Good morning. Welcome to the Sarepta Therapeutics conference call and webcast for the clinical update for Study SRP-9001-103, 12-week expression and safety data using commercially representative material. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press the star then the one key on your touch-tone telephone. As a reminder, today's program is being recorded. I will turn the call over to Mr. Doug Ingram, President and CEO, for opening remarks. Thank you. Good morning, and thank you for joining us for the report out from our 11-patient cohort study to characterize our DMD gene therapy 9001 using our commercial process material. Before I turn the call to Dr. Rodino-Klapac, let me contextualize these results. I have said before, and I will repeat it here, it is difficult to overstate the importance of this data. Indeed, these results are one of the most significant ones yet in Sarepta's history, and with the benefit of hindsight, I believe may be among the most seminal moments in the treatment of Duchenne muscular dystrophy. Why do I say this? First, because this is the therapy we will not only take forward into our next clinical trial, but it is also the therapy that we will, if successful, launch commercially, both in the U.S. and around the world. This data today will tell us if, at commercial scale, we have the differentiated, robust expression and safety profile that our earlier preclinical and clinical studies using clinical process material predict. Second, because it represents the culmination of an extraordinary and rapid journey from the mere vision to become one of the few genuine world leaders in gene therapy manufacturing to that reality. In early 2018, our aspiration was truly a moonshot. At the time that we began this journey, we needed to not only become experts in this nascent field and build a scalable process and release approach for SRP-9001, but to build more capacity than all of the known gene therapy capacity in all of the companies dedicated to gene therapy around the world combined. From that idea, we invested hundreds of millions of dollars and brought in hundreds of experts in technical operations. These results will tell us if we are achieving that aspiration. Third, it addresses one of the two issues that confounded our primary endpoint in Study 102, part I in January. We know that when we get the baseline characteristics correct in the four to five-year-old cohort, our therapy acted exactly as all of the preclinical and early clinical evidence would have predicted and showed strong, clinically meaningful, and statistically significant results. The top-line results were indeed confounded by two issues. One, an improbable imbalance in the six to seven-year-old cohort baselines, and two, titering variability from our clinical supply manufacturer's process and assays that resulted in lower than anticipated mean expression. The first issue is easily resolved in the next study by stratifying for baseline characteristics. As to the second issue, Sarepta developed a much more precise linear titering method that has been applied to Study 103. The results of this study today will tell us if the second of our two issues has been resolved. If it has, any setback from 102 will have been resolved. We will be moving rapidly forward with little delay. Now, let me turn the presentation to Dr. Louise Rodino-Klapac. Before Louise begins, I will remind you that we will likely be making forward-looking statements today. Please refer to our public filings for a discussion of the risks associated with making predictions about the future. With that, Louise? Thank you, Doug. If I could have the next slide. Good morning, everyone. I'm very pleased to share the safety and biopsy results from our first 11 patients in our Study 103 utilizing our commercial process material for SRP-9001. The need for an urgent treatment for Duchenne could not be more clear. It's a devastating disease that affects hundreds of thousands of children around the world. It affects the skeletal muscle, cardiac muscle, and the diaphragm, and we designed SRP-9001 microdystrophin specifically to treat all aspects of DMD. Next slide, please. We carefully selected and developed every aspect of our SRP-9001 microdystrophin vector, and this includes three key components. We selected rh74 for its optimal biodistribution to skeletal and cardiac muscle. Importantly, we see low levels of pre-existing immunity to RH74, and it's highly differentiated from a safety perspective. We're also using an MHCK7 promoter, and this contains a myosin heavy chain enhancer that leads to robust expression in the heart as well as skeletal muscle. Finally, we carefully selected and tested the key components of the dystrophin gene to optimize our microdystrophin transgene. I'll go into these in more detail in the next slide, but importantly, we include spectrin repeats two and three, which are critical for membrane stability and corresponding function. Next slide, please. Our optimized microdystrophin construct is the result of many years of rational design and iteration. The dystrophin gene is a large gene, and it codes for a 460 kilodalton protein, and it acts like a shock absorber in the cell. It connects the inside of the cell with the actin cytoskeleton or the contractile apparatus of the cell to the sarcolemma or the muscle membrane. It has anchor points throughout the sarcolemma, includes spectrin repeats one, two, and three, and then also through the cysteine-rich domain, which is critical for assembly of the dystrophin-associated protein complex or DAPC. The impetus for the development of miniature microdystrophin constructs came from a seminal paper from Dr. Kay Davies's lab that described a 61-year-old ambulatory patient with Becker muscular dystrophy. Upon sequencing his genome, it was noted that he was missing almost 50% of his dystrophin sequence. This work helped to define the domains of dystrophin that were critical for its function. His naturally occurring mini-dystrophin was too large to fit into AAV. Based on these results, we further designed and tested a microdystrophin that contains all the essential elements, which includes spectrin repeats one, two, and three, which, as you can see, anchor the dystrophin sequence to the membrane and are critical for membrane binding and stability. We've recently published additional work in the Journal of Neuromuscular Disorders that shows that inclusion of spectrin repeat three in particular is critical for the stability. We've also included three hinges in our constructs for flexibility of the construct, as well as the cysteine-rich domain for that important assembly of the dystrophin-associated protein complex. If I can have the next slide. We will turn to our results for Study 103, which is expression and safety data at 12 weeks using our commercial process material. Next slide, please. To remind you, Study 103 is an ongoing phase I-B study. It's an open-label study using commercially representative material for SRP-9001. This is multi-site. There are four sites included in this trial. Boys with Duchenne are enrolled between the ages of four to less than eight, so inclusive of four to seven. In total, 20 patients have been enrolled, but for today, we'll be discussing 11 patients. We previously disclosed that the first cohort of patients that were enrolled were favored towards the six and seven-year-olds just by happenstance, with nine patients being six and seven, and two patients being four to five. Patients were dosed at the intended dose of 1.33x 10 ^ 14th vector genomes per kilogram. Again, this is using our qPCR method with a linear standard. We biopsy patients at baseline and at 12 weeks, and those are the results we'll be sharing today along with safety data. All patients are then enrolled with Part two, which is an open-label extension study. Next slide, please. We've consistently shown our biopsy results sharing each key step of the biological process. First, has the vector reached the nucleus efficiently? This is measured by vector copies per nuclei. Next, is the microdystrophin protein being made at sufficient quantities? This is measured to measure total protein by Western blot. Next, is it properly localized to the muscle membrane, and is it doing so at meaningful levels? This is measured by percent positive fibers and intensity. Importantly, what is the safety tolerability profile? First, is SRP-9001 getting to the nucleus? Indeed it is at very high quantities. We see a mean of 3.87 copies per nuclei in our first 11 patients. Is that vector genome copies resulting in high quantities of microdystrophin protein? On the next slide, it certainly is. By Western blot, we see a mean of 55.4% across our first 11 patients by Western blot. This is important that we're generating high quantities of microdystrophin consistent with what we've seen previously. Next, is this correctly localized? Next slide, please. We see very robust expression of microdystrophin correctly localized to the membrane. First, let me walk you through the images. On the top, we see baseline images representing baseline images. In green on the left, this is merosin staining just to label the membrane. In the middle is microdystrophin staining, and on the right is the merged image. At baseline, you can see there's no microdystrophin present. Post-gene therapy, we see robust expression of microdystrophin correctly localized to the membrane, and you can see that it's co-localization by the yellow images on the right. We've measured this two different ways. In terms of dystrophin-positive fibers, we see a mean of 70.5% at 12 weeks with a mean intensity of 116.9% as compared to normal across these first 11 patients. If we turn to the next slide, these results are extremely critical, as Doug mentioned and as I mentioned earlier that we're showing consistency across our clinical and our commercially representative process material. What we've shown here is a comparison of the results of our Study 102. This is the first 11 patients from the placebo crossover that were all dosed at the intended dose of 1.33 x 10^14. Now, we've previously shared these results where we achieved in the first 11 patients of Part two, vector genomes copies per nucleus of 2.62 and 51.7% on Western blot. Now we've also seen 79.2% of dystrophin-positive fibers and 100.6% in terms of intensity, all at 12 weeks. If we look at the comparison of the Study 103, you can see there's remarkable consistency between these two studies in terms of our results with 3.87 copies per nucleus in the Study 103, 55.4% in terms of Western blot expression, 70.5% dystrophin-positive fibers, and 116% intensity compared to normal. This is all at 12 weeks, so very good consistency with our commercial process material. Now, equally important to consistency of expression is safety profiling. If I could have the next slide. With respect to safety, we're very pleased to show that we've consistent safety experience with our previous studies with SRP-9001. As you can see, we saw treatment adverse events in 11 patients. Most of these were mild. The most common adverse event was vomiting, as we have seen previously, with a typical onset within the first week, which is mild and treated with normal antiemetics. We also saw transient increases in liver enzymes, which were responsive to steroids. There were two SAEs in the study. One patient with increased transaminases who was treated with intravenous steroids, and another patient with nausea and vomiting. Importantly, there were no clinically relevant complement activation observed in this study. The next slide. To summarize, SRP-9001 provides a differentiated profile for Duchenne. We've importantly confirmed the characteristics of commercial process material for 9001. We've achieved robust transduction for a mean of 3.87 vector genome copies per nucleus. We've seen robust expression of microdystrophin correctly localized to the sarcolemmal membrane, and we've measured this three different ways. With a mean of 55.4% by Western blot, 70.5% positive fibers, and intensity of 116.9% correctly localized to the membrane. We see consistent safety profile with our clinical manufacturing process with no clinical complement manifestations. It can't be understated that Study 103 results provide confirmation of our manufacturing process and our analytics and production capacity to supply the entire Duchenne population. Next slide, please. In terms of next steps, we need to meet with the FDA, and as we've described, this will occur by mid-year 2021, this year, as well as other regulatory agencies. We need to commence Study 301 following that FDA meeting. In addition, we'll also be expanding Study 103 to include older ambulant and non-ambulant patients. Importantly, we will also have 102, Part two data at 48-week results by the end of this year. To conclude, we are quite pleased with the results from our first 11 patients from our 103 study for SRP-9001. We confirmed both expression and safety of our commercial process material, and importantly, it's consistent with our clinical material at the intended dose of 1.33 x 10^1 4th vector genomes per kilogram. Finally, I'd like to thank the patients and the families who participated in this trial, the trial investigators and their teams, and importantly, my Sarepta colleagues and our colleagues at Roche for their relentless dedication to our SRP-9001 microdystrophin program. With that, I'll now turn the call back to Doug for Q&A. Thanks. Thank you. We'll now open the call for questions. Ladies and gentlemen, to ask a question you will need to press the star then the one key on you touch-tone telephone. In the consideration of time, we ask that you please limit yourself to one question. Please stand by while we compile the Q&A roster. Our first question coming from the line of Debjit Chattopadhyay with Guggenheim. Your line is open. Hi, guys. Good morning. Thanks for taking the questions. This is Erin on for Debjit. I just have a question about when making comparisons with studies in Becker's patients from 2016, how different are the methods used to quantify dystrophin compared with the current method that Sarepta uses? Would it mean that earlier studies are overestimated or underestimated dystrophin? Erin, yeah. Sorry, I didn't mean to interrupt you. Thank you for that question, Erin. I know there's potential confusion. The answer is the methods that we use for Western blot related quantification of dystrophin are completely different than the methods that would have been used some years back. We built this Western blot approach not only to be precise, but we also built it in concert with and at the direction of the FDA and the neuro division of the FDA. It is very precise. It is far more precise than what was used for the research purposes some years ago. It's actually relatively conservative in the approach that it's taken as a result of having worked for years with the FDA to get to this precision. Comparing it to old studies is very difficult. If you look at that 2016 study that you're referring to and then look at what it refers to, that study itself mentions as an example, the problems that they were having with consistent quantification. They referenced a 2014 paper that makes the point. They tried to do laboratory to laboratory comparisons, and they had very poor concordance with those methods across laboratories, and they even had pretty low concordance within laboratories. You can't compare those old studies and those Western blots with the much more precise Western blots that we use today. I would point out Western blots that were sufficiently precise to form the basis of the three approvals that we've received with the neuro division from the FDA. With that said, Louise, is there anything else that we should comment on with respect to that? I think you captured the key aspects of it. I'd just add that extremely pleased and impressed with Sarepta, the rigor of our assay and the linear range of the assay, the standards that we employ with our Western protocol. I agree that it's certainly vastly different from the methods that were used back in 2016. We use a very rigorous reference standard as well, something that was missing historically. In any event, we're extremely excited about these results. There's an enormous level of dystrophin from a Western blot perspective, and then you look at the dystrophin positive fibers, and it's the vast majority of fibers are benefiting from the dystrophin. You ask the question, well, that's fine, but are they benefiting significantly? The intensity level here is above 100%. I think the answer to that would be anyone would say that it's very high. If you go back and look at the genome copies per nucleus, we're approaching four genome copies per nucleus, so we're getting extraordinarily good transduction. We feel very excited about it. We're really excited about this data as we track towards our meeting with the FDA so that we can commence our next study and get going as soon as possible. Our next question coming from the line of Gena Wang with Barclays. Your line is open. Thank you for taking my questions and also congrats on the data. I have a question regarding the protein level, the Western blot, slide 11. It seems like the standard deviation was pretty high, 43%. Wondering, are there any correlation regarding the disease severity and the age of the patients? For the remaining nine patients, were these mostly in the age of a four to five years old range? I'll turn this over to Louise. Let me comment briefly on the standard deviation. Look, firstly, we'll always see a certain amount of standard deviation. There is at a minimum a sampling bias that's going to occur. Remember what we do. The biopsies are extremely invasive. We take a single biopsy from a single point in a single muscle in a patient who has the muscle is the largest organ system in the body. As Louise has pointed out, I think a 2014 paper, you'll see a lot of variability just from single biopsies. In this paper from 2014, she notes that depending on where you happen to take a biopsy in a single muscle of an uneven plane, you could have gotten 94% or 9%. The means are in some regards more valuable than the individual points because of that sampling issue. We could improve it, but it would require something that would be unethical. We could do multiple biopsies per patient, and I think we would regress to the mean, but that, of course, is not acceptable from an ethics perspective. The final thing I'll say is on the standard deviation, if you throw out the high and low numbers in these data, you'll see that we're still at 50%. It's a significantly robust issue. The variability that I will note that doesn't exist in these data that existed in Part one is the variability that came from different titers. Remember, our manufacturer was using a different type of titering method, a so-called supercoiled PCR. With the benefit of hindsight, once we had developed a linear titering method that was much more precise, we could see that in the three lots from the prior study, there was variability in the actual dose versus the target dose, and 60% of the kids had lower than the target dose. You do not get that today because Sarepta's linear qPCR method is very precise. We had the target dose for all of the crossover kids and for all of the kids in 103, both just by happens tance or 11 each. As you can see, we get not only robust expression across all of the measures we see, not only robust genome copies per nucleus, but very concordant results between those two as well. I think this has been a really nice confirmation of where we are with this therapy, both from an expression perspective, but also importantly from a safety perspective. Louise, I know there were parts of that question that I missed. Yeah. No, I think you answered the first part of the question quite well. I'd just add for the second part with respect to the four to five. Certainly in the second part to fulfill the 20 patients, there will be additional four to five-year-olds included, and that was the point to make sure that we had a representative population across all four to seven. It is interesting. We did have a preponderance of six to seven-year-olds in this 11-patient cohort. One will remember that after the Part one readout, there was, I think, a concern. It turns out it was an unnecessary concern, but a concern by some that maybe there was an issue with expression in older kids because of additional fat and fibrotic tissue or the like. Such was not the case. We didn't see that at all in the Part two crossover patients. Of course, now we actually have an experiment where nine of the 11 kids are in the older set, and as you can see, you don't see that. You see really robust expression across the ages. We feel very good about that as well. Our next question coming from the line of Brian Abrahams with RBC Capital. Your line is open. Hi, good morning. This is Steve on for Brian. Congrats on the data, thanks for taking our question. Based on today's data and even the limb-girdle data presented earlier in the year, it seems that increases in vector copy number and protein expression don't necessarily correlate one-to-one. Can you share any thoughts as to why this might be and if there are any implications for maybe durability of expression or eventually redosing if the technology allows it? Thanks. Sure. I'll turn this to Louise. Sure. In terms of vector genome copies per nucleus and protein expression, we see a general correlation, but not always a complete one-to-one correlation. I think based on both these data and our limb-girdle data, we're certainly producing robust expression from the vector genome copies that we have. You also get accumulation of protein over time. In terms of durability, we're quite pleased with these results. 3.87 is an impressive copy number that bodes well for sustainment and durability over time. We're quite pleased with that. Thanks. Mm-hmm. Next question coming from the line of Alethia Young with Cantor. Your line is open. Hey, guys, thanks for taking my question. Congrats on the data today. I guess I just wanted to think about you dosed probably 60+ patients. You haven't seen a complement activation that some other gene therapy have seen. Do you have a deeper understanding of the why AAV9 may be causing a complement activation versus the RH74, which I mean, I guess so far, it hasn't? Thanks. Yeah. I'm going to turn this to Louise. I will say that we can at least speak empirically. Empirically, we haven't seen at obviously very robust doses, we're at 1.33E^1 4th using our linear process. We haven't seen any clinical manifestations of a complement. Of course, as you note, I think we're up actually probably near or over 60 patients now. A really big data set that gives us additional confirmation about the stable safety profile that we had. Of course, we know empirically that we have seen in other programs complement not only in DMD gene therapy but in other full body infusion gene therapy using AAV9. We are very pleased with what we're seeing, which would have also been predicted by our preclinical model. We would have predicted preclinically that we wouldn't see this. Louise could actually have some thoughts on the hypothesis for these. Sure. Yeah, just to reiterate, we have dosed over 60 patients with 9001 alone. Then we also have our limb-girdle program, which also uses RH74. We haven't seen complement activation as well. We know that there's been complement activation with other AAV9 trials. Just last week at the ASGCT meeting, there was a poster presented from Solid. It was a nicely done poster that showed that there are capsid AAV9 antibody complexes that lead to and promote complement activation. They did this study in vitro. They used patient serum samples with and without antibodies. This demonstrated, I'd say, conclusively that there was complement activation due to this formation of these complexes through a combination of the capsid and the AAV9 antibodies. That's one piece of evidence that may indicate why other programs might be seeing complement, but we're again just pleased that we have not seen that with our programs with RH74. Our next question coming from the line of Danielle Brill with Raymond James. Your line is open. Hi, guys. Good morning. Thanks so much for the question and congrats on the results. I guess I know we only have two patients in the four to five age range, just curious if there were any noticeable differences in mean expression or any of the other parameters by the different age ranges? Yeah. No, we haven't seen any difference. Louise, I should probably let you answer this since you're closer to the data. Yeah. That's the short answer, that there wasn't any differences between the four to five-year-olds and six to seven-year-olds. Obviously, there's only two patients in the four to five, but we did not see any meaningful differences between the two groups. That's supported as well by the Part two crossover as well. Those kids all got the target dose, and we wouldn't have seen any kind of difference between four and five and six and seven. I think that was just concern that filled the empty space, frankly, between Part one and then the crossover in 103. It doesn't seem to be an issue. Our next question coming from the line of Gil Blum with Needham & Company. Your line is open. Good morning, everyone, and thanks for taking our questions. I'd also like to add congratulations on the results. I know it's a little hard to compare, would you say that the commercial produced results were tighter than those seen in previous studies as in regards to patient-to-patient variation? Thank you. Louise, is the question whether there was higher variability? Is that the question? He was asking whether they were tighter. I think when we look across the two, looking at Part two crossover and 103, which received the same dose, we generally saw the same spread in the two processes, consistent results between the two. Yeah. You would've seen more, in fairness, the Part one results, you would've seen more variability. That wasn't sampling, that was relating to the fact that with respect to Part one, again, our manufacturer used a supercoiled PCR titering method, and that titering method, when we evolved to the Sarepta titering method, which is this linear qPCR standard, and then backward applied it to the lots from Part one, it was clear to us that there were, in fact, two of the three lots didn't hit the target dose, and about 60% of the patients then had less than the target dose. That, of course, created what would look like on its face, more variability. That was all solved. That was solved with the linear titering method, and then the confirmation first in the crossover patients and now 103 shows that it's solved. We are tighter as a result of that. I think our titering method is really performing very nicely right now, as is frankly, the rest of our CMC analytical work. It's all working very well right now. Our next question coming from the line of Salveen Richter with Goldman Sachs. Your line is open. Good morning. Thanks for taking my questions. I was just wondering if you could just remind us, and this just follows up on the last couple of questions about what the standard deviation was for 102 in the clinical research process and how it compares when you look at this number of roughly 40%. Secondly, as you look to Study 301, if that is still on track to start and maybe help us understand the plans to engage with the FDA to discuss the potency assay data. Right. I'll just make a few comments, I'll turn to Louise with maybe to quantify some of this. We're clear, the standard deviation is from Part one to 103, the standard deviation is certainly tighter because we're getting the titering method in the target dose correct. The standard deviation that one would see in the crossover patients at Part two of 102 and 103 are very similar because we are on the target dose, which is fantastic. Everyone's getting the right dose, any standard deviation that you see exists as a result of arguably some biological reaction, but probably more likely than not simply a sampling related issue about one biopsy per one muscle per patient. We feel very, very good about where we are and we're getting very consistent results there. We are on track to have our meeting. The biggest issue for us to have our meeting with the FDA are these 103 results. I got to tell you, we're very excited to meet with the FDA with these results in hand, and we'll get that process completed. Our goal is to have a meeting with the agency by the middle of the year. The reason for that, of course, is we've got to get a meeting date and we've got to get a briefing book, but we're very much on track to have all of that completed, and then we'll start our Study 301 as soon thereafter as we can. You can imagine we want to move as fast as possible. Louise. Yeah. I think you captured a lot. I think the only thing to add to the data about the comparison between the studies, consistent in terms of standard deviation when we look at the intended dose, and we mentioned it earlier, I think it's important to note that all patients responded to therapy and that when we did sensitivity analysis, removing the highest expression is at the mean, so it's not driven by extremes. We're pleased with the consistency of the results both within the study, Study 103 and in comparison to Part two of 102. To Louise's point, one should note that with respect to the 103 patients, they all had very robust transduction and very high genome copies per nucleus. As you can see there, nobody was under 1.6 genome copies per nucleus, which would have, to be honest, two years ago, have been a significant aspiration for us as a mean. We would've been giddy over that number. No patient has had less than that. We feel really good about where we are right now. Our next question coming from the line of Anupam Rama with J.P. Morgan. Hey, guys. Thanks so much for taking the question. Last week, the competition showed some expression data looking at kinetics over time, which suggest that there may be some increased expression with time with their gene therapy approach. Is there any thought about maybe getting one more biopsy in the OL to better understand expression with time from Study 103? Thanks so much. I assume you're talking about the Solid data. I would say it might be a leap to suggest that the data shows exactly that given the scant nature of the data. With that said, perhaps Louise, you can touch on this issue. I think certainly looking at long-term expression is something that we've anticipated. As you know, in our inaugural study, we've shown expression over two years, which importantly, sustainment of that expression. In our Study 102, we'll be looking at also biopsies over the course of having a second biopsy in some of our patients from the first study as well, from the first part. Certainly, we'll be looking at that, and we anticipate that we'll see the same. There is the potential to accumulate over time, but that's something we'll be certainly looking at. The data will speak to that as well. Our next question coming from the line of Colin Bristow with UBS. Your line is open. Hey, good morning. Congrats on the data. I was wondering, could you tell us what the 102 and the other data you've collected tells you about the expression threshold for functional improvement? As you look at these 11 commercial patients, just how many of them were above this level? Just on timing, could you just give us a bit more granularity when we should expect the phase III start, first patient dose? Do you anticipate enrollment timing, et cetera? Well, first I'd say, the expression that we're seeing out of 103 is significantly above what we would envision was necessary from a threshold perspective to see a functional benefit. I would note, in Part one, because of the titering issues, we saw a lower mean for expression. We were 28.1% because 60% of the kids had lower than dose. Notwithstanding that, when the baselines were right, and in the four to five-year-olds, they were spot on between the placebo group and the treated group, you will note that those kids hit strongly statistically significant benefit over the placebo and very clinically meaningful benefit as well. I think the results we're getting and the expression we're getting here ought to give us a significant margin for benefit and should correlate with really good durability over time. That's what we would anticipate. Looking at those genome copies gives us an enormous amount of additional confidence that we're going to see long-term durability when you're way over three genome copies per nucleus, almost going on four genome copies per nucleus. It gives us a ton of confidence. I'd say on the timing for the next study, the short answer is we need to set a meeting with the agency. That meeting will occur by around the middle of the year. It won't be longer than that. It's just a timing issue of getting the meeting called for and getting the date. Then as soon thereafter as is possible, we have everything in order to start our study, and we'll start that study immediately thereafter. People have asked us about recruitment. I think this study is going to be in high demand from everything we've heard from investigators and from families. I think this is going to be a very high-demand study. We're going to have, over time, a significant number of sites up and running in the U.S. and around the world, and so I do think it will be robustly recruited, and we'll get going with that ASAP. Louise, did I miss any part of that question? No, I think you captured it well. Our next question coming from the line of Ritu Baral with Cowen. Your line is open. Hi, guys. Thanks for taking the question. What are the current plans for capturing functional data from 103, especially given the significant 248-week tail? There's nothing on the slides about functional baseline. Could you address sort of where these 11 patients sort of rank in the spectrum, especially since there were no inclusion and exclusion criteria on function? I'll turn that to Louise. Apologies. I'm sorry for cutting you off, Ritu. I'll let Louise answer that. Obviously, for those who are wondering about functional results, it's too early to be providing functional results quite yet. This is 12-week biopsies. Louise, perhaps you want to chat about potential plans down the road. Sure. Yeah. As part of the study, we are capturing functional measurements at baseline and then at various post gene therapy measures. As you mentioned, it's too early to look in detail at 12 weeks, but we're certainly capturing those. An open label study. We will be making sure that we use this information to add to our data package in terms of corresponding function with these patients and certainly similar inclusion criteria to what we would anticipate for our next study. Our next question coming from the line of Difei Yang with Mizuho. Your line is open. Oh, sorry, I muted myself. Thanks. Congrats, and thanks for taking our question. Is the FDA meeting the only gating factor before starting phase III? Yes. Thank you. Our next question coming from the line of Joseph Schwartz with Leerink Partners. Your line is open. Thanks very much. Along those same lines as Ritu's question on functional measures, I was hoping to get your current thoughts on the clinical endpoint or endpoints that you think are best suited to demonstrate functional benefit from microdystrophin gene therapy. How confident are you that NSAA is the best endpoint and that you can control for any confounding that might arise, and what will you be proposing to the FDA in order to secure accelerated and full approval? Thanks for that. A couple thoughts. One, we used NSAA with 102. We've gained an enormous amount of insight out of Part one. I will say the insight that we have out of Part one is unique to us, and we've burrowed into it. A result of that, it has allowed us to refine the protocol for Study 301. Certainly, NSAA will play a role in Study 301, but the approach to the protocol is backed from the Part one, Study 102 results. A result of which, we feel very good about the Study 301. We feel very confident about the probability of success out of that study. Everyone knows, I'm going to back off giving any detail on that study quite yet because we all want to take that protocol to the FDA, get their blessing, and then start the next study. Then we can all talk about the parameters and the learnings that we've had from Part one of Study 102 that has, at least from our perspective, greatly enhanced the probability of success of the program in the next study. We will certainly look at that once we've had the meeting with the FDA. I think the protocol discussion will go quite well. I would say there's nothing exotic in the protocol, but it is definitely refined. Great. We look forward to hearing more. Thanks. Thank you. Our next question coming from the line of Tim Lugo with William Blair. Your line is open. Hey, this is Lachlan on for Tim. Thanks for taking questions. I was wondering how many validated batches have you now run through the manufacturing process using the FDA-agreed process, and what's the rate, if any, that they're sort of failing or having issues on any of those assays? Oh, my goodness. We've run a significant number of batches through. Even with respect to 103, we pulled from multiple lots for these patients. Again, all of them looked great. Do you have any other specific information on numbers of runs? The short answer is we have a lot, but that's probably not a satisfying answer. No, I just said multiple, and I think it's a good question because it is important to highlight that you got from multiple lots from the study. It wasn't an artifact of one lot in particular. It's multiple lots, and these are released using the potency assay that we agreed upon with the FDA back in the fall. We're quite pleased with these results and our new titering method as well. Yeah, that's one other point I will say on to that very good point. I mean, we really feel good about where we are from a manufacturing perspective, process development, analytical development, and capacity perspective. If one will recall back in 2019, this was a significant amount of work. If you read transcripts back in 2019, you would hear me repeatedly saying to people, "I'm confident we're going to get there, but we're not there yet." That had everything to do with yields, process, analytics, and then ultimately capacity. The great news is that we are in a very good place there. We feel very good about our capacity. Let's start there, which I think people have gotten now because we get less questions about that. That's a big, big deal. We'll go back and harken back to the beginning of this discussion. We talked about the fact that at the beginning of this journey in 2018, we had to become not only experts in gene therapy manufacturing, but we had to build the opportunity for more capacity than all of the gene therapy manufacturing capacity that existed in the world at the time. That was no small feat. We had to get yields right. We had to get analytics right. We had an issue last September with the division where we had what we believed to be a very fit for purpose potency assay. The FDA saw it differently. We were able to quickly resolve that issue with them, at least for purposes of Study 103. That provided us with an enormous amount of additional insight into the way the FDA looked at potency assays and therefore, by extension, other assays. As we sit here right now preparing ourselves for a meeting with the agency in the middle of the year, we do feel good about the CMC. We feel good about our manufacturing. We feel good about what we're doing from a technical operations perspective. Of course, we feel, as of today, very good about the characteristics of our therapy and what it may mean. We're patient, as confirmed by future studies. We're getting robust transduction, we're getting great expression, and we're seeing a safety profile that puts us in a place. It's not a nearly unique place. We don't see evidence of clinical complement manifestation. We transitioned from clinical supply to a commercial process, and one of the big concerns with that is that something might have changed in that process. We might have seen a different level of expression or a different level of transduction, and such is clearly not the case. One could have seen some addition of some safety signal that didn't otherwise exist. In the patients that we've dosed so far, we have seen not that case at all. We've seen a very stable safety profile and consistent. From a manufacturing perspective and a program perspective, we feel very good about where we are right now. Our next question coming from the line of Matthew Harrison with Morgan Stanley. Your line is open. Hi, this is Max Skor, on for Matthew Harrison. Thank you for taking our questions. Congratulations on the data today. Thank you. I was just wondering, is it reasonable to assume you're enrolling older patients to try and treat at peak NSAA scores? Basically, is it easier to evaluate differences between treatment arms when patients are losing motor function compared to ascending NSAA scores? Thanks. No. If the question is why are there more six to sevens than four and fives in the 103 first 11 cohort, the short answer is that's just the patients that were enrolled. We've actually added to the Study 103 with some fours and fives as well. All those kids have been dosed as well. One of the things you may have seen in Louise's presentation is that we're also going to be dosing non-ambulatory patients. Frankly, the reason we're dosing patients across the spectrum is our ultimate goal clearly is when this therapy is confirmed in our trials to have a therapy that's fit for purpose and benefits kids across the entire age spectrum, from the very young to the older and non-ambulatory child as well. We don't want to leave any children behind. That's the reason for that. When I was saying that in the 103, it was simply just the chance of who got enrolled that gave us more six and sevens. It's a nice little experiment because there was, I think, some questions that would have been at the hindsight were unfounded that maybe six and seven-year-olds don't get as much expression in this four and five-year-old. Of course, we're not seeing that at all either in the crossover in 103. It's nice to see, even with a predominantly six and seven-year-old group in the Study 103, we've got great expression and very at least concordant expression with what we were seeing with the clinical supply. 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. Thank you very much. Thank you all for joining us this morning. If you would indulge me for a second, I would just like to say to my colleague, Dr. Louise Rodino-Klapac, congratulations. I want everyone to understand that this is the culmination of an enormous amount of work over many years. You will recall that Dr. Louise Rodino-Klapac, even before she joined Sarepta Therapeutics, was the researcher that, along with her colleague, Dr. Jerry Mendell, was looking into microdystrophin as a treatment and built the very construct that we now call SRP-9001. I know it's a bit self-indulgent, but extemporaneously, I'd like to say, Dr. Louise Rodino-Klapac, congratulations for these results. Thank you so much for that. For everyone, let me just say thank you very much. I would echo again Louise's statement. Thank you to the patients and their families who have been willing to give themselves to these sorts of studies and have allowed us to develop this therapy through their hard work. Thank you very much to our colleagues at Roche for partnership and insight as we track forward. We really appreciate that. Thank you to the investors for your time today. We're very excited about these results. We're excited about what this means for us going forward. Keep in mind that we will have a number of important readouts coming. First, we'll have a meeting with the agency. We'll do that by the middle of this year. Second, if all goes well, we'll start our next study as soon thereafter as possible. I promise you we'll be moving as fast as possible to enroll that study. Next, at some point I'm sure we'll have an update on 103, but early next year, very early next year, we'll have an update on part two of 102. Remember, that's 41 children in Study 102. Approximately half of those children will have been on therapy for two years. The other half of those children will have been tracked for a year off of therapy, and then we've watched them for a year after therapy. That'll be fascinating data. All of that is blinded today. All of the analysis you'll see early next year from 102, they are pre-specified. This is not going to be anything like a post hoc analysis. We're really excited about that. We've got a lot of work to do, and we'll keep you informed as we do it. Thanks everyone for your time today. Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect.