Sarepta Therapeutics, Inc. (SRPT) CEO Doug Ingram on Q3 2021 Results - Earnings Call Transcript

Nov. 04, 2021 2:28 AM ETSarepta Therapeutics, Inc. (SRPT)
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Sarepta Therapeutics, Inc. (NASDAQ:SRPT) Q3 2021 Earnings Conference Call November 3, 2021 4:30 PM ET

Company Participants

Mary Jenkins - Senior Manager of Investor Relations

Doug Ingram - President & Chief Executive Officer

Ian Estepan - Executive Vice President & Chief Financial Officer

Dallan Murray - Senior Vice President & Chief Commercial Officer

Gilmore O'Neill - Executive Vice President of R&D & Chief Medical Officer

Louise Rodino-Klapac - Executive Vice President & Chief Scientific Officer

Conference Call Participants

Tazeen Ahmad - Bank of America

Anupam Rama - JP Morgan

Brian Abrahams - RBC Capital Markets

Salveen Richter - Goldman Sachs

Gena Wang - Barclays

Alethia Young - Cantor

Matthew Harrison - Morgan Stanley

Gil Blum - Needham & Company

Ritu Baral - Cowen

Colin Bristow - UBS

Brian Skorney - Baird

Hartaj Singh - Oppenheimer

Yun Zhong - BTIG

John Boyle - William Blair

Danielle Brill - Raymond James

Joseph Schwartz - SVB Leerink


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. [Operator Instructions] 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.

Mary Jenkins

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, 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?

Doug Ingram

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 3 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 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 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 of $40 million above our previous guidance, $70 million above our initial guidance this year and representing at the midpoint, a 34% growth over the prior year. Our performance this quarter represents our 20th consecutive quarter of positive growth. And 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 1 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 sub 77 Duchenne children with our therapy across 3 studies. And roughly 3 weeks ago, we provided a further update on the clinical evidence generated to date.

In our proof-of-concept study 101 at 3 years, Duchenne patients continue to perform markedly better than the natural history of this aggressively degenerating disease would predict, achieving a 9-point improvement on the 34-point North Star Ambulatory Assessment scaler, NSAA. And that's against natural history 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 to 5-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 in. For the 6-year 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 3 points better than natural history with a statistical significance of 0.0129.

And finally, but importantly, we reported that in our ENDEAVOUR study, at only 6 months, the first 11 patients in Cohort 1 have already improved against their own baselines by about 3 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, 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, and 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 focusing on rapidly enrolling EMBARK, we will present the results from Part 2 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 3 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/kg cohort compared to eteplirsen, we saw 18x greater exon skipping, an eightfold 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 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, 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 redose.

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 square foot genetic Therapy Center of Excellence in Columbus, Ohio. And 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 2020, 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 important role in our recent success. And 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.

And with that, let me turn the call over to Ian Estepan, who will provide an update on the financials. Ian?

Ian Estepan

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 third - 3 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 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 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 when compared to $159.9 million for the same year 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 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 a decrease 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, doing 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, cash equivalent 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.

And with that, I'll turn the call over to Dallan for an update on our commercial activities. Allen?

Dallan Murray

Thank you, Ian, and good afternoon, everyone. The third quarter of 2021 saw continued revenue growth in all 3 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. 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 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 3 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 and then 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 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 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 we'll 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 3 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?

Gilmore O'Neill

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 2 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 or rh74 in individuals with Duchenne and demonstrated that a majority of those screened, 84.9%, were 0 negative at a cutoff of 1:400 titer for anti-RA74 total binding antibody, and thus will be eligible for gene transfer therapy with an rh74 better.

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 quarter demonstrated that 86.1% were 0 negative of the Duchenne patients with a titer cutoff of 1:400. And that is 13.9% were 0 negative. Notably, the data also showed that 0 prevalence did not increase with age in Duchenne patients aged 4 to 18. This latter observation is very important for older individuals with more advanced disease considering therapies.

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 3-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 3 years, supporting a durable response and highlighting that the magnitude of benefit increases over time.

The data also shows that SRP-9001 is well tolerated with no new safety signals consistent with safety data from the wider SRP-9001 clinical program. Most recently, and as Doug mentioned, we presented a roll-up of data across the SRP-9001, 102 Part 1 and 103 studies at our October 11 microdystrophin day. As reported, we possess the wealth of data across 77 Duchenne patients dosed with SRP-9001 in 3 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 4 to 8 at the time of dosing. 12 boys were older than 8 years of age at the time of dosing and of those 12, 6 were nonambulatory.

In summary, we have experienced a broad population that includes a wide age range of 4 to 19 year olds and a very wide weight range between 13.7 to 80.1 kilograms. In this broad patient population, we are encouraged to observe a consistent safety profile with the most common AEs in vomiting. The increases observed in liver enzymes that we have responded favorably to transit increases in cortical steel, and we have not observed clinically relevant compete activation or thrombotic microangiopathy.

As Doug noted, we are thrilled to be initiating EMBARK or Study 301, the first global registration trial of the gene therapy for the treatment of Duchenne. The study will use our commercially represented SRP-9001 material. EMBARK has been designed as a double-blind, randomized, placebo-controlled study and is powered to confirm that our SRP-9001 microdystrophin commercial represented material at a dose of 1.3 to the 14 using a linearized casting standard for titrant confirms clinical functional benefit in 4 to 7-year-olds. The study will enroll on 120 patients with randomization using 2 strata, age, with a minimum of 50% patients enrolled in 4 to 5 year old age group and NSAA at baseline. So age and NSAA at baseline are the strata.

Building on the learnings from Study 102 Part 1, we are including patients with the time to rise from the floor or from supine of less than 5 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 end 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 dispersant, 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'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 phosphodiamedate Marcelino 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 at [indiscernible] demonstrated an 18-fold increase in exon skipping and more than 6.5% main discoloprotein 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 one brand dosing over time.

Further, we observed that baseline dystrophin levels are not a predictor of post-treatment inspection. In fact, we observed that 2 patients with the lowest baseline had the highest level of post-treatment expression. Importantly, SRP-5051 demonstrates a taller safety profile. We continue to believe the hypomagnesemia observed in the study remains monitorable and manageable by native 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 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 [indiscernible] 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 of 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 update for our PMO program. Enrollment for instance, for Tazmersenedologerst an admission study for a person continue. We maintain regular contact with the FDA to update on our progress toward delivering these important clinical data. In September, we also presented 2 new sets of supportive clinical data for casimersen [indiscernible] muscle. The first with an interim biopsy analysis from essence of casimersen treated patients, demonstrating that exon 45 skipping assessed by additional drop 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 Western blot significantly increased from baseline after 48 weeks of casimersen treatment with a p of less than 0.001 with a significantly greater increase in stroke levels compared to placebo at p of 0.004 and increased dystrophin positively correlated with exon skipping experiment rank correlation of 0.627 and a p of less than 0.001. Casimersen was well tolerated with most adverse events casted as mild and unrelated to casimersen with no suggestion of kidney toxicity. The second was a presentation of study 4658-102, the first clinical trial in patients aged 6 to 48 months, the eldest population Duchenne evaluated in the clinical trials to date. This trial demonstrated that a [indiscernible] IV 30 mg/kg once weekly was well tolerated with no new safe signals after 96 weeks of treatment and no discernible difference between age cohorts, the buyer has 6 to less than 24 months versus 24 to 48 months. These data are consistent with [indiscernible] 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 maintaining 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?

Doug Ingram

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

Question-and-Answer Session


[Operator Instructions] First question comes from the line of Tazeen Ahmad from Bank of America. Your line is now open.

Tazeen Ahmad

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?

Doug Ingram

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

Tazeen Ahmad

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

Doug Ingram

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

Gilmore O'Neill

Yes. So we use prednisone at many of the patients are indeed are already on a patient as a standard of care on prednisone standard of care. We require that they run in 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 simplistically put it, double the standing steward regime they're on. And they are - start that doubling at the time of infusion and maintain that regime and are tapered 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. 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


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

Anupam Rama

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 in-person health care conference in January in San Francisco? Or is it later in the quarter?

Doug Ingram

Anupam, I can't think of any conferences happening early in the year. I can't commit the exact date. Obviously, I'm joking, Anupam. I can't commit to the exact date. We have to get all the data in, in QC, and it will be in the first quarter, and 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. And 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.

Brian Abrahams

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 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?

Doug Ingram

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 with - 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. And 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, and 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 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. 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, of course, what one knows is that if you're going to seek an accelerated approval, you would have 2 elements, whether it's 1 study that leads into an extension or whether it's 2 studies, you have to have an element that provides confidence that using a biomarker in the case of TE would obviously be the beta cycloglycad protein that you have a protein that - expression that's reasonably likely to predict the clinical benefit. And 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 want to 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. So 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, 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 just about 3 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 will continue into 2022. And so we have the resources to bring all of these programs along. I mean 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, 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.

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.

Salveen Richter

Good afternoon. Thanks for taking my question. As we look to the 201 study reading out in the beginning of the year, so the 2-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 what - given what you saw in Part 1, how do you think about that translating to a positive outcome in part 2?

Doug Ingram

Yes. So there's a couple of things to consider. The biggest difference between Part 1 and Part 2, I would say, is in addition to the fact there are far more patients, of course, in a sense in Part 2 because all of the children now, 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 aren't [indiscernible] in the placebo arm to test against because all of the children in the crossover have now been dosed with therapy. So we have 41 children, some - half - about half of them will have 2 years' worth of data, and the other half will be 1 years' worth of data with a trajectory of the 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. So I guess there are 2 things that happened in Part 1 that were frustrating. One, of course, was the issue of the target dose and in the first cohort, we've learned about 60% of those children had lower than the target dose. On the crossover with the new tittering method that we have employed this linear tittering method, that does not exist. So 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, 1.33e to the 14.

And then, 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. So what I'll say is I think that Part 2 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 I now open.

Gena Wang

Thank you for taking my question. Have one regarding the momentum Part B PPMO program. Do you still need FDA confirmation on the pivotal study design? And I understand you have 3 cohorts. Can you give a little bit more color on study design and the powering assumption?

Doug Ingram

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 precede the 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. But with that, Dr. O'Neill, perhaps you can talk about the cohorts that are Part B cohorts.

Gilmore O'Neill

Yes. Thank you very much. So the Part B, there's actually 1 cohort, but it was [indiscernible] SRP-5051 naive patients who will be newly enrolled to 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. And then the patients will be randomized to 1 of 2 doses. And an answer to your far question, the study has been powered around dystrophin expression versus baseline.


Next one on the queue is Alethia Young from Cantor. Your line is now open.

Alethia Young

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 time lines and would they be similar or maybe some of the other studies of similar sizes of the past? And then also, I mean, should we think about this as kind of life cycle management on Templer center? Or how do we think about that?

Doug Ingram

So let's start with the first part. So in first dealing with enrollment, one must remember that MOMENTUM is different, for instance, in the 9001 study EMBARK in that it's a subset of children with Duchenne muscle dystrophy. And there - and it's SRP-5051 and there are other programs that we're competing with. So we will - 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 it 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, 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, there are very few places outside the United States where it's approved. Right now, we have a managed access program. So there are - there is some access outside the United States with 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. It can - first of all, if it's 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 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. So just the opportunity for the expansion is enormous.

And then 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 can make with the PPMO. And you can see what we can do with the therapy. We are - we have now about 29% of Duchenne covered just in the United States for the most part, just primarily in the United States with EXONDYS, VYONDYS and AMONDYS, and 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 will 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, it really is a significant opportunity for the Duchenne community, both in the U.S. and ex U.S. and also for those investors who have stayed with us and committed themselves to Sarepta.


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

Matthew Harrison

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 considerate from an FDA perspective?

Doug Ingram

So 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 and of course, the agency has blessed this study in its size. And then 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.

Gil Blum

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 had 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 LGMD?

Doug Ingram

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 gone in, in fact, Dr. O'Neill and I were both President, had meeting 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 exon and it will be in towards 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 - as an example, 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 by a long shot, the meetings with senior leadership or senior leadership at FDA has talked about some of these goals. And 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 population. So I do think on our strategic plan, the next group of PPMOs will look at - won't employ sort of - any sort of next-generation basket approach, but we will be getting to a place 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.

Ritu Baral

Hey guys thanks for taking my question. I wanted to ask about 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 FDA or you on sort of geographic split of patients?

Doug Ingram

Well, one of the agreements on 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 site 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. And I do - while I don't want to overpromise on the pace of the trial, it's - we're already enrolling patients even as we speak, which is exciting. 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.

Colin Bristow

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?

Doug Ingram

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. And I think that ought to be the view that 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 3 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 2 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 2 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 already are there, and I think 102 Part 2 will continue to justify that belief. But 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 - 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 3 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 3 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 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.

And I am extremely excited about that trial. It is well powered. The 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. And so we're very excited about executing that study. And we're very excited about the readout of Part 2 of 102. And 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.

Brian Skorney

Hey good afternoon, thanks for taking my question. Just on the baseline antibiotic titers. I think there's published work showing that greater than 1:800 titers associated with loss of transgene expression. I think your [indiscernible]. Maybe 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 2 that might be technically 0 negative, but still have some detectable levels.

Doug Ingram

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 of that. The 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 50% screen out, but we're in the midst of 0 prevalence study. And in fact, the screen-out rate is lower, at least in the 0 prevalence study, even then we were guiding. It's a little under 14% right now. So - and interestingly enough, another second really interesting 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, provide additional guidance.

Louise Rodino-Klapac

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.

Joseph Schwartz

Thanks very much. For Part 2 of 102, are you hoping to see the same kind of 3-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?

Doug Ingram

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. And if you look at those kids over 3 years, what you find is those kids are stable to improving. But more important than 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 9-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.

Hartaj Singh

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 2-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.

Doug Ingram

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 generating and dying. And so 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. And so, we have to - 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 making our commercial process material. That's the big rate limiter for us. So I think realistically, we can - 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. And it will be that study that will be the basis for an approval.

So 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 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. So 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, from our perspective, a significant potential impact in a high POS or moving along. And 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.

Yun Zhong

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 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 the either 5051 study or maybe future studies?

Doug Ingram

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 of it. 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 have conjugated peptides to them. We 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. So I can't give an exact date, but we've got 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, potential, 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. And 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. So 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 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, I think, is a good real possibility, maybe even a probability. So I do think there's going to be a real opportunity to move these therapies forward ex U.S. as well as U.S. And that's important because it's - we're doing really well as an organization. As you've seen, we've had our 20th straight quarter of tremendous revenue growth serving the community. And we're now going to do $605 million, $615 million. And I can tell you we're going to grow next year. We're brilliant next year as well from a revenue perspective.

But 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 because Duchenne is not a U.S. issue, it's an issue all around the world. And so 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.


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

John Boyle

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.

Doug Ingram

It's early days, but so far so good. We're enrolling patients, screening patients and get 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 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's only 120 total patients. So 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. And I think it's going to be a very important therapy and study for patients with Duchenne muscular dystrophy. So 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 sites initiated.


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

Danielle Brill

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.

Doug Ingram

Yes. So the short answer is that we - our view is that Pfizer is accurate in its assumption on the basis for its myositis. They've had 3 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 is reported by Pfizer, but we did have myositis and it was a SUSAR. That was - and 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 exon's 1 through 17 out of a theoretical concern that there might be a potential immune response. And the reason for that, of course, is that in that area, there could be - there was actually 2 elements to this. In that area, there is a risk that you may - 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 actually taken what is a very conservative approach. And for the commencement of EMBARK, we've excluded exon's 1 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. And here's the reason we believe that. It's evidence based. We've actually dosed 9 children in the 1 through 17 exon range, 9. Only one of these children had this issue. All the other 8 of 9 had no issues. And that 1 of 9 is very different than the others. So it's not a randomness issue, or at least we certainly don't believe it is. And that's because that child had an enormous deletion. It was, I think, over 40 exon the lesion that covered in the exon 1 through 17 range as well.

I suspect that Pfizer, we have something similar to that. And so we are confident that when we get done with this, there will be some very small percentage of kids, percentage or 2 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. And 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. And of course, that's already guided by the experience we have because we've already dosed 8 children in this range without any issue at all.

So short answer is we concur with Pfizer's belief in that issue. And we have a good way to address it, frame it, make sure that the that it's only kids there truly would be at risk of an immune response that would be excluded from the therapy.

Louise Rodino-Klapac

I just want to add one point is that we - in that particular patient, we did in ELISpot and showed specifically that the unique response to that portion of the transgene was both the costs for that, and we didn't see it in any of the patients who was very specific [indiscernible].


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

Doug Ingram

Thank you, Tino. Thank you all for joining us this evening. And thank you for your great questions this evening. 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. And 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. And to our colleague Anupam, we'll see what we can do. But obviously, when we get that data out and fully QC'd, we'll obviously present that and sharing that with the community.

And then 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 to them. And I think we're going to continue to do that over the course of this year and to next year. So 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.

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