REGENXBIO Inc. (RGNX) Earnings Call Transcript & Summary

Thank you for standing by, and welcome to REGENXBIO RGX-202 Interim Data Call. [Operator Instructions] I would now like to hand the call over to President and CEO, Ken Mills. Please go ahead.

Hello. Good afternoon, everyone. This is Ken. If you're joining through the webcast, there are slides available, and they are self-guided. If you're joining on the phone, the slides are available on the Investors section of our website. I'm going to start on Slide 2. Thanks for joining the call today. I'm very excited, so we'll get right into it. We have 2 updates today. First, we're reporting an update on patients dosed with RGX-202 from dose level 1 of our AFFINITY DUCHENNE study. This update will be presented at the World Muscle Society Conference in Charleston, South Carolina this week. Compared to our last update in July, this will include additional patient longer-term follow-up safety and first measures of RGX-202 microdystrophin expression from patient biopsies that are collected at 3 months. Second, we're reporting on updates to our program plans, including recent AFFINITY DUCHENNE trial amendments designed to support the acceleration of the development of RGX-202 to provide a clear path to a goal to submit a BLA using the FDA accelerated approval pathway with RGX-202 microdystrophin as a surrogate endpoint for clinical benefit. With us today to update are Dr. Steve Pakola, our Chief Medical Officer, who will walk us through the clinical data as well as Dr. Aravindhan Veerapandiyan, who is a pediatric neuromuscular neurologists at the Arkansas Children's Hospital and also a treating physician from one of our AFFINITY DUCHENNE trial sites, and he will share his observations and impression of the trial with us today. Moving on to Slide 3. But before I go further, I have to stop here and remind everyone that today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend, or other words of similar meaning. Moving on to Slide 4. In January of 2021, we introduced a program for the development of a potential onetime gene therapy for the treatment of Duchenne, which is based on a novel microdystrophin construct. Since then, our team has worked tirelessly and in meaningful coordination with the Duchenne community. These are some photos as members of the REGENX team sharing their passion and engagement with members of the Duchenne community. I wanted to stop here and thank the families, the advocates, the partners, many of whom have become friends and all of whom have provided our team inspiration and support over the last several years. You motivate our continued commitment to discover and develop new treatments for Duchenne. Thank you. On Slide 5. Today, we're here to discuss the lead programs in our pipeline of AAV Therapeutics that are designed to treat Duchenne, a rare disease caused by mutations in the DMD gene, which was responsible for making dystrophin, a protein of central importance for muscle cell structure and function. All of our treatment candidates are intended as a potential onetime gene therapy for the treatment of Duchenne. If you're listening today, you're probably already familiar with the fundamental science at the core of our approach AAV mediated microdystrophin, AAV microdystrophin treatment. Data from dystrophic laboratory trials and recent human trials suggest that AAV gene therapy is delivering a form of microdystrophin, such as our RGX-202 candidate, may provide new and substantial added muscle function for patients with Duchenne to support a change in the trajectory of the disease. Recently, we've seen the first FDA approval of an AAV mediated microdystrophin gene therapy. While in principle, all types of DMD gene mutations are addressable with this microdystrophin platform approach, clinical evidence from a number of sponsors of AAV microdystrophin gene therapy trials suggest that certain mutations where clinical backgrounds might need to be excluded from accessing certain treatments. In addition, not all microdystrophin gene therapies are created equal. And today, we'll talk about some evidence of important advances in science that present this potential improvement. With over 300,000 boys living with Duchenne worldwide, there continues to be an undeniable and important unmet need for patients in the care, and the potential treatments, including investments in novel approaches like RGX-202 for Duchenne. So let's jump to Slide 6. Depicted in the cartoon on the right is RGX-202 our novel, highly differentiated treatment candidate. The design of RGX-202 is based on innovative science and vector engineering by REGENX bioscientists and incorporates learnings from the laboratory of George Dickson University of London, pioneering figure in dystrophin research. The features of RGX-2 include -- RGX-202, excuse me, include a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal domain or the CT domain that's found in naturally occurring dystrophin. You're going to hear continued reference to me for the next few slides to the CT domain. You see the presence of the CT domain, perhaps our most differentiating feature has been shown to recruit several key proteins to the muscle cell membrane leading to improved muscle resistance to contraction induced muscle damage in dystrophic mice, especially when compared with transgenes for instance, without the CT domain. The data from dystrophic laboratory trials suggest that a gene therapy delivering a microdystrophin incorporating an extended coding region from the CT domain, such as RGX-202 may provide substantial added muscle function for patients with Duchenne. Another element of RGX-202 is a well-characterized muscle-specific promoter called Spc5-12. This feature further supports the delivery and targeted expression of RGX-202 microdystrophin transgene throughout the skeletal and the heart muscle that's where it's needed most. And finally, RGX-202 is designed to use the NAV AAV8 vector, a vector that's used in numerous clinical trials, both run by REGENXBIO and others, and therefore, with a well-established profile. Moving on to Slide 7 and with these elements and features in mind, our RGX-202 program has several distinct potential differences and advantages over alternative microdystrophin gene therapy candidates. Slide 7 shows more cartoons, but with RGX-202 features aligned with other familiar products and candidates that represent some of the class of AAV-mediated microdystrophin. With RGX-202 again, we can focus on our AAV capsid design. In addition to being a well-characterized AAV for targeting muscle, this time, the AAV capsid also represents an alternative for boys who may not be eligible for other AAV mediated microdystrophin with other acids due to the presence of preexisting neutralizing antibodies. We estimate that may be anywhere from 15% to 30% of boys, emphasizing the need for diversity and captive features to help address a broad population of Duchenne boys. Again, we look at the transgene. Achieving the same levels of expression as other gene therapies have demonstrated, our CT domain design has the potential to improve outcomes in boys with more biologically potent and stronger microdystrophin. You see, again, the CT domain is involved in recruiting and building a very complex set of proteins around dystrophin naturally. Dystrophin really acts as a hub in the muscle and cardiac cell attracting other proteins that serve all kinds of important physiological functions for the cell. We believe, and we've actually shown that adding the CT domain brings back more functionality in terms of getting together more proteins that are essential for more muscle function in animals. CT means more function. I'll circle back on this soon. Lastly, I just wanted to emphasize that we make RGX-202 with a commercial-ready high-quality process with high yield and purity to support the potential for rapid development and commercialization. We're recently encouraged that the FDA has supported the accelerated approval of the first in the class of microdystrophin AAV gene therapies, providing a much-needed new therapeutic alternative to the Duchenne community and important clarity on the regulatory pathway for this class of treatment. We believe this approval event provides a clear path for us to submit a Biologics License Application or BLA using the accelerated approval pathway with RGX-202 microdystrophin as a surrogate endpoint for clinical benefit. Now finally on to Slide 8 for some of my remaining points about our journey to support novel treatment for Duchenne. Basically, when you look at history, science have been guided for many years by the nature of mutations found in attenuated forms of Duchenne muscular dystrophy, which is called Becker muscular dystrophy, where patients have very large deletions in the protein, but still have some function left. And this has guided the design and development of gene therapy treatments. We've emphasized that with RGX-202 it's designed to deliver a microdystrophin transgene, which includes the extended coding region of the CT domain that's found in naturally occurring dystrophin. And throughout the literature, it's also reported to be that the CT domain is universally present in dystrophin from the Becker phenotype. This is nature supporting the biological possibility of the design feature itself. Now as we saw in the previous slide, Slide 7, the CT domain can be left out of some microdystrophin constructs. And that's what's been done before because it's not absolutely required for some essential functions. However, presence of the CT domain in nature shows clear evidence of the biological relevance. You can see, as is further indicated on this slide, the cartoons, where those CT binding domains for these necessary and important recruited proteins, which help stabilize muscle function and physiology. Protein like dystrobrevin has an important role. Syntrophin is a group of proteins that also attract other proteins and they are important for physiology of muscle. These protein species constitute what is referred to as the dystrophin-associated protein complex are on this slide, the DAPC. So while RGX-202 microdystrophin is a short version of dystrophin designed to fit into AAV vectors, its design is most similar compared to others in the class, so the dystrophin that is observed in the Becker muscular dystrophy phenotype, specifically because of the overlapping inclusion of elements of the CT domain. So while it's possible to build truncated dystrophins that are still active without the CT domain, it seems useful, if not essential, to include the CT domain, if you could do so. And it was this thinking that led REGENX bioscientists on the journey to design RGX-202. We began our design of RGX-202 only a few years ago, many of the references, you're looking at associated with earlier candidates in development for more than 10 or 15 years old. So it's a blend of innovation of science, the recent understanding of dystrophin, the design of microdystrophin gene and AAV vector development that is now well established that allowed us to start this promising journey. And I'd really like to turn the call over now to Steve to lead us through the interim updates on the AFFINITY DUCHENNE trial.

Thank you, Ken. Good afternoon, everyone, and thanks for joining us. We are thrilled to share our interim clinical data from our AFFINITY DUCHENNE clinical trial. Before I turn to the data, you can see on Slide 10, the main study design elements and the key interim outcome measures we are presenting today, which includes safety and 3-month biomarkers for RGX-202 microdystrophin expression. Importantly, we chose to measure microdystrophin expression by 2 separate methods. First, by western blot using an instrument and method called Jess, which provides an automated and more precise measurement than a traditional western blot approach. Our team has also developed a proprietary liquid chromatography-mass spec method, or LC-MS among the most sensitive means to assess expression. To our knowledge, we are the first and only sponsor to assess microdystrophin by these 2 different methods. Slide 11 shows the age, weight and duration of post-treatment follow-up of the 3 boys treated to date. RGX-202 has been well tolerated in all 3 boys with no SAEs observed. The first 2 treated patients have reached the 3-month time point and have had muscle biopsies collected. On Slide 12 are the results for the 4-year old patient. Change in microdystrophin expression from baseline was 38.8% as measured by western blot and reported as a percent of normal control. Meaning levels of wild-type dystrophin in boys without muscular dystrophy. Importantly, we see comparable results on the proprietary LC-MS method. Additionally, a reduction from baseline in serum creatinine kinase CK of over 40% was observed. On Slide 13 are the results for the 10-year-old patient showing microdystrophin expression of 11.1% compared to control with comparable results seen on LC-MS. This patient also had a decrease in CK levels of over 40%. On Slide 14, we also see assessed microdystrophin expression via immunofluorescence staining at 3 months where you can see clear microdystrophin expression in a high proportion of muscle fibers as well as localization to the muscle cell membrane. So in summary, results from the first 3 patients show RGX-202 was well tolerated and initial results from the first 2 patients show robust microdystrophin expression and appropriate localization to the muscle cell membrane. Now in addition to these new interim clinical results, we also present new preclinical pharmacology results in the mdx mouse model that are shown on Slide 17. The same 2 doses being evaluated in AFFINITY DUCHENNE, 1E14 and 2E14, manufactured by the commercial-ready process demonstrated highly statistically significant improvements in muscle function as assessed by grip strength and treadmill exhaustion compared to untreated mdx mice. It was also observed that the 2E14 dose restored both grip strength and treadmill performance to wild-type mouse levels. So these strong preclinical results further support our plans to immediately initiate dose escalation to dose level 2. We are also excited to announce the approved amendment of the protocol to allow accelerated development by being able to expand the dose level 2 cohort after dosing of 2 staggered patients instead of the 3 previously. We, in addition, expect to initiate pivotal phase development in 2024 with a clear path to submit a BLA using the accelerated approval pathway with microdystrophin expression as a surrogate endpoint for clinical benefit. And with that, I'm glad to have the opportunity to turn to Dr. Veerapandiyan principal investigator in the AFFINITY DUCHENNE trial. And for those of you on the call who don't know this, Dr. Veerapandiyan is affectionately known by patients and families and his colleagues and us by the name Dr. Panda. So Dr. Panda, first, thank you for joining us today to discuss the 202 program. You're not only a very experienced Duchenne clinical trialist, but you actually treated 2 of the boys within the trial that we discussed today. So I think it would be great to start off hearing from your standpoint as not only a clinical trialist, but a clinician who treats a lot of Duchenne boys in your clinic. Can you tell us how do you think of these results? And what are some of the key takeaways for you when you see these results?

Thank you, Steve. Hi, everyone. Steve, like we always say, I think there's still an unmet need for these boys with Duchenne muscular dystrophy for a treatment that can change the trajectory of the disease. Can you hear me okay?

Yes.

So I think while these results are early, I'm very excited and encouraged what we have seen so far, right? So when you talk about the safety, we know that overall with the gene therapy, stated AAV-based gene transfer therapies, there are adverse effects that can be seen within the first 2 weeks and then there's a set of adverse events that can be seen around 4 to 8 weeks after they [indiscernible] to your immune system. And I think I'm pleased to see that at least 2 of these patients have passed those thresholds, and we have not seen any serious adverse events on any of them so far. I think that's very encouraging. And from an efficacy standpoint, the robust expression of microdystrophin that you have presented, that we have seen in these boys. And also, the microdystrophin is actually seen where it should be staying on the muscle cell membrane. So I think this is all very encouraging and exciting. And I'm looking forward to continue to follow this boys long term and also to move on to the next dosing phase, which is a dose 2.

Excellent. Thanks, Dr. Panda. You mentioned not only the safety but also being pleased with the biomarker results that we're seeing. Maybe you can say a little bit more about that and maybe your perspective on what can elucidate it in terms of the differentiators of RGX-202 vis-a-vis the functional elements of the CT domain. Are those differentiators aspects that are important context when you look at the results here and you think of potential benefit for your boys with Duchenne?

Right. I think like Ken had explained about the construct and the importance of the C-Terminal domain. I know from -- we know from the preclinical studies and data we have that's actually the domain is important in maintaining the structural integrity of the muscle membrane and also for the other proteins to be involved in this whole complex of keeping the muscle membrane intact and the muscle fiber intact. But I think how that translates into a boy with Duchenne and how is that going to affect the disease trajectory. I think we would know from the study, and I'm excited to see that difference in the concept and see what -- how that can effect the microdystrophin levels and especially the functional outcomes related to that. I think we also touched upon the biomarkers. One other impressive thing that we noted here is the serum creatinine kinase level drop around more than 40% of their baseline, which is quite impressive. These boys have high serum creatinine or CK levels from the get-go, from their bond indicating the muscle damage and reduction of that, it's quite impressive. Now one could argue that could some of the steroids that are being given in some of the other immunosuppressive agents that were given proactively, could that play a role in the reduction of CK levels. Again, that's why we can't completely exclude that, I think still this amount of production is impressive. We need to collect that CK data long term as we continue to follow this boy, should be much more helpful.

Great. Thanks again, Dr. Panda, for sharing your insights. And now we'll turn the call over to the operator so that we can take questions from the audience. Operator?

[Operator Instructions] Our first question comes from the line of Gena Wang of Barclays.

I hope you can hear me okay. I don't know if my signal is good enough.

We can hear you, Gena. It's Ken.

Okay. Perfect. So first, I wanted to say congratulations. And I have tons of questions, but I will limit myself to 2 questions, and I'll leave my colleagues also ask other questions. I will jump back to the queue. So the 2 questions is the first, it seems like the protein level is very good, very -- for the 4 years old. So the question is why in rotation 4 to 11, when we look at across all the clinical trials or like the ongoing clinical trials usually the 4 to 7, and we understand the older patients, the muscle, you have more damage and more irreversible damage. So it will be a little bit more difficult to improve. So maybe first question is why going after an older patient, not limit to the younger patients that will be easier to show clinical benefit. And then my second question is regarding the regulatory path in the biomarker for approval. Was that based on the FDA feedback?

Thanks, Gena, for the good questions, and thanks for limiting it to 2. We know everyone's probably got a lot of questions, so we'll keep everyone moving. I think you bring up a good point about the data. We're being as, of course, transparent as we always are about everything that we're generating. We don't have access to all of the data from all patients that have been treated with AAV microdystrophin with respect to microdystrophin levels, for instance, in some patients in trials that have been dosed over age 7. So I think we do have sort of some of the best comparability data between sort of that age range of 4 to 7 and what we're seeing with respect to the 4-year old. With the 10-year old, we're excited about these levels. I think there's a lot of discussions going on with respect to the team and the physicians about how to think about what can be achieved in patients of those ages and sort of different backgrounds of disease. And the fact that we're seeing strong signals of expression on both western blot and LC-MS gives us confidence that this can, as Dr. Panda alluded to, have the potential to change the trajectory -- trajectory rather of patients in that age range as well, even maybe sort of let him speak to how he views the difference between the opportunity to preserve function in a 4-year old versus a 10-year-old. But on the biomarker point, Gena, look, we -- the accelerated approval of the first AAV gene therapy product on the basis of microdystrophin, I think, is a strong regulatory and legal precedent. We have been lobbying for that and emphasizing it with our colleagues for years. We formed the pathway development consortium with solid and teams with them on making arguments for the use of biomarkers to support accelerated approval in Duchenne. I know that a lot of industry participants support that, and we believe that FDA has made it clear to industry sponsors with respect to the class of microdystrophin, this is an acceptable endpoint. So we rely on that. We rely on the historical conversation of discussions in that action. Dr. Panda, I mean, thoughts about 4-year-old and 10-year olds and the opportunities in both cases to affect disease and preserve or improve function.

Sure. Yes, that's a great question, Gena. I think One of the things there is -- one, there's not a lot of possibilities or options available for those late ambulatory bodies. Number one, I think it's -- there's a greater unmet need for that group. And that way, I'm so happy to see that we're including boys older than 7. But to your point, I think from a safety perspective, right, I think the age really is not key. It's how much they weigh. I think the more vector load that you gave that some increase is adverse effects. I think the age factor doesn't play into role in that perspective. But obviously, when they're older, their disease is more progressive. So as the muscle there, I think it may be hard to show a functional improvement within a short period of time in those boys. But from a microdystrophin -- from a microdystrophin expression perspective, I think it's important to know that these older boys who have a more severe disease have more muscle gone also showing expression and where it's supposed to be there is critically important if you are looking at long-term approvals for these boys.

Thank you. operator?

Our next question comes from the line Dane Leone of Raymond James.

Congratulations on the first data set here, very exciting. I'll follow Gena's example and limit myself to 2 questions here. So 2 related questions. I guess the first one being the microdystrophin expression from both boys, I think came in at the higher end of expectations, which is great. Could you opine a little bit on, one, what you would expect in terms of a potential dose response when you're doubling the dose into dose level 2 and what that could be reasonably expect to effect on like our dystrophin expression levels? And then secondly, focusing on the older patient, patient 2, who is over 10-years old, the 11% microdystrophin expression does seem like you could potentially get into a clinically relevant range with the higher dose level. What would be the expectation of what you would need to hit on microdystrophin expression to feel good about seeing in real clinical effect on different functional assessments like the North Star Ambulatory Assessment.

Yes. Thanks, Dane, and thanks for your continued leadership on keeping it to 2 questions as well. So look, I think we're incredibly enthusiastic about the results that we're seeing early here with respect to microdystrophin expression. And we're eager to start to build the case for the relationship with functional assessments. I think -- we had a set of preclinical experiments that we had done to sort of design the study. And that was relying on the fact that we had a dose curve that sort of signaled that 1E14 was going to be -- starting to be a minimally effective dose. I think it has presented so far as having met or exceeded the expectation. But with respect to 2E14, and I think we brought this forward, we were running this preclinical study recently to really dig into a head-to-head comparison between 1 and 2E14. And we started to see functional benefit differentiation, not just from wild type and near normalization of wild-type function with 2E14. But separation, even between 1E14 and 2E14 that got us similarly excited. And that really between that, the safety data that Dr. Panda has been emphasizing the levels of microdystrophin. We think we can get more. Can we get 2x the levels of what we're seeing at 1E14, I think it's within the realm of possibility, but we need to see. I think functionally, though, we think we can achieve more at the higher dose. And we want to start dosing that dose as soon as possible, certainly before the end of the year. And be able to make a dose decision as efficiently as possible and as early as possible in 2024 to be in pivotal phase. So I think we'll be relying on safety and the other measures that we presented today to be able to affect that decision. Again, reflecting on, I think, the 10-year old, we have been aware of and familiar enough with kind of the points that Dr. Panda made that, look, there's less muscle, more muscle, more functional muscle has eroded in older children. And there's a higher unmet need and there's -- on a weight-based dosing, there's more virus that needs to get to these kids, which in some ways, present questions about are we presenting with something that can continue to show safety, which we so far have been really comfortable with and happy with. And on the other case, we really want to help these boys. I mean there's clearly still a significant unmet need here. I think there needs to be more data, more community engagement. I go back to that Slide 4 that I showed. I think the number of people in the community, a number of families, the number of physicians that have expressed significant interest in that unmet need. We're going to be really efficient about the execution of the development in the 4 to 7 age range. I mean there's a playbook there now that I think has been carefully curated and managed by a lot of stakeholders. And I think we want to follow that and I think in the 8 to 11 range, we want to continue to generate more data and have, I think, the advantages of things like the science of the CT domain potentially address more of the unmet need there as well. Dr. Panda, I feel like this question is going to keep coming up. I'm going to bring it back to you again. I mean anything else in the clinic that you see about a dystrophin level -- microdystrophin level in a 10-year-old that you can comment on?

I think -- yes, thank you, Ken. I think, Ken, the double dosing going up to the higher dose, double the dystrophin levels, I agree with Ken. We don't know it's still -- it may be possible, but [indiscernible] actually doubling it, right? But one thing we need to -- when we talk about the functional improvements and other things we need to keep in mind is, we have seen -- we have seen a change in the course of the [indiscernible] in treatment -- in dystrophin restoring treatments that make much lower level of dystrophin than what we are talking about. So I think that's -- so I think we need to keep that in mind. And also we are not -- we are going -- the microdystrophin expression we're going to see is going to be a range. I don't think every -- we're going to -- because every single voice differently, the same having seen generic change can look different in these boys. So every single one is individual boy. So there's not going to be one magic number that we're going to skip to, "Hey, all of these boys are going to have 50%, 60% dystrophin production." It is going to be a range. And we know overall, over a long period of time, you will find the difference in those boys who were treated versus non-treated. If that helps you get a picture.

Yes. Good context. Thanks, Dane. Operator?

Our next question Comes from the line of Alec Stranahan of Bank of America.

And I just wanted to offer my congrats on the data as well. Just a couple from us. Just to put a finer point on the baseline characteristics. Could you maybe speak to the commonalities or differences in enrollment criteria for RGX-202 compared to the study for crepitus drug. I imagine many people will be using the study as a benchmark for activity. And the second question, just going back to the point on regulatory setup with the FDA. Do you think that now there is an approved therapy for DMD that non-inferiority will be required to be shown even if a surrogate endpoints such as microdystrophin expression remains the bar for approval?

Sure. No, I don't think non-inferiority will be something that will be a requisite, I think we're looking at. And there's evidence of this, even in the existing exon-skipping treatments where NS Pharma came in with sort of a follow-on, relying on the same sort of biomarker evidence, if you will, of near full-length dystrophin from the exon-skipping products for an accelerated approval in the same mutation as a pre-existing Sarepta product. So I think we're pretty familiar and comfortable with what the regulatory pathway is here to navigate right now. And I think that, that remains the plan for how we execute efficiently as possible over the next several years. With respect to the enrollment criteria in this trial, I mean I'm not sure precisely which additional trial or a set of trials, you're comparing it to or you would like us to compare it to, Alec, I don't know all of the details. All I know is we certainly have an age range that's different and wider than many other trials that have been run in the background of the Sarepta program, but they've had other cohorts where they've included older patients as well. I just don't know that we've seen as much of the data from some of those cohorts and evidence. But certainly, groups including Pfizer and Solid have previously reported on older boys and also shown evidence of measurable microdystrophin protein expression. So I think we're just really pleased with the weight and age of this patient at this stage in our trial to see something that we think is a very pronounced signal and we'll be looking carefully as we alluded to, to more of the functional outcomes to be able to guide where we're going there. I do think that what we want to keep doing going forward is stay focused on board access for Duchenne boys with RGX-202 as long as the profile continues to be safe and is supported by our partners and the caregivers in particular, who are seeing the boys. There may be opportunities depending on what's available to us for enrollment. But on a regulatory basis, there is a precedent right now for 4 to 5. And I think also labeled evidence for data in the 4 to 7 range, which I think is leverageable. And I think 8 to 11, though will not be left behind. I think it's an important part of the unmet need. I think it's an important part of the execution and the reason for improving on pre-existing microdystrophin is if we can show more -- even if we show the same levels of protein, but we can show more function we might have responses in boys, as Dr. Panda alluded to, I think he might have been talking about ASOs as well as you [indiscernible]. But when you get new science involved, you might be able to show responses even with some of the same levels of "measured" biomarkers, but things that are more functional, more potent. And I think that's how we'll be approaching the next period of time is dose escalation, efficient enrollment to be able to support getting treatments to age ranges and mutational backgrounds and natural history background of boys with high unmet need as quickly as possible.

Our next question comes from the line of Ellie Merle of UBS.

And congrats on the data. Just in terms of the functional data next year, can you just give us more color on, I guess, what strength and functional assessment endpoints that you plan to report and how you expect these to compare to other gene therapies in the space? And big picture, just how we should think about like when and what could show proof of concept for the CT domain translating into potentially greater benefit. And then second question, just can you elaborate a bit on your western blot method you used, and I guess how we should think about that method relative to others using the field in thinking about data comparisons.

I'll let Steve and Dr. Panda maybe talk about how the functional assessments are conducted in the trial and where things are going.

Sure. So I'll start. Yes, so next year, will be great that we'll have longer-term follow-up. And we've talked before about 3 months, certainly being too early. But once you move into 6 months and even more so 1 year than some of these functional outcome measures take on more weight. So we'll certainly be looking at NSAA, of course, but also time function tests, measures of strength and also even caregiver reported outcomes. So these are all the totality of a lot of the different ways we can assess these patients. Dr. Panda, maybe you can elaborate on the types of functional outcomes that you'd look for.

Yes. I think you have covered it. I think it's kind of comparable like any other studies that need with outcome measures for functional assessments, the North Star [indiscernible] and I think these are some of the things, I think 10-meter walk, 10-meter walk and run tests, these are standard functional assessments that we use in the clinics and also being done in other clinical trials. I think we're also using some imaging, the MRI of the skeletal muscle and cardiac muscle as an exploratory end point as well in addition to the patient reported outcomes.