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spk19: Today, ladies and gentlemen, thank you for standing by and welcome to CERTA Territic's second quarter 2020 earnings conference call. At this time, all participants are on a listen-only mode. After the speakers prepare remarks, there will be a question and answer session. To ask a question during this session, you will need to press star 1-1. Please be advised that today's conference may be recorded. I would now like to end the conference with your speaker host today, Mary Jenkins, Senior Manager of Investor Relations.
spk02: Thank you, Livia, and thank you all for joining today's call. Earlier today, we released our financial results for the second quarter 2022. The press release is available on our website at Sarepta.com, and our 10Q was filed with the Securities and Exchange Commission earlier this afternoon. Joining us on the call today are Doug Ingram, Ian Esipan, Dallin Murray, and Dr. Louise Rodino-Klapak. After our formal remarks, we'll open the call for Q&A. I'd like to note that during this call, we will be making a number of forward-looking statements. Please take a moment to read the slide on the webcast, which contains our forward-looking statements. These forward-looking statements involve risks and uncertainties, many of which are beyond SRAPTA'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 SRAPTA'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 obligations 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?
spk15: Thank you, Mary. Good afternoon, everyone, and thank you all for joining Threat for Therapeutics second quarter 2022 Financial Results Conference Call. I will discuss our outstanding quarterly performance in a moment, but given it's important to the patients that we serve, to Sarepta, and in my view, to the entire field of gene therapy, I will begin by focusing on our progress this quarter with the largest near-term gene therapy opportunity in biopharma, and that's SRP 9001, our gene therapy for the treatment of Duchenne muscular dystrophy. As you will recall, we previously disclosed that we were engaging with the U.S. FDA about the possibility of submitting a biologics license application, or BLI, for the accelerated approval of SRP 9001 to treat Duchenne muscular dystrophy. We also cautioned numerous times that we would not change our base case assumption on the timing of approval unless we had strong conviction on the receptivity to an accelerated approval BLI by the FDA. As we announced last week, our discussions are now complete and our base case assumption has indeed changed. Over the course of the second quarter, we engaged with FDA in an in-depth review with the agency of the wealth of evidence that supports the safety and efficacy of SRP 9001 and the functional benefits associated with the robust expression of shortened but functional dystrophin when treated with SRP 9001. This included the safety and tolerability data unique to SRP9001, the preclinical of animal models supporting its benefits, the various function-related biomarkers associated with the nearly 90 patients dosed with SRP9001 across studies 101, 102, and 103, and the impressive and consistent functional results, which is, of course, NSAA and multiple time tests across those studies. I would like to thank the FDA for its time, its commitment, and its input as the review spanned multiple meetings and included input and guidance across the FDA, including CBER leadership, the Office of Tissues and Advanced Therapies, as well as the Center for Drug Evaluation and Research, including its Office of Neuroscience and Office of New Drugs. Based on that review and the written guidance provided to Sarepta last week, we announced that we intend to submit a BLA for accelerated approval of SRP 9001 to treat ambulatory patients that have Duchenne muscular dystrophy. We intend to compile and submit our BLA this fall. We will hear whether an advisory committee is requested by the FDA after our BLA is filed. If one is requested by the FDA, we would anticipate it in the spring of 2023, and we are planning and preparing for just that. Assuming a successful review, we anticipate approval and launch in mid-2023. To that end, in addition to completing and submitting our BLA, we are immediately readying ourselves for what will be the largest gene therapy launch in the United States. That will include augmenting our commercial and medical affairs organizations, site readiness, and importantly, building sufficient inventory to serve the community at launch without delay. As we prosecute our BLA, we continue to execute EMBARQ. That's our 120-patient pivotal trial for SRP 9001. Demand has been intense for EMBARQ, and site initiation and enrollment ramped enormously in the second quarter. Based on our current screen rate, we should be fully screened and enrolled in the next few weeks. One of the concepts that has been discussed both within the FDA and within Congress is is encouraging companies to have their confirmatory trial underway at the time of an accelerated approval. We anticipate Embark to act as our confirmatory trial for an accelerated approval, and Embark will be fully enrolled by the time our DLA is filed. Furthermore, we anticipate dosing an additional cohort in Study 103 to study what our research informs us are low-risk mutations in the currently excluded 1-17 range, with the goal to narrow the exclusions to a low single-digit percentage by the accelerated approval time we also intend to initiate a separate placebo-controlled non-non-ambulatory study later this year that study is designated study 303 or in vision on the rna platform encouraged by seeing 18 times greater exon skipping and eight times greater dystrophin production in half the time and one-fifth the dose of current standard of care, we initiated Momentum Part B, a pivotal trial for exon 5051, our next-generation RNA-based PPMO for the treatment of Duchenne patients amenable to skipping exon 51. While dosing continues globally, we announced in the quarter that FDA has placed a hold on dosing in the United States while we provide additional information and context around cases of hypomagnesemia. We have provided the requested information and we continue to guide to completion of enrollment for Momentum Part B in the second half of 2022. If confirmed in Momentum Part B, SLP5051 could be a profound improvement over current standard of care. So at the same time, we are progressing the preclinical work for additional PPMOs to treat a greater percentage of the Duchenne population. Our head of R&D and chief scientific officer, Dr. Luis Rodino-Claypack, will provide further color on the performance of our R&D pipeline. Now to quarterly performance. This afternoon, we announced another exceptional quarter of execution and performance as we continue to serve the Duchenne patient community with our approved, three approved therapies, Exondys 51, Myondys 53, and Demondys 45. Total revenue for the quarter was approximately $233.5 million. Net product revenue was $211.2 million, exceeding consensus and growing almost 50% versus the same quarter last year. Given our overperformance, we are now raising our full-year net product revenue guidance to between $825 million and $840 million. Summarizing. I could hardly be prouder of the Sarepta team for their tenacious execution this quarter. Even as we served the community with our currently approved therapies, we made what could be a monumental leap in the advancement of SRP 9001 to the broader patient community. My colleagues and I are confident that this work will translate into a better life for individuals and families living with Duchenne in the United States and around the world. I want to thank my Sarepta team. I want to thank our committed investigators and the patients who are participating in our studies. And I want to give a special thanks to the FDA for its time and guidance as we progress. All of these cohorts are necessary for the success of SRP 9001. And with that, let me turn the call over to our head of R&D and chief scientific officer, Dr. Luis Rodino-Clayfax.
spk24: Luis? Luis?
spk17: Thanks, Doug. The significant achievements we've made recently with respect to FRP 9001, our gene therapy candidate to treat Duchenne muscular dystrophy, represents not just an important moment for Sarepta, but more importantly for the patient community. Notably, we announced this past Friday, July 29th, our intent to submit a BLA seeking accelerated approval for FRP 9001. We're thrilled with this development as it speaks to the strength of the underlying science and the data we've generated to date. I want to thank the team for all their work supporting this positive outcome and engaging with the FDA, while also working on the DOA submission in parallel. Due to this major effort, we are well positioned to submit our DOA this fall. The data we announced in early July, including important functional clinical results from studies 101, 102, and 103, and our integrated analysis will support this DLA submission. To remind you, studies 101 and 102 use clinical material and study 103 uses commercially representative material. I'll now briefly recap these results for you. Starting with study 103 for Endeavor. We showed that patients in cohort one with an N of 20 improved four points from baseline on NSAA. Pretreatment had a mean baseline NSAA of 22 and at week 52, improved to a mean of 26, approaching the top end of the MSAA scale. For example, these patients can now perform two activities unassisted that they were not able to perform prior to therapy, or four activities that they needed assistance with that they now can do on their own. Equally impressive, SRP 9001 treated patients improved 3.8 points on unadjusted means and 3.2 points using least-squared means at 52 weeks, on an SAA compared to the propensity-matched external control group with a p-value of less than 0.0001. These results are impressive as they demonstrate that commercially representative SRP9001 improves motor function and further confirms our confidence in the treatment effect of our therapies, increasing the probability of success for EMBARQ or Study 301. Also, these data increase our level of conviction for Embark because the same commercially representative SRP 9001 material is being used in both Endeavor and Embark. Speaking of Embark, our clinical operations team has also executed flawlessly, and as a result, enrollment in the study is nearly complete. In summary, Study 103 demonstrated improvements across all key secondary functional endpoints, such as time to rise, 10-meter walk-run, time to ascend four steps, and 100-meter run. Based on these data, patients receiving SRP9001 improved significantly on every functional measure. I'll now recap our long-term results. These data are particularly important because they answer two of our most common questions. Are these data clinically meaningful, and is the effect durable? First, we will look at our original four patients after four years of treatment on SRP9001 from study 101. As a reminder, we conducted two analyses. NSAA changed from baseline over four years in the four treated boys, and then in comparison to an external control group using propensity score weighting. These data showed that patients in study 101 demonstrated a mean increase of seven points in total NSAA score from baseline in year four. Importantly, as these are older patients, around nine years old at year four, and because Duchenne is a disease that gets progressively worse, These patients would, according to the natural history of Duchenne, be in the steep decline phase of their disease. However, instead of declining, they have increased their function and maintained that increase, thereby demonstrating a distinct treatment effect that increases over time, supporting durability of SRP9001. Based on the individual patient-level data we showed, it's clear that all of these patients have remained stable and well above their baseline for this time period. No single patient drove the mean of the group. Further, when we compare the treated patients to the propensity-matched external control, we observe nearly a 10-point difference on unadjusted means and a 9.4-point difference using least-squared means, with a p-value of 0.01 at four years. As an example, the SLP9001 treated patients can now do five activities that those in the external control group were not able to accomplish. We are pleased to see that the treatment effect has continued to increase over time. It's also important to note that precipitous decline in years three and four of the external control group. These boys are now in the steep part of the decline phase of their disease, whereas the treated patients remain stable. Moving now to our two-year functional results from 20 patients who've received SRP 9001 in part one of study 102. At one year, we saw a three-point median difference between the SRP 9001 group and the external control group. At week 96, this grew to a five-point median NFAA difference with a p-value of 0.0001. The fact that only approximately half the patients in the treated group received the target dose makes these results even more impressive. I will now review the integrated efficacy analysis for all patients in studies 101, 102, and 103 who received the target dose of 1.33 times 10 to the 14th vector genomes per kilogram compared to an external control. In this integrated analysis of one-year functional data from patients who received the target dose of SRP9001, 52 in all, we showed that the treated patients improved 2.4 points in MSAA total scores from baseline. When compared to propensity-weighted external control groups, MSAA changed from baseline one year after treatment for the treated patients, with 3.1 points higher on unadjusted means and 2.4 points higher using least-scored means. with a p-value of less than 0.0001. As you can appreciate, these data now reinforce the consistency of MSAA improvement across three independent studies and show mean improvements across key secondary functional influence, such as time to rise and 10-meter walk-run. We were also pleased to share expression data from all of the studies, which demonstrated consistency for both our clinical and commercial manufacturing process. Further, the safety profile of SRP9001 remains consistent and manageable with no evidence of clinically relevant complement activation. In summary, these new data and our integrated efficacy analysis have demonstrated that SRP9001 performs well above what natural history will predict and supports potential as a disease-modifying agent. Now turning to limb girdle muscular dystrophy or LGMG programs in our gene therapy franchise. For SRP 9003 and our other LGMD programs, we continue to make progress with respect to building the necessary steps of our manufacturing process, including LGMD-specific assay development and validation. In addition, our natural history studies journey also continues to enroll and represents a key component of our LGMD development pathway. Our commitment to advance the best science and then translate that science into therapies for rare disease patients around the world remains strong. The progress we've made to date based on the clinical evidence, as well as the dedicated and tireless team of scientists and professionals positioned us favorably to deliver on this commitment. Thank you to the patients, families, and investigators for their role in bringing forth these important therapies. I will now turn the call over to Dallin for an important update on our commercial activities. Dallin?
spk13: Thank you, Louise. In the second quarter of 2022, the team delivered double-digit growth across all three approved RNA-based PMO therapies. We eclipsed $200 million in net quarterly product revenue for the first time, generating over $126 million for Exondys 51, $54 million for Imondys 45, and $30 million for Byondys 53. This represents roughly 12% growth over the prior quarter, and almost 50% compared to the second quarter of 2021. We are thrilled at this performance, and in order to properly contextualize, it's important to note that we experienced ordering volatility due to the July 4th holiday, which fell on a Monday this year. We believe that approximately 5 million may have been pulled forward from Q3 into Q2 as a result. I urge the analysts to incorporate this pull forward into their models for Q3. As a result of our performance in the first half of the year, as you've already heard from Doug, I'm happy to say that we're increasing our full year net product revenue guidance from over $800 million to a range of between $825 and $840 million. As we mentioned on our first quarter earnings call, there remain a number of important factors which could swing our final number in either direction for the rest of the year. These include competitive enrollment into some of our own clinical trials. They are somewhat hard to predict when it comes to the 30% of the Duchenne population that we serve. As such, we've provided this 15 million range, which we intend to narrow as we get closer to the end of the year. It goes without saying that I'm very proud of the execution and commitment across all our teams at Sarepta, which enables this kind of success and growth. Moving on to the performance of each of our three PMO therapies, Exondys 51 has continued to generate strong double-digit growth as we approach the six-year mark post-launch, representing more than 23 quarters of growth and generating nearly $2 billion in cumulative revenue since the 2016 launch. The growth of nearly 8% over the first quarter of 2022 represents another successful effort by the team in overcoming and managing the predictable headwinds caused by insurance changes at the beginning of each year. The team continued their efforts to find new patients. And overall, we expect very modest growth for Exondys 51 for the remainder of the year. Lyondis 53 grew more than 35% over the second quarter of 2021 and over 7% compared to the prior quarter. We have continued our market leadership position in the Exxon 53 amenable population, and our team is continuing their efforts to get new patients on therapy and maintain existing patients. We don't expect any substantial changes with Biondis in the coming quarters. Amondis 45 continued its very successful launch with a second straight quarter of more than 25% growth over the prior quarter. As we've previously mentioned, the pace of both start forms and conversion onto therapy has been faster than our launches for Exondys and Byondys. As such, we expect the growth rate to start to slow in the coming quarters as we continue to get more of the eligible population on therapy. The Amondys 45 launch has been Sarepta's most successful to date, and it's worth mentioning that the team used this launch as a dry run to sharpen our skills and execution. as we prepare the team for potential SRP 9001 launch. Assuming a positive outcome from a regulatory perspective, this will not just be the most important launch in Sarepta's history, but very likely the most important launch in the history of precision genetic medicine. I cannot emphasize enough how proud we are of our highly motivated team and the mission-driven work they do every day to support than nearly 30% of patients who are amenable to one of our three approved RNA-based PMOs. I'm pleased with our current momentum and success in the first half to 2022, and for our team's enduring commitment and unwavering execution. We'll continue to serve the Duchenne community with our PMOs while we evolve and prepare ourselves to launch SRP 9001 for an even larger segment of the Duchenne population. Our work won't stop until we have effective therapies for all patients living with Duchenne muscular dystrophy. And with that, I'll turn the call over to Ian Estepan for an update on our financials. Ian.
spk09: Thanks, Alan, and good afternoon, everyone. This afternoon's financial results press release provided details for the second quarter of 2022 on a non-GAAP basis as well as a GAAP basis. Please refer to our press release available on our website for a full reconciliation of GAAP to non-GAAP financial results. For the three months ended June 30, 2022, the company recorded total revenues of $233.5 million, which consists of net product revenues and collaboration revenues, compared to revenues of $164.1 million for the same period of 2021, an increase of $69.4 million. net product revenue for the second quarter of 2022 from our PMO Exxon Skipping franchise was $211.2 million, compared to $141.8 million for the same period of 2021. In the second quarter of 2022, individual net product sales were $126.4 million for Xondas 51, $54.7 million for Amandas 45, and $30.2 million for Vyondas 53. The increase in net credit revenue primarily reflects increasing demand for our product. As a result, we are raising our 2022 total revenue guidance to a range of $905 to $920 million, and our net product revenue guidance for our R&A franchise to a range of $825 to $840 million. In each of the quarters ended June 30, 2022 and 2021, we recognized $22.3 million of collaboration revenue, which relates to our collaboration arrangement with Roche. The reimbursable co-development costs under the Roche agreement totaled $26.4 million for the second quarter of 2022, compared to $18 million for the same period of 2021. On a GAAP basis, we reported a net loss of $231.5 million, or $2.65, and $81.1 million, or $1.02 per basic and alluded share, for the second quarter of 2022 and 2021, respectively. We reported a non-GAAP net loss of $103 million or $1.18 per basic and diluted share in the second quarter of 2022 compared to a non-GAAP net loss of $130.6 million or $1.64 per basic and diluted share in the second quarter of 2021. In the second quarter of 2022, we recorded approximately $37.8 million in cost of sales compared to $19.5 million in the same period of 2021. The increase in cost of sales is primarily due to increasing demand for our products, and right off of certain batches of our products not meeting quality specifications for the three months ended June 30th, 2022, with no similar activity for the three months ended June 30th, 2021. On a GAAP basis, we recorded $252.3 million and $239.6 million in R&D expenses for the second quarter of 2022 and 2021, respectively. a year-over-year increase of $12.7 million. The increase is primarily due to increasing in manufacturing expenses due to shortfall payment accrual related to our manufacturing supply agreement with Thermo Fisher, partially offset by decrease in upfront and milestone expenses during the second quarter of 2022 as compared to the same period of 2021. On a non-GAAP basis, R&D expenses were $230.4 million for the second quarter of 2022 compared to $220.7 million for the same period of 2021, an increase of $9.7 million. Now, turning to SG&A, on a gap basis, we recorded approximately $154.3 million and $72.3 million of expenses for the second quarter of 2022 and 2021, respectively, an increase of $82 million. The increase was driven primarily by an increase in stock-based compensation expenses due to the CEO grant modification agreement executed during this quarter. It's important to highlight, though, that this is a non-cash expense. On a non-GAAP basis, the SG&A expenses were $63.7 million, and for the second quarter of 2022, compared to $54 million for the same period of 21, an increase of $9.7 million. On a GAAP basis, we recorded $17 million in other expenses net for the second quarter of 2022 compared to $16.2 million in other expenses net for the same period of 2021. The increase is primarily due to losses on disposal of assets during the three months ended June 30, 2022. At the end of June 30, 2022, we had approximately $1.95 billion in cash, cash equivalents, and restricted cash in investments. So for once, it's finally nice to be last in the lineup because I actually get to conclude by saying that we're absolutely thrilled with the feedback we received from the FDA for 9001. I think as everyone knows, we've previously gated our spend and managed our expenses in this obviously very challenging market. However, based on the recent news, we'll now be ramping up our manufacturing capacity and further building out our commercial infrastructure. so that we're prepared to serve the maximum number of patients with SRP 9001 if approved by the middle of the year. I thought it was also actually important to highlight, though, that due to the timing of these activities, I actually don't anticipate a material change in our spend for the remainder of the year, and I still expect our cash runway to extend into 2024. So, finally, I just want to echo Doug's comments and thank the FDA for taking the time to evaluate our data, and we look forward to the review of our BLA submissions. So with that, I'll turn the call back over to Doug to start the Q&A. Doug?
spk15: Thank you very much, Ian. Olivia, let's open the line for Q&A.
spk19: Certainly, ladies and gentlemen. As a reminder, to ask a question, you will need to press star 1-1. Please stand by while we compile the Q&A roster. Now, first question coming from the line of Anupam Rama with JP Morgan. Your line is open.
spk06: Hey, guys. Thanks for taking the question and congrats on all the progress. Can you talk about the factors that led FDA to get comfortable with a potential approval in all ambulatory patients versus something more age-restricted to four to seven-year-olds? And how does this change the addressable population based on your market research?
spk15: Thank you very much. Thanks for the kind words as well, Anupam. I'm not going to give you a lot of detail about the back and forth with the agency. I'll give you the broad stroke answer. Broadly speaking, the way the agency got comfortable generally, of course, as our very pithy head of research and development would say, the data. We have a wealth of data that supports the therapy and its benefits over a broad group of patients. And so we think it's appropriate now, given the data that we have right now, to file a BLA for the ambulatory population. There's no reason to believe that if the therapy is a benefit to four- or seven-year-olds, as the data has shown repeatedly that it is in multiple studies, that it would be ineffective if the child was younger or older. It ultimately will not affect the addressable patient population. I want to be very clear. It is not our goal. to treat simply the ambulant population as large as that population is as a percentage of entire Duchenne. Our goal is to have the broadest possible label, and the regulations will provide for that given the fact that the mechanism of action of our therapy is equally applicable. It ought to be equally applicable across all age groups to the extent that patients have skeletal muscle, diaphragm muscle, and cardiac muscle that would benefit from this shortened but functional dystrophin protein properly localized. So we've got to do additional work to get that label expanded. There are a number of things we will be doing. We will start our non-ambulatory study. As I mentioned, it's called Envision or Study 303. We're going to get that started this year. We'll have data from that even before it reads out. It'll be a placebo-controlled trial, but we'll have data from that even before then because we'll have expression and safety experience that we can add to the expression and safety experience we already have with non-ambulatory patients. As you may know, in our cohort in study 103, we've dosed non-ambulatory patients, including much heavier patients over 80 kilograms and significantly older patients, non-ambulatory, nearly 20 years old, we've done that a few times. So, this will add to that, and then we would seek through a supplement to expand the label beyond ambulatory. So, the ultimate addressable population certainly is our goal to make it all patients.
spk27: Thank you.
spk09: And just to follow up, you know, obviously the ambulant population is approximately 50% of the population. If you were just modeling for seven-year-olds, you would at a minimum have to double the available patient populations based on now an ambulant patient population at a minimum.
spk19: Thank you. And our next question coming from the line of Gina Wang with Barclays. Your line is open.
spk25: Thank you for taking my questions. Also, congrats on the accelerated approval pass. So I have three parts of questions regarding the accelerated approval, the FDA feedback. So what were the main endpoints that served the basis of the submission of the accelerated approval? And did the FDA validate the propensity way to control? And lastly, do you expect FDA to request the embarked data before accelerated approval?
spk15: Yeah, thank you very much. So first of all, I mean, basically, To justify the accelerated approval, of course, it is the totality of all of the evidence, including all of the endpoints, and that includes even preclinical work. The ultimate endpoint that would be the surrogate endpoint would be the 9001 shortened functional dystrophin protein that would justify it. We certainly provided the entire data set, including our propensity data, And I think it's very compelling, and it certainly played a significant role in dialogue that we had with the agency. And then as relating Embark, there was never a discussion or a suggestion by the agency that they either would require or would await any of the Embark data, either interim or otherwise. So that was a good issue that arose in our multiple discussions with the agency.
spk27: Thank you. Thank you. One moment for our next question.
spk19: Our next question coming from the line of Stephen Mellon with RBC Capital. Your line is open.
spk01: Hi, thanks. This is Steve. I'm for Brian. Congrats on the progress, and thanks for taking our question. Can you share a bit more on what you learned from reviewing the totality of the 9001 data on the relationship between microgistrofren expression and functional endpoints, including CK, and what gives you comfort there that the FDA is is aligned with the relationship there between expression and function.
spk15: Thanks. What gives us comfort is that we've had multiple in-depth discussions and meetings, live, but, you know, Zoom and telephonic meetings with their division, both OTAC, CEDAR leadership, CEDAR, Office of New Drugs, the neurodivision, which has a particular expertise in And as a result of that, we have significant conviction based on the written feedback we've received from the FDA that we could seek a BLA for accelerated approval. Lise, do you want to comment any further on any of the underlying data or situation?
spk17: I'll add that certainly between the strength of our data-wise, in the preclinical data, and then what we've learned from our preclinical data linking the 9001-distrophin to function has, you know, continued through all of our clinical studies. You see consistency across those clinical studies with 9001-distrophin, and the data is compelling, so I'll just keep going back to that. The totality of the data, the expression data, the biomarker data and functional data is what bore up
spk15: on the animal data that predicted exactly what we would have seen in the studies that we've run. We've run, we'll just keep, we'll kind of go on a little bit. I would remind everybody we've dosed nearly 90 patients just in study 101, 102, and 103. I'm not talking about in March, which as you know, we will have in the next few weeks, I think fully enrolled that study and that'll be another 60 patients before we cross them over. And we've seen very consistent results, very consistent functional results in the 101, 102, and 103. Very, very strong key values across it. All the underlying biological markers support the conclusion that this therapy provided a significant benefit. All the protein was properly localized through the sarcolemma, acting as the shock absorber one would have envisioned it is. The CK, you know, CK is a very noisy endpoint, and yes, In every one of our studies, we see significant drops in CK. That is a great addition of the benefits that we're also seeing in the functional results of the NSA and time tests, all of which are concordant. We've seen third-party muscle MRIs that have been concordant in the reduction of fat and fibrotic tissue. So there's just a wealth of totality of evidence that supports the conclusion from our perspective that the SRP9001 therapy and the results in shortened but functional protein, which was rationally designed over 14 or more years through both design and review of natural history and then empiricism justified the conclusion that our protein is functional. We have a very laudable safety profile. And on the basis of all of that, plus the written feedback we've received from the FDA, we think it is Certainly appropriate, and we have an enormous amount of conviction about the pathway forward as we seek a BLA for an accelerated approval for the ambulant population and then follow up to the non-ambulant population as soon as reasonably possible. It's a very important part of our mission.
spk19: Our next question coming from the line of Judah Fulmer with Credit Suisse. Your line is open.
spk03: Hi. Thanks for taking the question and congrats as well. on the progress. You know, we were just kind of curious, given how close the timelines are between the accelerated BLA filing and the embarked data coming out. You know, in your mind, is the accelerated BLA somewhat of a low-risk option to explore approvability? And does it in any way compromise, if you didn't get the accelerated approval, the ability to quickly file with the embarked data thereafter? to the point where if it's not accelerated, we should still be thinking about the same timelines for a phase three filing.
spk15: Well, first I'll answer the last question first, which is this will actually speed up our discussion. We'll be in a BLA agency, but so we're clear, we would not file. I want to be very clear about this. We've said this many times over the last many months. we would not submit a BLA for accelerated approval unless we had developed strong evidence-based conviction that the BLA would be well-received and that we would get a very productive review. So we don't see this as, you know, a low-risk issue. It would have been even easier for us to simply await the embargo leave-out now waiting for the embarked readout, and then compiling a BLA thereafter, and then filing a BLA after. Timeline to get this therapy to children. Waiting for it by. as much as the year. And given the feedback, it is clearly the more appropriate and frankly ethical thing to do to submit a DLA for an accelerated approval. And given the data that we have, get this therapy to kids as soon as possible. I would remind you all that while, you know, the MTV on syreptin may be very similar between those two scenarios, it is not the same answer for the children who are waiting for this therapy. Every single solitary hour of every single day, not to be overly dramatic about it, but it is not dramatic in its objective fact. This horrible disease is degenerating these kids and stealing from them their muscle. So if we can get this therapy approved on an accelerated basis, there will be thousands of children that will have had that muscle saved that would have otherwise been lost as a result of probably a year gap between what a traditional approval would be if we filed a BLA after Embark Let Out versus our ability to file a BLA now and get an accelerated approval for the ambulant population. But again, I want to be very clear. People that might say, almost suggesting there's a flyer, no. It was a result of a significant an in-depth review and a significant number of meetings with the FDA that gave us the conviction to submit an accelerated approval BLA, which we will be doing this fall. Thank you very much for your question.
spk19: Thank you. One moment for our next question. Our next question, coming from the lineup, Tasin Ahmed with Bank of America. Your line is open.
spk18: Hi, guys. Good afternoon. Thanks for taking my questions. Ian, you had said not to expect a meaningful uptake in expenses in 4Q, but as you ramp up commercial supply, can you give us a sense of how expenses in 2023 could compare to this year? And then separately, can I ask on PPMO, when should we expect the next update, either data-wise or on path forward? Thanks.
spk09: Yes, just on the expenses front. You'll see an uptick in OpEx. However, because of the growth of our revenue, from a net cash burn perspective, I actually expect it to be relatively flat for 2022 and 2023.
spk15: I'll turn the PPMO question over to Luis. I'll comment on the interaction to the PPMO.
spk17: On the PPMO, we've submitted information to FDA and are waiting for their feedback, so we'll update as soon as we have the results from that.
spk27: One moment for our next question.
spk19: And our next question coming from Delana of Salve Inverter with Goldman Sachs. Your line is open.
spk22: Hi, thanks for taking our question, and congratulations on the feedback. We were wondering if you would be willing to divide the population, maybe accept a label in younger patients as part of this accelerated approval process, and how the discussions in Europe are progressing for a potential faster path to approval. Thank you.
spk15: Denise, do you want to take that call, that question?
spk17: The first part of the question, could you
spk15: I think the question is, I think it's a split. And I'd say it's, I think it's approximately 60-40 ambulatory to non-ambulatory on that. So, you know, we modeled that if you think about the accelerated approval versus the full approval.
spk17: That's correct. And then the European discussions are going well in our 301 trials, the global trials. with European patients included. Certainly, our partners, Roche, are driving the ex-U.S. development and conversations and discussions with health authorities are proceeding well, and obviously our developments in the U.S. are supportive of that as well.
spk27: Thank you.
spk19: And our next question coming from the line of Colin Risto with UPS. The line is open.
spk21: Hey, good afternoon, and a big congrats on the progress. So a few from my side. Regarding the discussions around the accelerated pathway, can you give us any color on what was discussed regarding the sort of titring or product consistency issues in part one and sort of what gets FDA comfortable with this? On the expression versus function data, this is something you've been teasing us with for a while. Now FDA has seen it, when should we expect to see it? And then just finally, the letter that you got from FDA, who was the signatory on the letter? Thank you.
spk15: Yeah, so I'll answer each of them in turn. So first of all, with respect to consistency, remember the issue that occurred with respect to the clinical material previously. that related to Part 1, didn't relate to Part 2 of Study 102, but it related to Part 1, had everything to do with the titering method that was being used by our partner, Nationwide Children's Hospital. They had this supercoiled titering method that resulted in, when we looked at them with a more accurate titering method, that we saw that 60% of the um the batches were um were less than the target does that doesn't exist anymore so just be very clear even before we move to our commercial manufacturing process itself we had already developed a linear titering method that was far more precise and then generally speaking our commercial um process is you know in in really all regards um much tighter So we feel very good about the consistency of the process. Generally speaking, we shared everything with the agency, including all of the biomarker data, preclinical data, expression data, functional data, expression, CK, and function data together. We're not going to provide additional updates, nor do I really want to provide any sort of blow-by-blows in the agency. I think the obvious next step for us with respect to this therapy and the patient community is to get this BLA filed, get this BLA reviewed, and if successful, get this therapy to as many patients who would benefit as possible. And then finally, as relates to the signatory on the letter, the letter that we received came from the head of CBER, Dr. Peter Marks.
spk27: Thank you.
spk19: And one moment for our next question. Our next question coming from the line of Ritubro with Colin Yelani-Solfin.
spk26: Good afternoon, guys. Thanks for taking the question. I want to move to gene therapy inventory for a second. Can you comment on the inventory that you have on hand, how long it's good for, and how much you intend to generate by the time of potential approval? And the flip side of that is, How much progress have you made on centers that are qualified to administer the therapy? I know that's something you guys have been working on like every single world muscle I've attended. Can you talk to the number of centers and what the administration capacity is?
spk15: Yeah, so I'm going to turn this question over, the question on the centers, to our head of um customer interaction um dylan murray but before i do that on gene therapy inventory generally we're we'll be in a very good place to launch the therapy we intend to be in a place where we can have sufficient capacity to launch this therapy um without um delaying and assuming that we are alone and launching our therapy to fully serve the community without delay and we'll have By then, our anticipation is a couple of years of shelf life on therapy so we can build a robust amount of inventory to ensure that we can do that. With that said, Alan, perhaps you want to touch on the question about our centers of excellence in the lab.
spk13: Yeah, thanks for the question, Ritu. And as you have noticed and seen at the prior world muscles, We've identified this as a critical success factor and have literally been working on it for years. We have seen this as a rate loader for prior gene therapy launches in terms of having sites ready to go and trained on day one. And so our aim for day one will be to allow, you know, to have enough sites ready to go to allow all eligible patients to be treated in a timely manner. As Doug previously mentioned, externally, the target is to do that is higher than, you know, a little bit north of 50 sites in total. And 50 centers, because these are highly specialized neuromuscular centers, will treat more than 80% or up to 80% of the eligible population. So that works for us. We can target some key centers of excellence, many of whom are already dosing with sultansma. As you said, we're making progress, and the plan is to have them ready to go on day one.
spk15: I will say also two things. Certainly, we have a lot of work to do, given that we're working through an accelerated approval, which is a very tight timeline. With that said, and that means we have real work to do, and we want to approach it with an enormous amount of energy and humility. But I would hope that over the last six years, we have shown the community what we can do to serve the Duchenne community with our therapies. The most recent results that we've seen with a quarter over a prior quarter growth of just about 50% hopefully gives people additional confidence that when SRP 9001 is approved, we'll be able to fully serve the community and robustly get that therapy to centers and also support centers in the appropriate use of the therapy so we get optimal results with patients, which of course is our goal.
spk19: And our next question coming from the line of Matthew Harrison with Morgan Stanley. Your line is open.
spk12: Hi. Thank you for taking our questions. This is Max Gore on for Matthew Harrison. I guess this question can extend to Envision, but how are you managing variability in the Phase III and BARQ trial, and do you think you can lower the standard deviation below, let's say, the four to five points we've seen in most of the natural history studies? Thank you very much.
spk15: Sure. Ruth, do you want to touch on the control that we have in the BARQ?
spk17: Sure. Thanks for that question. For why I would say we have a great deal of learnings from 102, which we applied to study 301 or embark. And so some of those included our inclusion, exclusion criteria. One of the things we did was the rise time less than five seconds, for example, to ensure a population, Mahoney Juniors population. Having said that, our study is extremely well powered and given the recent study 103, results, it gives us even more confidence in 301 in terms of the outcome of that trial. So we certainly have applied our learnings. In addition, as Doug spoke to earlier, the consistency of our titering in addition to the learnings that we put into the inclusion and exclusion criteria.
spk27: Thank you. One moment for our next question.
spk19: And our next question coming from the line up, with Guggenheim .
spk05: Hey, good afternoon. Thank you for taking my question. Just has there been a fundamental shift in how the FDA views gene therapy to proceed with a DLS submission with what feels like a priority review for a very broad population? And would you need to provide any biomarker data at month three from the EMBARQ study to complement the DLA? Thank you.
spk15: Thank you very much for the question. Look, I think that, I think the agency's always been committed to gene therapy, and I think the justification for this accelerated approval DLA, which it will be the first accelerated approval DLA in gene therapy, in vivo gene therapy, I think it's a result of the data that we have. I would remind you this is not a scant data set that justifies this filing. We have nearly 90 patients' worth of data. We have years of preclinical and animal data that shows how the surrogate endpoint, which is the 9001 protein, will perform and then You know, we translated it into patients, and we've seen great results. We've even seen great results over the longer term where you see what we would have anticipated and predicted, which is essentially a disease-modifying therapy where you get a very significant benefit in the first year, and then as you would expect from a disease-modifying therapy in a degenerative disease, you see that benefit grow significantly over time. You saw at the two-year mark in 102, we had a five-point delta. And then you look at these kids, small, I will admit, a very small cohort, but still pretty impressive. You see the, you know, nearly a 10-point delta versus natural history. And then finally on Embark, there has been no suggestion from the agency, as we stand right now, that they would need to see additional information from Embark.
spk19: Our next question coming from the line of Brian Scorning with Verity. The line is open.
spk07: Hey, good afternoon, everyone. Thanks for taking my question. Just to add to the questions around the FDA discussion, do you want to see if you had discussed with the FDA at all the thought about expanding the placebo-controlled portion of Embaric? I know both the size and the follow-up period of the placebo-controlled portion of Essence was increased after Exondys' approval in order to have definitive results from a larger two-year study. I was just wondering, was there any discussion about doing this for Embark if the AA pathway relieves a little bit of the pressure to get an early approval?
spk15: Yeah, there wasn't. No discussions like that have occurred. Obviously, we have not proposed that. With respect to Essence, one of the reasons that we increased the size of Essence, and it was actually, I think initially at the suggestion of the FDA was to ensure that we had Essence properly powered. And so we did just that. The issue with respect to Embark is, as we look at it right now, we're very well powered. So we're over 90%, strongly over 90% powering based on our analysis. So we feel very good about where Embark is. In fact, I would note that as we've looked at the various potential ends, the highest end that we could look to at the time was 120 patients. And that's where That's where we ended up, because we wanted to make sure we prioritized success in that trial.
spk14: Great. Thanks, Doug.
spk15: Thank you.
spk27: One moment for our next question.
spk19: Now, our next question coming from the line of .
spk16: Great. Thank you for, I just got two questions. And again, really nice update. You know, one is, I was just wondering, you know, as you mentioned, you've had a lot of conversations with the FDA over the last few months. You know, if there was to be an adcom, can you just maybe speculate on what aspects could FDA focus on? I mean, would it be various efficacy databases? Could it be the manufacturing? Could it be anything safety related? I mean, knowing full well, it's just pure speculation in part, but I imagine you would have gotten a sense of where FDA is comfortable and where they're not. And then just secondly, can you just remind us of the royalty or the cheering structure you have at Roche on ex-US sales for SRP 9001? Thank you.
spk15: Sure. I'll turn the royalty question over to Ian in a second. Look, thank you, Harkesh, for predicting in advance that I would be wildly speculating on the ad comp. I mean, I would say, look, we've been great about where we are. We've got An enormous wealth of data that justifies the approach that we're taking right now. Obviously, all of this is a review issue. We'll submit our BLA. It'll be filed. If all goes well, we'll have a very positive review. We haven't been informed by the FDA that we're going to get an adcom. We will prepare as if we're going to get an adcom. It wouldn't be at all surprising. If we had an ADCOM, we would actually invite it. We're excited. It could be another opportunity, frankly, for us to highlight our data about safety and efficacy and the like regarding it. And I am sure that ADCOM would go into all of the issues, which certainly the CMC issues always feel very solid on the CMC issues. Obviously, on the correlate, the ability of our SRP9001 protein to predict clinical benefit, which I think the data is, I think it is an understatement to say that it's powerful. I mean, we've got an enormous amount of data on that, given how many patients we've dosed, how many analyses we've done, and all of the preclinical work. And of course, safety. But even on that, as we've said, of course, this is a You have to take safety very seriously. We have a very laudable safety profile at least as we stand here right now. So we feel good about all of it. I'm sure if there was an APTOM, we don't know that yet, if there was an APTOM, we would expect them to explore all of those issues. But again, I think the totality of evidence that we have with respect to SRP 9001 and the justification for accelerated approval is very robust right now. We feel very good about where we are and how this review would track.
spk09: Yeah, and then as it relates to our royalty arrangement, the brooch is based on XUS sales. And surprisingly, the actual royalty rate goes from low double digits to the high teens. And that's actually based off of our manufacturing yield, though, determines the exact level.
spk27: Thank you, and one moment for our next question.
spk19: Our next question coming from the line of Tim Lugo with Will and Blair. Your line is open.
spk16: Congratulations on all the progress for patients in the quarter. And, you know, you mentioned that the expression of safety data from the non-ambulatory study would be available around the time of the potential approval. Is that something that could be available you know, or kind of supplemented in the filings? Is that something that could be available prior to approval, prior to an adcom? I guess, can you just talk a bit about when that could come out through 2023? Yeah, thank you very much for the question.
spk15: And, you know, thank you very much for making the point that I hope we're all making, which is the importance of this accelerated approval pathway It is, of course, important to select that. It's, of course, important, in my opinion, to the entire field of gene therapy. But it is particularly important to these patients, and that is the primary motivator for all of this. If we're successful with this and celebrated as we will, there will be in the United States thousands of patients who would have been degenerating over a period of time when, at least from our perspective, they will have a therapy that will be of great benefit to them. And then, apologies, the short answer on your other question is, I can't speculate on that right now. That's not a topic that has been discussed with the agency and it is something that we're going to have to consider independently whether there is a value to whether it would be received and whether we would be capable of providing out of the Envision study or study 303 any additional safety or expression data that's never been discussed with the FDA, and we'd have to discuss it internally. Our primary goal with respect to the non-ambulatory population right now is to get that study started, and we're working on getting that study started as soon as possible, and we certainly want to do that.
spk27: Thank you.
spk19: And our next question coming from Delana at Gale Plum with Neham. Your line is open.
spk11: Good afternoon, and thank you for taking our questions. And let me add my congratulations, especially considering what this means for patients. So in 2023, we might be facing a world that has both gene therapy and PMO at the same time, similar patient populations. Any thoughts of what kind of sales dynamics you might see between these two populations? Do you think patients are going to switch or go on one therapy and maybe go down to another? Thank you.
spk15: Yeah, so there's a lot that we have to, there's a lot of modeling we have to do with respect to this. And then some of it will just be empirical as we launch the therapy. Our current plan assumes a significant amount of cannibalization. I would say, you know, with respect to the initial approval, which would be for the ambulant population, obviously we would still have the PMO available to the non-ambulant population. And so it shouldn't have any impact there. And beyond that, we think there is potentially a very compelling argument for the PMO to continue even with patients who are planning to or have received gene therapy for a host of reasons. The first reason is that there is already evidence in the literature to support the proposition that there is a benefit to patients getting on a PMO in advance of gene therapy, that it would in fact not only protect them in advance of gene therapy, which is of crucial importance, but also that it might actually enhance expression and the benefits of gene therapy if one is on a PMO or if we get approved a PPMO. And then the coexistence of those two therapies may very well be a benefit to patients, and we're doing some work on that right now from a preclinical perspective. And then, as I said before, there will be certainly patients who will have available to them, either in the United States or around the world, an RNA technology and not a gene therapy or a gene therapy and not an RNA, so I think they're is a particular value of both the patients and to Sarepta to having both of these modalities coexist. So while our current modeling is relatively conservative and assumes a significant amount of cannibalization, we're going to have to play this out and see if that is actually the case over the long run or if these therapies coexist.
spk19: Thank you. And next person coming from the line of Joseph Swartz with SVB Securities, the line is open.
spk10: Thank you, and best wishes as you advance through this regulatory process. I realize some of you were not at the company when Exondys was approved, but given some similarities to today, at least on the surface and the fact that there were significant differences in opinion at the FDA back then, I was wondering if you can provide us with any insight into the degree to which those weighing in at the FDA today are unified or split at all in their opinion on the recent guidance to file for accelerated approval. In other words, how broad is the buy-in now at the agency versus when Exondys was in the limelight? And is there a strong and champion pushing for SRP 9001 approval of the agency now as there was for Exondys 51? or does there not need to be for any reason that you can point to?
spk15: Well, a couple thoughts on that. One, I wasn't here at the approval of Exandus, although I did come not too long after that approval occurred and the launch occurred. So some of my comments will be based on the historical record and not on my own personal experience. I have experienced With the Vyondis and Amondis, and I have experience with respect to 9001 today, obviously I wasn't here to recover from Exondus. This will be significantly different. So we're very clear. First of all, let's be very clear before I say anything else. I want to be clear. Exondus and Vyondis and Amondis are doing an enormous amount of good for patients in the United States and to some extent overseas as well. We have some real-world data that's going to be coming out. It's going to be published and then presented at World Muscle. It'll make exactly that point across basically every indicia of benefit. So it was a tremendous benefit to patients, and from my perspective, it was the right decision to have approved Exondys in the first place, and I certainly think Byondys and Amondys as well deserve the benefit. They are benefiting patients significantly. Now, with that said, there are going to be a lot of differences between this accelerated approval and the prior approval. The first of which, of course, is the amount of data that supports this. The data has really built from exonus. The exonus was approved on 12 patients. We're not talking 12 patients. We're 90 patients. We're multiple studies. The functional results are concordant. They're significant. The p-values on them are 0.0001 in that hunt on every one of them the underlying biological activity is unequivocal from my perspective um all of the ambition benefit is unequivocal and the safety is is laudable as well we're not making a small amount of this functional protein uh district in 9001 district we're making robust amounts right we're making upwards of 50 or more on western blot We're making over 70% on vitreous and positive fibers, and the intensity level is off the charts. If you've ever seen one of our unifluorescence images, you should know they're not enhanced, and they light up enormously. So it's unequivocal, the amount of expression there. And then the other thing that's going to be different is that our goal here is to win on the science with the division as a whole, and that is exactly what we're going to do. And I'm very confident about the approach that this team is going to make. I think we've done extraordinarily good work over the last five plus years in forging a very positive, science-based, respectful relationship with the agency. And that will persist through the accelerated approval pathway. And finally, I would note that with respect to the advice that we've received and the input that we've received in advance of our decision and conviction to submit this BLA, We have had broad cross FDA discussions on this topic. We had CBER leadership. We had OCAT. We had the CDER. Inside of CDER, we had the Office of New Drugs. We had the neuro division. So we've had a lot of discussions. None of that is to suggest that we're not going to have a full, robust review. They don't pre-approve a BLA. They approve a BLA you know, for filing, and then we'll have a full review, and then we may have an ad come, and then hopefully if all goes well, I certainly believe that we wouldn't be filing a DLA. We'll have our approval. But in that regard, this approach is going to be different than a Teflon. But I do want to say, with all of that said, the good news in the end of the day with respect to Teflon is that the FDA did the right thing. And as a result of doing the right thing, a lot of patients have benefited, and a lot of patients have benefited in advance. of what would be, if all goes well, a very transformative therapy.
spk09: Yeah, and maybe I'll just add, and Doug already said it, but I'll just kind of reiterate it. You know, we had just announced today that essentially Embark is practically fully enrolled. So, essentially, we would have to wait about a year. So, there's really no incentive for us other than Doug's good point about the patience for us to move forward if we didn't feel that we were going to get a fair review and that there wasn't broad support across the agency. And I certainly wouldn't, you know, obviously this market still remains challenging and we're not going to commit dollars unless we thought, you know, we were going to be successful in getting this patient to therapy. Obviously, that's the point. You know, we have to go through the review, but we're not going to commit dollars in this market unless we thought that there was a good chance for an ultimate approval.
spk19: Thank you. And our next question coming from the lineup, Yunsung with BTIC. Your line is open.
spk24: Great. Thank you very much for taking the question. So a follow-up question on the non-ambulative patient. Was that a study, the new study, required by the FDA during your discussion with the agency? And based on your My answers to the previous question, I guess, is not going to be part of the confirmatory studies required, again, by the FDA. And secondly, just wanted to confirm the timeline. I believe you talked about potential accented approval around mid-year 2023. So that should be before you get top-line data from the EMBARQ Phase III study. But what happens if the EMBARQ Phase III study misses the primary endpoint? possibility come up at all during your discussion with the FDA? Would that be any room of flexibility, depending on how the data look like?
spk15: So on the first question, the Envision North Bay 3x3 obviously is our decision, and we've been planning that for quite some time. So that did not come up. with the agency. That was our decision. With respect to the timing, yeah, if all goes well, the accelerated approval would be in advance of a readout at Embark. We haven't had detailed discussions about Embark and its results, but on the other hand, we're very confident about Embark. We're very well-powered. We're over 90% powered, so we feel very good about it. We were over 90% powered before we saw the readout on And we now have even more conviction, and frankly, the powering has only increased if you apply that. So we feel very good about where we are with that.
spk14: Oh, by the way, I want to update.
spk15: I think I said 60-40 ambulatory, non-ambulatory, the epi is more, I think. And, Dallin, you correct me, 50-50. I just want to make sure I didn't mistake things. Is that correct, Dallin?
spk13: Yes. Closer to 50-50 in the estimated problem population.
spk15: Apologies for that mistake.
spk19: Thank you. And our next question coming from the line of with Durenberg. Your line is open.
spk04: Great. Thanks. I want to add my congrats to the progress as well. Just a few clarification questions. First, on the Based on your communication with the FDA, I guess, has FDA explicitly encouraged you to file based on the excited approval? And secondly, I want to ask Ian around the SG&A uptick expense in the second quarter. You mentioned that was primarily driven by non-cash stock options. Should we assume the expenses in Q3 and Q4 should come down substantially? Thank you.
spk15: Yeah, so thanks. I was on the FDA communication. What I would say is that based on our communication and the written advice from the agency, we have enormous, we have significant conviction on the concept of submitting for an accelerated approval PLA. And we feel very good about the approach that we're taking. And then with that, Ian, perhaps you want to talk about the non-cash items.
spk09: Yeah, thanks. So as it relates to, yeah, you're going to see the biggest this quarter. There will be some smaller stock-based compensation expenses over the coming quarters, about $50 million that's spread out through probably over the next year. So much significantly less. But remember, you know, the most important thing to think about here is that this is a, you know, this expense is non-cash charge. So it has no impact at all to our overall net cash flow.
spk19: Our next question, coming from the line up, Danielle with Raymond James. Your line is open.
spk20: Hi, guys. Good afternoon. Thanks for the questions. Two quick ones. Given the proximity of the anticipated accelerated approval to embark reading out, I'm curious to hear what you're thinking on the payer's front. Is it possible that they'll drag their feet to implement coverage, or are you expecting full buy-in? I appreciate that you've generated much more data at this point, but have you set a new precedent here and do you anticipate that your competitors will follow suit with pursuing accelerated approval? Thank you.
spk15: Yeah, thank you very much for your question. So, on the second question first, our ability to submit for our conviction around the BLA is unique to our therapy and the wealth of data that we have on our therapy. and then 90-plus patients across three therapies of data that we have, and the 14 years of preclinical work that supports that, and the safety profile, which is unique to SRP 9-001. It is on that basis that we're filing for accelerated approval, and I don't think we're setting a new precedent. I mean, this is very consistent with the statutes and the regulations, frankly, the precedent at the FDA about where an accelerated approval is appropriate. But I want to be very clear that decision stands on the data in front of us, which is unique to SRP 9001 and unique to the SRP 9001 protein, which is, from our perspective at least, unequivocally beneficial to patients and we can safely deliver that therapy in great expression levels. As it relates to payers, I would say, you know, as challenging as payers can be, we've forged a very positive relationship with payers over the nearly six years since the approval of Exondys. And so I don't want to make it seem easy. Dallin and his team work every day and fight every day to ensure that patients get on therapy and stay on therapy across our three approved therapies. But hopefully you will see in the results that we've had, which is, I used to say 20 quarters, it's 20 something quarters of positive quarter over quarter over quarter over quarter growth. The category so far of over 40% annual compounded annual growth rate, and even a 50% growth over the same quarter last year. that given a therapy and having the opportunity to take that therapy to patients, we are a company that knows how to execute, knows how to work with payers, knows how to get this therapy, not only delivered to the community, but get community, you know, support community, the community and support patients getting on therapy and staying on therapy with respect to chronic therapies or in this case, getting therapy and getting it appropriately with respect to this one time team therapy. So, you know, there's a lot of work to be done, but I'm very confident that, that, There is no better team, certainly no better team with respect to Duchenne muscular dystrophy than the team that you have at Sarepta fighting every day for patients. And so I'm very confident about our ability to translate an approval into therapy that can benefit patients.
spk19: Thank you. And our next question coming from the line of Kristin Kliska with Cancer Fitzgerald. The line is open.
spk23: Hi, everyone. Congrats on a very exciting quarter for the company. So most of my questions have been asked, so I'll change topics a little bit here in gene therapy. So based off the path you took with SRP 9001 and your discussions with the agency, has this changed how you might envision some of the trial designs? for the limb girdle programs. And of course, I understand here that you'd want to see some supportive data before figuring out the path forward. But any initial thoughts at this stage?
spk14: Luis, do you want to touch on limb girdle?
spk17: Sure. Thank you for that question. So there's kind of work going on in limb girdle. As you know, we have five programs, and we've been working hard on all of the CMC-related activities, including the LGMD-specific assays to support the program. Certainly, all of the data that we've collected with SRP 9001 is supportive of the LIMB-GIRTLE program using the same RE74 vector and the promoter in many cases and delivery method. And so, the data that we generate today is supportive. We also have our data, which we've shared with LIMB-GIRTLE 2E that is been very promising in both expression and functional results as well. And so we're taking all that collective data and obviously learnings from our pathway with 9001 to apply where we can. These are obviously smaller populations, but there's a lot of learnings that we can apply and we're moving swiftly to get to our next set of trials and those in the LIMB hurdles. So thanks for the question.
spk27: Thank you.
spk19: And our last question coming from the lineup, Gavin Clark Gardner with Evercore ISI. Your line is open.
spk08: Yeah, hey, thanks for taking the question. I just wanted to ask if you could give any more granularity around the status of the CMC work and thoughts on the timeline for engaging with the FDA. You know, is it a maybe later this year thing or more like a 2023 event? Thanks.
spk15: On Lynn Goodall in particular?
spk08: Yeah, yeah, for limb girdle.
spk15: Yeah, so we're trying to get this. Look, we are working hard on the CMT for our limb girdle programs. There's a lot of work to be done. We've learned an enormous amount that we can capitalize on as a result of SIP 9001. We've always been captured, the same promoter, with respect to many of our limb girdles. But a lot of it just takes time. and it's an empirical process to build some of these assays in particular out. So we're working like mad, Melissa, if you want to touch on any of these issues in any more detail, but I do think we're working hard to try to get a lot of this done this year.
spk17: Yeah, I would add we certainly have learned in the development of the assays, but for each of the limb girdle subtypes, there's still specific assays that have to be developed for each one, and so those such as Doug alluded to, takes time. So that's what we're working on.
spk15: The good news is that we know exactly what we need to do, given SRP 9001. The other good news is that there's no significant or most inventive step in any of this. This is really just work and empirical assay development and confirmation. And the potentially frustrating thing sometimes is that it just takes time. And that's what we're working on right now. There's only so fast one can go in. You have to rely upon some of the preclinical studies that support these assets. But we're working like mad on that. I understand that it's a high-priority plan.
spk19: Thank you. And I'm showing no further questions at this time. I would now like to turn the call back over to Mr. Ingram for any closing remarks.
spk15: All right, thank you very much, and thanks for your time this evening. I think you will all hopefully come away from this call at least understanding how excited we are, both with respect to our current performance. I don't want to lose sight of that. I went down here, and you wouldn't let me lose sight of the fact that we really are doing an enormously great job, my view, of serving the current community with our approved therapies, and it shows in our performance, and it shows in our guidance. But we're very, very excited about where we are with SRP 9001, certainly with respect to our conviction around a DLA, and then, of course, with respect to the progress we've made with respect to our confirmatory trial at BARC. And now the hard work starts. It always seems like the hard work starts for Syretta. We don't afford ourselves much of a pat on the back, but we've got a lot of work to do in front of us. We have to get our DLA submitted. We have to get through the review process. We have to get our site readiness ready to go and really tune up our ability to launch what will be an enormous therapy. And we have to build an enormous amount of inventory to support this launch so that patients are not waiting because of manufacturing, and we're very confident we'll get there. But we'll give updates along the way as we do that. The final thing I'd like to say, and I made a comment briefly on this same thing last time, and I'll say it again, and that is that I know this year, has been a very challenging time for the biotech investor. And it seems sometimes, and I understand why, but it seems sometimes that hope and vision are lately replaced with a sort of blinkered pessimism that results from what has been a tough year. But I would remind us all that as challenging as it may be, what we all do together, and that's the biotechnology organizations and our scientists and professionals, but importantly also those On this call today, those of you who invest in biotechnology, it's unbelievably important to society, and it deserves our optimism. The science of genetic medicine, in particular, has made revolutionary advances over these years. And we and others will translate this science to therapies that will improve the human condition and make outsized returns for those like you who have taken the risk on genetic medicine. Sarepta, in my view, is a leader in genetic medicine for rare disease. And we intend through our scientific execution and our tenacity to lead that return to optimism. And when optimism returns, and optimism will, of course, return, it should be for companies like Sarepta that preferentially benefit. Companies like us with a strong balance sheet, with strong revenue, with best-in-class talent, and with a strong late-stage pipeline poised to improve lives, not some distant future, but literally very soon. Companies like Sarepta that, at least in my opinion, know how to execute and get things done. And with that, I would ask you all to have a lovely evening. Thank you for your time.
spk19: Ladies and gentlemen, that's our conference for today. Thank you for your participation. You may now disconnect.
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