REGENXBIO Inc. (RGNX) Earnings Call Transcript & Summary

Good morning. If you are recovering analyst, please join the link that was e-mailed to you by [ Dan Cormack ] McCormick instead of the public link so that you can be a part of the Q&A session. With that, I will now turn the call over to Ken Mills, CEO of REGENXBIO.

Good morning, everyone, and thanks for joining us. Today, we're excited to share new positive efficacy data from the AFFINITY DUCHENNE trial of RGX-202 for the treatment of Duchenne. Since our last update on February 7, we continue to be very encouraged by the data we observed in this trial. A couple of housekeeping items before I kick us off. For our covering analysts participating in the live Q&A today, you'll be muted throughout this presentation. Once we begin the Q&A section, please raise your hand if you have any questions. [Operator Instructions] Turning to the second slide of this presentation, you will see that today's event will include forward-looking statements, and here is our forward-looking statements disclosure. Please be advised that today's call is being recorded and webcast. Okay. Let's move to Slide 3, and here's our agenda. I will give an overview of today's positive update. Then Dr. Steve Pakola, our Chief Medical Officer, will review the data from the AFFINITY DUCHENNE trial. Importantly, we're pleased to have Dr. Aravindhan Veerapandiyan, Principal Trial Investigator on today's call and to engage in a discussion with him about the trial data and what he's seeing in the clinic. Dr. Panda, as he's known among his patients and families is joining us from the Muscular Dystrophy Association Clinical and Scientific Conference in Orlando, and will also be sharing these positive interim results on podium at the conference tomorrow. As part of his MDA presentation, Dr. Panda has a video featuring an early look at clinical videos from a couple of dose level 1 patients and home videos provided by the family of the first dose level 2 patients. Before I turn it over to Steve and Dr. Panda, let me share a few important reminders about RGX-202, our potential onetime therapy for the treatment of DUCHENNE and this new data we have today. On Slide 4, we highlight a few things that makes RGX-202 special, including among AAV mediated microdystrophin treatments. First, it expresses a new differentiated microdystrophin with important biology that is most similar to a natural shortened dystrophin found in boys and men that protects muscles from degenerating. RGX-202 has the only microdystrophin design to deliver a transgene that includes the functional elements of the C-terminal domain found in naturally occurring dystrophin. All this really means is that it's designed to be the closest thing to recreating healthy muscle throughout the body. Also, RGX-202 is designed to be great for targeting muscle and it represents an important potential alternative for many boys who may not be eligible for other therapies. Now Slide 5 presents our outline of our trial design for RGX-202 and its enrollment and safety status. We are enrolling boys who are generally confirmed genetically with DUCHENNE between the ages of 4 and 11 who are ambulatory. The primary endpoints of this study are safety and tolerability at 12 months, but across the 12-month period, we will complete a number of assessments including a strength and function of all the boys. At 3 months, we take our important measure of microdystrophin expression, which gives us the evidence that our gene therapy is expressing in muscle and exists as one of the strongest and most validated biomarker predictors for the likelihood of clinical benefit. We've announced that we've enrolled 5 boys in this study to date, 3 at the first dose and 2 at the second dose. We will have an opportunity to enroll additional boys in this study. Overall, the data shows that RGX-202 has been well tolerated in all 5 patients treated. This morning, we announced the first microdystrophin data from dose level 2. This was from a patient who was 12 years old at dosing, and we're thrilled to share that this microdystrophin levels are robust. Notably, this level of microdystrophin was significantly higher than that of a dose level 2 patient in a similar age range among, say, 8 to 11-year-olds. With that, I'm going to turn the call over to Steve now to share more details about this data and the interim results to date.

Thank you, Ken. I'm pleased to present today new positive interim results from the AFFINITY DUCHENNE trial. We'll start with the dose level 1 interim efficacy results on Slide 7, which has previously been presented. Microdystrophin expression was calculated via the Western blot Jess method and percentages listed or percent of normal control. Of note, all 3 patients showed robust microdystrophin expression, and reduction from baseline in serum creatinine kinase or CK levels, supporting evidence of clinical improvement. And this 202 activity was observed across the broad age range. And now on Slide 8, for the first time, we present the interim efficacy results for the first patient treated with RGX-202 dose level 2. RGX-202 of microdystrophin expression level at 3 months following RGX-202 administration was 75.7% of normal control. Additionally, there was a reduction from baseline in CK levels of 77%. Moving to Slide 9. These results in the dose level 2 treated patients are particularly striking when considering the age of this patient, 12 years of age at the time of dosing. We were already excited to see in dose level 1, not only robust microdystrophin expression in all patients, but greater than 10% expression even in the over 10-year-old boy with this lower dose. So to now see a dose level 2 in an even older patient, an expression level of 75.7% is quite remarkable. On Slide 10, we see that not only is their robust microdystrophin expression, this microdystrophin is appropriately localized to the muscle cell membrane as shown on immunofluorescence staining. To recap, RGX-202 has been well tolerated with robust microdystrophin expression at both dose levels in all ages. We are encouraged by the observations of early improvement seen in the videos that Dr. Panda will share. We remain on track to initiate a pivotal trial in the second half of this year. We continue to be excited about the microdystrophin expression data to date, and we are also pleased with what investigators are sharing about their patients. Now we will transition to the Q&A session. So Dr. Panda. Good afternoon, and First, of course, thank you for joining us. We know you're on the ground there in Orlando at the MDA conference, and we know you're busy, of course. So I think to kick things off, why don't we hear what your thoughts are on this data. And I think particularly your -- how you're feeling about the data that you're going to be presenting tomorrow.

Good morning, Steve. And good morning everyone. I think it's -- I guess, sure -- I think it's -- I'm very pleased to see the robust microdystrophin expression to begin with. And consistent with the dose level 1, also in the dose level 2 boy and also -- regardless of the agent, he's the older one, he was 12 years old, and this microdystrophin expression was robust, which I'm very excited to see that. And also the videos that I've shared from this mom is quite telling. These are the day-to-day activities that these boys will not be able to do without treatment, and now they're doing better. And the stories that the mom and the kids is sharing me, it's quite telling. So I'm very pleased with this preliminary results that I'm saying with microdystrophin expression as well as well as the functional improvement -- the early functional improvements that we are seeing. And from a safety perspective, like you said, I think it's -- we haven't seen any serious adverse effects on any of these boys we dosed so far. So I think that's also encouraging. And I'm very excited to share these results with our colleagues here in the Muscular Dystrophy Association Conference and spread this positive results here.

So you mentioned being pleased with the microdystrophin expression levels as we moved up to dose level 2. Do you have any perspective when you think of the differentiation of 202 that Ken discussed, the fact -- the actual results that we're seeing where at this age group, this much older age group, where there really hasn't been other data presented outside of what we presented when you get up to this age group, as far as now having this data when you consider the dose level 1 patient that was above 10 years old and now seeing this increase at dose level 2 with the 12-year-old patient. Any perspective on those findings?

No, I think it is encouraging. But of course, you're talking NF1 -- there's a lot of -- there could be some factors that could play into -- role in terms of the sampling and the muscle you choose and all of that. But regardless, I think in this age group, having this robust dystrophin expression is exciting to see. And we hope that this predicts a clinical benefit, and we continue to see the more outcomes, the continued more improvements. My expectation, I think at least was from a microdystrophin expression perspective, there is going to be a variable to regardless of the age and I think -- I don't -- I think we don't still completely understand why that variability is happening, but with NF1 to the older boy with 12-year old showing the 75% of normal dystrophin expression. I think it's very encouraging to see.

Thanks, Dr. Panda. I think for the audience, it would be helpful as well to step back. And given this data, just to hear how do you talk to your patients when you're considering potential participation in a gene therapy clinical trial in the context of the landscape that exists for treatment of Duchenne?

I think that's a good question with the therapies in pipeline, the approved therapies and the clinical trials. If I'm seeing a newly diagnosed Duchenne or if I'm seeing that for the first time -- no matter if I'm seeing them for the first time, I'm seeing them. I think it's our -- we're obligated to present options to them, right? So the -- what are the approved therapies that's available versus what's in the clinical trial pipeline, and you discussed what you have in hand from a data perspective and the risk benefits and commercial dosing versus dosing the research setting and making an informed decision based on all of this. And I think -- if I'm discussing the REGENX -- RGX-202 AFFINITY DUCHENNE trial, obviously, I would be showing that, that's publicly available so for -- to them, and to -- so they're making an informed decision based on what we have. And then I think also the therapies that are approved are, there are some restrictions I feel right from age perspective. And if you're looking at exon-skipping agents then that's also restricted to patients who have specific genetic change with [indiscernible] exon-skipping agents. And then -- so I think those things will need to be taken into consideration. We need to discuss these options of treatments and participation in clinical trials. And we just choose the best that's best for that particular boy with Duchenne and making firm decision.

Great. So since we're appropriately talking about the patient and the family perspective here for my last question before we turn it over for the group Q&A. Let's go back to those videos you showed. I wonder if you could give any additional perspective when you see these findings in the clinic and also the patient videos and even what you're hearing from the families when they are seeing these kind of findings?

Sure. I think and I've said this to some of our colleagues as well, I think. To me, yes, the assessments that we do in the clinics are important, like North Star or time to stand, but what's more important to me is how is it impacting the quality of life in this kid. If -- I think that's more impactful for me. And I think that's where -- that's what made me share this videos when the families are showing it is like if they're telling me -- my son wasn't able to play with his siblings, but now there is a chaos in the household. Always there's arguments between brothers because the brother who has Duchenne is unable to play with the younger brother who doesn't have than Duchenne. But now it's better. Now they're playing. Now -- so that is a significant change or impactful change that -- in the quality of life. And the riding bike video, I think that's -- this is the first time that he's doing ever in his. That's -- I think that's more impactful to me to get the real world quality-of-life data. How does -- how is that being changed or impacted? I think that's more important for me.

Great. So thanks again, Dr. Panda, for joining us and as well, of course, for your expert insights. So before we wrap up, we have time for a few questions. [Operator Instructions]

Actually, it's going to be me who's going to identify people for questions. This is Ken. So seeing people queued up with hands raised. We're going to start with the Barclays team and Gena, could you mute yourself? Do you have a question?

Yes. First wanted to say congrats on the great data. So I have 2 quick questions. One is for Dr. Panda, and one is for the company. For doctor, so how soon do you start to see patients show the functional improvement if we look at the protein level? So second question for the company. It seems like a dose level 2 is the path forward. Given this data, what would be the age group for your pivotal study? And also, did you get a confirmation from the FDA that single-arm study with protein level will be sufficient for approval?

All right. Thanks, Gena. Good question. Dr. Panda, do you mind answering here?

Sure. I'll go ahead and take the first question. I think on the experience of the RGX-202, the improvement that we're seeing is actually pretty early within a week or 2 after dosing. I think the videos that have been sent to me were also around the same time timeframe. So I think we started seeing these changes within a week to 2 after infusion.

In terms of plans moving forward, Gena, we obviously continue to be on track for initiation of a pivotal in the second half of the year. And yes, we have very dynamic and regular conversations with the agency about the data that's coming off. We're just so -- it's pretty amazing, pretty emotional the past week running up to this data and the share for some of the improvements we're seeing from Dr. Panda and what he is describing. So we've been able to even insert that into our conversations with the agency. We continue to feel strongly that there's really a broad application here age-wise for boys. And we'll be on track for making that pivotal dose selection and completing the idea behind the design of what we think will be an efficient and important pivotal trial. Absolutely, we continue to view that for pivotal microdystrophin as a surrogate that's reasonably likely to predict clinical benefit, we'll support that. Again, we want to stay in a broad age range, seeing the types of results we're seeing in 10-year-old, an 11-year-old who turned 12 just before they were dosed is really encouraging because I think there's been a paucity of data to support microdystrophin, but also evidence of potential clinical benefit there. So we're moving forward with that in mind. And more to come from us, but I think today, I can signal to you, we continue to have those discussions, have had those discussions and have been able to share the data even that we're looking at today with you also with the agency. Thanks for the question. Let's go back into the queue here. How about -- maybe the Morgan Stanley team, Vikram or Gospel are you on?

This is Gospel on for Vikram. We have 2 questions from my end. The first one is, will the MDA presentation contain updated data versus what was presented this morning. And the second one is how does this data impact your thoughts on the trial size and design.

Yes, thanks. So I can take both of those at this point. We have -- now Arvind is going to present the same data that we looked at this morning with all of you to his colleagues, clinical and scientific at the conference in Orlando tomorrow. So what you've seen from us today is going to be I think, a powerful encore presentation tomorrow midday. And sort of similar answer to Gena here, Gospel in terms of the direction of things that are going. We have a goal to initiate pivotal by the end of the year. I think we're looking to do something that's responsive to, I think, what the community needs in terms of unmet need for kids maybe in areas. I think Dr. Panda was talking a little bit about the experience in the clinic today with obviously already some options, including accelerated approved product in certain age range. I think what we've been seeing and what we've seen today has created a -- I mean a renewed sense of urgency for us to be able to program in a trial that is efficient that we can execute on efficiently and as Gena sort of alluded to, I think for us, the safety and the early evidence here of both microdystrophin expression and the beginnings of seeing a series of early observations about strength and function at dose level 1, 9 months and 6 months and early emerging data from dose level 2, we think we can put something in place. It reminds me to, Gena, and Gospel, I didn't answer the question about placebo control. And I think that we've heard loud and clear from the community, and I'm sure the physicians and the clinical trialists agree with this. There's just not really something that is acceptable for the Duchenne community at this stage in terms of installation of long term. But even short-term, placebo control arms in trials, there's too much unmet need. There's too much serious consequence for that. So -- and we're getting a real sense that, that understanding has landed into the FDA, and they're supportive of using ideas like natural history and sort of other types of control arm benefit assessments based on what's known. So I think that also will contribute to our ability to enroll and execute efficiently in Pivotal. Thanks for the question. Let's see. Maybe we can go to Bank of America and Alec.

Yes. Just 2 quick ones from us as well. Maybe first for Ken. What should we expect from the next MSA functional data I guess, what would be a good bar for the new data later this year? And then one for Dr. Panda, if you still on, given the data today in the 12-year-old, do you now see 202 as maybe the de facto study you'd recommend to new patients, especially if an older boy comes into your clinic, given there's currently limited options for these children?

Arvind, do you have a comment there? We will go in reverse order.

Sure. Can you repeat that first question? Sorry.

Yes. It was a question from Alec about your thoughts on recommending patients for trials and whether or not AFFINITY DUCHENNE and 202 stands out for you in general or for certain types of patients at this stage, maybe?

No. I think definitely for the -- with the current trial setup with the inclusion, exclusion criteria in mind, definitely, this is something that we would discuss as an option. Again, like I was alluding before, the options for those older boys is very limited at this point of time. And I think -- this opens up a door and it is encouraging for them to have a clinical trial that actually addresses that age group. And I think that is definitely something that we discuss with our patients.

Yes. No, thank you. Alec, your first question, I mean, obviously, we remarked today that several of the items in the clinic recordings are part of the time tasks are things that are also measured in North Star. And I think Dr. Panda has also emphasized that obviously, from his perspective, I think some of the quality of life heard him say and kind of evidence that comes in from sort of day-to-day activities is also important. I think as we have guided in the second half of the year about functional results that it would include strength in functional assessments for both doses, we're going to be continuing to play out the trial assessments from AFFINITY DUCHENNE, including North Star and the sub-domains thereof. And have a more complete data set for patients that have been dosed at dose level 1 and dose level 2 with respect to those assessments in the second half of the year, obviously, just given the passage of time and how the trial is designed. So we're excited to bring that forward in more full form. But when we had the opportunity to get the microdystrophin result this week, and Dr. Panda contacted us about some of the existing 9-months and 6-month evidence at dose level 1 and the emerging things you were seeing, even with the first patient at dose level 2, we felt it was important to insert this into our regulatory discussions and therefore, publicly as well. So definitely more of the full domain assessments in the second half of the year is what we would target as we continue to share data about the study and make final decisions about the pivotal. We can go to Annabel at Stifel.

Can you hear me?

Yes.

Right. So this is for Dr. Panda. So I was just curious if you saw any correlation between the microdystrophin expression in these patients of whom you had videos and improvement that they experienced. And just separately on the 12-year-old, which I realized he was 11 when he got into the study, but was there anything about this boy that suggest he would have a higher expression than what we saw in some of the younger boys and even seeing the level of functional improvement and strength? I assume this age group would have been already too far deteriorated. So maybe you can provide some color there.

No. I think -- kind of -- no, we talked about the sort of correlation between the function and dystrophin expression. I think it's kind of -- to sort of comment on the NSAA scores and so previously we don't have the functional assessment data. But definitely, we know dystrophin expression core -- it's -- they have no dystrophin and dystrophin expression correlated more improvements. From how he then as an older boy having higher dystrophin expression, I think I don't know if we have a clear answer for that, one, we expect that he have more muscle damage, the dystrophin expression could be lower, but I don't think there's a lot of factors that play in -- that come into play there. Is it a sampling probably in the muscle that you choose, but having said that, all of these patients had exam same biopsies from the exact same muscle. So I think that variability in the dystrophin expression is something you need to look into more and why is that happening? And this is something we have seen across other programs as well. Does that -- does that make sense?

Yes. And if I could possibly get a follow-up here. Is there any clarity at this point on -- you all refer to the NSAA for the functional test, but we see that score has tripped up some other companies. So is there any further clarity on what type of functional and strength measurements, the FDA may accept further on down the line when you're looking for not just the accelerated approval here, but for full approval? Maybe you can comment on that, Ken or Steve?

Yes, Dr. Panda, please.

No, that's fine. I can throw my 2 cents. I'm glad that he brought up the NSAA. I think the disease that we're dealing with here is so heterogeneous, and it's slowly progressive. I think to see a meaningful difference that is statistically significant with NSAA, it needs longer follow-up, more than a year or even 2 years and 3 years. I think practically in the stage where -- with the disease's unmet need, I don't think it's fair to keep these patients that long on a placebo or to see the treatment effects are difference, right? So I think some of the other endpoints that we could well, possibly use would be those -- which we -- the FDA had looked -- considered in some of the other trials would be the time to stand [indiscernible] were more on just approve. They are also trying to stand velocity as a primary endpoint and got the approval. And one of the other products that's being revealed right now with the PDUFA date coming up as soon as I think the givinostat I think they have [indiscernible] used as a primary endpoint. So some of those things could be considered as well.

I mean those are great insights from -- I think the source of people that like Dr. Panda, who see these patients and can provide a level of perspective for the agency and for us as sponsors into what we can rely on to show evidence of clinical benefit. And all I can add on top of that is that we absolutely see the receptivity of the agency and listening and understanding and not applying some strict set of rules about something like North Star, for sure. And I think -- look, we're talking about RGX-202 is something that's new and innovative in the class of microdystrophins, and we're starting to show data now for the first time in terms of strength and functional assessments, that are emerging that we don't rule out being able to incorporate North Star in a meaningful way and to the evidence about performance of RGX-202 both clinically and as we aim to bring it to patients and families on a basis where people like Dr. Panda can think about prescribing it. So again, we can't forget, RGX-202 with the C-terminus has biology that we've been emphasizing for a while is more presentative of naturally occurring dystrophin than anything else that has been brought forward at this stage and this far along clinically. So we think we can tackle things in principle that could be demonstrations that haven't been shown before. And while we're working through this, we're seeing really good progress on, I think, some of these early areas.

I think another important point is that microdystrophin is reasonably likely to predict clinical benefit. So these findings that Dr. Panda is showing as well as any additional functional benefits that we see are really a bonus from a regulatory standpoint because these functional questions of which end points will have more sensitivity and more power really relate to, from a regulatory standpoint, a confirmatory study.

Yes. Good point. Thanks, Annabel. Maybe we'll move to the UBS team and Ellie, are you on?

Guys, congrats on the data. Maybe just as you're thinking about dose selection and what would give you confidence to move forward into pivotal? I guess how many patients and at what ages would you want to dose with dose level 2 before making that pivotal dose selection? And just any more color on what in the second half you expect to start the pivotal trial.

Yes. Look, the trial design, which started at sort of 3 plus 3. And now with early evidence of safety demonstrated, we were able to amend with the FDA to the 3+2 design, I think, is a bolus of data that provides us the foundation to make a decision about safety, about some evidence of dose response. I've said for a while, look, we scientifically and we're led very much here by the science and being transparent about the science. We've rerun these 2 doses in our preclinical models, and we've continued to show separation between dose level 2 and dose level 1. Now we're seeing some early emerging evidence of 2 different boys, but in the same age range, kind of that 8 to 11 range of kind of some increase in expression from dose level 1 to dose level 2 of microdystrophin. And we're seeing good safety. I mean, all of this very much -- this is what we need. So I don't think that there's going to be some more passage of time. There's going to be a bit more inventorying. We, of course, have another patient at dose level 2 that we expect to be able to collect data on now and we just announced we completed that cohort about 3 weeks ago. So sometime in the second quarter, we would have additional results. And I think we'll be in a position as expected to make that pivotal dose decision by mid-year. But we've got a little bit of wind at our back now, in my view, and the feedback from Dr. Panda and investigators is giving us new resolves to move as quickly as possible into that initiation of pivotal phase. I can't say sitting here right now, Ellie, how much time we can gain on kind of our base plan, but this is the type of data that I see today that we're going to be redoubling our efforts to make sure that as soon as we have all the data that we need, we can get to the FDA, complete a pivotal design and move forward as quickly as possible. And it's a great time to be talking with the agency on the these topics because they've got a number of decisions and contemplations that are happening around Duchenne and around microdystrophin expression with Duchenne in other cases as well as ours. So -- and actually in our view sets up as a very good time to have that dialogue and move quickly. Looking at the hands raise a lot, maybe Brian in Baird.

Really impressive level 2 data here. I guess as we're kind of thinking about all pathway, one of the things that really didn't come up, but I'd be interesting in hearing your opinion on is sort of the non-ambulatory patient setting, where it seems to me like there's just the biggest delta in what is potentially available, approvable the data that we have from Elevidys or even from the PMOs and the unmet medical need here. And given your great expression in older patients, how do you think about looking at non-ambulatory patients, can you look at those patients in this current study? And this seems to me like maybe there's a very quick path to approval, perhaps even quicker than in the ambulatory setting, given Elevidys' pricings. And I guess for Dr. Panda, do you think sort of [Duchenne] in muscle biopsies is enough to have confidence in a non-ambulatory patient's efficacy at this point?

I can -- yes, I think my opinion about non-ambulatory is not just the dystrophin expression or it's not just age or ambulatory status, it's more about the weight and the [chronic research] from the learnings that we have had from the other programs. I think personally, I would be comfortable with dose limitations, with dose caveats, keeping in mind we're dosing them safely to move on to a non-ambulatory patients -- patient dossing, but of course, it's not my decision. It's always going to be hard for us to argue with the people that are experts in the disease, Brian, about the pathway for moving forward. And again, the influence that Dr. Panda and his colleagues would have on FDA's thinking about that will be important. Look, where we are is we've obviously focused early on in the differentiated benefits of 202 in 4 to 11 ambulatory and the fact that we're, I think, seeing the type of results in this older age range in the 8 to 11 is giving us some conviction and is allowing us to have conversations and discussions and thoughts specifically with Dr. Panda and other investigators about what are other types of cohorts, if you will, opportunities for expanding and sort of also accelerating the development. And that includes the notion of non-ambulatory, the notion of age ranges that haven't been studied as deeply and/or as transparently have been limited in terms of data that's been shared. And even concepts around mutation status and things that have been excluded previously. But I think Dr. Panda's point is an important one. Safety is paramount here. And so far we have -- not just in an age range, but in a weak range, been able to show a well-tolerated safety profile. So again, our goal here is about efficiency, transparency with data and finding new areas to contribute something to the community, both the physicians, the families, FDA and for ourselves, knowledge that doesn't exist. We think that is the recipe for success in terms of how we can benefit everyone that the stakeholder here and accelerate things as quickly as possible. So I love that you're taking that away, Brian, because I think it's telling us that I think it's reinforcing for us people that think on these topics that this is opening up a spectrum of things for us to look at not just to accelerate, but to grow value for patients. I think Danielle and Raymond James.

Yes, the question and congrats on the promising data. So I have 2, one for the company and one for Dr. Panda. For the company, trying to better understand the contributing factors other than dose that might explain the striking difference between the 2 older patients that were enrolled. And were there any notable differences in baseline characteristics such as baseline NSAA, dystrophin expression or mutation status? And then for Dr. Panda, I know the data are early, but curious based on the results to date, where do you see 202 fitting into the landscape with Elevidys on the market?

Thank you. And that's my question first. I think with the commercially available delandistrogene, as we all know right now, it's only approved for age 4 and 5. So I think -- but the clinical trial here, it's broader range for the age of 4 to 11. And I think that's definitely that's there. And even if I'm seeing a 4 to 5-year old in the clinic, I think in my clinical practice, I'm presenting all the possible options available for them, right? That is commercially available product versus the clinical trials as well. So I think we discussed that and we'll -- definitely, this is an option that comes up and we discussed that as well and make a decision from that. And also, it's, again, kind of there's still an unmet need in terms of like if someone is finding out before from a mutations perspective and also the antibody status would come into play as well. So there are several other factors that come into play. But definitely, this is something that we would discuss in the clinics to consider.

Yes. And Danielle, on the -- the correlations in terms of difference, I mean, really the strongest correlation has been the dose level. I mean there is not -- I mean the inclusion criteria in this study, I mean, obviously, we repeated the age range. I mean, genetic confirmation of Duchenne mutations in their baseline status in terms of meeting the test for ambulation and kind of how these patients are coming in we've seen. Obviously, some variability because we have -- and even Dr. Panda was just emphasizing, we've enrolled a 4-year-old. One of the videos from clinic today was looking at the observational evidence in that patient as well as the 6-year-old. We've been emphasizing that right now, we have that increase from the 10-year-old to the 11-year-old in terms of dose level 1 and dose level 2, because that's the evidence that we have in this moment. But that's the strongest correlation. We have the team -- the medical team and I think with investigators have been through and there's no other correlation that's popping out right now, which is, again, consistent with our science in the preclinical data set that we saw higher levels of expression with dose level 2, which is why we recommended it to FDA as part of our dose escalation, and we also saw separation between dose level 1 and dose level 2 in terms of function and strength in the animal models. And I think we're really encouraged and enthusiastic that, that will reproduce itself. So thanks for the question, Danielle. CRBC, Luca are you on? Or Lisa?

Two quick questions. Maybe one on prophylaxis here. Can you just remind us about the difference in prophy regimen versus Sarepta? I believe they're just steroids versus you're using also Solaris and sirolimus. So just 2 questions. One, is that correct, too? If that is the case, their verge in the future here where you may be going to align with them and just use steroids, getting any help, much appreciate it. And then maybe on the eligibility, can you just remind us what percentage of patients are not eligible for Sarepta just because of neutralizing antibody status. I remember you guys mentioned 15%, 30% in the past. I was just wondering if that's the latest thinking.

Sure. Dr. Panda, do you want to talk anything about kind of the protocols that we're using in terms of running for safety and your experience with it in terms of its manageability?

Sure. I think like we rightly pointed out, we used eculizumab, sirolimus and corticosteroids. And -- so far, it's been well tolerated. We haven't seen any adverse events even that protocol per se. And from a practical logistical standpoint, these kids taking that also, we haven't seen much of a challenge. But I think that's good. And even when we talk about this unmet need and some of those low exons, high-risk genetic change, having this proactive immunosuppressive regimen in my opinion is probably the way to go. And I think that's how the future holds. And as we get -- with that immunosuppressive regimen, it actually gives more comfort level to treat those patients with high unmet need, especially the high-dose mutations. Yes, we haven't seen any challenges with this immunosuppressive regimen in the trial.

Yes. Thanks for bringing up that point because I know it's been a specific discussion with you and for the community about how the application of an immunosuppression protocol may open up opportunities for treating boys where maybe other trials or other instances have presented themselves vis-a-vis concern. And I think that some of the mutations on the end terminal end of dystrophin naturally have been things that have been part of that discussion. So I do think that gets back to the kind of theme here of not just the difference in biology, but I think a broad spectrum approach to safety for as many boys as possible, different mutations, different age ranges, different weights and sort of -- has been an approach for this trial design from the beginning. So I think continuing to open up options not just for acceleration and efficient implementation of pivotals, but for exploring new areas that may be untouched right now by some of the previous microdystrophin products, which does get to the neutralizing antibody status question, Luca. And yes, I mean we generally have seen and we talk about the fact that AAVs have a kind of standard serological pre-existing prevalence in communities, especially children of these ages that we're talking about of, I mean it can be 30%, 40% of boys who may be ineligible for treatment that can have variability. When we've talked about a conservative insertion point for RGX-202, we've layered in the fact that we're aware that, of course, Elevidys has entered the market with a certain AAV serotype. The Pfizer is running a trial that has reported enrollment, and we'll -- we expect can report data at some point. And so we're kind of giving guidance to the market that in a scenario where there are 2 other AAV products, this would be true not just for us, but it would be true for the corollaries of those other sponsors that the Venn diagram may look more like 15% of boys that would be just unique and sort of indiscriminately available just to like the AAV8-based capsid that we use in RGX-202. So that's, I think, how we think about the AAV immunology. But then again, as you start to layer in changes in what we're seeing today and the impact of that, if you go to a population of boys either on an age basis or on a mutation basis, that is an access by those other treatments. And again, I think you would see 70% of those boys being eligible for something like RGX-202. So I think this is becoming a very important and dynamic conversation and one that we're just happy that our science and data is contributing to because we know there's still significant unmet need here for patients and families with Duchenne. Getting down here to the -- near the end, Mani and Leerink team, are you on? Able to ask your questions?

Congrats on very impressive data. A quick question around that Venn diagram dynamic that you brought up. Obviously, there's going to be patients who fall in the eligibility criteria for one or another AAV and a relatively modest number who are broadly available is sort of more of a -- sort of free for all. For Dr. Panda, how do you -- how does their parents think about choosing between these agents? Are there specific data points they are looking at? Do they see the safety as different? How does that decision get made in the conversation that you're having with the family?

I think that's a great question. There's a lot of factors again come into play like it was saying, we are discussing the options, right, the commercially available, what data that they have. And also the other options, it's quite variable. That depends on the family, that depends on how sophisticated, educated they are. I have had families who come up to me and said, "Hey, they look into the seat, seat terminals and then I want to have -- be in the study because of that specific reason and also the -- they have good knowledge of the preclinical data" and that is commercially available. I mean that's publicly available on RGX-202 with the same group, the 4 to 5. But on the other hand, I also have families who would come and say that this is approved by FDA, but I don't want to be in a trial -- in a research. So it's quite variable depending on the families. As long as we are putting out the options that we have and talk about the pros and cons, and I think that's important. And I know there are also in the clinical factors, sometimes they would say, yes, this is all good, but what would you do if this was your kid? I think that also comes into play. So I think there's a lot of factors, and it's very individualized based on the patients and the families that you're working with.

Thanks, Mani, for your question. And I think we're down to -- I see one more hand up to Danill and Chardan team.

Congrats on the data. One on safety. I was wondering if you could provide any additional color in terms of any adverse events? I know there's no serious adverse events, but maybe any other signals that you're seeing, liver enzymes. Do you see any correlation with age? And have you used any -- or have you have to use any interventions outside of prophylactic regimen?

Thanks for the questions. I think we haven't reported anything drug-related and certainly no serious adverse events today. We have evidence of this being well tolerated across all 5 boys. And I think very -- obviously, we've run a lot of trials as REGENXBIO and people have used a lot of our vectors. So I think that our context here for well tolerated in an important disease like Duchenne is an important one for us. And I think that we see -- what we want to see for being able to make the types of guidance statements about being able to move assertively and efficiently into pivotal phase. So good news from my perspective. I think that is it for the Q&A. I don't see any hands up. I appreciate the analysts. This is a little bit of a different format for us today with the Zoom. You were all really good at it, and I want to compliment you all. Dr. Panda, I'm just really grateful. I'm sure you're feeling some excitement and energy down there with a lot of things happening at MDA, and we're just so grateful for you to be presenting on behalf of REGENX and to the community on these updates. Good luck tomorrow, and thanks for your overview for everyone today. Look, our initial efficacy with the first patients with 202 is truly enabling us to accelerate this program. It's -- this is a market in Duchenne that they're still our view is a large unmet need for new therapies that's capable of supporting multiple gene therapies, and we think that RGX-202 is unique. It has differentiated features that support its potential to be a best-in-class product. Plans are for the remainder of this year, I think clear, we are intending to focus on accelerating and creating significant value for patients and our shareholders. The resources, I think, are focused in the right areas. The milestones today, reinforced for me that this year, we're well positioned for success. So thanks, everyone, for the questions, the conversations. Thank you again, Dr. Panda. Thanks, Steve. And everyone, have a great day. We'll connect with you all, I'm sure, again soon.