Good afternoon, ladies and gentlemen, and welcome to the Sarepta Therapeutics Third Quarter 2021 Earnings Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one on your telephone. As a reminder, today's program is being recorded. At this time, I'll turn the call over to Mary Jenkins, Senior Manager, Investor Relations. Please go ahead.
Thank you, Chino, 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 recent 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. 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 multi-platformed 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-$570 million. We have overperformed to 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 from the benefit our therapies provide to the lives of those with Duchenne. As I've mentioned before, even during the most difficult periods 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-$615 million, $40 million above our previous guidance, $70 million above our initial guidance this year, and representing, at the midpoint, 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. Consider where we stand 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 one of ENDEAVOR or Study 103, our first trial evaluating our commercially representative SRP-9001 material.
Across all measures, that's 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 some 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 continued 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 scale, or NSAA, and that's against natural history with a P value of less than 0.0001.
In our blinded placebo-controlled Study 102 part one, we had previously reported that in the baseline matched four to five-year-old cohort, at 48 weeks, the treated children performed statistically significantly and clinically meaningfully better than placebo at a P-value of 0.017. For the six to seven-year-olds, we recently reported that when properly baseline and age-matched against the natural history cohort, treated six to seven-year-olds performed three points better than natural history with a statistical significance of 0.0129. Finally, but importantly, we reported that 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 0.6 decline in NSAA over that same period of time.
After an enormous amount of work and progress in CMC, in manufacturing, in research, development, and regulatory interaction, the FDA cleared us to commence our pivotal trial for SRP-9001, known as EMBARK. That is the first gene therapy pivotal trial for Duchenne in the United States. In early October, we announced the initiation of EMBARK, and on October 11, at our SRP-9001 Micro-dystrophin 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 focusing on 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 representative SRP-9003 material. We intend to complete this work next year.
With our strengthened balance sheet, we intend to move our six-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. That 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/ per kg cohort, compared to eteplirsen, we saw 18x greater exon skipping, an eight-fold greater level of dystrophin production, and we saw this in half the time and at 20% of the drug exposure of eteplirsen.
We also saw 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, our work in new and improved delivery mechanisms and advanced AAV capsids, and our work to improve gene therapy to permit dosing in the presence of preexisting antibodies and to empower redosing. At the same time, we continue to further strengthen our first-in-class team of genetic medicine professionals across technical operations, research development, regulatory strategy, just to name a few. To that end, in early October, we celebrated the grand opening of our world-class 85,000 sq ft Genetic Therapies Center of Excellence in Columbus, Ohio. We continue also to build our Gene Editing Innovation Center in Durham, North Carolina, which is 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 medicine 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 important 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 disease. Your tireless work and focus on execution shows in our advancements this year, and I am confident that it will translate into a better life for the many patients who depend on our work. 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 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 of 2020, 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 of 2020.
For the third quarter of 2021, individual net product sales were $115.6 million for EXONDYS 51, $26.7 million for AMONDYS 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 in 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 decrease in manufacturing and milestone expenses. Now, 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. Now on a non-GAAP basis, R&D expenses were $115.1 million for the third quarter of 2021 compared to $159.9 million for the same period of 2020, a decrease of $44.8 million. Now turning to SG&A.
On a GAAP basis, we recorded approximately $61.1 million and $75.4 million expenses for the third quarters of 2021 and 2020, respectively, a decrease of $14.3 million. The year-over-year decrease was driven primarily by a decrease in professional services, personnel, and compensation expenses. On a non-GAAP basis, the 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 due to an increase in the outstanding balance 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 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 $167 million, representing a second straight quarter with double-digit growth versus the previous quarter, and we approached nearly 40% growth versus Q3 2020. The growth is being fueled by the strong launch for 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-$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, as with EXONDYS 51, where growth will be driven primarily 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 EXONDYS 51 launch. However, what's primarily 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 in Q3 2021 with AMONDYS 45. 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 drug, and offer best-in-class support services through Sarepta Assist. 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 this 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 will continue to assess over time. I'm 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 science 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 or RH74 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-RH74 total binding antibodies, and thus would be eligible for gene transfer therapy with an RH4 vector. 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 of these Duchenne patients with a titer cutoff of 1:400, and 13.9% were seronegative. Notably, the data also showed that seroprevalence did not increase with age in Duchenne patients aged four to 18.
This latter observation is very important for older individuals with more advanced disease considering therapy. These results, by the way, are also generally 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 improvements 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 wider SRP-9001 clinical program.
Most recently, as Doug mentioned, we presented a roll-up of data across the SRP-9001-101, SRP-9001-102 part 1, and SRP-9001-103 studies at our October 11 Micro-dystrophin Day. As reported, we present a wealth of data across 77 Duchenne patients dosed with SRP-9001 in three ongoing studies. 45 of these patients have been dosed with clinical process material, and 32 have been dosed with commercially representative material. 59 of the 77 were ambulatory boys aged four to eight at the time of dosing. 12 boys were older than eight years of age at the time of dosing, and of those 12, six were non-ambulatory. In summary, we have experienced a broad population that includes a wide age range of four to 19-year-olds and a very wide weight range between 13.7-80.1 kg.
In this broad patient population, we are encouraged to have observed a consistent safety profile with the most common AEs being vomiting. The increases observed in liver enzymes that we have responded favorably to transient increases in corticosteroids, and we have not observed clinically relevant complement activation or thrombotic microangiopathy. As Doug noted, we are thrilled to be initiating EMBARK, our Study 301, the first global registration trial of a 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 commercially representative material at a dose of 1.3 × 10^{14}, using a linearized capsid standard for titer, confers clinical functional benefit in four to seven -year-old boys.
The study will enroll up to 120 patients with randomization using two strata, age, with a minimum of 50% of patients enrolled in the four to five -year-old age group, and NSAA at baseline. Age and NSAA at baseline are the strata. Building on the learnings from Study 102 part 1, we are including patients with a 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 2022.
Now, moving to our limb-girdle portfolio, SRP-9003 is our lead limb-girdle program, in which a full-length sarcoglycan cDNA uses the same AAVrh74 capsid 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 commercially representative SRP-9003 material to start a registrational study for SRP-9003. We are using the learnings from the SRP-9001 program to advance SRP-9003 and the entire sarcoglycan portfolio in addition to our dysferlin, calpain, and other non-sarcoglycan programs. In passing , we attended the Cellular, Tissue, and Gene Therapies Advisory Committee meeting to discuss the toxicity risks of adeno-associated virus vector-based gene therapy.
Our key takeaway was that our RH74 capsid maintained a differentiated safety profile that's 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 phosphorodiamidate 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 2021 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 non-ambulatory patients. The data showed that the 30 mg/kg cohort dosed once monthly when compared to the current standard of care, eteplirsen, demonstrated an 18-fold increase in exon skipping and more than 6.5% mean dystrophin protein expression as measured by Western blot. These results were not driven by a single patient. All the patients responded well to therapy, and based on our predictive model, we should achieve greater than 10% dystrophin with once-per-dosing over time. Further, 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 demonstrated a tolerable safety profile. We continue to believe the hypomagnesemia observed in the study remains manageable with magnesium supplementation and is not correlated with changes in renal function. Importantly, 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 20-40 patients amenable to exon 51 skipping who are naive to SRP-5051 and are between the ages of seven to 21. Both ambulatory and non-ambulatory patients are eligible for participation along with previously treated, and treatment-naive patients.
Approximately 30 additional patients 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 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 updates for our PMO program. Enrollment for ESSENCE for casimersen and golodirsen, and MIS51ON study for eteplirsen continue. We maintain regular contact with the FDA to update on our progress toward delivery of these important clinical data. In September, we also presented two new sets of supportive clinical data for casimersen and eteplirsen at World Muscle.
The first was an interim biopsy analysis from ESSENCE of casimersen-treated patients, demonstrating that exon 45 skipping assessed by droplet digital PCR was significantly increased in all casimersen-treated patients compared with baseline with a P value of <0.001. Placebo-treated patients did not demonstrate an increase, a P of 0.8. Mean dystrophin levels by Western blot significantly increased from baseline after 48 weeks of casimersen treatment with a P of <0.001, with a significantly greater increase in dystrophin levels compared to placebo at a P of 0.004. Increased dystrophin positively correlated with exon skipping with a Spearman rank correlation of 0.627 and a P of <0.001.
Casimersen was well-tolerated, with most adverse events classified as mild and unrelated to casimersen, with no suggestion of kidney toxicity. The second was a presentation of Study 46-58-102, the first clinical trial in patients with Duchenne aged six to 48 months, the youngest population of Duchenne evaluated in a clinical trial to date. This trial demonstrated that eteplirsen 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 divided as six to less than 24 months versus 24 to 48 months. These data are consistent with what's been seen following treatment with eteplirsen in older patients and provide valuable data 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 done so much in contributing 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 mission to deliver new, highly effective therapies to people with rare diseases. I will now turn the call over to Doug to open the Q&A session. Doug?
Thank you very much, Dr. O'Neill. Chino, let's open the call for questions now.
All right. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Again, that is star one on your telephone. Please limit yourself to only one question. First question comes from the line of 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 gonna be in the study and how it's different from what you've allowed in Study 102?
It will be the same.
Can you tell us how doctors used steroids in 102?
Yeah. Dr. O'Neill, do you wanna address that?
Yeah. We use the prednisone. Many of the patients are actually indeed already on prednisone as a standard of care. We require that they run in on prednisone to avoid any adverse impact or spurious impact on signal. The way that the patients are dosed on prednisone is that we, just to simplistically put it, double the standing steroid regimen they're on, and they start that doubling at the time of infusion and maintain that regimen and are tapered after 60 days. In the event of any liver enzyme change, we titrate that prednisone up.
Our experience to date has been very positive in that those liver enzyme changes respond to the transient elevation of prednisone, and they've returned then after 60 days or after that initial titration to their baseline maintenance therapy, which is part of the standard of care for Duchenne.
All right. Next one on the queue is Anupam Rama from J.P. Morgan. Your line is now open.
Hey, guys. Thanks so much for taking the question. Just a really quick one from me. For the part two Study 102 results, the guidance is for 1Q data. Should we be thinking about in and around sort of an in-person healthcare conference in January in San Francisco, or is this later in the quarter? Thanks so much.
You know, Anupam, I can't think of any conferences happening early in the year. I can't commit to the exact day. Obviously, I'm joking, Anupam. I can't commit to the exact date. We have to get all the data in and QC it. It will be in the first quarter, and it will be in the earlier part of the first quarter. 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. 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 now 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's 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? 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? Thanks.
Okay. Great. Let me answer the second question first. We've made a lot of progress, as you can imagine, with respect to process development and analytical development for our commercially representative process for SRP-9003. We've been well informed by all of the work that we've done for SRP-9001 and been informed by all of the conversations that we've had with the FDA, so we have good guidance on there. But work remains. I wanna be very clear about that, particularly on the analytical side of things. A significant amount of work still remains, so this will occur in 2022, but the team is doing a brilliant job of continuing to progress this. On the study design, let me...
I'll say one final thing about the second part, which is, you know, we can and we already have simultaneously engaged 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 SRP-9001.
We can have one very thoughtful discussion about both the clinical design and 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 as well as the development side. Because it is clear, as we have all seen, it's very clear that being very buttoned down on the CMC side is extraordinarily important. 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's doing a lot of thinking around this issue. In the broadest of strokes, of course, what one knows is 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 2E, would obviously be the beta-sarcoglycan, sarcoglycan protein, that you would 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 to do and more thinking to do on that because 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 wanna start accelerating the 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. Short answer is we have a ton of work to do there. Good answer is that we have the resources to do all of that work. As you know, you know, we previously had been saying we had about $1.6 billion of cash and cash equivalents on our balance sheet. We went and raised more money, you know, 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, and we have really robust sales, and we've seen really good sales growth, and that'll continue into 2022. We have the resources to to bring all of these programs along. I mean, one of the things, you know, 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. We're 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.
Over on the PPMO side, same answer. With the signals we see 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 PPM, PPMO pipeline moving as fast as possible and hopefully in the patients as soon as possible.
Right. 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, the two-year data and the crossover data here, could you just comment on whether there's any changes being implemented to part two versus part one? Also what, you know, given what you saw in part one, how do you think about that translating to a positive outcome in part two?
Yeah. There's a couple of things to consider. The biggest difference between part one and part two, I would say, is in addition to the fact there are far more patients, of course, in a sense in part two, because all of the children now will all 41 of them will be on active therapy, is that we'll be looking at those children against a natural history cohort, right? There isn't a placebo arm to test against because all of the children in the crossover have now been dosed with a therapy. We have 41 children, about half of them two years' worth of data, and the other half will be one year's worth of data with a trajectory of one year leading into that.
We can look at all of that and look at it against the natural history cohort as well to see what insight we have. I guess there are two things that happened in part one that were frustrating. One, of course, was the issue of the target dose. In the first cohort of children, about 60% of those children had lower than the target dose. On the crossover with the new titering method that we have employed, this linear titering method, that does not exist. All of the kids in the crossover, that half that got dosed on crossover, all of those children will have had the proper dose, the target intended dose, 1.33 × 10^14.
The second thing is that using a natural history cohort, we can properly match them against not only their age but also their baseline characteristics. What I'll say is I think that part two will be very insightful as we execute EMBARK, our pivotal trial for SRP-9001.
Next question comes from the line of Gena Wang from Barclays. The line is now open.
Thank you for taking my questions. 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 a three cohort. Can you give a little bit more color on study design and the powering assumption?
Yeah. I'll broadly answer the first part, and I'll ask Dr. O'Neill to just describe very, very briefly the cohorts that are in MOMENTUM part B. I mean, the short answer is we have the agency's blessing to proceed to 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 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 the MOMENTUM study part B. With that, Dr. O'Neill, perhaps you can talk about the cohorts.
Yeah.
That are part B cohorts.
Yeah. Thank you very much. The part B, there's actually one cohort, but it will comprise two populations, and 40 SRP-5051 naive patients who will be newly enrolled to the study. We are allowing another 30 patients who have previously been exposed to reenter the study. There will be a run-in safety period, and then the patients will be randomized to one of two doses. In answer to your final question, the study has been powered around dystrophin expression versus baseline. Thank you very much.
All right. Next one on the queue is Alethia Young from Cantor. The line is now open.
Hey, guys. Thanks for taking my question. I was just curious with MOMENTUM. I know since it's, you know, getting underway, like, and it's only really 20-40 people, if you have any kind of perspective on timelines and where would they be similar, maybe some of the other studies of similar sizes of the past. I mean, should we think about this as kind of life cycle management on eteplirsen, or how do we think about that? Thanks.
Let's start with the first part. In first dealing with enrollment, one must remember that MOMENTUM is different, for instance, than the SRP-9001 study EMBARK, in that it's a subset of children with Duchenne muscular dystrophy, and it's exon 51, and there are other programs that we're competing with. It will take a bit longer to enroll than you might imagine, just given the total numbers. It'll be really second half of 2022 before it's fully enrolled. Then, you know, I would say I would look at it, the PPMO platform as a whole, as, you know, SRP-5051 itself and then the PPMO platform as a whole, as more than simply a line extension strategy.
I think 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, and there are very few places outside of the United States where it's approved right now. We have a managed access program, so there is some access outside the United States. The lion's share of the use of the therapy right now is in the United States. The PPMO can do a number of things. First of all, if it's confirmed in the trials, it'll be a transformative additional benefit to children who are already benefiting from our current PMOs.
It bears repeating that we're seeing in literally a shorter period of time, half the time of eteplirsen at 20% of the dose, we're seeing nearly an order of magnitude more dystrophin production. The literature would suggest that could be completely transformative to children with Duchenne, and we can do this repeatedly. We can fairly directly do it for 50% of Duchenne, and theoretically, we can get to over 80% of Duchenne. Just the opportunity for the expansion is enormous. Of course, ex-U.S., I think the opportunity to get approvals ex-U.S. increases dramatically with this increase in the amount of dystrophin that we could make with the PPMO. You can see what we can do with the therapy.
We are, you know, we have now about 29% of Duchenne covered just in the Unites States, for the most part, just, you know, primarily in the United States, with EXONDYS, VYONDYS, and AMONDYS. We've had our 20th quarter of sustained strong growth. We've had a CAGR from 2017 of 40%. If we hit the midpoint this year, it'll be over 40% CAGR. So the opportunity here to do good and do well for our investors with the PPMO, I think is cannot be overstated. I mean, this really is a significant opportunity for the Duchenne community, both in the U.S. and ex-U.S., and also for those of us who, you know, those investors who have stayed with us and committed themselves to Sarepta.
All right. Next question comes from the line of Matthew Harrison from Morgan Stanley. Your line is now open.
Great. Thanks very much for taking the 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, you know, 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. Thanks.
We'll have about 60 patients. That's significantly more than we've had for the other PMOs. We should have a fairly significant number of patients. Of course, the agency has blessed this study and 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. I would guide to one year for the safety follow-up as a basis for the accelerated approval.
Next question comes from the line of Gil Blum from Needham and Company. Your line is now open.
Good afternoon, and also congratulations on a very strong quarter. 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 to kind of approve each new targeted population by itself. Is there a basket approach here somewhere, maybe kind of like what you're looking at at LGMD? Thank you.
Yeah, it's a fascinating, 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 gone in fact, I know Dr. O'Neill and I were both present at a meeting with the FDA some years ago, where we started the dialogue about the potential for a basket approach with our PMO or PPMO technology. The thing I 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, you know, very lean, and relatively rapid studies. We can get therapies approved for, you know, up to 50% of the Duchenne community.
If you wanna get to that 80% level, if you wanna get up to the, you know, full opportunity to treat these kids, you're getting into rarer and rarer exons. It will be in toward that area that we'll have to really think about creating a basket approach, and then speaking to the agency about the approach to sort of create one study that takes a number of different constructs together to treat these patients and look at them together as opposed to separate studies. I've also been in meetings broader than Sarepta Therapeutics. I've been in meetings with senior leadership, where senior leadership at FDA have talked about some of these goals.
I think at least conceptually, you know, the FDA leadership is aligned with this idea of, you know, of looking at things like basket approaches to get to rarer and rarer, serious disease population. I do think on our strategic plan, the next group of PPMOs we'll look at won't employ sort of, you know, any sort of next generation basket approach, but we will be getting to a place where we'll wanna 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 the question. I wanted to ask about where you're gonna be enrolling EMBARK, given that Pfizer's 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? Do you have any agreement with FDA or E.U. on sort of geographic split of patients?
Well, we don't have any agreements on geographic split. In the U.S., we don't have a problem, frankly, you know, even in sites that might be dosing Pfizer. There will be sites around the world where one could envision the same site dosing patients from Pfizer and dosing patients with SRP-9001. In the United States, you know, where it is, at least for now, and I think based on what I heard yesterday, you know, will be for at least some time to come, it won't. There won't be any sites that have dosed in a 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., significant number of sites in Europe, and we'll have sites in Asia as well. What I said is that we're, you know, we believe that we'll have this study fully enrolled in the first half of next year. While I don't wanna overpromise on the pace of the trial, it's, you know, we're already enrolling patients even as we speak, which is exciting. I do think this is gonna be a program that's gonna be in significant demand, so we do anticipate robust recruitment.
All right, next one on the queue is Colin Bristow from UBS. Your line is now open.
Hey, good afternoon, and thanks for taking the questions. Just on part two of Study 102 and the potential for this to permit a discussion with the FDA around an expedited path to market.
Mm-hmm.
What is the minimum you guys are looking for, you know, to initiate that conversation with the agency? Thanks.
Yeah. Well, first, let me start by reminding everyone that EMBARK is our pivotal trial. I really wanna emphasize this. EMBARK is our pivotal trial, and that should be the base case assumption for the approval of the SRP-9001 in the United States and around the world. Probably one of the most exciting elements of part two 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 that we all have. Assuming that the signals from part two of 102 are positive, and given that we already have ex...
You know, from our perspective at least, very positive signals across what are, you know, already gonna be three trials. I think that we might have a dataset that would justify a discussion with the FDA about the potential for a faster pathway than the traditional pivotal trial. There's two things to consider on that, and I wanna 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, you know, make a compelling case that, you know, we have a therapy that based on the markers that we have already and expression that we already have, is reasonably likely to predict a clinical benefit. You know, I'm biased. I think we already are there, and I think 102, part two 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 is amenable to that, and we have to have a division and an agency that is amenable to that. You know, that is a significant unknown. 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 CBER side, OTAT, that has yet to occur. What I would say is, based on the part two 102 data, and only part two, we look at the part one, we look at those four- to five-year-olds, we look at what we've seen already in one, 103 and what other data we may have for 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, you know, a significant percentage or some portion of the DMD community. I would not assume in advance that 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 as 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.
We have 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. We're very excited about executing that study. We're very excited about the readout of part two of 102. I want to be clear about that. We're very excited about that.
All right, for the next question, we do have Brian Skorney from Baird. Your line is now open.
Good afternoon. Thanks for taking my question. Just on the baseline antibody titers, I think there's published work and showing that greater than one in 800 titer is associated with loss of transgene expression. I think your WMS data uses one to. If you could just discuss the differences there, and what cutoff specifically you're using for EMBARK and whether or not beyond sort of that loss of transgene expression, one might expect suboptimal expression at some level in between the two.
Sure.
That might be technically zero negative, but still have some detectable levels. Thanks.
Yeah. I will turn this over to Louise. The answer is one in 400, but I'll turn it over to Louise to give you more evidence of that. The one thing I will remind you of when we think about screen-ins and 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 50% of screen out, but we're in the midst of a seroprevalence study. In fact, the screen out rate is lower, at least in the seroprevalence study, even than we were guiding. It's, you know, a little under 14% right now.
Interestingly enough, two another really interesting element of that that Dr. O'Neill mentioned, not only is it about, you know, a little under 14% now that we've looked at it, but also it doesn't appear to appreciably increase 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. 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. With that said, you know, Louise, you can correct the record, provide additional guidance.
You're correct. Just to add, we originally got to the one to 400 titer because we did do studies that showed that above that, so one to 800 and above, we saw an impact on gene expression in non-human primates, and that's where the original one to 400 titer came. We are including patients with titers less than one to 400 in our studies.
All right, for the next question, we do have Joseph Schwartz from SVB Leerink. Your line is now open.
Thanks very much. For part two 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, you know, 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. 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, you know, the compelling example of this is 101 children. We will all remember back in the summer of 2018, we had this great benefit to these kids, you know, in the first year, and we were really excited about it. 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. More important than they're stable to improving, natural history is receding into the, you know, into the degeneration that we know is inevitable with Duchenne. These kids ended up with this, you know, p-value of greater than 0.0001, and a nine-point delta on NSAA. Really, honestly, the answer is that we hope to see compelling signals versus natural history when we look at the results of part two of 102.
Great. Next one on the queue is Hartaj Singh from Oppenheimer and Co. Your line is now open.
Great. Thanks. Thanks for the question. Looks like Sarepta's got a lot going on. Just a quick question on your limb-girdle programs. You know, 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, you know, for that for the higher dose there to be expanded into, let's say, an expansion cohort next year? You know, if your CMC gets worked out next year, then that could become sort of a study that preps you for accelerated approval. I mean, the study seems pretty comprehensive with the one that you report on is going on. Thanks so much.
Yeah. Yeah, thanks for that question. The, you know, I mean, I agree with you that the data is extremely compelling, and it shouldn't probably be a surprise. We're making 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 clinical supply from Nationwide Children's Hospital. That's why I say the biggest rate limiter for all of us, it's not even the discussions with the agency or designing the program. It's all of the CMC work that goes into our, making our commercial process material. That's the big rate limiter for us.
I think realistically, we can, you know, 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. It'll be that study that'll be the basis for an approval. Unfortunately, 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, you know, essentially take a small trial, but with our own commercial process and replicate that expression there, 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.
You know, 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 from our perspective, a significant potential impact and a high POS are moving along. Among those, some of the most significant ones we're thinking about are the limb-girdles. We wanna get these things moving as fast as possible.
All right, next one on the queue is Yun Zhong from BTIG. Your line is now open.
Hi. Thank you very much for taking the question. On PPMO program, can you remind us if SRP-5051 is using the same sequence as EXONDYS 51? How quickly do you think you will be able to move additional programs, whether you take basket approach or not into the clinic?
Yeah.
You talked about ex-U.S. opportunity, but given what your previous experience with EXONDYS 51, when you talked to the EMA, are you going to look at functional endpoint at all with the either you know SRP-50 51 study or maybe future studies?
Let me go to your first question, yes, it's the same sequence as eteplirsen, but with a conjugated, proprietary peptide that enhances the delivery of it. With respect to how fast we're moving now. The good news is we're moving other therapies forward. We have a number of constructs essentially already built and have conjugated peptides to them. We've got the first thing that one has to do, of course, is to get all of the tox and related work done as we advance those. I can't give an exact date, but we've got a lot of work to do there. 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-US opportunity, yeah, of course, we're going to have to look at function along the way at some point. You know, 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, 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. I think there is a real potential. If indeed what we've seen in part A of MOMENTUM can be replicated, and we're seeing dystrophin that would correlate to 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, I think is, you know, a good real possibility, maybe even a probability. I do think there's gonna be a real opportunity to move these therapies forward, ex-U.S. as well as U.S.
That's important because, you know, it's. We're doing really well as an organization. As you've seen, we've had the 20th straight quarter of tremendous revenue growth serving the community, and we're now gonna do $605 million-$615 million. I can tell you, we're gonna grow next year. We're gonna do brilliant next year as well from a revenue perspective. Beyond that, we need to get our therapies to children in other parts of the world as well, more aggressively than we are permitted to do right now. Duchenne is not a U.S. issue, it's an issue all around the world.
You know, getting these things moving, I think, and getting these therapies to kids, and our next generation therapy to kids around the world is of paramount importance to us and to the Duchenne community.
All right, for the next question, we do have Tim Lugo from William Blair. The line is now open.
Hi, this is John on for Tim. Thanks so much for taking our question. I was wondering if there was any early color you could give us on how enrollment is progressing so far for EMBARK. Thanks.
It's early days, but so far so good. We're enrolling patients and screening patients and getting them going. I have no... You know, every signal that I have so far is consistent with the optimism that I've had for some time that EMBARK, once we initiate it, is gonna move fast. You know, I've said before, I can give you anecdotes that are actually troubling. Families 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, you know, there's only 120 total patients. I wouldn't suggest that.
I think this is gonna be a very popular and important study. I think both from clinical investigators as we get the sites up and engaged. I think it's gonna 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 am quite confident that EMBARK is gonna robustly enroll as we get sites initiated.
Next question comes from the line of Danielle Brill from Raymond James. The line is now open.
Hey, guys. Thanks so much for the question. I saw that Pfizer's DMC more or less verified that the myositis events that they observed were driven by an immune response against micro-dystrophin. 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. Thanks.
Yeah. The short answer is that, you know, our view is that Pfizer is accurate in its assumption on the basis for its myositis. They've had three of these myositis events, and they believe that they're 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 a 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 one through 17 out of a sort of a theoretical concern that there might be a potential immune response. The reason for that, of course, is that in that area, there could be two elements to this. 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. They read it as foreign, and there's immune response. Now, for EMBARK, we've actually taken what is a very conservative approach, and for the commencement of EMBARK, we've excluded exons one through 17 as we commence 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's the reason we believe that it's evidence-based. We've actually dosed nine children in the one through 17 exon range. Nine. Only one of these children had this issue. All the other eight of nine had no issues. And that one of nine is very different than the others. It's not a randomness issue, or at least we certainly don't believe it is. That's because that child had an enormous deletion. It was a, I think, over 40 exon deletion that covered in the exon one through 17 range as well. I suspect that Pfizer would have something similar to that.
We're confident that when we get done with this, there will be some very small percentage of kids. You know, a 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'll be very. We think it'll be very small percentage of kids that have it. What we're going to do while we've excluded exons one through 17 from EMBARK, we're gonna actually start a study early next year, where we start bringing back into frame and the safety of dosing of other kids in the one through 17 range that we don't think have this risk.
Of course, that's already guided by the experience we have because we've already dosed eight children in this range without any issue at all. Short answer is, you know, we concur with Pfizer's belief in that issue, and we have a good way to address it, frame it, make sure that it's only kids there truly would be at risk of an immune response that would be excluded from the therapy.
Yes.
All right. Oh, sorry. Go ahead.
Yeah. I just wanted to add one point is that we, in that particular patient, we did an ELISpot and showed specifically that the immune response to that portion of the transgene was the cause for that, and we didn't see it in any other patients, so it was very specific.
Again, there are no further questions at this time. I'll now turn the call over back to CEO Doug Ingram for closing remarks.
Thank you, Chino. Thank you all for joining us this evening, and thank you for your great questions this evening. We 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 gonna be reading out in the next, you know, quarter or so. We're very excited about those. Of course, in the interim, the team continues to execute. We're gonna execute on SRP-5051. We're gonna execute on SRP-9001 and EMBARK, moving that as fast as possible. We're gonna get ourselves in a position so that we have the Study 102 part two data as soon as possible. To our colleague, Anupam, you know, we'll see what we can do.
Obviously, 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. Dallin and team have done a brilliant job protecting those kids during the pandemic, but also serving them and ensuring that they have therapies available to them, and I think we're gonna continue to do that over the course of this year and the next year. I look forward to continuing to update 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.