Good afternoon, everyone, and welcome to the Sarepta Therapeutics Third Quarter 2021 Earnings Call. Currently, all participants are in a listen-only mode. After the presentation, we will have a question-and-answer session. Please note that today's program is being recorded. Now, I will hand the call over to Mary Jenkins, Senior Manager of Investor Relations. Please proceed.

Thank you, Tino, and thank you all for joining today's call. Earlier today, we released our financial results for the third quarter 2021. The press release is available on our website at sarepta.com, and our 10-Q was filed with the Securities and Exchange Commission earlier this afternoon. Joining us on the call today are Doug Ingram, Ian Estepan, Dallan Murray, Dr. Gilmore O'Neill and Dr. Louise Rodino-Klapac. After our formal remarks, we'll open the call for Q&A. I'd like to note that during the call, we will be making a number of forward-looking statements. Please take a moment to review our slide on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta's control. Actual results could materially differ from these forward-looking statements, and any such risks can materially and adversely affect the business, the results of operations and 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 quarterly report on Form 10-Q filed with the SEC 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 now, I'll turn the call over to our President and CEO, Doug Ingram, who will provide an overview of our recent progress. Doug?

Thank you, Mary. Good afternoon, everyone, and thank you for joining Sarepta Therapeutics Third Quarter 2021 Financial Results Conference Call. I am pleased to report another quarter of strong and consistent performance as we continue to hit our milestones and report positive data readouts across our multiplatform portfolio. Starting with our quarterly performance; serving the Duchenne community with our three approved RNA-based therapies, revenue once again exceeds guidance. In our second quarter call, we raised our full year net product revenue guidance by $30 million to a range of $565 million to $570 million. We have outperformed that guidance and exceeded analyst estimates with net product revenue standing at $166.9 million for the third quarter. That's a 37% increase over the same quarter last year. As we have never taken a price increase for our therapies and have priced all of our therapies at parity, our revenue beat comes entirely from the team's ability to serve the Duchenne community and for the benefit our therapies provide to the lives of those with Duchenne. As I've mentioned before, even during the most difficult period of the pandemic, the adherence rates for our therapies have remained well above 90%, speaking to the value of our therapies to those living with Duchenne. Based on our overperformance, we have once again increased our full year net product revenue guidance. Our new guidance for full year 2021 is in a range of $605 million to $615 million, which is $40 million above our previous guidance and $70 million above our initial guidance this year, representing at the midpoint, a 34% growth over the prior year. Our performance this quarter represents our 20th consecutive quarter of positive growth. Based on our updated revenue guidance for 2021, we will have a compounded annual growth of 40% from full year 2017 to the end of 2021. We anticipate this strong growth to continue in 2022. Our Chief Commercial Officer, Dallan Murray, will comment further on performance in a moment. Having recently completed an equity raise, bolstering our cash position by approximately $550 million, we stand in a strong financial position to fund our pipeline successes with over $2 billion of cash and cash equivalents currently on our balance sheet, augmented with strong product revenue. With our cross-platform successes this year, we are fortunate to be so well funded as we track out of 2021. Starting with our gene therapy programs, we made great progress with SRP-9001, as the evidence base for this highly differentiated and potentially transformative therapy continues to build. Earlier this year, we announced the expression results from the first 11 patients in Cohort 1 of ENDEAVOR or Study 103, our first trial evaluating our commercially representative SRP-9001 material. Across all measures, including genome copies per nucleus, western blot expression, protein positive fibers, and intensity, we saw results that were as good or better than our previous experience with our clinical supply material. We have by now dosed 77 Duchenne children with our therapy across three studies. And roughly three weeks ago, we provided a further update on the clinical evidence generated to date. In our proof-of-concept study 101 at three years, Duchenne patients continue to perform markedly better than the natural history of this aggressively degenerating disease would predict, achieving a nine-point improvement on the 34-point North Star Ambulatory Assessment (NSAA) scale, with a p-value of less than 0.0001. In our blinded placebo-controlled Study 102 Part 1, we had previously reported that in the baseline matched 4-year-old to 5-year-old cohort, at 48 weeks, the treated children performed statistically significantly and clinically meaningfully better than placebo with a p-value of 0.017. For the 6-year-old to 7-year-olds, we recently reported that when properly baseline and age-matched against the natural history cohort, treated 6 to 7-year-olds performed three points better than natural history with a statistical significance of 0.0129. Finally, in our ENDEAVOR study, at only six months, the first 11 patients in Cohort 1 have already improved against their own baselines by about three points when natural history would have predicted a decline in NSAA over that same period of time. After significant work and progress in CMC, manufacturing, research, development, and regulatory interaction, the FDA cleared us to commence our pivotal trial for SRP-9001, known as EMBARK, which is the first gene therapy pivotal trial for Duchenne in the United States. In early October, we announced the initiation of EMBARK. On October 11, at our SRP-9001 micro-dystrophin R&D Day, we provided more details on the design and key elements of the EMBARK study. The study is actively recruiting and will enroll 120 patients at dozens of sites in the United States, Europe, and Asia. Looking forward, in addition to rapidly enrolling EMBARK, we will present the results from part two of Study 102 for SRP-9001 in the first quarter of 2022. Study 102 will provide additional insight as we execute EMBARK, which is our pivotal trial. Beyond SRP-9001, we have seen consistently strong expression, safety, and functional signals from our proof-of-concept study for SRP-9003, our gene therapy to treat limb-girdle muscular dystrophy Type 2E. We reported earlier this year that both U.S. and European regulators have suggested that the use of beta-sarcoglycan protein expression may be sufficient for accelerated and conditional approval, respectively. In addition to advancing this dialogue with the agency and designing an appropriate pivotal trial, our significant rate limiter is completion of the CMC work for commercially represented SRP-9003 material. We intend to complete this work next year. With our strengthened balance sheet, we intend to move our sixth program LGMD portfolio forward and are exploring the potential for a platform approach to simultaneously address our three sarcoglycan programs, covering LGMD Types 2E, 2C, and 2D. Now moving to our RNA franchise. Earlier this year, we announced positive results from Part A of our MOMENTUM trial, studying our next-generation peptide conjugated PMO, the PPMO SRP-5051, which is designed to be an enhanced version of our PMO technology for Duchenne patients who are amenable to exon 51 skipping. In the 30 mg/kg cohort compared to eteplirsen, we saw 18 times greater exon skipping, an eightfold greater level of dystrophin production, and we achieved this in half the time and at 20% of the drug exposure of eteplirsen. We also saw a dose-dependent hypomagnesemia, but believe that it is both monitorable and manageable with prophylactic magnesium supplements. We then gained FDA's concurrence on the commencement of Part B of MOMENTUM, which will serve as the pivotal trial for SRP-5051. If confirmed in upcoming trials, our next-generation PPMOs will greatly extend the reach and impact of our RNA platform with the potential to treat as many as 80% of individuals with Duchenne and opening up approval opportunities outside of the United States. With our bolstered balance sheet, we intend to advance multiple additional PPMO therapies for other Duchenne mutations. In addition to these prioritized late-stage programs, we have the balance sheet and expertise to continue to advance our broader 40-plus program research and development pipeline, including therapies for additional neuromuscular, neurological, and cardiomyopathy diseases. We are also working on new and improved delivery mechanisms, advanced AAV capsids, as well as improving gene therapy to permit dosing in the presence of preexisting antibodies and to empower redosing. Simultaneously, we continue to strengthen our first-in-class team of genetic medicine professionals across technical operations, research, development, and regulatory strategy, just to name a few. To that end, in early October, we celebrated the grand opening of our world-class 85,000 square foot Genetic Therapy Center of Excellence in Columbus, Ohio. We continue to build our Gene Editing Innovation Center in Durham, North Carolina, focused on the advancement of CRISPR/Cas9. We have made exceptional progress in 2021, advancing our large multi-platform pipeline and sharpening our vision to be the leader in genetic medicines for the treatment of rare neuromuscular diseases and beyond. I would like to thank our partners, the clinical investigators, and the families participating in our trials for their commitment and crucial role in our recent success. I would also like to thank my exceptional team of professionals at Sarepta, a team that embraces with dedication our mission of using cutting-edge science to improve the lives of those living with rare diseases. Your tireless work and focus on execution shows in our advancements this year. I am confident that it will translate into a better life for the many patients who depend on our work. And with that, let me turn the call over to Ian Estepan, who will provide an update on the financials. Ian?

Thanks, Doug. Good afternoon, all. This afternoon's financial results press release provided details for the third quarter of 2021 on a non-GAAP basis as well as a GAAP basis. Please refer to the press release available on Sarepta's website for a full reconciliation of GAAP to non-GAAP financial results. We are quite pleased to announce that for the three months ended September 30, 2021, the company recorded total revenues of $139.4 million compared to total revenues of $143.9 million for the same period in 2020, representing an increase of $45.5 million. Total net product revenue for the quarter of 2021 from our PMO exon skipping franchise was $166.9 million compared to $121.4 million for the same period in 2020. For the third quarter of 2021, individual net product sales were $115.6 million for EXONDYS 51, $26.7 million for EXONDYS 45, and $24.7 million for VYONDYS 53. The increase primarily reflects higher demand for our products and the launch of AMONDYS 45. As Doug said, due to this continued strong performance, we further increased our full year 2021 revenue guidance range for our RNA franchise by $40 million. In the quarter ended September 30, 2021, and for the same period of 2020, we recognized $22.5 million of collaboration revenue, which primarily relates to our collaboration arrangement with Roche. The reimbursable co-development costs under the Roche agreement totaled $29.4 million for the third quarter of 2021 compared to $16.9 million for the same period of 2020. On a GAAP basis, we reported a net loss of $48.1 million and $196.5 million, or $0.60 and $2.50 per basic and diluted share for the third quarter of 2021 and 2020, respectively. We reported a non-GAAP net loss of $15.6 million, or $0.19 per basic and diluted share in the third quarter of 2021 compared to a non-GAAP net loss of $111.5 million, or $1.42 per basic and diluted share in the third quarter of 2020. In the third quarter of 2021, we recorded approximately $23.4 million in cost of sales compared to $15 million in the same period of 2020. The increase in cost of sales is primarily due to increasing demand for products. On a GAAP basis, we recorded $139.1 million and $190.4 million in R&D expenses for the third quarter of 2021 and 2020, respectively, a year-over-year decrease of $51.3 million. This decrease is primarily due to a decline in manufacturing and milestone expenses. The decrease in manufacturing expenses is related to the timing of our gene therapy batches, and we expect these expenses to return to recent historical levels. On a non-GAAP basis, R&D expenses were $115.1 million for the third quarter of 2021 when compared to $159.9 million for the same period in 2020, a decrease of $44.8 million. Turning to SG&A, on a GAAP basis, we recorded approximately $61.1 million and $75.4 million of expenses for the third quarter of 2021 and 2020, respectively, a decrease of $14.3 million. The year-over-year decrease was driven primarily by reductions in professional services, personnel, and compensation expenses. On a non-GAAP basis, SG&A expenses were $43.6 million for the third quarter of 2021 compared to $57.2 million for the same period of 2020, a decrease of $13.6 million. On a GAAP basis, we recorded $20.6 million in other expenses net for the third quarter of 2021 compared to $14.3 million in other expenses net for the same period of 2020. The increase primarily reflects an increase in interest expense incurred from our term loan debt facilities, as well as an impairment loss related to a strategic investment, partially offset by a reduction in interest expense incurred on our convertible debt related to the adoption of ASU 2020-06. We had approximately $1.6 billion in cash, cash equivalents, and investments as of September 30, 2021. Furthermore, in October, we bolstered our cash position by approximately $550 million as a result of the net proceeds we received from our equity offering. With that, I'll turn the call over to Dallan for an update on our commercial activities. Dallan?

Thank you, Ian, and good afternoon, everyone. The third quarter of 2021 saw continued revenue growth in all three of our PMO-based exon-skipping medicines. As mentioned, total net product revenue reached approximately $106 million, representing a second straight quarter with double-digit growth versus the previous quarter. We approached nearly 40% growth versus Q3 2020. This growth is being fueled by the strong launch of AMONDYS 45, which has accelerated even further over the third quarter and is exceeding all our expectations around launch uptake. Due to this continued overperformance, as Doug mentioned, the new guidance is $605 million to $615 million. We are pleased to see our 2021 net product revenues increase by more than $150 million. I'll now outline individual net product revenues for our three approved PMO medicines. I'll start with EXONDYS 51. Revenue for EXONDYS 51 totaled over $150 million in Q3 2021, representing a roughly 3% increase over the prior quarter. This modest growth represents primarily incident patients, and we expect EXONDYS 51 revenue to continue at a similar trajectory in the coming quarters. Moving on to VYONDYS 53, revenue totaled nearly $25 million in the third quarter, representing nearly 10% growth versus the second quarter of 2021. This reinforces our leading position in the exon 53 amenable market, our expertise in Duchenne, and the flawless execution of our team. As mentioned last quarter, the growth rate for VYONDYS 53 will predictably decrease as we work through the remaining start forms from the launch phase and approach the mature phase, similar to EXONDYS 51, where growth will primarily be driven by incident patients. The vast majority of exon 53 treated patients choose to be on VYONDYS 53 even with the competitive launch. Now moving on to AMONDYS 45, where the growth is tracking ahead of the EXONDYS 51 launch trajectory. Adjusting for relative population sizes, the rate of new patient start forms for AMONDYS 45 is in line with what we saw for the EXONDYS 51 launch. However, what's driving the rapid growth for AMONDYS 45 has been the decreased time to getting patients access to and on therapy. That time has been faster for AMONDYS 45 than what we saw for EXONDYS 51. As a result, the team has delivered nearly $27 million in revenue for AMONDYS 45 in Q3 2021. The successful launch of AMONDYS 45 is our third since 2016 and represents the dedication of our team who work every day on behalf of patients. Our deep experience with Duchenne has enabled us to serve more patients, expedite access to drugs, and offer best-in-class support services through SareptAssist. Our initial forecast models in the published epidemiology had suggested that the exon 45 and 53 amenable populations were similarly sized. However, given the strength of the AMONDYS 45 revenue uptake and the fact that it has now surpassed that of VYONDYS 53, we believe the exon 45 skip amenable patient population may be larger than the 53 skip amenable population, and we'll continue to assess over time. I am extremely proud of the flawless execution of our team, and we will continue to apply learnings toward our number one priority: serving the nearly 30% of individuals living with Duchenne who may benefit from our PMO-based exon-skipping therapies. Now that we've demonstrated what we can do with our first three launches, we stand ready to support the Duchenne community as we rapidly advance both our gene therapy and PPMO pipeline. We have built best-in-class U.S. field and case management teams focused on supporting patient access to therapy for appropriate patients. As such, we are ready to adapt to and execute on any potential scenario that comes our way in the coming months and years. Now I’ll turn the call over to Gilmore for an update on our research and development activities. Gilmore?

Thank you, Dallan, and good afternoon, everyone. Over the course of 2021, including up to and through the third quarter, our R&D group has successfully delivered on its goals to support and advance Sarepta’s leading position in RNA and gene therapy. Both the strategy we set forth and the investments that we have made over these past two years to build and nurture our size and talent and to leverage our expertise have yielded numerous and notable achievements. I'll begin with the impressive progress we've made in advancing our gene therapy programs. At the World Muscle Society Virtual Congress in September, we presented new data evaluating total binding antibodies against rAAVrh74 in individuals with Duchenne and demonstrated that a majority of those screened, 84.9%, were seronegative at a cutoff of 1:400 titer for anti-rAAVrh74 total binding antibody and thus will be eligible for gene transfer therapy with rAAVrh74. Now it's important to remember that the WMS-presented data were derived from an interim data cut. A more recent analysis of the complete patient cohort demonstrated that 86.1% were seronegative among the Duchenne patients with a titer cutoff of 1:400, while 13.9% were seropositive. Notably, the data also showed that seroprevalence did not increase with age in Duchenne patients aged 4 to 18. This observation is crucial for older individuals with more advanced disease considering therapies. These results are consistent with our own screening experience in our clinical interventional trials. Also at World Muscle, we presented our three-year safety and functional outcomes data from study SRP-9001-101. Specifically, functional assessments measured by NSAA showed overall improvement in motor abilities compared to baseline, and those improvements were maintained over three years, supporting a durable response and highlighting that the magnitude of benefit increases over time. The data also show that SRP-9001 is well tolerated with no new safety signals consistent with safety data from the broader SRP-9001 clinical program. Most recently, as Doug mentioned, we presented a roll-up of data across the SRP-9001, 102 Part 1, and 103 studies at our October 11 micro-dystrophin day. As reported, we possess a wealth of data across 77 Duchenne patients dosed with SRP-9001 in three ongoing studies. Forty-five of these patients have been dosed with clinical process material and 32 have been dosed with commercially representative material. Fifty-nine of the 77 were ambulatory boys aged 4 to 8 at the time of dosing, while 12 boys were older than 8 years of age at the time of dosing, six of whom were nonambulatory. In this broad patient population, we are encouraged to observe a consistent safety profile with the most common adverse event being vomiting. The increases observed in liver enzymes responded favorably to transient increases in corticosteroid use. We have not observed clinically relevant complement activation or thrombotic microangiopathy. As Doug noted, we are thrilled to be initiating EMBARK, Study 301, the first global registration trial of the gene therapy for the treatment of Duchenne. The study will use our commercially representative SRP-9001 material. EMBARK has been designed as a double-blind, randomized, placebo-controlled study and is powered to confirm that our SRP-9001 micro-dystrophin commercial representative material at a dose of 1.3x10^14 using a linearized casting standard for titrant confirms clinical functional benefit in 4 to 7-year-olds. The study will enroll 120 patients with randomization using two strata: age, with a minimum of 50% patients enrolled in the 4 to 5-year-old age group and NSAA at baseline. Building on the learnings from Study 102 Part 1, we will include patients with the time to rise from the floor or from supine of less than five seconds. Patients have been randomized, and we expect to fully enroll the study in the first half of '22. Now, moving to our limb-girdle portfolio. SRP-9003 is our lead limb-girdle program which is a full-length sarcoglycan cDNA using the same AAVrh74 titer and MHCK7 promoter as the SRP-9001 program and has generated already exciting expression and functional data in the ongoing SRP-9003 101 study. We are currently in dialogue with OTAT and the FDA about the suitability of our commercial representative SRP-9003 material to start a registration study for SRP-9003. We are using the learnings from the SRP-9001 program to advance SRP-9004 and the entire sarcoglycan portfolio in addition to our dispersing Calpine and other non-sarcoglycan programs. In passing, we attended the cellular tissue and gene therapies advisory committee meeting to discuss the toxicity risk of adeno-associated virus vector-based gene therapy. Our key takeaway was that our rh74 maintains a differentiated safety profile that is consistent and manageable using a single drug steroid immunosuppressive regime. Additionally, I'm pleased to report that our limb-girdle 501 natural history study is active and enrolling. This study represents our commitment to understanding the complexities of this rare group of diseases. Now, let me turn to the important advances from our proprietary RNA platform. I will start with our next-generation peptide conjugated phosphodiamidate morpholino oligomer, or PPMO SRP-5051, which demonstrated unprecedented clinical results in individuals with Duchenne who are amenable to exon 51 skipping. We reported in early May 21 positive clinical data from the 30 mg/kg arm in Part A of the MOMENTUM study, which evaluated safety and change from baseline at week 12 for exon skipping and dystrophin expression in both ambulatory and nonambulatory patients. The data showed that the 30 mg/kg cohort dosed once monthly, when compared to the current standard of care, demonstrated an 18-fold increase in exon skipping and more than 6.5% dystrophin expression as measured by Western blot. Importantly, these results were not driven by a single patient. All the patients responded well to therapy. Based on our predictive model, we should achieve greater than 10% dystrophin with one-dose dosing over time. Furthermore, we observed that baseline dystrophin levels are not a predictor of post-treatment expression. In fact, we observed that two patients with the lowest baseline had the highest level of post-treatment expression. Importantly, SRP-5051 demonstrates a tolerable safety profile. We continue to believe the hypomagnesemia observed in the study remains monitorable and manageable through native supplementation and is not correlated with changes in renal function. We are currently initiating Part B of the MOMENTUM study, which we anticipate will serve as our pivotal trial for SRP-5051. To remind you, at the end of September, we announced the trial design. The study will enroll between 20 to 40 patients amenable to exon 51 skipping who are naive to SRP-5051 and are between the ages of 7 to 21. Both ambulatory and nonambulatory patients are eligible for participation, along with previously treated patients. Approximately 30 additional operations previously treated with SRP-5051 will be eligible to participate in Part B. As we initiate Part B, we remain very excited by the SRP-5051 clinical results and the potential that the therapy holds to offer patients with Duchenne a more convenient once-per-month treatment option with a manageable safety profile and superior dystrophin expression. Now moving to an update for our PMO program. Enrollment for instance, for Tazmersenedologerst an admission study continues. We maintain regular contact with the FDA to update on our progress toward delivering these important clinical data. In September, we also presented two new sets of supportive clinical data for casimersen. The first was an interim biopsy analysis from essence of casimersen-treated patients, demonstrating that exon 45 skipping assessed by digital droplet PCR has significantly increased in all casimersen-treated patients compared with baseline, with a p-value of less than 0.001. Placebo-treated patients did not demonstrate an increase of 0.8. Mean dystrophin levels by Western blot significantly increased from baseline after 48 weeks of casimersen treatment with a p-value of less than 0.001, with a significantly greater increase in drug levels compared to placebo at p-value of 0.004, and increased dystrophin positively correlated with exon skipping experiment rank correlation of 0.627 and a p-value of less than 0.001. Casimersen was well tolerated, with most adverse events categorized as mild and unrelated to casimersen, and with no suggestion of kidney toxicity. The second set of data presented was from study 4658-102, the first clinical trial in patients aged 6 to 48 months, the oldest population with Duchenne evaluated in clinical trials to date. This trial demonstrated that a casimersen IV 30 mg/kg once weekly was well tolerated with no new safety signals after 96 weeks of treatment and no discernible difference between age cohorts, that is, those aged 6 to less than 24 months versus those aged 24 to 48 months. These data are consistent with encouraging trends in older patients and provide valuable information for families and prescribers. In closing, and very importantly, I want to thank all of the patients, their families, and the study investigators and coordinators who have contributed significantly to our study design in addition to participating in our many clinical trials. I also thank my R&D colleagues and our partners who have done so much work under prolonged difficult circumstances caused by the pandemic to maintain our urgent ambition to deliver new, highly effective therapies to people who have diseases. I will now turn the call over to Doug to open the Q&A session. Doug?

Thank you very much, Dr. O'Neill. Tino, let's open the call for questions now.

First question comes from Tazeen Ahmad from Bank of America. Your line is now open.

Hi, good afternoon. Thanks for taking my question. Doug, as far as EMBARK goes, can you just remind us again what the use of steroids is going to be in the study and how it's different from what you rolled out in Study 102?

It will be the same. It will be the same. So...

And can you tell us how doctors use steroids in 102?

Yes. Dr. O'Neill, do you want to address that?

Yes. We use prednisone in many of the patients who are indeed on prednisone as standard of care. We require that they remain on prednisone to avoid any adverse impact or a spurious impact on signal. The way that the patients are dosed on prednisone is that we, just to simplify, double the standing steroid regime they're on. They start that doubling at the time of infusion and maintain that regime, tapering after 60 days. In the event of any liver enzyme change, we titrate that prednisone up. But our experience to date has been very positive in that those liver enzyme changes respond to the transient elevation of prednisone. They return then after 60 days or after that initial titration to their baseline maintenance therapy, which is part of the standard of care for Duchenne.

Next one on the queue is Anupam Rama from JPMorgan. Your line is open.

Hey guys, thanks for taking my question. Just a really quick one for me. For the Part 2 Study 102 results, the guidance is for 1Q data. So should we be thinking about in and around sort of an in-person healthcare conference in January in San Francisco? Or is it later in the quarter?

Anupam, I can't think of any conferences happening early in the year. I can't commit to the exact date. Obviously, I'm joking, Anupam. I can't commit to the exact date. We have to get all the data in and QC'd, and it will be in the first quarter. It will be in the earlier part of the first quarter. But I can promise that as soon as we have it in and fully QC'd and it's ready to present, we'll do that. If it's early enough for a particular event, we'll consider that. But we can't make that commitment yet because we just don't know how long it will take to get the data in and QC it.

For the next question, we do have Brian Abrahams from RBC Capital Markets. Your line is open.

Hi good afternoon. Thanks for taking my question and Congrats on all the progress. A question on the limb-girdle program. I'm curious, your latest views on how you're envisioning a potential trial if indeed, expression is sufficient for approval. Might this be a 12-week study with longer follow-up as a confirmatory study? Would you look at 2E or all the different subtypes, placebo-controlled versus open label? And then along those lines, I'm curious sort of how far along you guys are with respect to the manufacturing process and assay development for limb-girdle. Is this something where you'd need to complete that process and any bridging work before you meet with regulators? Or might you meet with the regulators to start to contemplate a pivotal trial design in parallel?

Okay. Great. Let me answer the second question first. So we made a lot of progress, as you can imagine, with respect to process development and analytical development for our commercially representative process for 9003, and we've been well informed by all of the work that we've done for 9001 and been informed by all of the conversations that we've had with the FDA. And so we have good guidance on there, but work remains; I want to be very clear about that, particularly on the analytical side of things, a significant amount of work still remains. This will occur in 2022, but the team is doing a brilliant job of continuing to progress this. On the study design, and let me - and I'll say one final thing about the second part, which is we can, and we already have, simultaneously engage with the agency about clinical design while we're working on the process development and analytical development and GMP release for the material. That's why we have some initial signals from both the U.S. and ex-U.S. agencies that the potential for an accelerated or conditional approval is possible. I do think that the most productive next meeting will be a meeting where we can have a discussion. At the same time, this is what we did with 9001. We have one very thoughtful discussion about both the clinical design the appropriate clinical design and show the agency where we are from a CMC perspective and get them comfortable both about the technical operations side and the development side because it is clear, as we have all seen, that being very buttoned down on the CMC side is extraordinarily important. So we'll work on those discussions and eventually have to get both of those done before we commence our next trial. On the clinical design itself, we've got more work to do and the team has done a lot of thinking around this issue. In the broadest of strokes, one knows that if you're going to seek an accelerated approval, you would have two elements; whether it's one study that leads into an extension, or whether it's two studies, you have to have an element that provides confidence that using a biomarker in the case of TE would obviously be the beta-cycloglycan protein that you have a protein that - expression that's reasonably likely to predict the clinical benefit. Then you have a second part post-approval, where you confirm through additional work, the functional benefits predicted by the biomarker. We've got more work and thinking to do on that. As you may have seen or heard in my opening remarks, one of the things we're pondering at least as we track into 2022 is if we want to start accelerating no other sarcoglycans; that CMC work as well and perhaps have an approach that brings them together — perhaps even into one basket study or close together so that they're actually tracking closer together. So short answer is we have a ton of work to do there. The good answer is that we have the resources to do all of that work. We previously stated we had about $1.6 billion of cash and cash equivalents on our balance sheet. We went and raised more money just about three weeks ago. We're sitting in a position right now where we have over $2 billion, significantly over $2 billion in cash and cash equivalents. We have really robust sales, and we've seen really good sales growth, and that will continue into 2022. We have the resources to bring all of these programs along. One of the things this hasn't been asked yet, but I'll answer, one of the things we really wanted to ensure is that we had the resources not only to execute a lot of our late-stage programs to make sure that we're accelerating the limb-girdles and getting all of those limb-girdles moving as fast as possible, given what we see as an extraordinary opportunity to do good with a high probability of success and together, a compelling commercial rationale. And over on the PPMO side, same answer. With the signals we've seen now on SRP-5051, one of the things we really wanted to make sure we could do is start getting the work done on other constructs beyond SRP-5051 so that we get the broader PPMO pipeline moving as fast as possible and hopefully in the patients as soon as possible.

Next one on the queue is Salveen Richter from Goldman Sachs. Your line is now open.

Good afternoon. Thanks for taking my question. As we look to the 201 study reading out in the beginning of the year, so the two-year data and the crossover data here, could you just comment on whether there's any changes being implemented to Part 2 versus Part 1? And also, given what you saw in Part 1, how do you think about that translating to a positive outcome in part 2?

Yes, there are a few things to keep in mind. The main distinction between Part 1 and Part 2 is that there are significantly more patients in Part 2 since all 41 children will be on active therapy. We will be comparing these children against a natural history cohort. There are no control subjects in the placebo arm available for comparison because all crossover participants have received therapy. Among the 41 children, approximately half will have two years of data while the other half will have one year, along with the data leading into that. We will analyze this data in relation to the natural history cohort for insights. Two elements from Part 1 were particularly disappointing. First, we found that about 60% of children in the first cohort received doses below the target. However, with the new linear titration method used in the crossover, this issue will not occur, as all children who received the crossover treatment will have been given the intended target dose of 1.33e to the 14. Secondly, by utilizing a natural history cohort, we can accurately match subjects based on their age and baseline characteristics. I believe Part 2 will provide valuable insights as we move forward with EMBARK, our pivotal trial for SRP-9001.

Next question comes from the line of Gena Wang from Barclays. Your line now open.

Thank you for taking my question. I have one regarding the momentum Part B PPMO program. Do you still need FDA confirmation on the pivotal study design? I understand you have three cohorts. Can you give a little bit more color on study design and the powering assumption?

Yes. I'll broadly answer the first part. And I'll ask Dr. O'Neill to just describe very briefly the cohorts that are in MOMENTUM Part B. I mean, the short answer is we have the agency blessing to proceed with Part B. Part B will be our pivotal trial. We'll be using the accelerated approval avenue. The good news with the neurology division and Duchenne muscular dystrophy and dystrophin reduction is that we have a very good precedent for that. In fact, there's a guidance on dystrophinopathies around this. So our pathway is pretty direct and certain and the agency has blessed us to commence MOMENTUM study Part B. But with that, Dr. O'Neill, perhaps you can talk about the cohorts that are Part B cohorts.

Yes. Thank you very much. So in Part B, there's actually one cohort, but it was designed for SRP-5051 naive patients who will be newly enrolled in the study, and we are allowing another 30 patients who have previously been exposed to reenter the study. There will be a running safety period. Patients will be randomized to one of two doses, and in answer to your far question, the study has been powered around dystrophin expression versus baseline.

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

Hey guys, thanks for taking my question. I was just curious with MOMENTUM. I know since it's getting underway, like - and this only really 20 to 40 people, if you have any kind of perspective on timelines and would they be similar or maybe some of the other studies of similar sizes of the past? And then also, should we think about this as kind of life cycle management on Templer center? Or how do we think about that?

So let's start with the first part. So in first dealing with enrollment, one must remember that MOMENTUM is different from, for instance, the 9001 study EMBARK in that it's a subset of children with Duchenne muscle dystrophy. There are other programs that we're competing with. So it will take a bit longer to enroll than you might imagine, just given the total number. So it will be really second half of 2022 before it's fully enrolled. And then, I would say - I would look at the PPMO platform as a whole, SRP-5051 itself and then the PPMO platform as a whole, as more than simply a line extension strategy. There is a real enormous potential at least to have something that is significantly transformative, both in the U.S. and outside of the U.S. As we know, given the approach that was taken to the approval of EXONDYS, our approvals in the United States, there are very few places outside the United States where it's approved. Right now, we have a managed access program. So there is some access outside the United States, with the lion's share of the use of the therapy right now being in the United States. The PPMO can do a number of things. If confirmed in the trials, it will be a transformative additional benefit to children who are already benefiting from our current PMOs. It bears repeating that we're seeing in a literally a shorter period of time, half the time of eteplirsen, and at 20% of the dose, we're seeing nearly an order of magnitude more dystrophin production. The literature would suggest that this could be completely transformative to children with Duchenne. We can directly benefit 50% of Duchenne, and theoretically, we can reach over 80% of Duchenne. So just the opportunity for expansion is enormous. More importantly, there is a real necessity to get these therapies into the hands of children who need them around the world, so it's paramount we proceed quickly.

Next question comes from the line of Matthew Harrison from Morgan Stanley. Your line is now open.

Great. Thanks very much for taking my question. I was just wondering if you could comment a little bit in more detail for MOMENTUM Part B as well, just around safety and the size of the safety database or the duration of the safety database that you might need there or any special considerations from an FDA perspective?

So we'll have about 60 patients. That's significant more than we've had for the other PMOs. We should have a fairly significant number of patients. And of course, the agency has blessed this study in its size. From a safety monitoring perspective, the look from an expression perspective is 28 weeks. Our working assumption is the agency would like to see longer follow-up than 28 weeks, so I would guide to 1 year for the safety follow-up as a basis for the accelerated approval.

Next question comes from the line of Gil Blum from Needham & Company.

Good afternoon and Congratulations on a very strong quarter. But maybe a bit of a question on PPMOs more broadly. So we can reach around 80% of patients. But so far, in the PMO programs, you have had to approve each new targeted population by itself. Is there a basket approach here somewhere, maybe kind of like what you're looking at LGMD?

Yes, a really insightful question. The answer is that we think there will be, at some point, both an opportunity and, frankly, a need to have a basket approach. I can tell you that we've engaged, in fact, Dr. O'Neill and I were both present, had meetings with the FDA some years ago when we started the dialogue about the potential for a basket approach with our PMO or PPMO technology. The thing I'd say, the reason that it will become important over time is that we can in a very straightforward way, just doing the kinds of studies we're doing now— which are very lean and relatively rapid studies— we can get therapies approved for up to 50% of the Duchenne community. But if you want to get to that 80% level, if you want to get up to the full opportunity to treat these kids, you're getting into rarer and rarer exons, and it will be towards that area that we'll have to really think about creating a basket approach and then speaking with the agency about the approach to create one study that treats a number of different constructs together and looks at them together as opposed to separate studies. I've also been in meetings broader than Sarepta by a long shot, the meetings with senior leadership or senior leadership at the FDA has talked about some of these goals. I think at least conceptually the FDA leadership is aligned with this idea of looking at things like basket approaches to get to rarer and rarer serious disease populations. So I do think on our strategic plan, the next group of PPMOs will look to not employ sort of any sort of next-generation basket approach. We will get to a point where we'll want to do that with the concurrence of the agency.

Next question comes from the line of Ritu Baral from Cowen. Your line is now open.

Hey guys, thanks for taking my question. I wanted to ask about the layer you're going to be enrolling EMBARK, given that Pfizer has been enrolling for a while, but it's all ex-U.S. Do you anticipate that U.S. sites will be mostly untapped for EMBARK? And do you have any agreement with the FDA or you on sort of geographic split of patients?

One of the agreements on the geographic split. In the U.S., and we don't have a problem, frankly, even in sites that might be dosing Pfizer. There will be sites around the world where one could envision the same site dosing patients with Pfizer and dosing patients with SRP-9001. In the United States, where it is at least for now, and I think based on what I've heard yesterday, will be for at least some time to come. It will— there won't be any sites that have dosed in the pivotal trial a patient with Pfizer. I will go back to the statement— and just so you know, broadly speaking, our goal is to have sites in the U.S., a significant number of sites in the U.S., a significant number of sites in Europe, and we'll have sites in Asia as well. What I said is that we believe that we'll have this study fully enrolled in the first half of next year. I do think this is going to be a program that's going to be in significant demand. So we do anticipate robust recruitment.

Next one on the queue is Colin Bristow from UBS.

Hey, good afternoon. Thanks for taking my question. Just a Part 2 of Study 102 and the potential for this to permit a discussion with the FDA around an expedited path to market. What is the minimum you guys are looking for to initiate that conversation with the agency?

Yes, but first, let me start by reminding everyone that EMBARK is our pivotal trial. So I really want to emphasize this. EMBARK is our pivotal trial, and that should be the base case assumption for the approval of the— of SRP-9001 in the United States and around the world. Probably one of the most exciting elements of Part 2 of 102 is that it provides additional conviction and insight into this therapy as we execute EMBARK. I think that ought to be the view we all have. The— assuming that the signals from Part 2 of 102 are positive, and given that we already have, from our perspective at least, very positive signals across what are already going to be three trials, I think that we might have a data set that would justify a discussion with the FDA about the potential for a faster pathway than the traditional pivotal trial. But there's two things to consider on that. I want to be very clear about it. The first is, I think everyone's working assumption has to be that EMBARK is the pivotal trial and that will be the basis for approval. The second is that when we consider anything different than that, there are two elements to that, both of which are important. The first, of course, is that the totality of the evidence has to make a compelling case that we have a therapy that based on the markers that we have already— an expression that we already have— reasonably likely to predict the clinical benefit. I'm biased. I think we are already there, and I think 102 Part 2 will continue to justify that belief. The second part of it is important to remember as well is that we have to have a division and an agency that are amenable to that. And we have— that is a significant— I know both of those issues have to come together. You look over at MOMENTUM and we say about MOMENTUM that we have a high degree of confidence around the use of the accelerated approval pathway, but that's because we have very good precedents. We have three therapies already approved on the accelerated approval pathway. We've had direct discussions with the agency about the accelerated approval pathway. They have built a guidance around dystrophinopathies, that gives us a lot of confidence around that. Over on the super side, not that has yet to occur. So what I would say is based on the Part 2 102 data; over in Part 2, we look at the Part 1, whether it was 4 to 5 year olds. We looked at what we've seen already in 103 and what other data we may have from 103 down the road. We look at our 101 kids over three years. And if all of that is compelling, and I would argue today it already is compelling, that might give us an opportunity to sit with the division and talk about the value of a potential faster pathway for some— for a significant percentage or some portion of the Duchenne community. But I would not— I would not assume in advance, but that's the pathway. The assumption I would make, and I'll keep repeating this, the assumption I would make for everyone is that the EMBARK study, formerly known Study 301 is the pathway for our approval in the United States and around the world. I am extremely excited about that trial. It is well powered. There are 120 patients, one of the largest, if not the largest study, interventional study in Duchenne muscular dystrophy that I'm aware of that's ever existed. I might be overstating that, but I think that's the case. It's certainly the largest in gene therapy. So we're very excited about executing that study. We're very excited about the readout of Part 2 of 102. I want to be clear about that. We're very excited about that.

So for the next question, we do have Brian Skorney from Baird. Your line is now open.

Hey, good afternoon. Thanks for taking my question. Just on the baseline antibody titers. I think there's published work showing that greater than 1:800 titers associated with loss of transgene expression. I think your— Maybe you could just discuss the differences there and what cutoff specifically you're using for EMBARK and whether or not beyond that loss of transgene expression, one might expect suboptimal expression at some level in between the two that might be technically seronegative, but still have some detectable levels.

Yes. I will turn this over to Louise. The answer is 1:400, but I'll turn it over to Louise to give you more evidence on that. One thing I will remind you when we think about screen-in, screen-outs is what Dr. O'Neill mentioned in his prepared remarks, which is we've always guided based on our experience that we're in the kind of 15%, maybe a little more than 15% screen out, but we're in the midst of zero prevalence study. Interestingly enough, the screen-out rate is lower, at least in the zero prevalence study, even than we were guiding— it's a little under 14% right now. So, and interestingly enough, another significant element of that, that Dr. O'Neill mentioned. Not only is it about a little under 14% now that we've looked at it. But also, it doesn't appear to appreciably— the screen-out rate doesn't appear to appreciably increase over age, which is fascinating because, I mean that was a big concern that you'd have to catch these kids early or if they were 16, 17, 18, 19 years old, they might have a significant amount of screen out. But that's not what we're seeing in our study nor is it what we've seen in our previous experience, and we've looked at it across a wide age range because of the limb-girdles. But with that said, Louise, you can correct the record and provide additional guidance.

You're correct. Just to add, we originally got the 1:400 titer because we did do studies that showed that above that, so 1:800 and above, we saw an impact on gene expression in nonhuman primates, and that's where the original 1:400 titer came. So we are including patients with titers less than 1:400 in our studies.

So for the next question, we do have Joseph Schwartz from SVB Leerink. Your line is now open.

Thanks very much. For Part 2 of 102, are you hoping to see the same kind of three-point improvement on NSAA? Or would you hope to see more or less based on the age of the patients who are enrolled in this cohort and how they were treated with steroids or anything else that could sway the results?

Well, I think the real answer is it's difficult for me to give you an answer because I haven't seen the full blown natural history cohort that they need to look against because that's the thing we always have to remember that we have to look at versus. I mean, I think the most interesting and compelling information is going to be what would natural history predict versus what we see with these kids? Like as an example, the compelling example of this is 101 children. We all remember back in the summer of 2018, we had this great benefit to these kids in the first year, and we were really excited about - we're all very excited about it as everyone will remember. If you look at those kids over three years, what you find is those kids are stable to improving. But more importantly, they're stable to improving; natural history is receding into the degeneration that we know is inevitable with Duchenne. These kids ended up with this p-value of greater than 0.0001 and a nine-point on NSAA. So really, honestly, the answer is that we hope to see compelling signals versus natural history when we look at the results of Part 2 and 102.

Next one on the queue is Hartaj Singh from Oppenheimer & Company.

Great, thanks. It looks like Sarepta's got a lot going on. Just a quick question on your limb-girdle programs. You presented data recently, a poster in September on some patients both up to two-year data on the low dose and now on the higher dose. What's the potential for that, for the higher dose there to be expanded into sort of, let's say, an expansion cohort next year? And if your CMC gets worked out next year, then that could become sort of a study that perhaps for accelerated approval. I mean the study seems pretty comprehensive that the one that you report on is going on.

Yes. Thanks for that question. I mean, I agree with you that the data is extremely compelling, and it shouldn't probably be a surprise. We're making a very significant amounts of the properly localized protein that is the structural protein, the absence of which is the sole reason these children are degenerating and dying. We're seeing great results. We saw great results from the low dose. We're seeing great results from the high dose. The issue for us, remember, is that all of that was done with creative supply from Nationwide Children's Hospital. We have to— that's why I say the biggest rate limiter for all of us, CMC work that goes into making our commercial process material. That's the big rate limiter for us. I think realistically that information is all supportive valuable evidence. But we need to get commercial process material released, and we need to dose children with our own material that's fit for commercial distribution. That will be the basis for an approval. So I don't think it's a realistic avenue to assume that we could somehow expand what we've already done. I think we have to replicate that expression, which of course we're confident will be the case, once we get the CMC worked out. We're very excited about it. We need to move. Again, I will say, one of the reasons that we really wanted to bolster our balance sheet is that we have this enormous pipeline, and we wanted to make sure that all of the programs that have such a significant potential impact in a high probability of success are moving along. Among those, some of the most significant ones we're thinking about at least in limb-girdles, we want to get these things moving as fast as possible.

Next one on the queue is Yun Zhong from BTIG. Your line is now open.

Thanks very much for taking question. So PPMO program, can you remind us if 5051 is using the same sequence as EXONDYS 51? And how quickly do you think you will be able to move additional programs whether you take a basket approach or not into the clinic? And also, you talked about ex-U.S. opportunity. But given what you were previously experienced with EXONDYS 51 when you talked to the EMA, are you going to look at functional endpoint at all with either 5051 study or maybe future studies?

Yes. So let me go to the— so to your first question, yes, it's the same sequence as eteplirsen but with a conjugated proprietary peptide that enhances the delivery. With respect to how fast we're moving now. So the good news is we're moving other therapies forward. We have a number of constructs essentially already built and conjugated peptides to them. We got— the first thing that one has to do is to get all of the tox and related work done as we advance those. I can’t give an exact date, but we have a lot of work to do there. But with our bolstered balance sheet, we can make sure that we fully fund that and move that as fast as good science allows us to do. On the ex-U.S. opportunity, of course, we're going to have to look at function along the way at some point. The accelerated approval pathway allows you to get an approval with signals before you have the full functional set. One of the reasons we get more confident on the potential, at least for instance, for conditional approvals earlier than full functional benefits in other parts of the world, is based on discussions we've had with European regulators. Both Dr. O'Neill and I were together in Europe for the review with CHMP and EMA for eteplirsen. While certainly there's nothing binding in the comments that were made at the time, it was quite clear to us that had we made a significantly greater amount of dystrophin, I think the discussion would have been different. If indeed what we've seen in Part A of momentum can be replicated, and we're seeing dystrophin that would correlate to a 10% or more dystrophin over time, I think the potential to have a very fruitful discussion ex-U.S. about a fast approach to getting these therapies to other kids around the world will be good real possibility, maybe even a probability.

For the next question, we do have Tim Lugo from William Blair.

This is John on for Tim. I was wondering if there's any early color you could give us on how enrollment is progressing so far for EMBARK.

It's early days, but so far so good. We're enrolling patients, screening patients, and getting them going. So I have no— every signal that I have so far is consistent with the optimism that I've had for some time that EMBARK once we initiated is going to move fast. I've said before I can give you anecdotes that are actually troubling them. Families are so in need of therapy that they would consider moving from country to other countries just in the hope of being enrolled in one of our studies for SRP-9001. An idea that I do not think is wise because there are only 120 total patients. I wouldn't suggest that. But I think this is going to be a very popular - an important study. I think both from clinical investigators as we get the sites up and engaged. I think it's going to be a very important therapy and study for patients with Duchenne muscular dystrophy. We're guiding to the first half of next year for enrollment. But I'm quite confident that EMBARK is going to robustly enroll as we get the sites initiated.

Next question comes from the line of Danielle Brill from Raymond James. Your line is now open.

Hey guys, thanks so much for the question. So I saw that Pfizer's DMC more or less verified that the myositis events that they observed were driven by an immune response against microdystrophin. So I'm just curious whether you've done a similar assessment or further investigated the root cause of the SAE you guys saw in Study 103 at all.

Yes. So the short answer is that we— our view is that Pfizer is accurate in its assumption regarding the basis for its myositis. They've had three of these myositis events, and they believe that they are related to certain mutations. Our assumption is— our working analysis is exactly the same. You will recall that in Study 103, we had a single case of myositis. It wasn't as severe as the myositis reported by Pfizer, but we did have myositis and it was a SUSAR. We were quite confident based on our analysis that it was mutation-driven. You may also recall that we had in Study 101 and in Study 102, we had excluded exons 1 through 17 out of a theoretical concern that there might be a potential immune response. The reason for that, of course, is that in that area, there is a risk that a child may have a certain kind of deletion that puts him in a position where he's never made a tolerizing level of dystrophin with that part of the dystrophin construct present. So they readied us for it and there's immune response. Now for EMBARK, we've taken what is a very conservative approach. For the commencement of EMBARK, we've excluded exons 1 through 17 as we begin the trial. With that said, we don't believe when we're done with this and when we're ready to commercialize this therapy that that restriction needs to be as restrictive. Here are the reasons we believe that. It's evidence-based. We've dosed nine children in the 1 through 17 exon range. Only one of these children had this issue. All the other eight out of nine had no issues. That one of nine is very different from the others. That child had an enormous deletion. It was, I think, over 40 exons, the lesion that covered in the exon 1 through 17 range as well. I suspect that Pfizer, we have something similar to that. We are confident that when we get done with this, there will be some very small percentage of kids— percentage or two of kids who have this combination of mutations in a certain area and then big enough mutations that they have a potential risk. But it will be very— we think it will be a very small percentage of kids that have it. What we're going to do, while we've excluded exon 1 through 7 from EMBARK, we're going to actually start a study early next year where we start bringing back into frame the safety of dosing of other kids in the 1 through 17 range that we don't think have this risk. For us, however, we concur with Pfizer's belief in that issue. We have a good way to address it, frame it, and make sure that it's only kids that have that risk who are excluded from therapy.

I just want to add one point: we—in that particular patient, we did an ELISpot and showed specifically that the unique response to that portion of the transgene was both the cause for that, and we didn't see it in any of the patients. It was very specific.

Again, there are no further questions at this time. I will now turn the call over back to CEO Doug Ingram for closing remarks.

Thank you, Tino. Thank you all for joining us this evening. Thank you for your great questions tonight. I look forward to reporting out at our next quarterly earnings results and presenting additional evidence and information across the way. We've got some really important milestones that we're going to be reading out in the next quarter or so. We're very excited about those. Of course, in the interim, the team continues to execute. We're going to execute on 5051. We're going to execute on SRP-9001 and EMBARK, moving that as fast as possible. We get ourselves in a position so that we have the Study 102 data as soon as possible. To our colleague Anupam, we'll see what we can do. When we get that data out and fully QC'd, we'll obviously present that and share that with the community. We'll continue to serve the Duchenne community with the therapies that we have approved today. Dallan and team have done a brilliant job protecting those kids during the pandemic, but also serving them, ensuring that they have therapies available. I think we're going to continue to do that over the course of this year and into next year. I look forward to updating you as we execute. Thank you, and have a lovely evening.

This concludes today's conference call. Thank you for participating. You may now disconnect.