resulting in more than a 30% year over year increase in second quarter sales. Based on early observation, we anticipate this strong performance will continue into the second half of the year. Patient engagement, case, and market access managers, identified new patients at a high rate this quarter, and has helped accelerate time to commercial therapy.
Patients previously on bridge therapy and patient assistance programs transition to commercial therapy even more rapidly in the second quarter. These new Emflaza patients included both naive and former prednisone patients. Among our existing base of patients, compliance and adherence remains very high and discontinuation rates remain low on our Plaza. Now turning to TEGSEDI, Launch activities in Latin America continue to progress well and we continue to find new patients in Q2. We remain engaged in pricing discussions in Brazil and Also, in Brazil, during the second quarter, we filed with ANVISA for approval for Waylivra.
Patient finding and early access programs for Waylivra are ongoing and we continue to anticipate revenue from this product in 2020. To echo folks do in Matt's comments, while COVID-nineteen has impacted certain aspects of the commercial business, We continue to drive key areas of the business forward. I will now hand the call over to our chief financial officer, Emily Gil, to review our financial progress.
Thanks, Eric. I'm proud that PGC is in an excellent position to invest in our growing business and accelerate growth while maintaining fiscal discipline and a strong balance sheet. We recently completed the transaction with Royalty Pharma that brought forward $650,000,000 in non dilutive capital. As a reminder, we retain nearly 60 percent of the Vista Plan Royalty Stream, up until a 1,300,000,000 threshold is reached. After the threshold is reached, PTC retains the entirety of the Rizdiplam royalty stream.
This deal structure allows us to benefit from Rizdiplam's meaningful sales potential. We believe Rizdiplam has the potential to be the most competitive commercial product in the SMA market and believe that its market potential exceeds current analyst consensus. Importantly, we also retain all economics associated with the approximately $400,000,000 in remaining risk to claim milestone payments from Roche. As a reminder, we expect a 15,000,000 milestone payment imminently associated with the filing of the MAA with the EMA. And following the first commercial sale in the U S, we would receive an additional $20,000,000 outbound payment.
Now want to take a few minutes to highlight the second quarter 2020 financial results, which are summarized in the press release issued earlier today. Starting with our top line results, we reported $75,200,000 in total revenues in the 2nd quarter of 2020 compared to total revenues of $85,500,000 for the second quarter of 2019. As Eric mentioned, Emflaza had an outstanding quarter, and Translarna saw continued growth revenues were $38,600,000 for the quarter. This compares to $57,800,000 for the second quarter of 2019. As I've said, sales for the quarter were impacted by a delay of the Brazil group purchase order, which accounts for the year over year decrease in 2nd quarter revenue, For Emflaza, we reported net product revenues of $36,200,000 for the second quarter of 2020 compared to $27,600,000 reported for the second quarter 2019.
Growth in net product sales were driven by new patient prescriptions and continued operational improvements and efficiencies in our commercial business. Non GAAP R and D expenses were $168,000,000 for the second quarter of 2020, excluding $8,600,000 in non cash stock based compensation expense compared to $54,500,000 for the second quarter of 2019, excluding $5,500,000 in non cash stock based compensation expense. The increase in R and D expense includes one time charges associated with a recent acquisition and a manufacturing agreement. Specifically, it includes $53,600,000 related to the acquisition of Sensea Pharmaceuticals and $41,200,000 related to the MassBio Commercial Manufacturing Agreement for our lead gene therapy program and AADC deficiency. The majority of these one time expenses are non cash charges for the current fiscal year.
Non GAAP SG and A expenses were $45,300,000 for the quarter of 2020, excluding $8,300,000 in non cash stock based compensation expense compared to $43,800,000 for the second quarter of 2019. Excluding $5,400,000 in non cash stock based compensation expense. The relatively flat year over year change in SG and A expense reflects our ability leverage our existing global infrastructure. Net loss was $181,400,000 for the second quarter of 2020, compared to net loss of $41,800,000 for the second quarter of 2019. Cash, cash equivalents and marketable securities totaled $498,900,000 as of June 30, 2020, compared to $686,600,000 as of December 31, 2019.
Now including the $650,000,000 in cash received in July upon the closing of the deal for royalty pharma, unaudited pro form a cash cash equivalents and marketable securities as of the 2nd quarter would be greater than 1,100,000,000. I will now hand the call over to the operator
Thank you. Our first question comes from Raman Karnaus of Truist Securities. Your line is open. Hi, everyone. Thanks for taking my question.
So I'm gonna ask you a question that I get all the time, up front. So can you clarify for us given the last bill you did, how important is business developed for you versus say the development of your slicing platform, which I think a lot of people are really excited about. Help us understand how you prioritize your businesses. I think that's the most common question I get so I'm going
to ask it on the call.
Sure. So, thanks for the, thanks for the call. Obviously, our overarching goal is always to bring, innovative therapies to patients with high endometriosis. And I think we As you can see, we've built the company, over the last 22 years in Virginia for the building to have a strong pipeline over the over the next 20 years and the strategy has really been to use the internal discovery capabilities that we've built as well as business opportunities to continue to grow. And the slicing platform, as you see, I think, has created a substantial value or risk to plan.
And I think from the deep dive, you could see how the opportunities that they're in available. So we plan as part of what we've done is to expand into that. So the way I look at this is really in a sense, shots on goal and that you need a relatively broad pipeline in order to bring a number of products, critical for growth. But that's also true for development, right? Some of you never know for sure when things are going to be ready for getting to commercialization.
So we look to fill the pipeline as needed through business development. And it's helped us go about and develop additional new core expertise such as gene therapy, the redox and the inborn euros and the tablet. So these are important to us as well. And we think there's some near term value creators like in the same voneeras and metabolism, we'll be starting to registration studies IIE programs will be starting the 2 platforms that are also pivotal studies that could be, that are starting now that could be in the 2023 timeframe. So there's a lot of value that we think we can do in terms of creating value.
So way we're looking at that is we're highly excited about our innovation capabilities, and we're going to be pursuing them with great net moving forward. And we look for business development opportunities in the in the query strategically. And in this case, now that we've built a pipeline and platform, vertically strength and if we see something, that's interesting. And then the other point is obviously the current platform is important. So the therapeutic area of the platform and the commercial footprint, I think is how we're going to continue to grow both the innovation, but also the revenue for the company.
Does that help you?
Yes, I mean, I think the big question is, is focusing on business development in any way, distraction from developing your current drugs in particular that from the splicing platform within the near term catalyst?
Like, that's a more directed question.
Yes. And I think that's and the answer is no, it doesn't. It isn't like where the our pipeline is not yet big enough to say that we're prioritizing A versus B. And that we have the resources to be quite focused to make sure especially now to really go whole hog through the slicing platform. And so I don't think it's a diversion, because there are obviously different people that are moving forward on the the way we've actually constructed the team now or the company in terms of his organizational structure isn't sort of pulling from one group to another.
It's building out teams to be able to handle that and then have the infrastructure for them to be autonomous enough with enough oversight. So I think I know we're pretty focused on that. We're strengthening our current platform. So I don't think that's a very important point. It's not like we're deprioritizing one for the other right now.
We're not big enough yet to be able to to say that we're going to be doing that.
Thank you so much.
Got it.
Thank you so much. Thank you. Our next question comes from Joel Beatty of C. Your line is open.
Hi, thanks for taking the question. The first one is to follow-up on that last question from Ravin. Furthermore, business development standpoint, what types of programs, what would you be looking for that would have the best fit with PTC, you know, at least from a high level?
I get from a high level. Thanks, Joseph. I mean, when we tend to think of a kind of a high level, it's really to look at within the vertical. If you think about it, we now have either seeing therapy, you know, bioE, the splicing platform. Right?
So it's it's within the platform that we built. That will be moving, that will probably we're not looking to create or inwards the areas of the tablet. We're not looking to go outside of that area. So we're looking carefully for, selective and strategic BD opportunities that the focus efforts on the current therapeutic areas and platforms that we have in place. And so, and therefore, and that could also help enhance our commercial footprint.
Okay. Got it. That's helpful. And then a question on risdiplam. Have there been discussions with FDA on the potential indication and anything you can give to help give us confidence on FDA meeting the PDUFA date And how do you anticipate that the label could compare with the approved estimator?
Yes. So obviously we're waiting for the PDUFA date. We strongly believe that certainly going to be approved by that time. And we strongly believe it's what gets the best in class product and we think it's the most commercial the competitive product out there. We think that obviously from our point of view, it's going to be a have broad efficacy will be the standard of care.
We expect that the label is going to be, very broad for all FMA types, including 1, 23. Obviously, we have the data for placebo controlled trials, both for SNA type 1 for those younger patients. And even in I think even there when you compare the data sets in terms of even in the type 1, the older patients in seen benefit there that wasn't seen by others. So we think it's really quite strong in the Type II III in the older patients we saw in the SUNFISH even strong data as well. And then it's also supported by the other programs of Jewelfish and Rainbow Fish.
So, at the end of the day, we think it's going to be a very strong label for both the type ones as well as adolescents and adults. Obviously, the first and only treatment that's an orally bio available product. So it's home administration. And in particular, in this environment, now that's a huge benefit. You don't have to go to the hospital to be a physician.
There's a strong safety profile. And we think that it's done doing quite well. So we're very excited about that.
Thank you. Our next question comes from Althea Yongea. Your line is open.
Hi. This is Lee on for Lydia. Thanks for taking our call. Maybe just one on ADT. Can you just give us more color on the remaining steps to file the a, and then how confident that you can file by year end.
And then another one under U. S. Just your the study. Just wondering if you think the COVID challenges might make it harder to integrate the results given the delay And then is there any specific FDA guidance on it? Thanks.
Sure.
So let me remind you that we will talk about the BLA, but the MAA is submitted. So we're moving through Europe. The key, gaining item, as you know, is the surgery with the commercial Cambular. And I'll let Matt, you want to talk a little bit about that Matt?
Yeah. Absolutely. So as Steve said, the the key gating items, the surgical procedures with the intended commercial cannula, which is a SmartFlow cannone. Now this is CE marked for gene therapy delivery in the EU. In the U.
S, it's an approved device just unexplicitly for the delivery of gene therapy into the containment. It has been used in clinical trials with a good safety record for gene therapy deliveries containment of adults. And so really that last piece is getting some experience in the surgical administration of our gene therapy products with the SmartFlow device. So it's really an assessment that we've been asked to provide of the device and the surgical procedure for the, for delivery of gene therapy products and to contain Once we have those, procedures completed, we'll, of course, move forward, for final PDLA discussions with the agency, and and move forward with preparation for the submission. With regard to the dystrophin study, obviously, We're all, frustrated by the delays from the COVID trial.
I mean, PTC, as you know, has an credible, long standing, long standing history of being dedicated to developing therapies specifically Translarna for DMD patients where Obviously, incredibly excited to receive the 6th annual renewal in Europe. The evidence that we're continuing to collect on a number of fronts showing long term benefits through our STRISE registry. And now we're at the point that we're just waiting for these last eight patients to come in and get their final biopsies so we can analyze all the results. And clearly, we want to get this study read out by year's end. Obviously, there's some unpredictability due to the pandemic, which is obviously affecting not only the study site in California, but also in the state where some of the patients live, such as Texas and Arizona, And of course, first and foremost, we want to make sure the safety, of the procedures.
We're still in the process of sorting out the exact timing of biopsies at UCLA. Fortunately, it looks like, pandemic numbers may be slowing. And so we're in constant communication with the site to see when we can get a better idea of the specific timing for those final biopsies. And of course, most importantly, we're ensuring that these patients don't have any disruption in the supply of Translarna so that when we're able to get their biopsies, we'll be able to do some of the context of ongoing Translarna treatment.
Thank you. Our next question comes from Joseph Thomas of Cowen And Company. Your line is open.
Hi there. Thank you for taking
my questions. The first one on the MAA for AADC, I think you indicated that the EMA had some feedback on some additional information that they need from you. If you could just qualify kind of what sort of information do they need? And did they put you on a stop Do you have that extra time to respond or is there a time limit? And then second, if
you could just update us on
the progress for INDs for PTC for Progycexia and Angel Business.
Sure. So,
Matt, do you want to talk a
little bit about the MAA?
Yes, absolutely. Thank you for the question. So as we mentioned, we submitted the MAA in January. And based on the standard MAA timelines, we expected the final CHMP opinion in late December of this year. That's just based on the pre specified timeline from the from EMA.
During the review process, we needed to be asked for some pretty standard questions launching additional manufacture related analyses done on drug products. These are all done by our external, commercial manufacturing organizations, they have been impacted by COVID in a few ways. One is, obviously, decrease in the number of available personnel, but also our lead CMOs are involved with other companies in developing solutions for the COVID pandemic. So obviously, they redirected their resources toward the personnel and other resources towards the COVID related activities. Therefore, in order to be able to satisfactorily respond to the EMEA's questions to us, we were granted a stop clock.
So that we can then obviously come back and address the questions, which are easily addressable once we have the available resources to do so. And plan now on the file opinion in Q1 of 2021.
Great. Thank you. And then just the update on what we could see the IND for free to taxi after that gene therapy, if there's any update.
I think we said it was delayed a quarter. We announced last quarter that We're continuing to work to advance them both, but there's been a number of COVID related delays for at least a quarter. So what we really do remain enthusiastic about both of these programs, and we're working to really get it all done. We can get that done. So that's where we're at now.
So it's similar to what we reported the last time.
Thank you. Our next question comes from Brian Abrahams of RBC. Your line is open.
Hi. This is David Stacey on for Brian. Thanks for taking my question.
Hello. Someone I think your line is not muted. Ma'am? No worries.
So just another one on AADC. From your ongoing prelaunch activities, maybe engaging in the same market, Can you just update us on your evolving sense of the clinical pathway to identify, AADC patients? And if there are perhaps differences in the U. S. Versus EU
I'm just trying to get a sense of what your
current level of confidence is in, to EPI here. And then I have a follow-up after this.
Sure. So, Eric, you want to talk a little bit about our patient finding efforts?
Yeah. Sure, Steve. I think we we have we are continuing to work very hard to identify patients just, you know, despite COVID nineteen We've not even raising disease awareness and driving testing, particularly in areas that are patients that are in high risk. So to resolve the equipment to clinics and epilepsy clinics, we've accelerated a lot of our mass to class symposium, the agency opinion leaders, programs, AdWords, steering committee symposium, actually published clinical data. So in terms of rating this awareness, we've really linked our level of of activities, for awareness and identification.
We've actually expanded a lot of our activities to a number of different countries as well, both in Europe, Asia Pacific, in Latin America, increased our funds in addition to that. We've been having a lot of payer discussions. And they really do like the clinical data to understand the gene therapy landscape and to look at the physician. So, patient identification continues to progress well. And as we said, our goal is to is to find 300 patients.
And, by the time we'll prepare to launch in our first key markets globally.
Thank you. And then maybe a quick follow-up, I'll try to log on a jab. So going back to your opening remarks discussing the recent CSMD recommendations to open the label to patients who become non ambulatory. I was just wondering if you could provide maybe an update on any other evolving dynamics among physicians in the EU. And if you have any perspective on expanding unwanted label to amortization among non ambulatory patients?
Yes. Thanks for that question. We were really heartened by this and had substantial positive feedback from both physicians of payers on their revision. And this really does allow the patients to keep that path to remain upon translarna even if they transition to the non ambulatory part. And so that's actually really important.
And certain countries have already had the willingness to do this. In terms of non ambulatory, that really is sort of country by country as well right now. Certainly, when you think about it, it makes sense from this point of view that if you're down ambulatory, from going from inventory, not inventory that you'd like to. We have been working on that. Maybe a little bit, do you want to talk a little bit about the Eric in terms of what Europe is doing?
Yes. First of all, we've had a lot of questions. I can meet you with after the announcement. Physicians and payers have looked at this as being a positive step forward. So immediately after that announcement, a number of patients that might have been actually considered for, to stop because they went on ambulatory, continued treatment.
So this this willingness, if you will, to not implement a stopping criteria in which critically important. So we've already actually, since we've already actually seen patients that aren't, that have been on Translarna, go down inventory and stay it gives a lot of the physicians positive feedback and continue, if you will, this dialogue that they could have right now, they couldn't with certain payers. In Northern Europe, in Southern Europe, and even in places like Latin America where payers use the label the wording of the label as a sort of stopping barrier or stopping criteria. So now there's a much there's going to be now future. I think patients and physicians will have a positive benefit discussion with payers.
And by removing that in the label, provides, if you will, a constructive dialogue, that can be handled by the physician and repair.
And then the other things that
we've had done a fair amount of work, folks, in our stride registry, as well as the non ambulatory patients following them. And what's really nice is that the results that we saw in the clinical data controls with patients. And actually you can use now much harder endpoints. The publications on the slide data is really quite clear in terms of the substantial improvement on not only the walk team longer, but multiple other time function test measurements, we can see substantial improvement. And also what we've seen is in the non ambulatory patients, clearly better pulmonary function.
I mean, very clear demonstration when compared to natural history. So we're excited about this and we're really we do try and work to make sure if that non ambulatory patients have a way to get Translarna as well.
Thank you. Our next question comes from Raju Prasad of William Blair. Your line is open.
Hi there. This is a
Sami on for Raju. I had a question regarding the dystrophin study. At what point, or what would be the scenario in which you forego the biopsies or a portion of that in order to file that BLA and trying to understand, which event you're prioritizing?
So the I think, you know, the so we have 12 out of the 20s have been done. And so that have been treated and they've not been they're still blinded, so we don't know them either within that we just the study was the study was performed with 20 patients precomposed. And they're still being treated So we we just think that it's a better, it's better to have all the patients if possible. If this continues and extends on, will we, you know, there is a possibility we could say maybe we should just look at the data now and live in an interim way and take a look at that. So we'd obviously need to align with the FDA on that, before we were to do that.
So we don't want to look at the data before we agree with that. But it's really a question of if we think it's going to take forever. Or not. So that's our thought on that.
Thanks. That was really helpful. And just a just a quick follow-up. How are, patient identification efforts for the, mitochondrial epilepsy trial, just to get an idea how quickly. You'll be able to enroll patients in that trial.
Sure. Mac, you wanted to sort of talk a little bit about update the nice application for the product.
Yes, absolutely. So just for some historical background, 743 was really the first drug to be brought into the clinic explicitly for pediatric mitochondrial disease patients and has an enormous amount of brand recognition the mitochondrial communities, globally. We also have very good working relationships with the patient foundations, both in the U. S, EU, Australia, Japan. And so we've been relying on this network, to help us if the work out that this trial is starting.
There's already a great deal of enthusiasm in a number of, live countries in which the trial is going to be conducted And we are really excited to be able to launch the trial and believe that we can rapidly enroll the trial, again, COVID permitting.
Great. Thanks for taking my question.
Thank you. Our next question comes from Gina Wango Barclays. Your line is open.
Hi, thanks for taking our questions. This is Peter Pacheen. I guess two questions for me. First on Translarna, how much of the quarter over quarter decline is due to COVID-nineteen and any color on impact? On new and existing patients.
And for back half of the year, do you expect some growth relative to the 1st 2 quarters? For largely stable, excluding the Brazil order, and I have a quick follow-up.
Thank you.
Okay. Say the first part again. For Shansbarnier, how much of the quarter over quarter decline due to the synthetic?
Okay, great. Yes, so, Eric, do you want to talk a little bit about that?
Yes, sure. I think there's very little decline if we look at the major markets. In fact, in Translarna, key markets outside of Brazil, continue to grow. And we've seen seen new patient identification and new patients come on to therapy, even in some of the most affected countries like in Southern Europe, like Spain and Italy where we've had new patients go on to treatment. We've also seen very high adherence clients rates and very, very low dropout.
So essentially in the main area, the main region, we haven't actually seen, impacted all from COVID-nineteen. The main issue in decline is primarily the administrative delay, from Brazil in the group purchase order at this time?
Yeah. I think also you might remember, Peter, in my first, in my comments initially. I said outside of Brazil, we saw a 20 approximately 20% increase.
I guess, on my second question is to the extent that you can provide any color on, with the plan CAC, would you be able to give color on, like, how the enrollment rate has been impacted by COVID-nineteen relative the expectations. And any color on, you know, folks switching from this person? Thank you.
Yes, sure. I guess, I don't think we've ever given numbers on how things are going, but things actually in terms of EAP has gone actually quite well. And I know that Rose is quite satisfied with how the VIP has been going. We do expect, on approval that we think that we're going to, obviously, we're confident, roaches of roaches ability the launch this quickly. And we think in particular, there'll be a lot of transition from SPINRAZA to to Risdiplam.
So we're we think that's going to be a very strong part of the growth of Risdiplam over time. As well as obviously the naive, in particular, the adolescent, there's so many patients that are not being treated there. I think Risdiplin is a orally bioavailable agent, is very well suited for these patients. So we're excited about this a launch, which we think, which we anticipate will occur quite quickly.
Thank you. Our next question comes from Eric Joseph of JP Morgan. Your line is open.
Thanks for taking the question. On Translarna picking up on your prior comments about discussions with EMA And Health Authorities. Can you talk a little bit about the extent that we they are interested in results from Study 45 as they look to potentially renew conditional approval again in 2021. And I guess from health authorities, do you know, I guess is there any sensitivity on their end on the 3045 outcomes versus how to look at the STRIDE Registry data?
Oh, yes, sure. Thanks for that, Eric. I think one important point for you is that it was very clear that the European authorities didn't look at description as a biomarker that really predicts any efficacy. So it really everything was based on the clinical results. And so we've kept them appraised not only the clinical data that one has, but also the clinical data from the STRIDE and the non ambulatory data.
So they know that data quite well. And so the, if, the results from W45, I don't think will be of any service in the EMA sense, whether good or bad because I don't think that, you know, it isn't a biomarker that Acthar recently predict clinical benefit. And so They had no interest in it in the past. I think you could see it from, another company when they talked about the remote that they didn't make any headway either. So they're not using this as something that's an approvable, biomarker.
So And that's, I think, true with most other countries outside of the United States. Got it. That's helpful.
And maybe a follow-up on Emflaza. I'm just wondering if you could help us unpack the dynamic to the strong quarter here how much is sort of driven by efficiencies in the prior auth process versus growth in new patient adds? Among naive patients, which should be anticipated a similar benefit in the second half of the year. And I guess also you also just noticed that the Phase 3 Limb Girdle study also completed enrollment recently. Can you just remind us whether this is a potentially labeled expanding trial and what regulators might be looking forward to enable that?
Sure. So
in terms of the implied, obviously we've been spending the last couple of years in terms of gathering data and the publication I just think I saw it clear in terms of demonstrating, why it's not on the is the superior the data that shows that the superior product relative to prednisone. And I think that there's been a lot of hard work done on that to get to this point. And so I think this growth maybe, Eric, do you want to talk a little bit about the growth of being plasma in terms of patients and such?
Yes, sure, Eric. Two questions. We're really pleased with the growth right now that we've seen from Plaza. This is the majority of the growth right now is that we've been able convert patients that have been on bridge and app as a patient assistance. We've been able to convert them much, much faster than commercial therapy.
Which is extremely important because that's free drug. In addition to that, we have continually increased the number of new prescription start forms during the quarter, and we saw a nice increase there. And an influx of both a nice combination of naive and former prednisone the other thing that's driving is that the base of patients are being, again, like Translarna, we're seeing very high adherence. It's very a very good compliance rate and very low dropout. We also come into a period of reauthorizations and our team is staying way ahead of the reauthorization process and with the insurance companies, so that patients can spend less time in that bridge environment if we drug it more personal therapy.
So it's a combination of a lot of these different efficiencies that have really driven this growth. And we're seeing that again it's looking real strong as we're moving into the second half of the year. And and on Limb Girdle.
Oh, the Limb Girdle. Yes. Yeah.
My recollection, I can't remember where that was actually located or receiving that, but Yeah. I do think it was, but that's one where I don't think we've actually completed the enrollment. And I think it's been, especially with COVID. It's been, it's been had substantial recruiting challenges.
Understood. Thanks for the clarification there.
Thank you. Our next question comes from Martin Oscar of Credit Suisse. Your line is open.
Hi, this is Nat Toro on for Marty. Thanks for taking my question. Regarding the Hyattense program, you mentioned that phase 1 health volunteered data will include information on Huntington lowering and plasma. And I believe you presented some data on mice on the relationship between Huntington lowering and plasma versus the brain. Does your therapy lower Huntington protein in non human primates?
And if so, can you describe the relationship you saw in HP in terms of hunting and lowering and plasma relative to various regions of the brain? Thanks a lot.
Sure. Yes, so you're absolutely right where the No. It's really to to remind everyone, if the Huntington program, which you might have seen on the deep dive, was was that we said that you pick what we call the pseudo intron, as they were tricking it to be able to go be part of the messenger RNA. Which exactly makes the RNA unstable because of a premature stop. And you don't make either the protein or the RNA.
So that's really actually quite important, and that's the human form of it. My recollection is that the non human primate because it's within the intron doesn't have that sequence in it, so you wouldn't necessarily see that. That's my recollection of that. So you're not in a sense, a model, where you can do the substrate, where you can actually look at the substrate, the human substrate in that case.
Great. Thanks so much for the question.
Right. But it is very true that in the inpatient we're very much be able to measure any blood, the reduction of the RNA and potentially protein especially in the multiple ascending dose, whether if you have time to see the protein go down. And we do know from measurements that the blood brain levels are pretty much fifty-fifty. So what you're seeing in the blood paper will be similar to what we see in brain and that will indeed be the case in the animal model. So it's really quite exciting.
It's actually very similar to analogous to what we saw in the SMA program or what we anticipate to see. So you have really an idea from the very early stages of programs that you're on mechanism on target. You see these effects, and then you go on to measure clinical benefit.
Perfect. Thanks again.
Thank you. I'm showing no further questions at this time. I would just turn the call back over to management for any closing remarks.
Oh,
okay. Well, thank you folks for staying on the call and then asking these questions. We're obviously very pleased with the strong performance this quarter across both the commercial and clinical programs. And I'm very proud on how the teams have continued to execute in the environment that we're in. If you know, we've been trying to do our part to reduce consequences of the pandemic.
You saw that we're and that we're very excited about $2.99 and its potential. To be part of the solution for COVID-nineteen. We've also, as I talked about before, recently launched our internship program for finding opportunities for graduates, which we call the talent pipeline program or TPP. It offers a 1 year internship to provide a real world experience for graduates during the challenging economic time. All graduates, although all graduates are eligible, we've use this program to reach out to institutions' minority communities.
And I'm gratified to say we approximately have about a 3000 applications. So it's been quite successful. So we're excited to be able to work alongside and mentor what we hope will be future leaders in the biopharmaceutical community. So thanks again for listening. We hope that everyone stays safe.
Ladies and gentlemen, this does conclude today's conference. Thank you for participating. You may all disconnect. Have a great day.