Ladies and gentlemen, thank you for standing by, and welcome to the PTC Therapeutics First Quarter 2020 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen only mode. After the speakers' presentation, there will be a question-and-answer session.

[Operator Instructions] Please be advised that today’s conference is being recorded. [Operator Instructions] I'd now like to hand the conference over to your speaker today, Alex Kane, Head of Investor Relations of PTC Therapeutics. Thank you. Please go ahead, sir..

Good afternoon and thank you for joining us to discuss the PTC Therapeutics first quarter 2020 corporate updates and financial results. I hope that everyone is doing well and staying safe.

Joining me on today's call is our Chief Executive Officer, Stuart Peltz; our Chief Financial Officer, Emily Hill; as well as Matt Klein and Eric Pauwels, who are recently appointed Chief Development Officer and Chief Business Officer, respectively.

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 slides posted on our Investor Relations website in conjunction with the call, which contains our forward-looking statements.

Our actual results could materially differ from these forward-looking statements, 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. We will disclose certain non-GAAP information during this call.

Information regarding our use of GAAP and 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, Alex and thank you for joining us today, as we provide an update on the first quarter. I hope that everybody is staying safe and healthy amid these challenging time. I’m incredibly proud of how the PTC team has responded to the COVID-19 crisis, recognizing the seriousness of COVID-19 and acting early.

In late February, we understood the threat and set up a COVID-19 task force that included individuals from all areas of expertise of PTC, including physicians, public health experts, and epidemiologists that understood the implications of the viral pandemic.

This team immediately implemented a plan to safeguard the health and safety of our employees and ensure that they have the necessary equipment to work effectively from home. This task force continues to meet and refine processes that allow us to remain productive and safe.

We have a second task force that focuses on critical aspects of our business to ensure access to our therapies. This task force is continually assessing issues that could arise with our clinical programs, manufacturing, supply chain, research, as well as the commercial business.

We have revised strategies to mitigate potential issues in our businesses and continuously assessing how well they are functioning. Patient services and engagement teams are now working together to ensure that patients have the necessary access to treatment.

We have also created a third COVID-19 task force whose mission is to look at what is next and think through the strategies we should employ as the world begins to open from being locked down. Their job is to strategize multiple scenarios of what will be needed to be successful in different places around the globe.

As a result of these efforts, our teams have adapted and have continued to execute. Field teams are engaging with the physicians, identifying patients and driving awareness of our commercial products. Given the limited ability for personal interaction, they are doing so remotely using a number of digital approaches.

Our scientists have also continued to work in the laboratory to drive critical research programs forward. We have put safeguards in place, including staggered shift to allow reduced interaction, so that they can work in a safe environment.

As all companies in the industry have experienced ongoing and planned clinical trials have been impacted as hospitals and health care providers focus on treating COVID-19 patients and have slowed or closed sites. The effects of COVID have also impacted regulatory filings in our gene therapy program. Matt will talk more about these programs.

Overall, I'm proud of the organization's response to COVID-19 crisis. We have a strong capital position with more than $595 million on our balance sheet as of the end of first quarter. We are being both strategic and prudent about capital allocation.

As an example, because of COVID's potential impact, we have deferred certain capital expenses at our Hopewell facility and now anticipate that GMP manufacturing of clinical material at this facility will begin in early 2021. I also want to highlight other aspects of PTC business that keep us well-positioned, both in the crisis and beyond.

These include the strong team that we have in place, our global commercial infrastructure and commercial products that can be delivered and administered to the patients at home. And for the first time, SMA patients will have the potential opportunity for an at home therapy.

In addition, we have a diverse rare disorder pipeline with multiple upcoming catalysts. Let me now focus on the progress we made during the first quarter, starting with SMA.

We recently disclosed the meaningful and positive results for risdiplam in both the SUNFISH pivotal study for type 2 and 3 SMA patients and the FIREFLASH pivotal study in the type 1 SMA patients. We anticipate an approval with a broad label later this year.

Earlier this week, along with our partners Roche and the SMA Foundation, we shared the positive 12-month results of the FIREFLASH Part 2 pivotal study.

The FIREFISH Part 2 study results are quite exciting, and so the importance of increasing SMN protein systemically demonstrating the achievement of motor functions and developmental milestones since its ability to roll over, sit and stand.

The study met its primary endpoint of patients sitting without support at 12 months and was highly statistically significant. 12 of 41 patients with 29% met the milestone with a P value of less than 0.0001.

Considering the median age and enrollment was 5.3 months and that these infants already had progressed disease, these results are particularly exciting. The safety data were consistent with the known safety profile of risdiplam. Importantly, this study also met all its key secondary endpoints.

This included the CHOP-INTEND, HINE-2 and event free survival. 90% of all infants in this study showed a CHOP-INTEND improvement from baseline with a median change from baseline of 20 points. Part 2 showed even greater improvements in patients' ability to stand and walk as assessed by HINE-2 than were observed in Part 1 to 12 months.

One patient in FIREFISH Part 2 reached the bouncing milestone, a key component of developing the ability to walk. After 12 months of treatment with risdiplam, 93% of infants were alive. 85% were without permanent ventilation and 95% of patients maintain the ability to swallow. As Dr.

Servais pointed out on the Roche call, this is particularly impressive when compared to other therapies as well as the bulbar function benefits may reflect a small molecules ability to reach the brain stem.

In contrast, in the natural history of the SMA type 1, the median age of death or permanent ventilation is 13.5 months and all infants with type 1 SMA older than 12-month require a feeding support. Overall, it's clear that these results are highly compelling.

As we communicated recently, the FDA extended the PDUFA date of risdiplam to August 24 due to the submission of additional data from SUNFISH Part 2. The inclusion of these data in the submission is anticipated to support broad access and reimbursement to risdiplam for the widest range of SMA patients.

Importantly, the FDA has identified no substantive issues to date during the review. Roche's careful preparation has assured ample risdiplam drug supply. Roche is working proactively with its partners of the SMA community and its logistic providers to ensure drug supply upon launch in the current COVID-19 environment.

As part of Roche's pre-launch commercial efforts, several early access programs have been initiated. Earlier this year, early access programs were open to the United States and European countries for type 1 SMA patients. Recently, it was announced that the program has been expanded to include type 2 SMA patients.

Importantly, in response to requests received from type 1 and type 2 patients whose current treatment has been interrupted as a direct consequence of the COVID-19 pandemic. Roche has decided to amend the program to allow for these patients to be able to receive risdiplam.

These requests for risdiplam demonstrate that a significant unmet need exists within the SMA population. The need for an oral therapy that is taken at home is shown to be even more critical for patients as they try to navigate through the COVID-19 pandemic.

In fact, risdiplam would be the only available SMA therapy that does not require clinic visits for administration, an important concern for patients with respiratory complications. We expect that risdiplam will be the most competitive global product for a broad range of SMA patients and anticipate a robust launch following approval.

Risdiplam was the first compound arising from our splicing platform. One advantage of being compound is that it's systemic so that it is in the blood and can get to all affected tissue. The second advantage is the ability to measure risdiplam's pharmadynamic effect on SMN2, mRNA and SMN protein in blood or other easily accessible tissues.

As you may recall, we successfully utilized this approach in risdiplam Phase 1 studies where we demonstrated proof-of-concept of its activity in healthy volunteers. We plan to use the same approach in other splicing program.

The same approach will be used in PTC-518 in Huntington's disease, PTC-518 is a development candidate from a Huntington program and an IND toxicology studies are ongoing. Let me now turn to our commercial efforts in the first quarter. We had a strong year-over-year first quarter growth with our DMD franchise with revenues of $68 million.

We are reporting $40.5 million in worldwide Translarna sales at $27.5 million in U.S Emflaza sales. In addition, we continue to see positive trends in the weeks following the first quarter. Nevertheless, we cannot predict the duration and severity of the COVID impact on our commercial business over the coming months.

Therefore, until we have further understanding of the effects of COVID on the revenues, we are withdrawing our 2020 financial guidance at this time. I also want to talk about Analyst Day.

It's becoming increasingly clear that hosting an Analyst Day in mid-June in New York City would not be in the best interests of the health and safety of either our employees or guests. We will postpone the meeting and switch to hosting multiple webinars in which we do deep dives into our programs and platforms.

We'll be shortly posting the data, which the first deep dive will occur. We believe this will be a productive way to update you on all our programs and platforms. I'll now turn the call over to Matt and Eric and Emily. For Matt and Eric, we welcome them to the executive team and their first debut on the quarterly calls.

Matt will now update you on the status of the clinical program. Eric will cover more on the commercial business update, and Emily will give a financial update. So let me now turn it over to Matt.

Matt?.

Thanks, Stu. I'm thrilled to join the executive management team at PTC, and I look forward to the continued progress at our clinical programs. It's an exciting time to step into this role with our multiple upcoming clinical catalysts, even in light of the current environment.

In terms of timing updates for our clinical programs, I will start with the Study 045, the U.S. Translarna dystrophin study. Due to COVID-19, the 045 study site is closed to elective procedures, which has delayed the study completion has a few patients still require final study muscle biopsy.

Based on the site's current timelines, we now anticipate reporting top line data in the third quarter. We expect that in combination with our existing clinical data, statistically significant results in 045 would be sufficient for accelerated approval in the U.S.

As a reminder, this is a single site, 40-week study that enrolled 20 boys aged two to seven years with nonsense mutation. The primary endpoint is percentage dystrophin change from baseline as measured by electrochemiluminescence or ECL.

In close collaboration with the FDA, we developed and validated an ECL liquid based assay that is highly sensitive, highly linear and particularly well suited to identify large proteins, such as [indiscernible] dystrophin.

Turning now to our splicing platform, Stu detailed the exciting results for risdiplam, our first small molecule from this platform. Our next splicing program in Huntington's disease remains on track with initiation of clinical studies in healthy volunteers to start prior to the end of the year.

These Phase 1 studies will include both single and multiple ascending dose regimens in order to inform safety and pharmacokinetic parameters. We expect these studies will be relatively straightforward and support those selection to achieve target Huntington RNA reduction levels in the range of 50%.

Shifting to our bio e-platform due to COVID-19, we now expect to initiate potential PTC743 registrational trials in refractory mitochondrial epilepsy in the third quarter and in Friedreich ataxia in the fourth quarter.

We will initiate these studies once the planned study sites reopen and are available for clinical trials, and of course, once we can ensure patients can safely travel to and from study sites. The Phase 1 trial of PTC857, which is being developed for GBA Parkinson's disease as its first indication, remains on track to start in the third quarter.

As we have discussed previously, the Bio-e platform is complementary and synergistic with our other platforms. PTC743 and PTC857 target 15-lipoxygenase, a key enzymatic hub that regulates the inflammation and oxidative stress that underpin mitochondrial and CNS disease pathology.

PTC743 has been tested in over 400 patients, primarily in children with inherited mitochondrial disease.

And it's demonstrated promising efficacy as well as favorable safety signals, and expanded access and compassionate use studies in patients with mitochondrial disease, PTC743 has had a clear impact on refractory seizures, reducing the number of patients seizures as well as seizure related morbidity, including hospitalizations.

In addition, in a Phase 2 trial in Friedreich ataxia, the PTC743 demonstrated statistically significant impact on disease severity, at 24 months, relative age and stage matched natural history controls as assessed by the validated bar score.

For PTC857, the compelling preclinical data and its target mechanism of action strongly support its development for Parkinson's disease.

The target of 15-lipoxygenase is a very important upstream modulator of multiple pathways known to be key to Parkinson's disease pathogenesis, including alpha-synuclein oxidation and aggregation and microglial activation, a driving factor in neuroinflammation.

Therefore, targeting 15-lipoxygenase allows us to simultaneously affect multiple pathways, while many current therapies in development target only one of these pathways. Moving onto our gene therapy platform and associated updates, as you noted, COVID-19 has impacted our gene therapy program timelines.

With respect to the Friedreich ataxia and Angelman Syndrome gene therapy programs, COVID-19 has impacted multiple IND labeling activities. We currently anticipate the IND filings will be delayed at least one quarter. Now we plan to provide an update in filing timing as we better understand the ultimate impact of COVID-19 on these programs.

Moving to our AADC deficiency program, manufacturing activities are continuing and remain on track. The gating factor for the BLA submission remains the study of the use of the commercial canola in patients. These treatment procedures have been delayed by hospital cancellations of elective procedures due to COVID-19.

Therefore, we now expect the BLA submission for AADC deficiency to the FDA will be in the second half of 2020. As reminder, the MAA for the AADC deficiency program was submitted to the EMA in January and timelines remain in place for the CHMP final opinion by the end of the year.

Overall, despite COVID-19 related delays, we still expect a number of exciting and impactful clinical catalysts in the coming months. I'll now pass the call to Eric Pauwels to provide an update on the commercial business..

Thanks. [Technical difficulty] Matt's comments, I am delighted to join the executive management team at PTC.

With a strong first quarter behind us, an important upcoming milestone this year, we will continue to build on our existing portfolio of revenue generating products, prepare for future launches and remain selective with business development opportunities.

Currently, on the commercial side of the business, our top priority is ensuring that patients on treatments have the necessary drug supply. And we have not seen significant disruptions to date.

With personal promotion from our sales team worldwide limited by COVID-19, we continue to engage with health care providers, patient advocacy groups and payers by driving DMD, disease awareness activities through virtual calls, DMD master class webinars and educational podcasts, as well as leveraging virtual platforms to host local advisory boards.

Additionally, social media is playing an even important role in the current environment, especially for DMD patients seeking information about our products. We had a solid first quarter with Translarna and Emflaza, both in terms of maintaining our existing patients and in new patient growth.

New patient growth was driven in part by diagnostic and educational efforts over the last several months. And we continue to see these efforts positively impacting the business into the second quarter. For Translarna, we saw continued growth in Q1 and positive trends both in diagnosis and prescriptions globally.

In the EMEA region, we have successfully maintained adherence in compliance with patients on Translarna and have seen minimal disruption. In the LatAm region, we continue to have ongoing discussions with the Ministry of Health in Brazil to secure future purchase orders.

And we have seen the number of positive injunctions that will allow patient access to increase. Importantly, we continue to highlight comparison of the impressive real world results from the Stride Registry and Cinergy DMD Natural History Study, highlighting the long-term efficacy of Translarna. For Emflaza, our U.S.

commercial and PTC Care's case management team has been fully engaged and made significant impact in the first quarter of 2020. Driving enhanced customer service and improving efficiencies with new patient starts, reauthorization and patient adherence and compliance. We expect these ongoing improvements will continue through the next quarter.

In the first quarter of this year, patients moved faster from time of new prescription to commercial therapy. And patients previously on bridge [ph] therapy and patient assistance programs, transitioned to commercial therapy more rapidly. In addition, physicians continue to see the differentiated benefits of Emflaza.

Continued by multiple publications, including the recent data from Cincinnati Children's Hospital Real World Outcomes, demonstrating camouflages benefits such as the laying loss of ambulation better compared to prednisone. Now, let's turn to TEGSEDI.

Our launch activities are still progressing despite the current environment, with our focus now on pricing discussions in Brazil, which we expect to be completed in the second quarter. TEGSEDI is well differentiated as the first and only approved at-home therapy in Brazil with slowing disease progression and quality of life indicated in the label.

In the first quarter, we saw continued growth in new patient identification and prescriptions in LatAm. As a reminder, Brazil has the largest prevalence of hATTR amyloidosis polyneuropathy patients worldwide.

Building on our core capabilities in LatAm, we anticipate a Waylivra filing with ANVISA in the second half of this year and continue to identify new SGS [ph] patients for Waylivra therapy. Turning to AADC deficiency, prelaunch activities continue to progress.

We have adapted to the current environment by implementing virtual education and patient finding initiatives, including conducting multiple master classes with over 200 health care providers in attendance from over 20 countries. We also rolled out a program called, "The Road Less Traveled" for finding a path towards early patient diagnosis.

We've also held multiple European Steering Committee meetings. We recently launched social media campaigns utilizing expert videos, focusing on symptoms and directing viewers to disease state websites.

Finally, patients continue to be identified as our teams push forward with virtual healthcare provider meetings to diagnose new patients in cerebral palsy and epilepsy clinic.

Looking back at the quarter, the home based administration of our commercial products allowed us to maintain our current base of patients and add new patients, even as the COVID-19 pandemic started to take hold.

As a result, the near -- in the near-term, we anticipate continuity of supply to the existing base of patients, some continued growth with new patients for both Translarna and Emflaza and continued operational improvements. I will now hand the call over to our Chief Financial Officer, Emily Hill to review our financial progress..

Thanks, Eric, and congratulations to Eric and Matt for their promotion. We are happy to have you on the management team. We're also happy to have reported such a strong first quarter with our DMD franchise growing 28% year-over-year and with the positive tailwinds from the first quarter continuing into April.

We feel well prepared to handle the current environment, as we have highlighted this afternoon. But due to lingering uncertainty regarding the duration and the degree of the impact of COVID, we are withdrawing financial guidance for 2020.

As you have heard reflected throughout today's call, we have given a great deal of thought to cost, timelines and prioritization throughout the COVID-19 pandemic. We're fortunate to have a portfolio of home administered commercial products, diverse assets across multiple platforms and the ability to shift resources as needed.

Strategically, we've identified trade-offs where we can push forward certain programs and be more conservative with capital intensive programs, such as deferring some capital expenditures for our Hopewell biologics manufacturing facility for future commercial products.

It doesn't impact our production of near-term commercial in the clinical programs such as AADC deficiency and Friedreich ataxia gene therapy that allows us to conserve some cash as we move through this uncertain time. Now I want to take a few minutes to highlight the first quarter 2020 financial results.

The press release issued earlier this afternoon summarizes the details of our first quarter 2020 financial results and I will review these details now. Starting with our top line results. We reported $68.3 million in total revenues in the first quarter of 2020 compared to total revenues of $53.6 million for the first quarter of 2019.

Translarna net products revenues were $40.5 million for the quarter. This compares to $35.3 million for the first quarter of 2019. Growth was driven by an increase in net product sales in existing markets, as well as continued geographic expansion into new territory.

For Emflaza, we’ve reported net product revenues of $27.5 million for the first quarter of 2020, compared to $17.8 million for the first quarter of 2019. Growth was driven by an increase in net product sales due in part to the operational improvements and efficiencies noted by Eric earlier.

Non-GAAP R&D expenses were $81.9 million for the first quarter of 2020, excluding $8.2 million in non-cash stock-based compensation expense compared to $47.9 million for the first quarter of 2019, excluding $4.7 million in non-cash stock-based compensation expense.

The increase in R&D expense reflects costs associated with advancing the gene therapy and Bio-e platforms and increased investment in research programs as well as advancement of the clinical pipeline.

Non-GAAP SG&A expenses were $51.2 million for the first quarter of 2020, excluding $7 million in non-cash stock-based compensation expense compared to $36 million for the first quarter of 2019, excluding $4.6 million in non-cash stock-based compensation expense, reflecting continued investments to support our commercial activities including our expanding commercial portfolio.

Net loss was $112.7 million for the first quarter of 2020, compared to net loss of $72.1 million for the first quarter of 2019. Cash, cash equivalents and marketable securities totaled $595.9 million at March 31, 2020 compared to $686.6 million at December 31, 2019.

Before I wrap up, I wanted to share the details of a transaction we completed this week with the former shareholders of Agilis that removed liabilities from our balance sheet. As you are probably aware, as part of our acquisition of the gene therapy platform, we owed Agilis future cash milestone.

We are pleased to have exchanged a subset of those cash milestones for cash and PTC stock. The future milestones include $40 million of time-based milestones that were owed in August 2020 and $185 million of cash milestones expected to pay in 2021 upon the approval of the AADC Deficiency BLA and the receipt of a Priority Review Voucher.

Almost 95% of former Agilis shareholders elected to exchange those 2021 milestones for approximately 2.8 million shares of PTC stock and an early receipt of the 2020 cash. This alleviates PTC a significant cash liability, especially in 2021 while we advance our gene therapy platform.

I will now hand the call over to the operator to start our question-and-answer session.

Operator?.

[Operator Instructions] Our first question comes from the line of Brian Abraham from RBC Capital Markets. Your line is now open..

Hi. This is [indiscernible] for Brian tonight. Congrats on all the progress in your handling of the COVID situation.

I just wonder if you could talk a little bit about how much progress you've been able to make on the additional study of the AADC gene therapy and gathered a combination prior to the pandemic? And then I guess what types of data from that study do you need to complete the following?.

Yes. Hey, thanks for that question. So yes, so we were making progress with the AADC clinical trial. Matt, why don’t you actually talk through what you would do -- what we were doing and next step..

Yes. Thanks, Stu and thank you for the question. As you mentioned, towards the end of 2019, we had received feedback from the FDA on additional data around the use of the intended commercial cannula in young patients. As a reminder, the clinical efficacy in our AADC deficiency program is quite strong.

We've demonstrated durable impact with 5 years of continued effect as well as evidence of continued benefit to 10 years, and we of course have a strong safety profile. Manufacturing also remains on track and we were able to submit the MAA to the EMA in January.

And so the key gating item for the BLA was the treatment of young children with the commercial cannula.

We had identified two patients that we were prepared to treat before the end of the first quarter and due to the hospital closure for elective surgeries, those procedures have been pushed back, likely to be done sometimes towards the end of Q2, possibly early Q3.

And so once we have those surgeries and the data from that, we will be able to continue preparations for BLA submission..

So we made [indiscernible] just the pandemic [indiscernible] so that -- it just take a little time to move forward on..

Great. Thank you so much..

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

Hi there. This is Eileen for Alethia. Thanks for taking our questions. I guess the first one is on COVID-19.

Just wondering, are you seeing any changes in buying patterns for Translarna? And then how do you manage to keep the access for patients? And then second, for the FIREFISH data, how do you think a risdiplam matches up to SPINRAZA and Zolgensma in type 1 patient? And then for SUNFISH data, is there any plan to present subgroup analysis, particularly around age, from the data set? Thanks..

Okay, great. Well, thank you. So the -- maybe we'll start with the first one, which is on Translarna, for that matter as well. So I think you could see from the numbers we have actually a good first quarter. And I think as both Eric and Emily talked, we are in -- we saw the numbers continually known. So the distribution remains ongoing.

And I think we feel patients have been able to be in order.

Eric, maybe you want to talk a little bit about how you see what's coming up in for the next quarter or two?.

Yes. Sure, Stu, and thanks for the question. We're seeing continued growth in the number of patients on both products with DMD, Translarna and Emflaza. And we haven't seen any actually decline in orders.

But actually what happens is, is we've actually been able to establish even deeper relationships with our health care providers and in some cases payers and advocacy groups during the pandemic. I think our main focus right now is really to provide that current base of patients we have on Emflaza and Translarna a continuity of supply.

And we haven't seen any sort of major upticks. If the question is centered around are people asking for multiple months, there have been a few patients that have asked for 90-day supplies of Emflaza. But generally, the vast majority of patients have been getting monthly supplies in the quarter.

That may tick-up a little bit, but it's not very significant. But most importantly, we've been able to really establish our case management team in the U.S., been able to establish a strong sort of connection with many of the DMD patients to ensure that they have all the resources they need.

And we currently have adequate -- and we assure them that we have adequate supply both in Emflaza and Translarna..

Yes. And so the second question relates to risdiplam and in a sense that contextualize how we feel the risdiplam will do relative to the other products that are out there. And it's really our contention that risdiplam is the best-in-class molecule with efficacy potential.

And I think, what you could see from the recent FIREFISH data is both Part 2, but as well, Part 1, that this was compelling efficacy that was seen in that. And that occurred even despite the older age, when you do comparisons of that.

And that we saw -- we not only did we see that, but we're able also to show durable increases in the SMN proteins and changes in the RNA, both in the CNS as well as the periphery. So that's actually really critical. I think we're the only ones who've been able to show that. We're not only we showed that, but it was in the periphery.

And we -- not as much has been talked about of how SMA, but it's becoming clearer and clearer is a whole body disease. Well, the CNS is critical, it also affects other tissues as well. And then we take another advantage is that it's really the risdiplam itself.

That is the treatment, you don’t need an intrathecal [ph] injection for that, nor do you need to take a immunosuppression as a consequence of taking the drug. So we think that's really a major advantage.

And then we also think that so far what we've seen to date was that there was no drug related safety findings and that we're very proud that we've had the broadest clinical trial program thus far in treating patients in SMA one, two and three patients from 2 to 25 years old, where we've had placebo controlled trials there.

We also have pre-symptomatic to older adults. So from naïve to pretreated. So we really have a breadth of a program that demonstrate the efficacy of that and then shown that both in the placebo controlled SUNFISH trials as well as in the risdiplam trial.

So when you contrast that, say for gene therapy, I think it's what you asked for and we think that there's little data beyond 3 years in terms of durability and even that one thing that can potentially confounded by the follow on therapy that were used, a compound which drug did what in terms of keeping the patient well.

We think there were more safety concerns in terms of both liver injury warnings, systemic corticosteroids are needed and then you need to be on immunosuppressants for greater than 2 months. And then it's really just not approved for all populations. And there's limited data in patients greater than three years old.

So taking that and we even think when you compare it nusinersen where the burden of the sick administration is more difficult than patients, say, with scoliosis, and then you have you continuous accumulation of the lumbar punctures.

And there have been meningitis and have hydrocephalus that’s been observed on the safety front and that there's a lack of trial data in patients greater than 9 years old. We think if you take all that into consideration and look at what risdiplam has done in the whole patient population, again, we think it's the best-in-class molecule..

Okay, great..

Then I think you had one other question which is the SUNFISH?.

Yes, the SUNFISH subgroup, yes..

Yes. That, you know, I'm sure we'll be having addition of posters over time on the data as it accumulates..

Okay, great. Thanks..

Thank you. Our next question comes from the line of Tazeen Ahmad from Bank of America. Your line is now open..

Hi, good afternoon, guys. Thanks so much for taking my questions. Maybe one on AADC, and then I have a couple more on a couple of other programs. Stu, in the past, you had been starting to give us updates on a number of patients that you've been able to identify.

Can you give us a refresh number on how many patients you have as of today? And also whether you're thinking still is that they're around, let's say, 6,000 patients worldwide that you hope to find over the course of the next several years..

Yes. Great, thanks for that. Yes. So I'd say that, yes, as we said in January, we had about 200 -- greater than 200 patients identified in the J.P. Morgan meeting. We continued to search. We obviously have some issues as a consequence of COVID and I'll have Eric talk a bit about that.

But we're still comfortable with the numbers that we said that we think is there. And now it's really a matter of patient identification. And to do so in the -- right now in the COVID environment is obviously more difficult than previous. And so we're still working hard at that.

Eric, maybe why don’t you talk a little bit about how we're doing this in the current environment..

Sure. So, hi, Tazeen. I think right now it's pretty safe to say that, the COVID environment has had a direct impact on patient identification efforts, but we're doing a lot of activities right now and adapting to this new environment. As Stu said, we've identified more than 200 patients at this point.

And our goal is to actually get 300 patients identified by the first country launch, whether that's in the U.S. or Europe. We have had a number of different initiatives, particularly in Q1. And when things started to slow down a little bit, we shifted and we increased our web presence in online efforts substantially.

We had a master class that had about 200 health care provider physicians in 20 countries.

We rolled out this program that was very, very well received, called "The Road Less Traveled" and it really helped sort of health care providers to understand how to diagnose AADC deficiency patients earlier, as well as recognize various symptoms, particularly in areas where we're trying to target right now to cerebral palsy clinics on epilepsy clinics.

In addition to that, we've actually had -- we’ve rolled out quite a few of the European AADC Steering Committee meetings. And we executed quite a number of those and had surprisingly really good reception from key opinion leaders in the virtual education classes to help with patient identification.

Now, with all that said, it's clear that COVID-19, have had an impact given that patient -- fewer patients are seeing physicians and tests are being done. But we're still doing quite a bit of activity virtually to keep up the educational noise level..

Okay. Thanks for that. And then maybe, Stu, a question on Translarna.

For the study that you're doing to measure dystrophin, can you give us an idea of what percent of patients have not yet received that biopsy? And does it make any meaningful difference if, let's say, a patient was scheduled to get a biopsy in March or April, but they don't end up getting it until May or June?.

Yes, that's a good question. So we -- probably we've gotten, I'd say we're waiting to get the last biopsy on approximately 40% of the patients somewhere around there. They were all scheduled to come in and this is sort of interrupted there. We don't think there's a real issue in terms of getting -- and took the biopsy for treating them longer.

We don't think that will be a real problem, right? So we should be able to be able to -- once the sites are back and running and open, be able to -- to be able to get this accomplished. So we don't think that that’s -- think that will be a big deal..

Okay.

And is there something that you've discussed with FDA, this delay?.

I think in general, they know that sites are having issues. And so I don't know if we've actually talked to them directly, but they put out things already about -- because they know some sites are just closed down, especially in metropolitan areas.

So -- and in this particular case, I mean, you might recall from the Sarepta case that they actually had a 9 month and 18 month. So we don't look at this as a real issue..

Okay. Thank you..

Thank you. [Operator Instructions] Our next question comes from the line of Joel Beatty from Citi. Your line is now open..

Hi. Thanks for the question.

So risdiplam launches, should we anticipate that payers will only cover as a monotherapy, or could there also be situations that payers could be open to paying for it as combo therapy, like Zolgensma or SPINRAZA?.

So maybe a couple of points to think about. When -- you’ve got to remember that, let's start with Translarna -- I mean, risdiplam with SPINRAZA. We don't understand actually why that was occurred necessarily, because they both sort of promote this alternative splicing into the SMA transcript.

And I think what -- I think -- and we've shown pretty clearly that you can actually make all of the SMA to our nation, to the appropriate RNA to make the protein. So risdiplam does a very good job in terms of being able to make the appropriate RNA and therefore proteins.

In the case of Zolgensma, our guess is that we'll be competing with them in order of getting type -- order to get type 1 patients in that.

My guess is that as patients feel a need to get additional treatment, they want -- and we know from our trial that we currently have that there are patients who -- from Zolgensma who are now on open-label trial, who are now getting risdiplam as well.

So we would anticipate that there'll be patients who probably would want to get risdiplam as well especially in light of, we don’t know how durable or the variability of how patients do when they get this..

Makes sense. And then I have one more question on risdiplam.

Are there certain regions that you anticipate have a little bit more favorable dynamics for more rapid launch than other regions? And what type of factors would help the region have a rapid launch of risdiplam?.

Well, we say -- I mean, I think that Roche will -- obviously Roche is in charge of -- in charge of commercialization, but they're certainly going to want to get moving rapidly in the U.S. and then really throughout the world, will want to be done. But the U.S. is the first, the first country that they will go for.

The other point actually I wanted to make on the previous question also was that when I think about it, there were precedents and where SPINRAZA was covered after Zolgensma. So I think, certainly that also goes along with the notion of we anticipate that risdiplam would probably be given [indiscernible]..

Great. Thank you..

Thank you. Our next question comes from the line of Joseph Thome from Cowen and Company. Your line is now open..

Hi, there. Thank you for taking my questions. Just the first one on the GMP manufacturing in early 2021. Can you just articulate how this maybe slight delay would impact any sort of initiation of gene therapy studies as those are tied together.

And then my second question is, it looks like there is a study on clinicaltrials.gov for Translarna in DMD patients aged 6 months to 2 years. Just wondering, what you're hoping to show here and is this related to a potential U.S. submission or the ex-U.S label? Thank you..

Sure. Yes, thanks. So the GMP manufacturing in terms of Hopewell site was really just so when we're thinking about COVID, we've already -- we already started making toxicology level material in the Bridgewater site. So we -- based on being able to do that, and we don’t anticipate really it would be slowing it down in any way.

So a lot of this is just for the opening the plant and we get 2021 in the current environment we have so that it will -- there'll be no delays as a consequence of pushing it forward by four months.

So we didn't think it was a real issue and it concerned a considerable amount of cash, so we thought we might well do that because we already created the tucked up access in our Bridgewater site.

In terms of the 6 months to 2 years, they just really just to get the extension and to be able to bring -- we've done the work to get the -- and we did that and we've gotten that actually approval in the U.S.

That was -- I mean, in Europe, sorry -- to expand the label so that people with [indiscernible] mutations can get it earlier and so that's what we’ve report towards. So that's just to continue to get earlier and earlier patients..

Great. And then, if I could just do one more on AADC. I see you're having some data presentation at ASGCT, outline changes of the body scale and aims and kind of functional endpoint.

In terms of the regulatory review and maybe what physicians are interested in, how are they each going to look at these different efficacy endpoint? Is the one that's most important, or they look at them kind of holistically..

Sure.

So, Matt, do you want to take that?.

Yes, sure. Thank you, Joseph, for the question. I think what we -- when we think about the AADC data package, first, it's very important is the fact that we're able to show on PET scan that there is a significant increase in dopamine production in all the patients.

So that's the first very important sign that we're addressing the critical underlying biochemical defect. That's very compelling evidence that we're really targeting the fundamental pathology of the disease.

Then as you look at the data package in its whole, including the primary endpoint of head control, we're able to show that there's benefit in every patient treated.

And what we're now seeing with the long-term data as shown in some of the abstracts you mentioned is that we're seeing durability of effect out past five years, even close to 10 years in some patients. That's a very strong, compelling data.

So what we believe is that physicians will appreciate the totality of the data that one we're addressing, the fundamental biochemical defect in all patients; and two, across the board we're seeing correction and evidence of correction of the key motor function defects in the disease, and that those effects, those favorable effects are sustained..

Great. Thank you so much..

Thank you. Our next question comes from the line of Vincent Chen from Bernstein. Your line is now open..

Congratulations on all progress and thanks for taking the questions. A couple for me. The first one is just on, I guess, revisiting the COVID-19 impact. I was wondering if you could elaborate a little bit further on what impact you’ve seen so far or a slowdown related to COVID.

It sounds like the franchises have been pretty resilient so far and have to imagine the [indiscernible] largely been in April. It was basically made to withdraw guidance given potential COVID related impacts.

Just want to get a better sense for whether you're indeed seeing any slowdown in demand for return to market products over the course of the last couple of months, whether end of Q1 or in April to date? Or is pulling guidance just in case things were to get worse going forward. And then the second one is -- I will pause there. Yes..

Okay. So -- yes, that’s a good question, because it goes to the pulling of guidance was more on -- or withdrawing it at the moment, really on the uncertainty of the -- of where things are going. In the long-term, you just don't know.

I would say in the short-term, we feel pretty good where in the first quarter and even after how they slow in terms of maintaining the patients already on drug and using new prescriptions. So it wasn't like we saw a slowdown.

And maybe, Eric, maybe you want to put a little bit of -- around this a bit?.

Yes. Sure, Stu. Yes, Vincent, thanks for the question. I mean, in terms of the top line, I mean, we've seen the trends right now, both in Europe with Emflaza that are very encouraging still. As I mentioned, we haven't had any kind of increases at all, patients asking for more product.

We've been shipping mostly -- most the patients on a month-to-month basis. And we continue to see those positive trends in Q2.

The existing patient base and new patient growth is still there, although new patient diagnosis and new prescriptions have decreased a little bit now, as we've seen, because patients are not seeing physicians as frequently, but we have protected the base, which is very good and the trends are good there.

We have gone back to make sure that everybody realizes we have an adequate amount of supply. And there have been some requests in addition to the uptake. There have been a few patients and we're seeing more and more requests for potentially 90 days of supply for Emflaza, but it's still a small percentage.

I think what we were concerned more about is the unknown. And I think as Stu highlighted, there's -- if the pandemic continues and there is a shift of unemployment and payer mix or potentially disruption to some of our Translarna shipments that might be in various markets.

Keep in mind, we have patients in close to 50 countries with partners as well as direct business. If some of that is disrupted because of the pandemic, at this point in time, we're just trying to be cautious.

But there's no indication now that based on our strong results in the first quarter and what we're seeing so far right now, that we're losing patients or that growth would go down. And I will give it back to Stu..

Right. And maybe one quick follow-up on that point.

If you think about the price for Emflaza in the U.S., how does the price paid on Emflaza differ between patients on commercial insurance and patients who are on government insurance? Take another way, if more patients were -- if you were to see a meaningful shift in payer mix, how might that impact the net price paid on average?.

Yes. Well, the simple answer is, it's basically the statutory rebate from CMS, which is more -- which is higher right now. Our current payer mix is about sort of 60-40 with commercial payer thing the majority. If obviously that shifted our gross to net would shift because there would be more patients moving onto Medicaid. So far, we haven't seen that.

And that seems to be that DMD families in general have pretty good insurance and have covered. And then in addition to that, if patients do go from private payers to Medicaid programs, a number of the states actually have disability programs for children and they can move very quickly.

So, again, I think the only effect there, Vincent, would be the statutory rebates that we would have to pay to CMS, if the payer mix shifted..

I see. And let me ask another one, just on Translarna and the ongoing study. I was just wondering if you could give us a sense for how the powering calculations were done in terms of using the number of patients in the ongoing U.S. dystrophin study.

What data did you have sort of draw upon in terms of estimating the likely effect size, like are there -- is there data you collected from other patients treated with Translarna to see just how much of an increase you see in dystrophin, whether from your studies or from clinical experience, I guess, in territories where Translarna is used?.

Yes. Yes, thanks for that. That's a good question. We did look at other studies as well, and it was based on data that we saw from Sarepta and some just making some assumptions based on that and what the assays like that we got there.

Matt, do you want to sort of -- is there anything else you want to answer that?.

Yes, just that we believe with the 20 subjects in the trial that we would be able to achieve -- we have 90% power, which we thought would be sufficient to show the Translarna effect. And, of course, we expect a baseline to be very, very low levels of dystrophin expression..

When you say 90% power, do you -- can I just ask, what was the effect size and the variability?.

Correct. As Stuart said, base we'd be looking at other trial data and running simulations..

Okay. Thanks for taking all the questions..

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

Hi. This is Peter for Gena Wang. Thank you very much for taking the questions. I guess, my first question -- my question is on risdiplam.

I guess, do you expect to -- do you expect risdiplam to generate meaningful revenue this year, or do you anticipate some patient initiation impact to COVID? And my second question on the related note is could you remind us when the EAP was opened and how many patients have been sort of enrolled in U.S.

and OUS? And whether pre-COVID and post-COVID EAP enrollment rate has sort of changed? Thank you..

Sure. So maybe the big picture on COVID and revenues. So I think on the big picture, COVID, I think in some ways I think people will start thinking about how do I make sure I get -- have drug supply to patients. So I think in some ways that might be helpful from a commercial launch perspective.

I think in terms of revenues that would be royalty, maybe Emily, you want to talk a little bit about that?.

Sure. I mean, we have the potential for up to $42 million in milestone this year on our collaboration with Roche on the risdiplam programs. Obviously, we have tiered royalties up to the mid teens and with the MAA having them submitted earlier this year and PDUFA in the U.S. now in August 24, I'd expect this to ramp up more significantly next year.

I think as far as COVID impacts the rate and ramp of those revenues, there's really some advantages and potentially being the only SMA therapy that can be delivered at home..

And then the patient numbers. Well, I don't think Roche has discussed that. But I think what they did say on the call previously, and what they have chosen is a lot of interest.

And so they are bringing patients in, already -- that are already on the EAP and they're continually do that both in the U.S as well as then to set it up also in Europe as well. So it'll be a global, in a sense EAP program. It was certainly in the U.S. all over and then in countries that allow you in Europe to have these EAP programs..

Got it. Thank you very much..

Thank you. Our next question comes from the line of Raju Prasad from William Blair. Your line is now open..

Thanks for taking the questions.

On risdiplam, when do you anticipate presenting additional JEWELFISH and RAINBOWFISH data? And do you have any general -- aside from what you’ve already mentioned, do you have any general commentary on how many patients are Roche is bringing in on the expansion of the Early Access Program, or any details around how -- what types of scenarios that they’re expanding it too, just if patients are off spin rather, don’t want to go in, they apply, or is there more stringent criteria? And then I have one on Translarna..

Sure. Yes, so that’s an important point too, is that they’re now planning presentations for that probably be an update on the [indiscernible] SMA. And then, yes, they have changed the EAP program to allow patients to who are in other therapies to get into the EAP program as well. And they’ve also added type 2 as well to the program.

So, yes, so patients who can't get, say, intrathecal injections or naive patients, that they certainly can. It's really based on the physician discretion based on what they think the need is. So COVID is obviously making limited access. So this is really a nice way which they can get it at home and take it.

So that's also adding to the number of patients who are hopefully transitioning to risdiplam. Very strong interest in this though..

Yes. Do you have any idea of how many in the U.S.

versus EU are getting on the early access program, just kind of a general percentage wise?.

No. Yes, that hasn't been disclosed yet..

Okay. And then one on Translarna. I know obviously, you pulled guidance and you've commented on it enough on this call.

But just wondering, usually, you have a Q2, Q4 bolus from Latin American orders, is the general pattern of revenue recognition going to be similar?.

Yes. I think -- so I think maybe Eric could comment on that..

Yes, sure. We are -- with regards to Latin America, for Translarna, as you can recall, we had approval from ANVISA last year, and we've been building a very nice base of patients. And we saw new patients coming in the first quarter, not only diagnosing these patients, new prescriptions.

But the base of patients that received positive injunctions for therapy continues to increase. So we've seen growth on all those parameters. With regards to that base, we have ongoing negotiations with the Minister of Health and with ANVISA to require that we get those group purchase orders.

We're working towards securing a new purchase order in the second quarter. We've shifted a lot of our virtual communications right now with the Minister of Health because of COVID-19 to virtual-type meetings, and we continue to have a very strong working relationship with the payers in Brazil.

So our goal is, as we've seen continuous number of increases in patients right now, our goal is to get and secure an order for Q2, barring any kind of exceptional acceleration of the pandemic or some kind of government diversion of resources.

You got to keep in mind though that the rare disease bucket for cost centers at Minister of Health is relatively small in comparison to the overall health care budget. So we think we can work through some of these things and negotiate and hopefully obtain an order in Q2 and ensure that patients continuity is there.

But we are -- again, we are very encouraged with the continued growth, and it's going to continue to put pressure on the Minister of Health to secure those orders..

At this time, I'm showing no further questions. I would like to turn the call back over to Stu for closing remarks..

Okay. Well, look, I want to thank all of you for joining the call today. I want to remind you that at the end of March was our 22nd anniversary at PTC. And so I look back upon now our long history, I'm very proud of how the company has evolved.

It's gratifying to see the progress that we've all made and continue to make in discovering, developing and commercializing treatments with -- for patients living with rare disorders. And I think really a consequence of the hard work and dedication of the team.

We're well positioned to be able to push forward and even thrive, even under this uncertain environment. So again, thank you for joining the call. I look forward -- I hope to see you all soon..

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