Good day, ladies and gentlemen, and welcome to the Sarepta Therapeutics First Quarter 2020 Earnings Call. At this time, all participants are in a listen-only mode. After the speaker presentation there will be a question-and-answer session. [Operator Instructions] As a reminder, today's program is being recorded.

And now I would like to introduce your host for today's program, Ian Estepan, Senior Vice President, Chief of Staff and Corporate Affairs. Please go ahead..

Thank you all for joining today's call. Earlier today, we released our financial results for the first 2020. The press release is available on our Web site at www.sarepta.com, and our 10-Q was filed with the SEC earlier this afternoon. Joining us on the call today are Doug Ingram, Sandy Mahatme, Bo Cumbo, Dr. Gilmore O'Neill, and Dr.

Louise Rodino-Klapac. After our formal remarks, we'll open up the call for Q&A. I'd like to note that, during this call, we'll be making a number of forward-looking statements. Please take a moment to review our slides on the webcast, which contains our forward-looking statements.

These forward-looking statements involve risks and uncertainties, any of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements, and any such risk can materially and adversely affect the business, the results of operations, and the trading prices for Sarepta's common stock.

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

The company does not undertake any obligation to publicly update its forward-looking statements, including any financial projections provided today based on subsequent events or circumstances. And with that, let me turn the call over to our CEO, Doug Ingram, who will provide an overview of our recent progress.

Doug?.

Thank you, Ian. Good afternoon, and thank you all for joining us for Sarepta Therapeutics' first quarter 2020 financial results conference call. Let us begin with a topic that is on all of our collective minds, COVID-19.

I am very proud that the Sarepta team is still rapidly responding to this crisis, focusing on the safety and welfare of our patients and our workers, while ensuring that our operations run smoothly, and that our programs proceed.

We are able to do this not only due to our execution-oriented ability to adapt and remain focused, but also because of good advanced planning.

Numerous of our functions, including in particular, our information technology group, our clinical operations function, and our commercial organization began contingency planning as early as January of 2020 in the event that what came to be COVID-19 became a crisis.

For that reason we were able to rapidly respond [technical difficulty] situation unfolded.

By Friday, March 13, I had ordered that all but a small but dedicated facility-dependant staff would work from home, and because of our advanced preparations and the systems and the infrastructure in place to seamlessly transition, execute, and remain connected as we commenced work in that Monday morning.

About 10% of our workforce is designated as facility-dependant, and we have worked to keep them safe and comfortable as they come in to the facility to run labs and experiments, continuing our manufacturing activities, and the like.

We also immediately reached out to our partners, suppliers, and other important third parties to assess new working arrangements with them and to assure that they and we would continue to deliver, and we reached out to our patients and patient advocates to ensure that we were fulfilling their needs to the fullest extent possible.

It is for these reasons and others, that while COVID-19 has created some challenges for Sarepta and for our plans, Sarepta is in a privileged position even in these difficult times. Yes, as with all biotech companies, COVID-19 has created some challenges and uncertainties, and will continue to do so for the next few quarters.

[But on the whole] [Ph], we are uniquely positioned to drive our strategic plans, and to stay on mission during these difficult times. In that regard considering the following, first, anticipating that we would need greater certainty around cash and capital in 2020 and beyond 2020.

In late 2019, we entered into the Roche transaction, which added another $1.15 billion to our balance sheet, [technical difficulty] through cost sharing, and entitles as to milestones along the development and regulatory pathway.

Along with our Roche infusion, at the end of the first quarter, we had nearly $2.2 billion of cash on hand not including another $250 million in a debt facility that we have not drawn down.

This level of cash on hand places us in a rarefied position among biotech companies, and of course, that is before considering our revenue from EXONDYS 51, VYONDYS 53, and if and when approved, Casimersen.

We are in a strong position to weather any COVID-related uncertainties, stay focused on executing our plans, and emerge from this pandemic on track. Second, the greatest development challenge reported in the biopharmaceutical industry right now is the commencement of the trails.

Fortunately we are already in 10 human clinical trials, all of which are intact and progressing, and our talented development and clinical operations team work diligently to minimize the impact of COVID-19.

Moreover, with respect to Study 102, our gene therapy trial for microdystrophin, this is a one-time therapy in all patients for the primary 48-week analyses have been dosed. That trial progresses and there is no foreseeable risk of a delay in trial readout.

Next, with respect to our currently available therapies, EXONDYS and VYONDYS for the treatment of Duchenne Muscular Dystrophy, our supply chain is fully intact and we are able to manufacture its supply therapy without any interruption, and we do not anticipate this changing.

And finally, one of our most significant strategic activities is building out commercial gene therapy manufacturing capacity, and we made less progress in the last 12 months. COVID-19 could have caused significant disruption. Fortunately our progress has kept us on track during this crisis. The necessary facilities and suites are largely built.

All of our assays are built, and all but two of the 24 necessary assays are either already validated or qualified as required, with the remaining two near completion even as we speak. Our process development is complete, and our engineering runs and commercial GMP runs are on track.

Hence notwithstanding this pandemic we remain on track to have SRP-9001 GMP material this July, as originally anticipated. With that, I will comment on current period performance, and then I will touch on the status of some of our most significant development programs.

I am pleased to report that in the first quarter our net sales were $100.4 million; that is a 15% increase over the same period last year. There was a modest impact on revenue in the quarter as a result of the COVID crisis, but as you can see from our reported performance it was not significant.

Looking forward, while we have a number of elements that are encouraging and protected, such as the high percentage of infusions that occur in-home, we do anticipate that COVID-19 will have a negative short-term impact to revenue. For instance some patients may have difficulty getting or keeping infusion appointments in hospitals.

This impact will be more significant for VYONDYS which is just launching than EXONDYS as most existing patients are already on home infusions for that treatment. Additionally, while we anticipate that this will not occur often, some patients could forgo an infusion to avoid a third party in their homes during the peak of this crisis.

Finally, any payer delays in processing reauthorizations could impact revenue, although we assume that payers, both state and private, will understand the duty in these difficult times to make reauthorization efficient and will not take advantage of this crisis to profit by slowing the reauthorization process, and we are working with payers and patients to remove any COVID-related roadblocks to reauthorizations.

We currently anticipate the COVID-related impact on sales to be both modest and short-lived. Given the dynamic and unprecedented nature of this pandemic however we do not have sufficient clarity yet to accurately forecast and provide updated revenue guidance that reflects the impact of the virus.

We will monitor, and in our second quarter earnings call we'll provide an updated view. Moving to our clinical programs, as noted above, our plans remain intact with only a modest impact on the timing of some programs anticipated.

With respect to SRP-9001, our microdystrophin gene therapy program, our Study 102 evaluating the safety and efficacy of SRP-9001 in patients with Duchenne Muscular Dystrophy is proceeding and it is in good shape. All patients for the 48-week analysis have been dosed.

And while there were some delayed functional visits, we worked to minimize any disruption and documented the few delays in accordance with the FDA's guidance on this topic, and our statistical analysis indicates there is little risk to the powering or the integrity of this study.

We anticipate that going forward there should be few substantial delays. We have two sites to Study 102. Our site at Nationwide Children's Hospital, with Dr. Jerry Mendell as Principal Investigator, imposed restrictions on some in-hospital visits.

However, Nationwide Children's Hospital has loosened those restrictions already while maintaining the safety of our trial participants. Our site at UCLA, with Dr. Perry Shieh as investigator, continued throughout to permit visits uninterrupted.

So in short, Study 102 is on track, it is progressing well, and it is said to read out in the first quarter of 2021, as anticipated. As relates to the commencement of Study 301, we continue to progress. To remind you, Study 301 is our planned multi-center, multi-country Study for SRP-9001 using commercial process material.

We are continuing to make progress toward the initiation of trial sites; however COVID-19 does create some challenges here. While the team is making progress, COVID-19 creates uncertainties around the status of some clinical sites and will likely delay some necessary site initiation visits.

Moreover, we do not want to commence dosing at sites until we're confident not merely that they can initiate, but that they will be able to remain operational, can dose, and can consistently and timely assess participants. We hadn't anticipated commencing Study 301 around the middle of 2020.

We are on track to have GMP material for Study 301 by July of this year. However, in light of COVID-19, we may modestly delay initiation, but we'll still anticipate commencing Study 301 in the second-half of this year.

Moving to LGMD2E, as you will recall, our goal was to have expression and safety data from our three patient cohorts in our high dose arm for SRP-9003 to treat LGMD2E in the second quarter. The team has addressed and overcome COVID related obstacles, and we are indeed on track to evaluate and release that data this quarter.

Given that live conferences have been canceled, we will reflect on the best approach and we will update, but again, our goal is to release this quarter as anticipated.

Beyond that, the remainder of our plans are also on course, manufacturing is progressing, we have commenced our first commercial GMP run for LGMD2E, and we intend to commence what we hope to be the pivotal trial in 2021 as previously anticipated.

With respect to MPS III A, our gene therapy trial with Lysogene, that trial has enrolled and dosed 19 of the 20 patients in that trial, and is on track to dose all patients by mid-year as previously indicated.

Now, moving onto the RNA platform, as you know, we are in our rolling submission for our third RNA therapy, Casimersen intended to treat DMD patients who have a mutation amenable to Exon 45 skipping. That submission is proceeding and it has not been impacted by COVID-19. We should have that submission complete this quarter, as anticipated.

Our two RNA confirmatory trials and that's mission for EXONDYS and essence for VYONDYS and if approved Casimersen, or chronic therapy trials and largely ex-U.S. and thus COVID-19 has created more disruption in our gene therapy trials, both in terms of missed visits, and some missed doses.

However, the team is working diligently to reduce impact, ensure trial integrity is preserved and that the trials are proceeding. Next we're in our multi-ascending dose trial for SRP-5051, our next generation RNA technology founded on our peptide conjugated PMO or PPMO platform for short.

This is a significant program and the goal of our multi-ascending dose study is to evaluate whether we're able to safely reach high doses of the PPMO.

If we're able to safely achieve therapeutic doses with this technology, our preclinical models predict that the PPMO could be a potentially profound advancement over our current RNA technology, the PMO. It was our intention to provide a data release on SRP-5051 by mid-2020.

While we still intend to announce those results in 2020, it will likely come in the second-half of 2020 for two independent reasons.

COVID-19 did interrupt some dosing, which caused a very modest delay, but importantly, the team quickly address the obstacles permitting infusions to continue, but more significantly still, this is a dose escalating study, and the timing of readout depends in large measure on the doses achieved.

At the inception of this program, we had anticipated that we could achieve robust expression between 6 mgs per kg to as high as about 12 mgs per kg. However, we have escalated through those doses, and we're already dosing at 20 mgs per kg, nearly 100% higher than the top end of original expectations.

Reaching higher doses than we anticipated when the study commenced has necessarily resulted in some delay in reading out that study. Although as you can imagine, it is not the sort of delay with which we're particularly upset. Again, we still anticipate a readout for our PPMO in the second-half of this year 2020.

Speaking of our PPMO program, you will have seen on April 28th, a press release in which we announced that Sarepta and the United States Army Medical Research Institute of Infectious Disease or USAMRIID, the lead medical biologics labs for the Department of Defense have entered into a cooperative Research and Development agreement to evaluate our PPMO to treat COVID-19.

While, we are not currently focused on antivirals, it was a focus of Sarepta in the past, and our RNA platform has shown promise in treating viruses, including coronaviruses. The head of USAMRIID has a detailed knowledge of our PPMO technology, and on that basis, reached out to us to propose working on COVID therapies.

Informed by USAMRIID's knowledge of the SARS-CoV-2 virus and potential hotspots that might be targeted, even before the agreement was executed, we built a number of therapeutic candidates based on our PPMO platform and had them manufactured in sufficient supply to be evaluated.

We have already transferred them to USAMRIID, which will be responsible for testing and evaluating them in their proprietary in vitro models to determine their potential in reducing viral replication. With one or more of our candidates shows promise, USAMRIID and Sarepta will discuss a plan to move forward.

Sarepta is a mission-driven organization dedicated to using our science to bring a longer, richer, more liberated life to those living with and far too often dying from rare genetic diseases, diseases like Duchenne Muscular Dystrophy, or DMD, and the like.

It has been critically important to us that we do not find ourselves thrown off mission by this current crisis, and that our patients do not suffer delay in our programs to the fullest extent that we can avoid that, and I am proud to say that we have been able to largely fulfill that goal.

Nevertheless, we are in a crisis, and like others we have technology that may benefit society in this fight. So, when crisis came, we answered the call, and through this cooperative agreement with USAMRIID, have been able to employ our technology rapidly, and to do so without distracting us or taking substantial resources away from our main mission.

Moving to infrastructure and talent, things are going quite well, our employees are removing obstacles and staying on mission with our strong cash position and revenue stream, we are able to focus on executing our plans and hitting our milestones, with only limited delay.

All of our facilities are operational, including our technical operations and CMC related facilities. Our Gene Therapy Centre of Excellence in Ohio, and our Gene Editing Innovation Centre in Durham, North Carolina where we are already in our facility and hiring scientists all under the leadership of Dr. Charlie Gersbach of Duke University.

I would like now to give a big thanks to our dedicated facility depended workers who have been coming into the facilities and laboratories during this difficult time, to ensure that experiments and other facility dependent activities, proceed without delay.

In summary, I do apologies that this discussion has been dominated with references to COVID-19, but it is indeed a crisis. And it is a crisis that must be taken seriously.

No rational person desires a crisis and certainly not a crisis like COVID-19, which has caused so much fear, suffering and loss of life, but the one thing that is clarifying about a crisis it does indeed test our mettle, our resourcefulness, our creativity, our optimism, and our commitment.

We often learn far more about ourselves in time of crisis than in times of ease, and in that regard, we all have much about which to be proud, first, we should all be proud of this biotechnology industry.

In times of crisis, this industry has answered the call with energy and passion and investment, building diagnostics, quickly developing therapies, working on vaccines. Consider the great work of the many companies that have joined this fight.

I am proud that Sarepta with our proprietary RNA technology is playing a role in fighting this disease, even as we remain laser focused on advancing our rare disease mission and serving our patients.

This COVID-19 may seem fierce to some, but it is by no means invincible and it is no match for biotechnology innovation, along with the science and commitment, our industry will defeat this pernicious disease. And second, I am particularly proud of my Sarepta team, we've spoken about the importance of our mission often.

When driven by a commitment to develop therapies, with a pace that allows us to intervene in trying to save lives. The diseases we fight are unrelenting. They do not take time off for this crisis, and so, our Sarepta family is unrelenting, we have not taken time off of this crisis.

When this crisis came, this team answered the call adapted and kept executed.

And like so many people today, we did all of this while dealing with new challenges, new working environments, having to juggle work and childcare and level one concerns and concerns from themselves, and because of their commitments, Sarepta remains on mission, on strategy, and our programs have been largely unaffected by this crisis.

So, to all of the dedicated Sarepta workers who spend their days focused on moving our goals forward while protecting the patients that we serve, I want to say thank you, and I couldn't be prouder. And with, that I'll turn the call over to Bo.

Bo?.

Thank you, Doug. Good afternoon, everyone. Despite the headwinds facing our healthcare system due to the COVID-19 pandemic, I am pleased to report that our product revenue for the first quarter of 2020 totaled $100.4 million.

Our experienced teams at Sarepta are actively working to navigate through the challenges of the COVID-19 pandemic and allow us to mitigate major treatment disruptions for patients taking EXONDYS 51 or VYONDYS 53.

We will continue to navigate the environment, and are learning more each day on how to better serve our patients in this unprecedented time. We continue to work closely with our manufacturers, distributors, and specialty pharmacies, to provide an uninterrupted supply of our therapies.

As a result, we've had no disruptions in supplying EXONDYS 51 or VYONDYS 53 to patience. Consistency of supply is key. Therefore, we will continue our efforts to ensure that EXONDYS 51 and VYONDYS 53 are supplied to patients throughout the COVID-19 pandemic.

We have modified our commercial execution strategy in response to the strain to COVID-19 pandemic has placed on health care workers, hospitals, and distribution channels.

Due to recent shutdown to restrictions at hospitals and clinics, our team is working closely with health care providers and specialty pharmacies, to transition patients to weekly home infusions. Fortunately, the vast majority of patients on EXONDYS 51 are already receiving home infusions. Patient safety remains our top priority.

And since many of our patients are choosing not to delay or stop therapy, we have thoughtfully deployed measures to minimize the risk of COVID-19 for all our patients, and we'll continue to assess these efforts. We are working towards initiating patients on VYONDYS 53.

However, this environment is challenging because physicians typically wants to monitor patients in the clinic for the first couple of infusions, and many patients are having difficulty maintaining regularly scheduled appointments with healthcare providers. We will continue exploring options for patients to safely initiate treatment with VYONDYS 53.

We are still engaging with key opinion leaders and other healthcare providers on a weekly basis. Additionally, we're having ongoing conversations with payers, about the need for patients to start and stay on therapy regardless of ambulation status, age, or gender.

While many of our face-to-face meetings have been placed on hold, the strong relationships we've established with our partners over the years has helped us transition from in person interactions to virtual engagements.

To help minimize access and reimbursement barriers, we continue to work with commercial and state Medicaid plans on reauthorizations, so that patients are able to stay on therapy. We are encouraged by the efforts payers have made to not disrupt patient's treatment plans during this difficult time.

Transitioning to our performance for the first quarter, many biotechnology companies often face headwinds related to typical health plan enrollment cycles that impact revenue. The team has been able to successfully navigate these challenges and maintain patients on EXONDYS 51 without significant disruptions.

In the current environment, the dynamics of initiating treatment with EXONDYS 51 or VYONDYS 53 are affected. While many clinics are closed or not seeing patients for normal in-person appointments, the impact has resulted in fewer patients initiating treatment.

However, we do anticipate this will change as restriction fees and clinics resumed normal operations. As a reminder, VYONDYS 53 or Golodirsen received accelerated approval from the U.S. FDA on December 12, 2019. VYONDYS 53 treats patients with Duchenne Muscular Dystrophy who are amenable to exon 53 skipping.

We anticipate that patient demographics for VYONDYS 53 will be similar to EXONDYS 51 with regards to the average age of patients on therapy, and the mix of commercial versus Medicaid patients.

Over the past three-and-a-half years, we've continuously reviewed and refined our approach for EXONDYS 51, while we're leveraging our deep knowledge and expertise from that launch, we will continue to monitor the impact that COVID-19 pandemic has on the VYONDYS 53 launch trajectory.

We feel confident that over time patients will ultimately receive access and reimbursement for VYONDYS 53 and start therapy in a timely manner. Launching a new rare disease drug is already a complex undertaking and we're very proud of the accomplishments the team has made to-date, particularly in light of the extraordinary circumstances.

The knowledge we gather strengthens our plans for future launches including Casimersen in 2021.

The depth of experience on their teams has helped us navigate through this unprecedented time and we feel confident that the lessons are and will make us a stronger company, better able to serve our patients and deliver on our mission as a global leader, precision genetic medicine. And with that, I'll turn the call over to Sandy.

Sandy?.

Thanks, Bo. Good afternoon, everyone.

In the first quarter total revenues in line with expectations and following the close of the agreement with Roche, and the sale of the Priority Review Voucher that we received in conjunction with the approval of VYONDYS 53, we are in a strong financial position with significant capital to fund our pipeline and ramp up manufacturing while maintaining our overall timelines.

In addition, we not have the ability to access Roche's significant expertise and greatly enhance our global opportunity for SRP-9001. Moving to the financials, this afternoon's press release provided details for the first quarter of 2020 on a non-GAAP basis as well as the GAAP basis. The press release is available on Sarepta website.

Please refer to our press release for full reconciliation of GAAP to non-GAAP. Net product revenue for the first quarter of 2020 from our products EXONDYS 51 and VYONDYS 53 was $100.4 million, compared to $87 million for the same period of 2019. The increase primarily reflects higher demand for our products.

In the quarter-ended March 31, 2020, we recognized $13.2 million of collaboration revenue, which relates to our collaboration agreement with Roche. In February 2020, we received an aggregate of approximately $1.2 billion in cash consideration from Roche consisting of an upfront payment and an equity investment in Sarepta.

From an accounting perspective, $342.7 million is being recognized in revenue on a straight line basis over the performance period, which we estimate to be through the fourth quarter of 2023. This revenue has been excluded on a non-GAAP basis per Sarepta's policy.

For the quarter, co-development under the Roche agreement totaled $16.4 million and are included as a reduction to R&D expenses. On a GAAP basis, we reported a net loss of $17.5 million and $76.6 million or $0.23 per share and a $1.07 per share for the first quarter of 2020 and 2019 respectively.

We reported a non-GAAP net loss of $79.8 million or $1.04 per share in the first quarter of 2020, compared to non-GAAP net loss of $53.8 million or $0.75 per share and the first quarter of 2019. In the first quarter of 2020, we recorded approximately $12.6 million in cost of sales, compared to $12.1 million in the same period of 2019.

The increase was due to royalties paid to BioMarin Pharmaceuticals and University of Western Australia as well as higher product cost as result of increasing demand for our products. This is partially offset by the write offs of certain batches of EXONDYS 51 that did not meet our quality specifications for the first three months of last year.

There is no similar activity for the first three months that ended March 31, 2020 i.e. this year. On a GAAP basis, we recorded $136.1 million and $90.6 million in R&D expenses for the first quarter of 2020 and 2019 respectively, which is a year-over -year increase of $45.5 million.

This increase is primarily related to a $43.3 million increase in clinical and manufacturing expenses. On a non-GAAP basis, R&D expenses were $114.2 million for the first quarter of 2020, compared to $81.4 million for the same period of 2019, an increase of $32.8 million.

The year-over-year growth in non-GAAP R&D expenses has been primary due to a continuing ramp up of our microdystrophin program as well as our essence program. Turning to SG&A on a GAAP basis, we recorded $82.8 million and $60.6 million of expenses for the first quarter of 2020 and 2019 respectively, a year-over-year increase of $22.2 million.

On a non-GAAP basis, SG&A expenses of $54.5 million for the first quarter of 2020, compared to $47.8 million for the same period of 2019, an increase of $6.7 million. The year-over-year increase was driven by significant organizational growth and expansion.

It supported our commercial launch plans as well as 40 therapies in various stages of development across several therapeutic modalities. On a GAAP basis, we recorded $7.4 million in expenses net for the first quarter of 2020, compared to $0.2 million other expenses net for the same period of 2019.

The unfavorable change primarily reflects the interest expense on our deck facility entered into in December of 2019. In February of 2020, we entered into an agreement to sell the rare pediatric disease Priority Review Voucher WC from the FDA in conjunction with the approval of VYONDYS 53.

In March of 2020, we completed our sale of the PRV and received proceeds of $108.1 million net of commissions which was recorded as a gain from the sale of the PRV, as it did not have any carrying value at the time of the sale. There was no similar activity during the three months ended. March 31, 2019.

We had approximately $2.2 billion in cash, cash equivalents and investments as of March 31, 2020. With that, I'd like to turn the call over to Gilmore for an update on a research and development activities.

Gilmore?.

Thank you, Sandy, and good afternoon. I would dive a little deeper into the top R&D related activities that Doug has highlighted with particular emphasis on the actions the team has taken to minimize and where possible eliminate the distractions and obstacles caused by COVID-19.

First, our SRP-9001 microdystrophin program, we look forward to the imminent publication of the one year safety and functional data from the four clinical trial participants, who received microdystrophin in Study 101. As with any onetime therapy, we know you are interested in the durability of the functional response in these patients.

As Doug mentioned, Study 102 is in very good shape. We have dosed all patients in part, which is the randomized double-blind placebo-controlled portion of the 102 Study. Notwithstanding some of the constraints arising from restrictions of patient visits to the sites, we have been able to continue monitoring patient safety as data quality.

Some clinical evaluations would take place "Outside of the protocol defined window." These are not critical outcomes and we are already evaluating how to mitigate the impact of out of window assessments in our analysis and regulatory plans.

We are also pleased to see that Nationwide Children's hospital is loosening COVID-19 restrictions and starting to resume clinical trial activities. And I should note that our second Study 102 site UCLA with Perry Shieh as investigator has not imposed restrictions. So, Study 102 is proceeding and we anticipate no delay in the readout of that study.

As far as our Study 301 plans go, I am pleased to report that we have adapted rapidly to the COVID-19 related uncertainties of the next few months. We are maintaining close contact with all of our sites around the world. Investigators remain very excited about the program and want to start as soon as possible.

Nevertheless, we must acknowledge that uncertainty hovers over the readiness of individual countries and hospitals to remove travel and visit restrictions.

Further, the bandwidth of ethics review boards and regulatory agencies to engage in reviews of new protocols may be affected as they deal with a large volume of requests from multiple sponsors in multiple therapeutic areas to amend current studies impacted by the COVID-19 pandemic.

Fortunately, the global footprint of our clinical sites gives us significant flexibility to enable dosing this year, Doug has told you about the status of our ongoing study of SRP-9003 in limb-girdle muscular dystrophy type 2E.

To remind you of the study design, we are comparing the safety and expression data of a low dose arm of 5 to the 13 VG per kilogram to dose arm of four times that dose. We plan on releasing 48 weeks functional data from the low dose cohort and expression data from the high dose cohort in this second quarter.

After a final safety review, we will make a form of dose selection decision in the third quarter. These results will not only inform the development path to the 2E program, but should also inform the dose selection and accelerate the development pathway for our other sarcoglycan programs.

We also believe that this data will have some read through to our microdystrophin study, because the programs share the same factor and promoter and if you recall are both dosed at high dose equivalents of two to the 14th therapeutic genomes per kilogram.

We will also gain experience with this dose in an older and larger patient population as three patients in the high dose arm of 9003 are older and larger than the four to seven-year age range of boys included in the microdystrophin study.

Now moving on to our PPMO platform, and more specifically our SRP-5051 program, I'm very excited about this program because it has potential to improve upon the ability of PMO to increase dystrophin expression by fusing a cell-penetrating peptide to the PMO to enhance intracellular and internuclear delivery.

We have made a lot of progress over the past year and through modifications of the original development plan achieved single dosing of 20 mg per kg in healthy human volunteers, and are already achieving multiple doses of 20 milligrams per kilogram in boys with Duchenne.

If the 20 milligram per kilogram or 20 mg per kg dose continues to be safe and well tolerated, we plan to continue to dose escalate to 30 mgs per kg and then potentially even to 40 mgs per kg. To remind you, these doses are significantly higher than expectations at the commencement of this program.

Preliminary biomarker data from our healthy human volunteers study support our hypothesis for enhanced potency of the PPMO compared to PMO. In the coming months, we plan on analyzing the 12-week biopsies from the SRP-5051 20 mg per kg cohort.

We will measure Exon skipping by digital drop PCR, allowing us to directly compare the efficacy of our PMO and PPMO candidates. And we were finding appropriate forum this year to provide the safety biomarker and other data from the program to-date.

If we're able to reach a therapeutic window for SRP-5051, the data will read through to our other DMD programs, where we have a total of six PPMO candidates already built that could treat over 50% of the Duchenne population.

We're also formulating developing strategies that could bring the PPMO platform to the rarer Exon populations, which together make up about 35% of the addressable population. And finally, the results of SRP-5051 will also inform the viability of the PPMO platform for new therapeutic areas.

One of our research goals is to identify conditions suitable for treatment with PPMO. If we have positive data from SRP-5051, we will be able to rapidly accelerate the development of the PPMO platform, both within DMD and beyond DMD to other therapeutic areas.

Further highlighting the potential versatility of the PPMO platform, as you recall, we just announced collaboration with USAMRIID to explore therapeutic agents to combat COVID-19.

This collaboration builds on the antiviral therapeutic potential of PMOs identified and published by the company in the early 2000s.That original work found that PMOs had demonstrated antiviral activity in in-vitro models against coronaviruses like SARS-coverage, which is the cause of SARS.

The antiviral effects of PMO derived from its ability to inhibit the viral replication process. It does this by duplexing to specific candidate sequences in the coronavirus RNA, for example, the transcription regulatory sequence, and thus, sterically inhibiting translation initiation, and downstream suppressing viral replication.

In this new collaboration, USAMRIID would use in-vitro assays to evaluate the ability of the PPMO to suppress viral proliferation and spread. This collaboration will enable Sarepta to contribute to the efforts to treat COVID-19, while adding to our understanding of the PPMO platform.

We did consider utilizing the PMO, PMO-X, PMO plus platforms in the research collaboration. However, based on our recent experience with our PPMO platform we are confident that it was the right approach for this act.

We are quite pleased to be able to collaborate with USAMRIID in a way that allows us to contribute to the fight against COVID-19, but does not distract us from our R&D priorities.

Our mission to deliver precision genetic medicines to patients with rare and serious genetic disorders have severed as our north star to guide us in how we are maintaining work on, one, RNA and gene therapy discovery portfolios, two, non-clinical toxicology studies needed to support our portfolio, and three, the translational biomarker development of validation and execution that is so vital to our clinical trials.

I too am very proud of my colleagues in R&D and the work they have done to enable us to deliver on the promise of our therapeutic portfolio that is so critical to the people who are desperately waiting for help. There will be multiple data readouts over the next few quarters that will guide our next steps. And with that, I would hand back to Doug.

Doug?.

Thank you, Dr. O'Neill. Let's open the lines now for questions..

Thank you. [Operator Instructions] Our first question comes from Salveen Richter with Goldman Sachs. Your line is now open..

Good afternoon, and thanks for taking my question.

So with regard to limb-girdle, when you present this high dose dataset in the second quarter, could you just comment post dose selection what the options are going forward with regard to trial designs for the registrational study?.

Sure, thanks for that question, Salveen. So, broadly speaking, we're working with the agency on those questions and the development pathway even as we speak. So, as we quote earlier, the good news is that notwithstanding the COVID-19-related issues, all of the kids have been dosed, all of the kids have been biopsied.

We will provide an update both on biomarker data, expression data, and safety data this quarter, and then shortly thereafter we'll make a dose selection. That will inform -- limb-girdle 2E will inform the rest of the sarcoglycan dosing as well. And then over the course of the rest of this year we're doing two things.

The one thing we're doing is building manufacturing supply. You may have heard during my opening remarks that we actually are already in a GMP run for limb-girdle 2E, which I would just linger on for a second and give kudos to our technical operations group for being able to get to that point even during these very disruptive times.

And then with respect to the development pathway, we're in an ongoing dialogue with the agency on that, we'll update toward the end of this year.

Our broad view is that we need to find a development and regulatory pathway that takes into account severity of this disease so that it is executable, a pathway that is fast and efficient, and one that considers the fact that with respect to this particular gene therapy the gene that is being inserted in these children and the protein that's being expressed is the native protein, the absence of which is causing the degeneration and ultimately the demise of patients who have limb-girdle 2E, which one might argue should create a very efficient pathway to an approval, but I can't give you the specifics of that yet.

We're in the midst of discussions with the agency over the course of this year. By early next year we should have two things complete.

We should have our process development complete as we do, GMP material ready, and a good understanding with the CBER and FDA on the development pathway for limb-girdle 2E, and then the development pathway for the rest of the limb-girdles. And we'll come back and we'll talk about all of that next year.

Our goal certainly is to start a pivotal trial in 2021 with respect to limb-girdle 2E..

That's helpful. Thanks, Doug..

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

Hey, thanks very much for taking my question. On microdystrophin regulatory path, I'm curious your latest thoughts as to what you'd aim to bring to regulators for Study 3 to potentially support approval.

I guess I'm wondering if that may change -- if there may be any changes given what you might be able to collect or what FDA might require given the pandemic and the later start? And then I guess along those lines, have you had any specific feedback from FDA on this out-of-window data collections of Study 102, and if at all you think that might impact your ability to use it as registration enabling without full functional data from the commercial scale material in Study 3? Thanks..

Yes, thanks for the questions. Let me start with the second part of the question first, and then go to the first. So on the second part of the question, we have documented the few out-of-window functional visits as the FDA's guidance has suggested.

So the good news for all of us dealing with this pandemic is that the FDA is being very forward-thinking and thoughtful about addressing the disruption associated with COVID-19 in ways that ensure that we don't find ourselves with studies that are significantly delayed as a result of COVID-19.

So there's already guidance on that, and we're documenting any delayed visits in accordance with that. The second thing I should note is that there have not been a significant number of delays. That even independent of that documentation process to ensure that we don't have any technical problems.

As we look carefully at the study there is no reason to believe there's an affect on the powering of the study, or on the readout, or on the viability of the study, or on the timing of the study.

So I just want to be very clear, in an abundance of transparency there have been a few instances of patients with out-of-window functional visits in light of the fact that there was a period of time, which is coming to an end now, at Nationwide, where Nationwide Children's Hospital was limiting some of those in-clinic visits, that's disappearing, but that will not, from our analysis, have any impact on the viability of the study or the integrity of the study or the readout or the timing, or the probability of success of the study.

So I think we're in really good shape with respect to Study 102 right now. And honestly I say this, and I'm giving my own team a lot of credit. I should give credit to two groups.

I'm certainly very proud of our clinical operations team and the like for the work they've done to minimize any kind of disruption in Study 102, but I should equally give an enormous amount of credit to Nationwide Children's Hospital and their operations team, and frankly massive kudos to Dr.

Jerry Mendell who has just been a hero through this process. Going to Study 301 or the broader group of studies, Study 3, the short answer on that is that we are proceeding right now with the same approach that we had before COVID-19, and we're executing along those pathways.

So Study 301 will be four to seven-year-olds, it will be a placebo-controlled trial. We are reaching out to study sites even as we speak.

I will tell you actually the study sites themselves on the whole are not only very enthusiastic about Study 301, the commercial supply trial study, but actually quite optimistic about their ability to start that study and to start it on time.

Notwithstanding that, I do want to point out that we have to be realistic that we -- and so some of this is choice. The biggest rate limiter up till now has been ensuring that we can get GMP material released on time.

And as I've said before in my opening remarks, and I'll repeat again, through the great work of our technical operations group we are on track right now to have GMP material, by July, just as we had anticipated before COVID-19. The next issue there's a choice.

We want to make sure as we're tracking forward that with respect to sites, they're not only ready to start taking patients and that we get through all of the various processes, and the IRB processes and the like, but then we're confident that those sites will continue on into the fall, and into the winter, and into 2021, and beyond.

And that may modestly delay us, but as I've said before, I really am talking about modest delays. It's still our goal to start the Study 301 and its progeny in the second-half of 2020. And right now we feel confident that is not going to be an issue..

Thanks very much, Doug..

Thank you..

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

Hi, good afternoon, guys. Thanks for taking my questions.

I'm sorry if this question was already asked, but Doug, can you clarify for me, for Study 102, how often are the patients actually being monitored for the functional visits, and specifically I just wanted to get a sense for the biopsies that were scheduled to be taken for the patients in Study 2, do they have to be taken per protocol at a certain point of time after they were dosed or is there any flexibility in when the biopsies can be taken?.

So, I'm going to turn this over actually to Louise Rodino-Klapac to respond to both of those questions..

Sure. Thanks, Doug. There is a certain visit window for the biopsies but as Doug mentioned, in terms of flexibility, any out of window just needs to be documented as per the FDA guidance. So, as we look at it, there's no particular delays or misses within the protocols that will be meaningful to the outcome of the study..

Okay, and did you know what percent of patients were a little bit delayed in getting the biopsies?.

No, I'm sorry. We're distant, for those who may wonder why there was an enormous delay, we're distant from one another, and I actually insisted that I direct the questions, so, apologies for that, Louise.

So, Louise, I'm sorry, could you answer the question?.

No, there was just -- I don't know the exact number of visits that were delayed, but it's due..

Okay..

Very small, very small number..

Okay. And then as we think about limb-girdle to follow-up for the pivotal study that you're going to start next year for the 2E subgroup.

Can you just remind us of how big of a population that is relative to the rest of all GMP?.

Well, it's very rare. This is an ultra rare population.

I don't think we've gone out and given the exact numbers as one of the things we've said, if you look at the entire epidemiology and population of all of the patients that we're looking at, we're talking about a group of patients that are about 70% of the size of Duchenne Muscular Dystrophy, but the limb-girdle 2E is a very rare form of limb-girdle and very severe form of limb-girdle.

So we haven't nailed that, we haven't nailed the size of the trial down but obviously with that in mind, when you consider the rarity of the disease, and you consider that this is really, this is kind of the perfect sweet spot opportunity for a gene therapy. This is a monogenic disease, well-characterized, well-understood.

It is the lack of a structural protein, it is a single structural protein that is causing all of the damage and degeneration and loss of life that comes with 2E and the gene therapy that we have created and that Louise has created, we'll introduce a gene that codes for the actual native protein, the lack of which has gone through.

So again, I don't have an answer yet on the exact development pathway.

We're working on that actively with the agency over the course of 2020, but it is certainly our goal to have a very, have a development pathway, regulatory pathway that that has the speed, and leanness that one would imagine, with the disease of this rarity, well characterized monogenic and with, if we can get very high expressions and we're already there with our current dose that return to these patients, the very protein, the lack of which is causing their disease..

Okay, thank you..

Just a reminder everyone, one question, we have really full queue. The line is going to be silenced after you ask one question, thanks..

Thank you. Our next question comes from Debjit Chattopadhyay with H.C. Wainwright. Your line is now open..

Hey, good afternoon guys, and thank you for taking the questions.

So given that you're at the 20 mg per kg dose with SRP-5051, what should be the 12-week dystrophin expression that would excite you to advance the 45 and 53 programs rapidly?.

Yes, thank you very much for that, Debjit. Look what I can say broadly about this is that, first of all, 12 weeks is a very early period of timing we're looking for dystrophin.

So I wouldn't commit in advance that we will even be looking for dystrophin at the 12 weeks, what we will be looking at is Exon skipping and what you will find within and of course through reminds us I'm sure everyone knows this, but the Exon skipping is the very activity that results in the truncated form of the RNA that in turn creates the protein that is the slightly truncated but otherwise fully functional dystrophin that we're trying to achieve, and what we know, at least in animals, we know two things, we know number one, there is an obvious direct correlation between amount of Exon skipping as you would well imagine and amount of dystrophin production.

So looking at Exon skipping is a perfect, a brilliant marker for what kind of dystrophin we might find over time.

I'll give you an example with respect to Golodirsen, we had made some fairly bold statements about what we probably would see with Golodirsen versus Eteplirsen and that was all because of what we had seen early days and the relative Exon skipping that came from Golodirsen versus Eteplirsen.

So I think Exon skipping is a great marker, and what we're going to be looking for, of course, that would get us excited is the relative amount of Exon skipping you might see from PMO at 12-weeks, versus the amount of Exon skipping that we will see with the PPMO at the doses that we're talking about right now. We don't have it yet.

We'll see it in the second-half, and we'll all come together, and we'll have data on tissue exposure and Exon skipping and safety and the like and dosing levels, but I can at least tell you that in animal models, we were we would have been getting excited at doses significantly below the doses that were now dosing through.

And I think at the inception of the single-ascending dose, and then the multi-ascending dose study, when we started this, our animal models or mouse modeling and then our non-human primate models got us to a point that where we would be very happy with six mgs but we get increasingly happy up to about 12 mgs per kg, which is what we envisioned would be the ceiling and how high we can get and certainly with respect to this peptide conjugated PMO, more is better with respect to dosing if we can get the higher dose safely, and the fact that we're at 20 mgs per kg right now, it makes us very, very pleased, I will say.

And while it hasn't affected as a delay in the program as we have to continue dosing, I don't think it's a delay that any rational person is going to complain about..

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

Hi, this is Emma on for Alethia.

Can you give us any color on what the actual processing requirements look like for a patient to transition to home infusion, just what the percentage of patients are currently on home infusion for VYONDYS and EXONDYS and what those trends might look like next quarter?.

Sure, I'm going to turn this over to Bob before I turn it over just to remind everyone with respect to EXONDYS, as it stands today, the vast majority of patients are on home infusion and well with respect to a launching product line VYONDYS, we will see a greater percentage of patients that start in hospital, it will over time be the same case that the vast majority of VYONDYS patients will become home infusion as well.

Of course, Bo can talk to you about the things that we're doing today to accelerate that process.

Bo, with that?.

Yes. Thanks, Doug. And to Doug's point, the majority of our patients are already at home infusion, but for the patients that are being dosed in the hospital, it's really just an authorization like a reauthorization process with payers. So it's just more of a paperwork process of transferring the authorization from in hospital infusion to home infusion.

So, there is a couple weeks delay for those patients that do need to transition but we do expect this to ease over the next couple months..

One other thing, I would say on this topic is this, there's a lot of process involved both in the launch of VYONDYS and EXONDYS.

And one of the things you might have heard in my opening remarks was about the fact that we're watching very carefully how payers are going to react in the middle of this crisis to ensure that payers don't themselves tend to take advantage of the disruption that's occurring with COVID-19 in ways that might profit them to the detriment of children.

In fairness, I should note that payers are based on everything we're seeing right now doing exactly the opposite that in fact, I think that very laudably payers have been looking for ways to reduce some of the obstacles that might be imposed as a result of COVID-19 to ensure that kids could stay on therapy. I'll give you just one example.

With respect to State Medicaid, I'm informed every single state, all 50 state Medicaid have been have requested and have been granted by CMS waivers that allow them in turn to waive prior authorization requirements and to extend kids on therapy without the need to go through the prior authorization process.

I don't want to suggest that that means that they're not going to impose prior authorizations. They likely still will, but certainly that is a significant step in the direction of ensuring that COVID-19 doesn't get in the way of kids who have access to therapy, and I really do think they deserve kudos for that..

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

Thank you for taking my questions. I have one regarding limb-girdle beta. So, there was an abstract 503 on cohort one data at the ASGCT, PDF abstract, but somehow the final Web site doesn't have this abstract anymore.

Just want to double check that there will be no data at the ASGCT from limb-girdle, and also given good safety so far we see from microdystrophin program, limb-girdle program has the same factor and the promoter, is it fair to say higher dose safety should be largely in line with microdystrophin program..

Well, on the latter part, I'm going to say that we're going to comment on that when we release the data and we'll have that data released this quarter. So, you won't have to wait very long to get an update on limb-girdle about the expression and safety. But your point's well taken.

Just so we're clear and it's actually, you're exactly right, which is - this is the same promoter.

This is the same vector and what we're currently calling this is a prior dose or high dose on limb-girdle is the same dosing level that the kids with Duchenne Muscular Dystrophy ever received, both in 101 and 102, and together that is significant number of patients that have that dose.

With that, I'm going to turn it over to, Louise, who might comment on ASGCT and limb-girdle, but maybe give an overview of what kind of abstracts or posters we might have at ASGCT?.

Sure, yes. In terms of the clinical data, it will be -- we will release it later this quarter. So we will add ASGCT there are two preclinical abstracts that will be presented as poster for limb-girdle, and that will be focused on long-term expression data and then also expression in later stages of disease.

This is all preclinical, and then of course we'll have our symposium, where we'll outline the background on the development of our constructs, and also talk about the microdystrophin data -- nine months data..

Thank you. Our next question comes from Ritu Baral with Cowen. Your line is now open..

Hey, guys, this is [Sushant] [Ph] on for Ritu. A question on Study 102, I'm wondering what some of the assessments being outside of the window, have you had to revisit the statistical analysis plan and what adjustments are about to be made? Thanks..

Yes, thanks for asking the question. We've looked at it carefully and there is no adjustments necessary. We don't have a concern on the statistical analysis plan. In broad strokes you're going to have this concern on powering.

We don't think there's any impact from the modest number of out of window functional visits to calm any concern regarding integrity, and certainly as we've said before, it won't have any effect on timing. Dr. O'Neil, if there is anything I've missed in that, feel free to add to that, or correct me if I misstated anyhow..

No corrections necessary. I told Doug we have looked and these out-of-window assessments are not absolutely critical and have no impact on our statistical analysis plan..

So, we remain on time..

Thank you. Our next question comes from Joseph Schwartz with SVB Leerink. Your line is now open..

Thanks very much. So, based on the age of the patients that you've enrolled in Study 102, how do you expect their North Star scores to change over the duration of part A? And how is the study powered to detect a difference between the two arms? There is a copious literature suggesting that North Star can increase during this age range.

So I'm just trying to think about what kind of an increase 9001 will have to produce in order to succeed?.

Let me give you the broad stroke. I'll give you a broad stroke answer on that. Some of the nuance I'm probably going to avoid simply for confidentiality, competitive reasons. I can do the broadest stroke. The broadest stroke is the following. I suspect that no one has better patient level data on Duchenne Muscular Dystrophy. It's epidemiology.

It's of course then Sarepta. Obviously the leaders in Duchenne Muscular Dystrophy would've been close to the patient community and the data for eons.

We have not only all of the literature, we have our own data, patient level data we have access to synergy data, we have access to all of the data from BioMarin that they had back in the day that we negotiated, and so, we're well-informed to build this, the study that we built to your point in a nuanced way, what you see across four to seven year olds in broad strokes is that there is the possibility for a couple point potential linear -- not linearized, I apologize, non-linearized a couple points increase potentially between the four and five year range, but you will see them coming over the top and actually declining, starting to significantly decline in the six and seven-year-old range.

As you know, these kids are four to seven. All of that nuance understanding of the course of this disease that has been used for inform the protocol that we've used, and beyond just that, we of course have the benefit of the first four patients that we've had.

We've had about some of that data as well, but we've used some of the data that we have gleaned from the first four patients to help us consider the powering of this study.

I will note by the way, I don't know if we've talked about this, but the one-year publication on the first four kids, that cohort will be published very soon imminently, and it was all that went into this, and just to make the broad stroke point, the powering of this study was over 90% when we got to 40 patients.

So we feel confident about the protocol, about the powering, and certainly about the progress, the Study 102..

Thank you. Our next question comes from Christopher Marai with Nomura. Your line is now open..

Hey, good afternoon. I'm just thinking about the path forward for limb-griddle muscular dystrophy with regulators and the potential for using expression data.

I was wondering, just how much expression data it might need to see there and if the FDA has any concerns or if you have any concerns about also I suppose, just the sarcoglycan complex being sort of reformed by re-expressing the protein and making sure that's intact and if you are prepared to provide any localization data in that regard, if it's required.

And then just real quick with PPMO, I mean, how much data will really satisfy you guys with respect to safety at any given dose call it 20 mgs per kg. What kind of timeframe are we looking at before, we can get confident that you could move forward and say 20 or 50? Thank you..

Okay. So, as it relates to limb-girdle, we're still working on the development and regulatory pathway itself as you've anticipated. We certainly think that this should be a very lean approach, and frankly, in a perfect world, we think that this would be a perfect opportunity to be approved on a biomarker of expression.

You raise a really interesting point about what about the reconstitution of the dystrophin associated protein complex and the fact that we think that is a very important element to looking at this. And that's another important biomarker.

Is there, when you upregulate as an example, beta-sarcoglycan, do you see that dystrophin associate protein complex itself also begins to upregulate so that other proteins in that complex would start to come together and be express where they would be missing before because the DAPC is not coming together. That is important.

And that regardless of whether the FDA of its face would demand it, we do think that's something important that we should show and be able to prove.

And the good news is by the way, we have seen that repeatedly that one of the things that should get someone very excited about this is that it's -- that this is the native gene, the native protein already at our previous dose, very strong expression, properly localized to the right place.

And to your good point, associated with the upregulation of the other proteins that make up the dystrophin-associated protein complex, this is one example.

You see a very strong correlate between upregulation of beta-sarcoglycan and alpha-sarcoglycan, which these kids have a gene that's to properly code for alpha-sarcoglycan, but you don't see this significant amount because in the absence of beta-sarcoglycan there is DAPC.

So, I think all of the facts and circumstances around that are going to come into play when we think about the development plan, what we think we should be able to avoid would be a lengthy trial that would require for instance, a placebo control trial and the like, and we're still working with the agency.

We still have a lot of discussions to go with the agency to land on the right answer. There are -- what if there are a lot of places to land between an accelerated approval on a biomarker, which would of course be our -- the answer we think is great.

And on the other hand, a full blown placebo-controlled trial, but we'll come back early next year and provide an update to everyone..

Thank you. Our next question --.

Nope, before we go on, I've been promised that even though there were two questions; I will turn this over to Dr. O'Neill to answer the question on the PPMO..

So today we are actually happy with the safety profile that we're seeing, and with the numbers in our ascending cohorts, ascending cohorts, and the ascending dose, we believe that we have sufficient numbers.

I think we are able to judge safety by looking both at the clinical outcomes, but actually are obviously able to monitor the target talks that were identified not to the top. So, we believe with those numbers we can comfy make decisions.

Obviously looking forward, safety is always a matter of numbers, but these numbers are I -- we believe adequate for making that initial dose selection..

Thanks..

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

This is Shawn Egan calling in for Joel. Thank you for taking my questions. On the PPMO congratulations on the 20 mg per kg dosing, maybe you can just count on or talk a little bit about any preclinical data or work you've done on microdystrophin gene therapy plus the PPMO combo and what you've seen there..

So I think at this point all we'll say is that it's an area of keen interest to us, and we are doing a preclinical work on those on two different concepts. One concept is the value of three treatments with a PMO or PPMO in advance of a gene therapy to enhance the competent the value of this therapies into enhance expression.

And as relates to that, I can't lean over and talk about literature that already exists. Dr. White is an example has some literature where he in the mouse model pretreated with a -- I believe it was a peptide conjugated PMO, and then dose with gene therapy and he found enhanced expression. That's one area and we're looking at that area.

The second one of course is a very significant one, which is to explore the benefit of a commutated value of a PPMO on the one hand, and gene therapy and the other, and you can envision a world in which you would get a synergistic value between a really significant expression from the gene therapy construct, like our SRP-9001, coupled with robust expression of a truncated district then that you would get from a PPMO.

We're doing a bunch of work on that. We're not ready to discuss it in any detail, but it is certainly something that we need to continue to work on in advance of the launch of our gene therapy program.

Assuming that we're successful in clinical development as well as in advance of the success of our PPMO program as well, I think, people in their models that we're working assumption that gene therapy will entirely cannibalize the RNA platform, and while I can understand why some people look at the exciting aspects of our gene therapy and imagine that, I think it's probably early to it to believe that's the case and we have some tantalizing research that might say there is a value to these two therapies together..

Thank you. Our next question comes from Matthew Harrison with Morgan Stanley. Your line is open..

Thank you. This is Max Skor on for Matthew Harrison. Sorry if I missed this, but can you confirm that all microdystrophin release essays have been built, but do you still need to be validated, and are these In Vitro potency assets? Thank you..

Yes, great question. So yes, I can confirm that all of the assays are belts. I can confirm it up 24 assays. All of them are either validated or qualified. Some assays need to be qualified. What assays need to be validated, I mean there are two that are in the later stages of that validation.

I can also tell you that it's not the potency assay, but all of the really crucial bespoke assays are either validated or qualified. The last two that are in the last stages are really that are very routine. These are very sort of nearly off the shelf routine assay, so all of the really significant ones have already been validated..

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

Thanks for taking the question.

Just want to follow-up quickly in your comment earlier on looking for exon-skipping at 12 weeks, but not necessarily dystrophin, after you started getting exon-skip dystrophin, or in the case of gene therapy, after you start expressing microdystrophin mRNA, how quickly would you expect to start seeing meaningful dystrophin levels and then how does this continue to trend over time? How long does it take for example to reach steady state?.

So, I'll give you the broad stroke, and then Dr. O'Neill, if you have additional color on it. I mean, first of all, we got it -- we definitely have to take RNA and microdystrophin gene therapy and put them in two different buckets. They're very different.

With respect to microdystrophin, we know the answer is three months, so what we've seen as you know with respect to SRP-9001 in our first four kids, we took biopsies after three months and those kids had 90% and higher dystrophin expression, so clearly we get a really fast onset for the gene therapy.

For RNA, it is a slower process and it occurs over time, probably for a host of reasons, but it occurs over time in fact we saw a significant difference over a long course, a period of time with both EXONDYS and with respect to VYONDYS and then we saw I think the one between one year and four years there was a significant difference in the amount of dystrophin and that may be in part because with this chronic therapy.

The cryotherapy keeps increasing the benefit over the long-term. One of the reasons, frankly, during this difficult COVID crisis that we're so focused on ensuring the kids don't skip dosing because skipping a dosing, isn't simply missing a dose.

They may be missing the cumulative benefit that you're getting from being on therapy over a long period of time, but with that said, I'll turn to, Dr. O'Neill, maybe provide some more color..

So, Vincent thanks for your question. The half-life of wild type, your full-length dystrophin is in the order of weeks, this we know, and as Doug has said the -- not surprisingly, the time to transcribe as high fidelity and translate the high fidelity dystrophin, which is such a large gene, actually, is it measurable in many hours.

I think, so those are important biological questions then from the point of view of looking at 12-week data. The key decision will be driven by the relative potencies of PPMO to PMO.

And what we really -- the robust data set that we have at that timeframe, really forces us for crisis to compare exon-skipping, which I think is actually a very valuable way of making the decision about going forward as selecting doses, and as Doug has said, as you can expect from what I just said about the half-life of dystrophin, and the synthetic timelines for the dystrophin one would expect to see ongoing accumulation over many weeks and months.

So that's the reason why we're actually focusing on the exon-skipping at 12 weeks, but also, we are measuring tissue levels off the PPMO, and we'll be able to compare that with PMO as well, so that really enables us to really test multiple types of the hypothesis..

Understand this about -- let's talk a moment about what we know about our RNA technology to PMO generally, so we -- thinking about our PMO that make it so clever, is that number one is precise, then we know we get the PMO to the right place, it induces excellent skipping, it transforms messenger RNA, it puts it back in for making dystrophin.

We know that. We know it's safe, right? The PMO, we can dose at very high level and that's a very significant safety window, and there with it's therapeutic window. Then, the one limitation and it is a significant limitation of our PMOs, is that as a neutrally charged molecules, I think it entered the cell well and as a result of that.

A lot of the PMO that is infused, it doesn't get into the cells until it is utilized, it's urinated out, so the goal of all of this -- the unlocking of RNA technology and the potential profound improvement of the RNA technology comes from something that is, it is simple to discuss, frustratingly simple and difficult to execute, which is, can you find a delivery vehicle that can safely get the PMO in the cells in much greater exposure? That's the question in animal models, the PPMO does that very mechanically, it's a positively charged peptide, it interacts with the negatively charged elements on the outside of the cell, it creates warbling and uses vesicle to get into the cell in great abundance, an order of magnitude greater than you would see with a PMO.

And so, that's the biggest issue for us right now. Can we get to strong therapeutic doses, what we envision to be therapeutic doses of the PPMO without inducing your safety signal, and if we can, I think mechanically, we're going to be very excited about the potential of the PPMO.

And in that regard, we need to see this data and we'll have a data readout in the second-half of 2020. The exciting thing about where we're right now is that we're 20 mgs per kg when we envisioned at least some time ago that our ceiling was going to be about 12 mgs per kg..

Thank you. Our next question comes from Anupam Rama with JPMorgan. Your line is now open..

Hi, all, this is [Sacks on the call tonight] [Ph] for Anupam. Hope you're all well, and thanks for taking our question.

I think in the prepared remarks, Doug, you mentioned that you do not yet have clarity to provide updated guidance for EXONDYS, but maybe from a high level, what were the levers for growth from $31 million in 2019, and maybe how are you thinking about the push and pull levers for the guidance to consider with the ongoing COVID-19 pandemic? Thanks so much..

Yes, look, I'll give you the broad strokes. So our growth with respect to EXONDYS doesn't relate to price. Let's make sure we're clear about that. So there is only one lever and it's patients on therapy, staying on therapy, and we're finding more patients and more patients coming on therapy.

That is it because as hopefully people know, and I think I've said in other forums many times, we launched EXONDYS in 2016, we have taken no price increases over that period of time and we don't envision taking a price increase.

Our goal is to grow through serving this community and having more kids benefit from our therapies, and as an example with respect to VYONDYS, we priced it at parity with EXONDYS, obviously take a price increase there.

So we look forward, that's the level and the risk to revenue is modest for the second-half of the year certainly with respect to EXONDYS because with respect to EXONDYS, the great majority of kids are already in home infusions.

And while there are a number of different elements that could be disruptive over the course of 2020, that's significant disruption in kids that don't have the ability at the peak of this crisis to get into a hospital to get it in fusion if you're in hospital, and the good news is most of the kids are not.

So when I talk about EXONDYS in particular, we're talking about it.

Basically, everything we see today, and as I said, I'm not giving updated guidance, because we're in the middle of something and we don't have sufficient clarity to give guidance that we feel confident about other than to say what we're seeing right now would be a modest and short-term in that.

We'll see a little more significant delay and impact on VYONDYS for the simple reason that we're in launch phase with VYONDYS that a more significant number of patients will start in the hospital although we're working to try to reduce that number, but even with respect to that, we think that's going to be modest, and we think that's going to be a short lived issue.

So, broadly speaking, I think we're in good shape. We're serving the patient community, we're trying our very best and I think we're so far succeeding and keeping them safe.

And any impact on revenue ought to be really quite modest and quite short lived, but with that, Bo, am I missed anything?.

No, Doug, you covered everything. Thank you..

Thank you. Our next question comes from Tim Lugo with William Blair. Your line is now open..

Thanks for taking the question.

For the commercial supply trial, the ongoing issues around COVID impact, how you think about that Study size, maybe adding additional sites than you originally anticipated or additional geographies where you may enroll patients or even just the overall powering of that Study?.

Thanks for the question. Now the Study remains on pace and on track as originally envisioned, both the size of this study, the fact that it's a multi-country multi-institute, the fact that it's placebo-controlled, et cetera. So the design hasn't changed on that study.

I have said that the one logistical risk in the start of that study is that you've got to get studies up and running, you've got to get -- in a perfect world you have in-person site initiation visits from our clinical operations team and the like.

We want to make sure everyone is properly trained so that we have consistency across all of the sites all around the world. So there's a lot to do. And so, we envision that there will be a modest delay in the initiation of that trial just to make sure that we're being thoughtful and cautious about that the COVID-19 as we're starting.

That means there'll be a modest delay. I say modest because we still have every intention of starting Study 301 in the second-half of this year.

So we're talking delays measured in a couple of months, not measured in significant amounts of time, but beyond that I think things are proceeding, and we haven't made any significant changes to the approach that we're taking..

Thank you. Our next question comes from Liisa Bayko with JMP Securities. Your line is now open. Liisa, if your line is muted, please unmute..

Oh, sorry. Thanks for taking the questions, and congratulations on the strong quarter. Just wanted to know if you could give us a little bit more detail and color from the quarter itself in terms of how many patients actually started on VYONDYS just so we can better understand the dynamics there.

And then also any changes in gross-to-net or any of those kind of details that we should be thinking about given patients' insurance and maybe kind of levels of unemployment there might. What's the right way to think about some of those dynamics? Thank you..

Sure. I will turn this question over to Bo, although I think some of the nuance we're probably not at liberty to disclose..

Yes, Liisa, obviously we're not going to give -- in regarding to patient numbers for EXONDYS, and we won't with VYONDYS, but I will tell us even though VYONDYS is obviously smaller than EXONDYS from a population standpoint, we were very pleased with the progress that we were making with payers and coverage, we were much further ahead than we were with EXONDYS.

We have 148 million lives that are covered either restricted policy or two labels, so we were very pleased with that, and the launch was going to our expectations. So it's just the small hiccup of the pandemic that put the little things and pushes into, but we were overall very, very happy..

Thank you. I am not showing any further questions at this time. I would now like to turn the call back over to Doug Ingram for closing remarks..

All right, thank you. I'll be brief. Thank you all very much for joining us for our earnings call.

And hopefully you've seen here that like so many other companies, and frankly individuals, not just in the United States, but around the world, this pandemic has caused enormous numbers of challenges and obstacles for the Sarepta team by -- as I've said before, I'll say it again because it bears repeating, I am unbelievably proud of the Sarepta team for the ability to stay on mission.

90% of this team transitioned to working from home, and yet we did that on the Friday, we got up on Monday, I have taken a careful look at every metric you can see, and not only externally, when you see the way we're tracking against our milestones, but through all of the metrics you'll see that this organization remains as productive as it was on the Friday before we all went to working from home.

So there is a lot of learning in this, probably not just for Sarepta, but for all of us about the ability to be efficient even in a virtual manner. We are mission oriented as an organization. We have never taken our eye off the need to bring a better life to these kids.

And even through this difficult and distracting period of time, even in a period of time when our workers themselves have to worry about their own loved ones and about themselves, they have not lost sight of the fact that Sarepta is on mission.

We're going to continue to execute across 2020, and we're going to be excited to give you additional updates across the year. We can give you better clarity on sales in our second quarter earnings call. We have a number of significant milestones across the rest of this year.

I think the rest of this year into 2021 is going to be an enormously consequential period of time, not only for Sarepta, but for the patients that we serve. So, thank you all very much. Everyone please stay safe, wash your hands, and let's get this crisis behind us..

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